JP2011004620A - Genus lactobacillus strain and food and medicine containing the strain - Google Patents
Genus lactobacillus strain and food and medicine containing the strain Download PDFInfo
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- JP2011004620A JP2011004620A JP2009149173A JP2009149173A JP2011004620A JP 2011004620 A JP2011004620 A JP 2011004620A JP 2009149173 A JP2009149173 A JP 2009149173A JP 2009149173 A JP2009149173 A JP 2009149173A JP 2011004620 A JP2011004620 A JP 2011004620A
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Abstract
Description
本発明は、新規なラクトバチルス・ペントーサス（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｐｅｎｔｏｓｕｓ） の新菌株、その培養物、含有物、乾燥菌末、さらには該菌株の培養物、その含有物またはその乾燥菌末を含有する食品および医薬品に関する。 The present invention relates to a novel strain of Lactobacillus pentosus, a culture, a content thereof, a dry fungus, a culture of the strain, a food containing the content or the dry fungus, and Regarding pharmaceuticals.
乳酸菌は、整腸効果を有する他、最近では様々な疾患の予防・治療効果に関する研究が進んでいる。予防・治療効果の対象は、大腸癌、今後わが国でも増加すると見られる炎症性腸疾患（Ｉｎｆｌａｍｍａｔｏｒｙ Ｂｏｗｅｌ Ｄｉｓｅａｓｅ，ＩＢＤ）、過敏性腸症候群（Ｉｒｒｉｔａｂｌｅ Ｂｏｗｅｌ Ｓｙｎｄｒｏｍｅ，ＩＢＳ）等の腸管疾患のみならず、胃のヘリコバクター感染症（胃・十二指腸潰瘍）、泌尿器疾患（***症や膣感染症）、腸管免疫、アレルギー疾患、循環器疾患、糖尿病、肥満等全身疾患にまでひろがっている。中でも乳酸菌のインターロイキン１０（ＩＬ−１０）産生を介した免疫調節作用が種々の疾患の予防・治療に効果を示すと期待され、注目を浴びている。 In addition to having an intestinal effect, lactic acid bacteria have recently been researched on the preventive and therapeutic effects of various diseases. The target of the preventive / therapeutic effect is not only intestinal diseases such as colon cancer, inflammatory bowel disease (Inflammatory Bow Disease, IBD), irritable bowel syndrome (IBS), which is expected to increase in Japan, but also stomach Spread to systemic diseases such as Helicobacter infections (stomach / duodenal ulcers), urological diseases (urinary tract infections and vaginal infections), intestinal immunity, allergic diseases, cardiovascular diseases, diabetes and obesity. Among them, the immunomodulatory action through the production of interleukin 10 (IL-10) by lactic acid bacteria is expected to be effective for the prevention and treatment of various diseases, and is attracting attention.
ＩＬ−１０はサイトカインの一種で分子量３５−４０ｋＤのｈｏｍｏｄｉｍｅｒの糖蛋白である。ヒトでは主として２型ヘルパーＴ細胞（Ｔｈ２細胞）から産生され、他にも単球、活性化Ｂ細胞、角化細胞など様々な種類の細胞より産生される。その生物活性は多岐にわたるが、他のサイトカインと際立って異なる特徴は「抑制性活性」が中心となっていることにある。 IL-10 is a kind of cytokine and a homodimer glycoprotein having a molecular weight of 35-40 kD. In humans, it is mainly produced from type 2 helper T cells (Th2 cells), and also produced from various types of cells such as monocytes, activated B cells, and keratinocytes. Its biological activity is diverse, but the distinguishing feature from other cytokines is that "inhibitory activity" is at the center.
即ち、ＩＬ−１０は主に単球系細胞に作用して、ＩｇＥなどの炎症性サイトカインの産生を始めとする免疫機能を抑制的に制御する他、リンパ球に対しても単球系細胞を介して間接的に抑制作用を示す。また、アレルギー状態において、ＩＬ−１０はＴ細胞が産生するサイトカインを抑制する働きを持つことが推測できる。アレルギーの患者においては、末梢血単核球からのＩＬ−１０の産生がコントロールに比べ低下しており、ＩＬ−１０を誘導すると、アレルギー反応を抑制できる可能性も示唆されている（非特許文献１）。 That is, IL-10 mainly acts on monocytic cells and suppresses immune functions including the production of inflammatory cytokines such as IgE. Indirectly suppressive action. Moreover, it can be estimated that IL-10 has a function of suppressing cytokines produced by T cells in an allergic state. In allergic patients, the production of IL-10 from peripheral blood mononuclear cells is lower than that of controls, and it has been suggested that induction of IL-10 may suppress allergic reactions (Non-Patent Documents). 1).
乳酸菌等によりＩＬ−１０の産生を誘導した文献としては、ラクトコッカス属乳酸菌によるＩＬ−１０産生の誘導（特許文献１）、ラクトバチルス・アシドフィルス菌株によるＩＬ−１０産生の誘導（特許文献２）、ＩＬ−１２産生誘導能を有さない細菌若しくは酵母又は微生物処理物とＩＬ−１２産生誘導能を有する細菌を組み合わせてなるＩＬ−１０産生促進剤（特許文献３）、ビフィズス菌によるＩＬ−１０産生の誘導（非特許文献２）、ラクトバチルス・ペントーサス菌株によるＩＬ−１０及びＩＬ−１２産生の誘導（非特許文献３）等が報告されている。しかし、これらのいずれについても未だ十分な効果は得られていない。 Examples of literature in which IL-10 production is induced by lactic acid bacteria and the like include induction of IL-10 production by Lactococcus lactic acid bacteria (Patent Document 1), induction of IL-10 production by Lactobacillus acidophilus strain (Patent Document 2), IL-10 production promoter (patent document 3), IL-10 production by bifidobacteria, which is a combination of bacteria or yeast having no IL-12 production induction ability or a processed microorganism and bacteria having IL-12 production induction ability Induction of IL-10 (non-patent document 2), induction of IL-10 and IL-12 production by Lactobacillus pentosasus strain (non-patent document 3) and the like have been reported. However, sufficient effects have not yet been obtained for any of these.
ＩＬ−１０の産生不足による疾患、例えばＩＢＤ、アレルギー疾患、リウマチや膠原病などの自己免疫疾患、細菌感染による炎症疾患、乾癬、臓器移植時の拒絶反応等の予防・治療に有用であり、かつ日常的に安全な食品、医薬品として利用できるＩＬ−１０産生誘導能の高い新規乳酸菌の探索とその製品開発が強く望まれている。 It is useful for the prevention and treatment of diseases caused by insufficient production of IL-10, such as IBD, allergic diseases, autoimmune diseases such as rheumatism and collagen disease, inflammatory diseases caused by bacterial infection, psoriasis, rejection at the time of organ transplantation, and the like Searching for new lactic acid bacteria with high IL-10 production inducing ability that can be used as daily safe foods and pharmaceuticals and development of their products are strongly desired.
本発明は上記の問題点に鑑みて為されたもので、発明者等が見出した新規なラクトバチルス・ペントーサスＴＪ５１５（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｐｅｎｔｏｓｕｓ ＴＪ５１５）（ＦＥＲＭ Ｐ−２１７９８）である菌株に関するものである。 The present invention has been made in view of the above problems, and relates to a strain which is a novel Lactobacillus pentosus TJ515 (FERM P-21798) found by the inventors.
また本発明は以下の（１）から（９）の菌学的性質を有する菌株：
（１）グラム陽性
（２）桿菌
（３）運動性なし
（４）無胞子
（５）通性嫌気性
（６）カタラーゼ陰性
（７）生育温度 １５〜４０℃ （至適生育温度 ３７℃）
（８）生育ｐＨ ３．６〜８．６
（９）Ｄ−キシロース、Ｄ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化する
に関する。
The present invention also relates to a strain having the following mycological properties (1) to (9):
(1) Gram positive (2) Neisseria gonorrhoeae (3) No motility (4) No spores (5) facultative anaerobic (6) Catalase negative (7) Growth temperature 15-40 ° C (optimum growth temperature 37 ° C)
(8) Growth pH 3.6-8.6
(9) It relates to assimilating D-xylose, D-arabitol, D-raffinose, dulcitol and D-melezitose.
また本発明は、前記菌株の培養物、その含有物またはその乾燥菌末に関する。ここで、菌株が生菌であることが好ましい。 Moreover, this invention relates to the culture of the said strain, its content, or its dry microbial powder. Here, it is preferable that the strain is a living bacterium.
また本発明は、前記菌株の培養物、その含有物またはその乾燥菌末を含有する食品および医薬品に関する。 Moreover, this invention relates to the foodstuff and pharmaceutical which contain the culture of the said strain, its content, or its dry microbial powder.
本発明のラクトバチルス・ペントーサスＴＪ５１５は、ＩＬ−１０産生誘導能に優れているので、本菌株を摂取等すれば、ＩＬ−１０の産生不足による疾患、例えばＩＢＤ、アレルギー疾患、リウマチや膠原病などの自己免疫疾患、細菌感染による炎症疾患、乾癬、臓器移植時の拒絶反応等の予防・治療において有用な効果を示す。また該菌株は発酵食品由来のため、日常的に安全な食品として免疫調節に有用に利用できる。 Since Lactobacillus pentosas TJ515 of the present invention is excellent in IL-10 production inducing ability, if this strain is ingested, diseases caused by insufficient production of IL-10, such as IBD, allergic diseases, rheumatism and collagen diseases This medicine has useful effects in the prevention and treatment of autoimmune diseases, inflammatory diseases caused by bacterial infections, psoriasis, and rejection at the time of organ transplantation. Moreover, since this strain is derived from fermented food, it can be usefully used for immunoregulation as a daily safe food.
本発明の菌株であるラクトバチルス・ペントーサスＴＪ５１５は受託番号：ＦＥＲＭ Ｐ−２１７９８として２００９年４月６日付で、独立行政法人産業技術総合研究所特許生物寄託センターに寄託されたものである。 The strain of the present invention, Lactobacillus pentosas TJ515, was deposited at the Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology, on April 6, 2009, under the accession number: FERM P-21798.
本発明のラクトバチルス・ペントーサスＴＪ５１５は、タイの植物性発酵食品の中から分離・発見された乳酸菌である。ＴＪ５１５はタイの植物性発酵食品から分離・発見された約５００種の乳酸菌のなかでも優れたＩＬ−１０産生誘導能を示す菌株である。 Lactobacillus pentosas TJ515 of the present invention is a lactic acid bacterium isolated and discovered from Thai plant fermented foods. TJ515 is an excellent IL-10 production-inducing ability among about 500 lactic acid bacteria isolated and discovered from Thai plant fermented foods.
本発明のラクトバチルス・ペントーサスＴＪ５１５の菌学的性質を以下に示す。
（１）グラム陽性
（２）桿菌
（３）運動性なし
（４）無胞子
（５）通性嫌気性
（６）カタラーゼ陰性
（７）生育温度 １５〜４０℃ （至適生育温度 ３７℃）
（８）生育ｐＨ ３．６〜８．６
（９）Ｄ−キシロース、Ｄ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化する。
The mycological properties of Lactobacillus pentosus TJ515 of the present invention are shown below.
(1) Gram positive (2) Neisseria gonorrhoeae (3) No motility (4) No spores (5) facultative anaerobic (6) Catalase negative (7) Growth temperature 15-40 ° C (optimum growth temperature 37 ° C)
(8) Growth pH 3.6-8.6
(9) Assimilate D-xylose, D-arabitol, D-raffinose, dulcitol and D-melezitose.
本発明の菌株はグラム陽性、無胞子、通性嫌気性、カタラーゼ陰性の桿菌（約０．５×０．１μｍ）であり、糖から乳酸を生成し、ガスを発生しないことからホモ型発酵のラクトバチルス属に属するものと考えられる。 The strain of the present invention is a Gram-positive, aspore-free, facultative anaerobic, catalase-negative gonococcus (approximately 0.5 × 0.1 μm), which generates lactic acid from sugar and does not generate gas. It is thought to belong to the genus Lactobacillus.
本発明の菌株の培養的性質を以下に示す。
（１）ＭＲＳ寒天平板培地
コロニーは、３７℃、２日間培養で直径約２−３ｍｍまたはそれ以下の円形、半レンズ状突起、不透明の白色である。
（２）ＭＲＳ液体培地
３７℃、２４時間培養で菌体が増殖して培地が白濁し、綿毛状の沈殿を生ずる。
（３）ＭＲＳ寒天培地（穿刺培養）
穿刺によって一様に生育する。
The culture properties of the strain of the present invention are shown below.
(1) MRS agar plate culture colonies are circular, semi-lens-like projections, opaque white having a diameter of about 2-3 mm or less when cultured at 37 ° C. for 2 days.
(2) MRS liquid medium Cultured at 37 ° C. for 24 hours, the cells grow and the medium becomes cloudy, resulting in fluffy precipitation.
(3) MRS agar medium (puncture culture)
Grows uniformly by puncture.
本発明の菌株の生理・生化学的性質を以下に示す。
（１）生育温度 １５〜４０℃ （至適生育温度 ３７℃）
（２）生育ｐＨ域 ３．６〜８．６
（３）酸素との関係
通性嫌気性。酸素存在下でも嫌気的条件でも生育できる。
（４）糖類発酵性
Ｄ−キシロース、Ｄ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化する。
（５）リトマスミルク：酸性化、脱色および凝固し、液化はしない。
（６）カタラーゼ：陰性
（７）でんぷんを加水分解しない。
The physiological and biochemical properties of the strain of the present invention are shown below.
(1) Growth temperature 15-40 ° C (Optimum growth temperature 37 ° C)
(2) Growth pH range 3.6 to 8.6
(3) Relationship with oxygen facultative anaerobic. It can grow in the presence of oxygen or under anaerobic conditions.
(4) assimilate saccharide-fermentable D-xylose, D-arabitol, D-raffinose, dulcitol and D-melezitose;
(5) Litmus milk: Acidifies, decolorizes and solidifies, does not liquefy.
(6) Catalase: negative (7) Does not hydrolyze starch.
本発明の菌株とラクトバチルス・ペントーサスの標準菌株であるラクトバチルス・ペントーサスＪＣＭ１５５８（ＪＡＰＡＮ ＣＯＬＬＥＣＴＩＯＮ ＯＦ ＭＩＣＲＯＯＲＧＡＮＩＳＭＳ、独立法人 理化学研究所）の糖資化性を比較すると、本発明菌株は標準株が資化しないＤ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化するという特徴を有する。また、培養温度帯に関して、標準菌株が１５℃で生育できないことに対し、本発明の菌株は生育可能であるという特徴を有する。 When the saccharide utilization of Lactobacillus pentosus JCM1558 (JAPAN COLLECTION OF MICROORGANISMS, RIKEN) is compared with the strain of the present invention, the strain of the present invention does not assimilate the standard strain It has the feature of assimilating D-arabitol, D-raffinose, dulcitol and D-melezitose. In addition, regarding the culture temperature zone, the standard strain cannot grow at 15 ° C., whereas the strain of the present invention can grow.
本発明の菌株は、１６Ｓ ｒＲＮＡ遺伝子解析により、ラクトバチルス・ペントーサスＪＣＭ１５５８と５５４ｂｐ中、９７％以上の相同性を示すことが好ましく、９９％以上の相同性を示すことがより好ましい。 The strain of the present invention preferably shows 97% or more homology among Lactobacillus pentosas JCM1558 and 554bp, more preferably 99% or more by 16S rRNA gene analysis.
本発明の菌株はタイ国北部の発酵食品およびその原料となる野菜、例えばネギ、ニラおよびタマネギなどから公知の方法により単離する事ができる。例えば、発酵食品または野菜を滅菌した生理食塩水に懸濁し、その懸濁液を滅菌した生理食塩水に段階的に希釈し、ＭＲＳ寒天培地や他の分離用寒天培地に塗布し培養することにより分離可能である。培養条件は３７℃で、２日間培養し形成したコロニーを分離する。 The strain of the present invention can be isolated by a known method from fermented foods in northern Thailand and vegetables as raw materials thereof, such as leek, leek and onion. For example, by suspending fermented foods or vegetables in sterilized physiological saline, diluting the suspension stepwise in sterilized physiological saline, applying to MRS agar medium or other separation agar medium, and culturing. Separable. Culture conditions are 37 ° C., and the colonies formed by culturing for 2 days are separated.
本発明の菌株であれば、菌株を培地に接種するだけで培養することができる。本発明の菌株を培養するための培地としては、通常の、炭素源、窒素源、無機塩類、有機栄養素などを含む培地を用いることができる。本発明の菌株であれば、特別な栄養培地を用意する必要がないので、調製に手間がかからず、そのため培地成分のロット差による培養収率のぶれがなく、大量培養も可能である。ここで、培養に使用する培地には目的に応じて寒天培地や液体培地を選択することができる。培養温度は１５℃〜４０℃、好ましくは３７℃で、増殖可能ｐＨはｐＨ ３．６〜８．６、好ましくはｐＨ６．０〜７．０である。培養時間は１〜２日間が好ましい。 If it is a strain of this invention, it can culture | cultivate only by inoculating a strain into a culture medium. As a medium for culturing the strain of the present invention, a normal medium containing a carbon source, a nitrogen source, inorganic salts, organic nutrients and the like can be used. In the case of the strain of the present invention, it is not necessary to prepare a special nutrient medium, so that it takes less time to prepare, so that there is no fluctuation in the culture yield due to lot differences in medium components, and large-scale culture is possible. Here, an agar medium or a liquid medium can be selected as a medium used for culture according to the purpose. The culture temperature is 15 ° C. to 40 ° C., preferably 37 ° C., and the growth possible pH is pH 3.6 to 8.6, preferably pH 6.0 to 7.0. The culture time is preferably 1 to 2 days.
本発明の菌株は、その培養物、含有物、乾燥菌末の形態として利用できる。上記培養物、含有物、乾燥菌末に含有される乳酸菌としては、生菌又は死菌を用いることができるが、生菌において十分なアレルギー症状を抑制する効果が認められ、かつ菌体が腸内に定着することにより持続的に効果が発揮されるので、死菌体を断続的に作用させるよりも有利であると推測できる点から、生菌が好ましい。生菌は本菌株を適当な培地で培養して得られる培養物から得ることができる。死菌は、生菌に対して加熱、紫外線照射、ホルマリン処理等を行うことにより得ることができる。 The strain of the present invention can be used in the form of its culture, inclusions, and dry bacteria. As the lactic acid bacteria contained in the culture, inclusions, and dry bacteria powder, live bacteria or dead bacteria can be used. However, sufficient effects of suppressing allergic symptoms in live bacteria are observed, and the bacterial cells are intestinal Since the effect is exerted continuously by fixing in the inside, viable bacteria are preferable from the point that it can be estimated that it is more advantageous than intermittent action of dead cells. Viable bacteria can be obtained from a culture obtained by culturing this strain in an appropriate medium. Dead bacteria can be obtained by subjecting live bacteria to heating, ultraviolet irradiation, formalin treatment and the like.
菌株の培養物とは、菌株そのものを培養して得られたものである。 A culture of a strain is obtained by culturing the strain itself.
菌株の含有物とは、菌株を含む粉状、液状、生地状、もしくは固形状の製品である。 The content of the strain is a powdery, liquid, dough-like or solid product containing the strain.
菌株の乾燥菌末とは、減圧状態で培養物の水分を昇華させて得られた粉末のことである。菌株の減圧は１５〜１００Ｐａ、凍結時温度−５０〜−８０℃、乾燥時温度２２〜２５℃で行うことが好ましい。 The dry bacterial powder of the strain is a powder obtained by sublimating the water in the culture under reduced pressure. The strain is preferably decompressed at 15 to 100 Pa, a freezing temperature of −50 to −80 ° C., and a drying temperature of 22 to 25 ° C.
本発明の乳酸菌の培養物、含有物または乾燥菌末は、免疫調節作用を有する薬学的組成物として用いることが好ましい。例えば、食品、医薬品等を挙げることができる。 It is preferable to use the lactic acid bacteria culture, inclusions or dried powder of the present invention as a pharmaceutical composition having an immunomodulatory action. For example, a foodstuff, a pharmaceutical, etc. can be mentioned.
食品として用いる場合には、免疫調節作用を有する健康食品とすることが好適である。公知の甘味料、酸味料、ビタミン等の各種成分と混合して嗜好性の高い食品とすることが好ましい。 When used as a food, it is preferably a health food having an immunomodulatory action. It is preferable to mix with various components such as known sweeteners, acidulants, vitamins and the like to obtain highly-preference foods.
食品としては、特に限定されないが、乳酸菌の安定性、摂取・携帯の簡便性の点で、例えば、錠菓、カプセル、ドリンク、加工食品、デザート類、菓子等の形態で提供することが好ましい。特に、錠菓は、防湿を目的とするコーティングが可能であり、乳酸菌の安定性が良好であり、また、摂取量が正確、摂取・携帯が簡便、腸溶被包が可能である点で好ましい。ドリンクとしては、例えば、青汁、野菜果汁、果物果汁などが挙げられる。野菜果汁は、特に限定されないが、人参、カボチャ、キャベツ、セロリ、ブロッコリー、トマト、アスパラガス、ホウレンソウ、カリフラワーの果汁などを挙げることができる。これらは、１種類の野菜果汁であってもよいが、２種類以上の野菜果汁の混合液であってもよい。また、果物果汁としては、ぶどう、メロン、イチゴ、ブルーベリー、パイナップル、バナナ、マンゴー、桃の果汁などを挙げることができる。また、これらは１種類の果物果汁であってもよいが、２種類以上の果物果汁の混合液であってもよい。また、発酵を促進するため、発酵前にｐＨ調整剤を添加することもある。 The food is not particularly limited, but is preferably provided in the form of, for example, tablet confectionery, capsules, drinks, processed foods, desserts, confectionery, etc. from the viewpoints of stability of lactic acid bacteria and ease of intake and carrying. Particularly, tablet confectionery is preferable in that it can be coated for moisture prevention, has good stability of lactic acid bacteria, is accurate in intake, easy to ingest and carry, and can be enteric-encapsulated. . Examples of drinks include green juice, vegetable juice, and fruit juice. The vegetable juice is not particularly limited, and examples thereof include carrot, pumpkin, cabbage, celery, broccoli, tomato, asparagus, spinach, and cauliflower juice. These may be one kind of vegetable juice, but may be a mixed liquid of two or more kinds of vegetable juice. Examples of fruit juice include grape, melon, strawberry, blueberry, pineapple, banana, mango, peach juice and the like. These may be one kind of fruit juice but may be a mixed liquid of two or more kinds of fruit juice. Moreover, in order to accelerate | stimulate fermentation, a pH adjuster may be added before fermentation.
これらの投与形態に加工するには、本発明の乳酸菌を純粋培養し遠心分離などの方法により集菌後、適切な安定剤を加え凍結乾燥等して得られる乾燥菌末を加えて通常の製菓方法に従って製造することができる。 For processing into these dosage forms, the lactic acid bacteria of the present invention are purely cultured, collected by a method such as centrifugation, and then added with an appropriate stabilizer and dried lyophilized powder is added to obtain a normal confectionery. It can be manufactured according to the method.
また、本乳酸菌はヨーグルトなどの発酵乳及び醗酵食品としての形態としても投与が可能である。例えば牛乳、羊乳、豆乳などにヨーグルト製造上のスターター菌であるラクトバチルス・ブルガリカス、ラクトバチルス・アシドフィルス、ラクトバチルス・ヘルベチカス、ストレプトコッカス・サーモフィルス、ストレプトコッカス・ラクチスなどの乳酸菌と本発明の乳酸菌を接種し混合培養あるいは各々単独培養後に混ぜ合わせることによってヨーグルトを製造することができる。 The lactic acid bacteria can also be administered in the form of fermented milk such as yogurt and fermented food. For example, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus helveticus, Streptococcus thermophilus, Streptococcus lactis, and other lactic acid bacteria of the present invention, which are starter bacteria for producing yogurt on milk, sheep milk, soy milk, etc. Yogurt can be produced by inoculating and mixing after mixed culture or individual culture.
また、医薬品として用いる場合には、その投与形態としては例えば散剤、顆粒剤、錠剤、カプセル剤、シロップ剤などの形態が好ましく、投与経路としては、経口投与、直腸投与、経腸投与等により投与することができる。これらの各種製剤は常法に従って、主薬に賦形剤、結合剤、崩壊剤、コーティング剤、潤滑剤、安定剤、矯味矯臭剤、溶解補助剤、懸濁剤、希釈剤などの医薬の製剤技術分野において通常使用しうる既知の補助剤を用いて製剤化することができる。投与量においては対象疾患、疾病の程度によって異なるが、例えば成人に対して１日１ｍｇ〜２，０００ｍｇを症状に応じて１日１回または数回に分けて投与することができる。 When used as a pharmaceutical, the dosage form is preferably a powder, granule, tablet, capsule, syrup or the like, and the administration route is oral administration, rectal administration, enteral administration, etc. can do. These various preparations are pharmaceutical preparation techniques such as excipients, binders, disintegrants, coating agents, lubricants, stabilizers, flavoring agents, solubilizers, suspension agents, diluents, etc. It can be formulated using known adjuvants that can usually be used in the field. Although the dose varies depending on the target disease and the degree of the disease, for example, 1 mg to 2,000 mg per day can be administered to an adult once or several times a day according to symptoms.
１．ラクトバチルス・ペントーサスＴＪ５１５の分離方法
タイのネギ、ニラ、タマネギを使用した発酵食品を生理食塩水に懸濁し、その懸濁液を滅菌した生理食塩水に段階的に希釈し、ＭＲＳ寒天培地に塗布し培養することにより分離した。培養条件は３７℃で、２日間培養し形成したコロニーを分離した。
1. Separation method of Lactobacillus pentosas TJ515 Fermented foods using Thai leek, leek and onion are suspended in physiological saline, and the suspension is diluted stepwise into sterilized physiological saline and applied to MRS agar medium. And separated by culturing. The culture was performed at 37 ° C. for 2 days to isolate colonies formed.
２．菌学的性質の同定
ラクトバチルス・ペントーサスＴＪ５１５の形態的性質をＭＲＳ液体培地により同定した。ＭＲＳ液体培地は市販のＤｉｆｃｏ Ｌａｃｔｏｂａｃｉｌｌｉ ＭＲＳ ｂｒｏｔｈ （Ｃａｔ＃． ２８８１３０）５８．０ｇを水１０００ｍｌに加え、１２１℃で２０分間滅菌したものを使用した。ＭＲＳ液体培地での２４時間培養において、約０．５×０．１μｍの桿菌であり、単一または連鎖状に存在した。胞子は形成せず、非運動性で、グラム陽性であった。各種菌学的性質の同定は「乳酸菌実験マニュアル」（朝倉書店）に従い、また分類同定の基準としてバージーズ・マニュアル・オブ・システマティック・バクテリオロジー（Ｂｅｒｇｅｙ’ｓ Ｍａｎｕａｌ ｏｆ Ｓｙｓｔｅｍａｔｉｃ Ｂａｃｔｅｒｉｏｌｏｇｙ）Ｖｏｌ．２（１９８６）を参照した。得られた菌学的性質を以下に示す。
2. Identification of mycological properties The morphological properties of Lactobacillus pentosas TJ515 were identified by MRS liquid medium. As the MRS liquid medium, 58.0 g of commercially available Difco Lactobacilli MRS broth (Cat #. 288130) was added to 1000 ml of water and sterilized at 121 ° C. for 20 minutes. In a 24-hour culture in MRS liquid medium, the gonococcus was about 0.5 × 0.1 μm and existed in a single or chain form. Spores did not form, were non-motile and were Gram positive. Identification of various bacteriological properties follows the “Lactic Acid Bacteria Experiment Manual” (Asakura Shoten), and as a standard for classification and identification, Bergey's Manual of Systematic Bacteriology Vol. 2 (1986). The obtained mycological properties are shown below.
（１）グラム陽性
（２）桿菌
（３）運動性なし
（４）無胞子
（５）通性嫌気性
（６）カタラーゼ陰性
（７）生育温度 １５〜４０℃ （至適生育温度 ３７℃）
（８）生育ｐＨ ３．６〜８．６
（９）Ｄ−キシロース、Ｄ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化する。
(1) Gram positive (2) Neisseria gonorrhoeae (3) No motility (4) No spores (5) facultative anaerobic (6) Catalase negative (7) Growth temperature 15-40 ° C (optimum growth temperature 37 ° C)
(8) Growth pH 3.6-8.6
(9) Assimilate D-xylose, D-arabitol, D-raffinose, dulcitol and D-melezitose.
３．培養的性質の同定
本発明の菌株の培養的性質を（１）から（３）の各培地で調べた。
（１）ＭＲＳ寒天平板培地
コロニーは、３７℃、２日間培養で直径約２〜３ｍｍまたはそれ以下の円形、半レンズ状突起、不透明の白色であった。
（２）ＭＲＳ液体培地
３７℃、２４時間培養で菌体が増殖して培地が白濁し、綿毛状の沈殿を生じた。
（３）ＭＲＳ寒天培地（穿刺培養）
穿刺によって一様に生育した。
3. Identification of culture properties The culture properties of the strains of the present invention were examined in the media (1) to (3).
(1) The MRS agar plate culture colonies were circular, semi-lens-like projections and opaque white having a diameter of about 2 to 3 mm or less when cultured at 37 ° C. for 2 days.
(2) MRS liquid medium At 37 ° C. for 24 hours, the cells grew and the medium became cloudy, resulting in fluffy precipitation.
(3) MRS agar medium (puncture culture)
It grew uniformly by puncture.
４．生理・生化学的性質の同定
本発明の菌株の生理・生化学的性質の同定は、「乳酸菌実験マニュアル」（朝倉書店）に従い行った。本発明の菌株の生理・生化学的性質を以下に示す。
（１）生育温度 １５〜４０℃ （至適生育温度 ３７℃）
（２）生育ｐＨ域 ３．６〜８．６
（３）酸素との関係
通性嫌気性。酸素存在下でも嫌気的条件でも生育できる。
（４）糖類発酵性
Ｄ−キシロース、Ｄ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化する。
（５）リトマスミルク：酸性化、脱色および凝固し、液化はしない。
（６）カタラーゼ：陰性
（７）でんぷんを加水分解しない。
4). Identification of physiological and biochemical properties Identification of physiological and biochemical properties of the strain of the present invention was carried out according to the “Lactic acid bacteria experiment manual” (Asakura Shoten). The physiological and biochemical properties of the strain of the present invention are shown below.
(1) Growth temperature 15-40 ° C (Optimum growth temperature 37 ° C)
(2) Growth pH range 3.6 to 8.6
(3) Relationship with oxygen facultative anaerobic. It can grow in the presence of oxygen or under anaerobic conditions.
(4) assimilate saccharide-fermentable D-xylose, D-arabitol, D-raffinose, dulcitol and D-melezitose;
(5) Litmus milk: Acidifies, decolorizes and solidifies, does not liquefy.
(6) Catalase: negative (7) Does not hydrolyze starch.
５．遺伝子解析
本発明のラクトバチルス・ペントーサスＴＪ５１５の遺伝子解析を次のように行った。ラクトバチルス・ペントーサスＴＪ５１５の分類学的位置を確認するために、１６Ｓ ｒＲＮＡ遺伝子の塩基配列データと既知種の配列データとを比較した。ＤＮＡの抽出は、ＭＲＳ液体培地で、３７℃、２４時間培養した菌液を定法に従って行った。１６Ｓ ｒＲＮＡ遺伝子解析の結果より、ラクトバチルス・ペントーサスの標準菌株であるラクトバチルス・ペントーサスＪＣＭ１５５８（ＪＡＰＡＮ ＣＯＬＬＥＣＴＩＯＮ ＯＦ ＭＩＣＲＯＯＲＧＡＮＩＳＭＳ、独立行政法人 理化学研究所）と５５４ｂｐ中１００％の相同性を示した。
5. Gene analysis The gene analysis of Lactobacillus pentosas TJ515 of the present invention was performed as follows. In order to confirm the taxonomic position of Lactobacillus pentosus TJ515, the base sequence data of 16S rRNA gene and sequence data of known species were compared. Extraction of DNA was performed according to a conventional method using a bacterial solution cultured in an MRS liquid medium at 37 ° C. for 24 hours. The result of 16S rRNA gene analysis showed 100% homology with Lactobacillus pentosus JCM1558 (JAPAN COLLECTION OF MICROORGANISMS, RIKEN), which is a standard strain of Lactobacillus pentosus.
６．ラクトバチルス・ペントーサスＴＪ５１５と標準菌株の比較
本発明の菌株とラクトバチルス・ペントーサスＪＣＭ１５５８の糖資化性を比較したところ、標準株がＤ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化しないことに対し、本菌株は資化するという特徴を有していた。また、培養温度帯に関して、標準菌株が１５℃で生育できないことに対し、本発明の菌株は生育可能であるという特徴を有していた。よって公知の菌株と比較すると、細部にわたって一致しない点もあるので、本発明の菌株は新規なラクトバチルス・ペントーサスＴＪ５１５と命名した。
6). Comparison of Lactobacillus pentotosus TJ515 with standard strains When the saccharide utilization of Lactobacillus pentotosus JCM1558 was compared with that of the present invention, the standard strains did not assimilate D-arabitol, D-raffinose, dulcitol, and D-melezitol. In contrast, this strain had the characteristic of assimilating. Further, regarding the culture temperature zone, the standard strain cannot grow at 15 ° C., whereas the strain of the present invention has the feature that it can grow. Therefore, since there is a point which does not correspond in detail compared with a well-known strain, the strain of the present invention was named novel Lactobacillus pentosas TJ515.
試験例１（乳酸菌株のＩＬ−１０の産生誘導能）
タイの発酵食品８６４種から単離した３０３株のラクトバチルス株とパイエル板リンパ球細胞との共培養試験によりＩＬ−１０の産生誘導能を調べた。使用した菌液は以下の方法で調製した。菌株をｓｅｍｉ−ｓｏｌｉｄ ＭＲＳ ｂｒｏｔｈより釣菌しＢＬ寒天培地に画線した。３７℃、嫌気条件下で２日間培養し、単一コロニーを拾い、５ｍＬのＭＲＳ ｂｒｏｔｈにて３７℃で１８時間培養した。培養後、ＰＢＳ（ｐＨ６．８）を用いて洗浄し、ＰＢＳ５ｍＬに懸濁した液を菌液とした。６〜８週齢の雌のＢＡＬＢ／ｃマウスからパイエル板リンパ球細胞を採取し、これらの細胞を９６穴の培養プレートに１８０μＬのＲＰＭＩ１６４０培地とともに加えた（２×１０６個／穴）。各穴にラクトバチルス菌株の菌液を２０μＬ加え、３７℃で４日間培養した。菌液は予め濁度を測定しておき、菌数を１．０×１０７ｃｆｕ／ｍＬとなるように調整し、培養液に加えた。培養終了後、９６穴プレートを遠心分離し（１２００ｒｐｍ×１０ｍｉｎ）培養上清を回収し、Ｂｉｏｌｅｇｅｎｄ社のｍｏｕｓｅ ＩＬ−１０ ＥＬＩＳＡ Ｑｕａｎｔｉｔａｔｉｏｎ Ｋｉｔを用いてＩＬ−１０量を定量した。５００菌株の中から、ＩＬ−１０産生誘導能の高かった６６菌株を選び、再度同じ試験を繰り返した。ＩＬ−１０産生誘導能の高かった上位２０菌株の結果を表１に示した。
Test Example 1 (IL-10 production inducing ability of lactic acid strain)
IL-10 production induction ability was examined by co-culture test of 303 Lactobacillus strains isolated from 864 kinds of Thai fermented foods and Peyer's patch lymphocytes. The used bacterial solution was prepared by the following method. The strain was picked from a semi-solid MRS broth and streaked on a BL agar medium. The cells were cultured at 37 ° C. under anaerobic conditions for 2 days, a single colony was picked, and cultured at 37 ° C. for 18 hours in 5 mL of MRS broth. After culturing, the cells were washed with PBS (pH 6.8) and suspended in 5 mL of PBS to obtain a bacterial solution. Peyer's patch lymphocyte cells were collected from 6-8 week old female BALB / c mice, and these cells were added to a 96-well culture plate along with 180 μL of RPMI 1640 medium (2 × 10 6 cells / well). 20 μL of Lactobacillus strain was added to each well and cultured at 37 ° C. for 4 days. The bacterial solution was measured for turbidity in advance, and the bacterial count was adjusted to 1.0 × 10 7 cfu / mL and added to the culture solution. After completion of the culture, the 96-well plate was centrifuged (1200 rpm × 10 min), and the culture supernatant was collected. The amount of IL-10 was quantified using a biolegend mouse IL-10 ELISA Quantification Kit. 66 strains having high IL-10 production inducing ability were selected from 500 strains, and the same test was repeated again. The results of the top 20 strains with high IL-10 production inducing ability are shown in Table 1.
ラクトバチルス・ペントーサスＴＪ５１５のＩＬ−１０産生誘導能は単離した乳酸菌株の中で最も強力であった。 The ability to induce IL-10 production of Lactobacillus pentosus TJ515 was the strongest among the isolated lactic acid strains.
試験例２（ラクトバチルス・ペントーサスＪＣＭ１５５８ （標準株）とのＩＬ−１０産生誘導能の比較）
試験例１の方法に従い、ラクトバチルス・ペントーサスＪＣＭ１５５８ （標準株）を対照菌株として、ラクトバチルス・ペントーサスＴＪ５１５のＩＬ−１０産生誘導能を比較した。結果を表２に示した。
Test Example 2 (Comparison of IL-10 production inducing ability with Lactobacillus pentosas JCM1558 (standard strain))
According to the method of Test Example 1, the ability to induce IL-10 production of Lactobacillus pentosas TJ515 was compared using Lactobacillus pentosas JCM1558 (standard strain) as a control strain. The results are shown in Table 2.
ラクトバチルス・ペントーサスＴＪ５１５はラクトバチルス・ペントーサス標準株より強いＩＬ−１０産生誘導能を示した。 Lactobacillus pentosas TJ515 showed a stronger IL-10 production inducing ability than the Lactobacillus pentosasus standard strain.
試験例３（ラクトバチルス・ペントーサスＴＪ５１５のＩｇＥ産生抑制効果）
ＩＬ−１０の産生不足による疾患の代表としてのアレルギー疾患モデルに対する、ラクトバチルス・ペントーサスＴＪ５１５株の投与効果を調べた。４〜５週齢、雌、ＢＡＬＢ／Ｃ無菌マウスにＴＪ５１５株を１０８個経口投与し、ＴＪ５１５株定着マウスを作出した。対照として特定の病原微生物を持たないＳＰＦマウスの糞便を無菌マウスに経口投与して作出したマウス菌叢マウスを用いた（各群６匹）。各マウスにＯＶＡ（ｏｖａｌｂｕｍｉｎ）を２週間ごとに合計４回腹腔内に投与した。最終投与から１週間後に、血清中の総ＩｇＥをＢＥＴＨＹＬ ＬＡＢＯＲＡＴＯＲＩＥＳのＭｏｕｓｅ ＩｇＥ ＥＬＩＳＡ Ｑｕａｎｔｉｔａｉｏｎ ｋｉｔにより測定し、結果を表３に示した。
Test Example 3 (IgE production inhibitory effect of Lactobacillus pentosus TJ515)
The administration effect of Lactobacillus pentosus strain TJ515 on an allergic disease model as a representative disease caused by insufficient production of IL-10 was examined. 108 TJ515 strains were orally administered to 4-5 week old, female, BALB / C aseptic mice to produce TJ515 strain-fixed mice. As a control, mouse flora mice produced by orally administering stool of SPF mice without specific pathogenic microorganisms to sterile mice were used (6 mice in each group). Each mouse received OVA (ovalbumin) intraperitoneally for a total of 4 times every 2 weeks. One week after the final administration, total IgE in the serum was measured by the Mouse IgE ELISA Quantitation kit of BETHYL LABORATORIES. The results are shown in Table 3.
ＴＪ５１５定着マウスでは、マウス菌叢を定着させたマウスに比べて血中の総ＩｇＥ産生が有意に抑制された。 In the TJ515-fixed mice, the total IgE production in the blood was significantly suppressed as compared with the mice in which the mouse flora was established.
実施例１（ラクトバチルス・ペントーサスＴＪ５１５の乾燥菌末の調製）
ラクトバチルス・ペントーサスＴＪ５１５をＭＲＳ液体培地に接種後、３７℃、１８〜２４時間静置培養を行った。培養終了後、７，０００ｒｐｍ、１５分間遠心分離を行い培養液の１／１００量の濃縮菌体を得た。
Example 1 (Preparation of dry bacterial powder of Lactobacillus pentosas TJ515)
Lactobacillus pentosas TJ515 was inoculated into MRS liquid medium, followed by static culture at 37 ° C. for 18 to 24 hours. After completion of the culture, centrifugation was performed at 7,000 rpm for 15 minutes to obtain 1/100 amount of concentrated bacterial cells of the culture solution.
次いで、濃縮菌体にグルタミン酸ソーダ５％（重量）、可溶性澱粉５％（重量）、ショ糖５％（重量）および硫酸マグネシウム７水和物１％（重量）を含む分散媒と同量混合し、ｐＨ７．０に修正後、−４０℃以下で凍結してから凍結乾燥を行った。得られた凍結乾燥菌末を６０メッシュのフルイで粉末化して乾燥菌末を調製した。 Next, the concentrated cells are mixed with the same amount of a dispersion medium containing 5% (by weight) sodium glutamate, 5% (by weight) soluble starch, 5% (by weight) sucrose and 1% (by weight) magnesium sulfate heptahydrate. After correction to pH 7.0, the sample was frozen at -40 ° C. or lower and lyophilized. The obtained freeze-dried bacterial powder was pulverized with a 60-mesh sieve to prepare a dry bacterial powder.
実施例２（ラクトバチルス・ペントーサスＴＪ５１５含有錠菓の製造）
実施例１で調製したラクトバチルス・ペントーサスＴＪ５１５の乾燥菌末１５ｇに、キシリトール（東和化成製）１５０ｇ、レシス（東和化成製）５４ｇ、メチルセルロース（信越化学製）６ｇ、部分α化デンプン（旭化成工業製）４５ｇ、ポリデキストロース（和光純薬工業製）３０ｇ、ショ糖脂肪酸エステル（三菱化学フーズ製）６ｇ、カスターワックス（日油製）６ｇ、軽質無水ケイ酸（フロイント産業製）３ｇを加えてビニール袋中でよく混合した後、打錠機（６Ｂ−２、菊水製作所製）を用いて打錠し、直径１５ｍｍ、重量１０００ｍｇの錠菓を製造した。
Example 2 (Production of Lactobacillus pentosas TJ515-containing tablet confectionery)
To 15 g of dried bacteria powder of Lactobacillus pentosas TJ515 prepared in Example 1, 150 g of xylitol (manufactured by Towa Kasei), 54 g of cis (manufactured by Towa Kasei), 6 g of methylcellulose (manufactured by Shin-Etsu Chemical), partially pregelatinized starch (manufactured by Asahi Kasei Kogyo) ) 45 g, Polydextrose (manufactured by Wako Pure Chemical Industries) 30 g, Sucrose fatty acid ester (manufactured by Mitsubishi Chemical Foods) 6 g, Custer wax (manufactured by NOF) 6 g, Light anhydrous silicic acid (manufactured by Freund Sangyo) 3 g After mixing well, tableting was performed using a tableting machine (6B-2, manufactured by Kikusui Seisakusho) to produce tablet confectionery having a diameter of 15 mm and a weight of 1000 mg.
実施例３（ラクトバチルス・ペントーサスＴＪ５１５含有発酵乳の製造）
酵母エキス（オリエンタル酵母製）０．２％と砂糖２％を含む２０％脱脂還元乳を１００℃にて１０分間加熱し、これに等量の市販牛乳を加えてヨーグルトミックスとした。これに、予めＭＲＳ液体培地（Ｄｉｆｃｏ製）で培養した後生理食塩水で置換したラクトバチルス・ペントーサスＴＪ５１５の懸濁菌液を２％接種し、３７℃で１８〜２４時間静置培養を行い、発酵乳を製造した。得られた発酵乳は、マイルドな酸味の美味な食品であった。
Example 3 (Production of Lactobacillus pentosus TJ515-containing fermented milk)
20% non-fat reduced milk containing 0.2% yeast extract (made by Oriental yeast) and 2% sugar was heated at 100 ° C. for 10 minutes, and an equal amount of commercially available milk was added thereto to make a yogurt mix. This was inoculated with 2% of a suspension of Lactobacillus pentosus TJ515 previously cultured in MRS liquid medium (manufactured by Difco) and then replaced with physiological saline, and statically cultured at 37 ° C. for 18 to 24 hours. Fermented milk was produced. The obtained fermented milk was a mild, sour and delicious food.
実施例４（ラクトバチルス・ペントーサスＴＪ５１５含有発酵青汁の製造）
市販の粉末青汁（ケール）を滅菌水で調製し、予めＭＲＳ液体培地（Ｄｉｆｃｏ製）で培養した後、生理食塩水で置換したラクトバチルス・ペントーサスＴＪ５１５の懸濁菌液を０．１％接種し、３７℃で１８〜２４時間静置培養を行い、発酵青汁を製造した。得られた発酵青汁は、さわやかな酸味があり、特有の青臭さが抑えられた、嗜好性の高い食品であった。
Example 4 (Production of Lactobacillus pentosus TJ515-containing fermented green juice)
Commercially available powdered green juice (kale) was prepared in sterile water, cultured in advance in MRS liquid medium (manufactured by Difco), and then inoculated with 0.1% of a suspension of Lactobacillus pentosus TJ515 that had been replaced with physiological saline And static culture was performed at 37 degreeC for 18 to 24 hours, and fermented green juice was manufactured. The obtained fermented green juice had a refreshing acidity and was a highly-preference food with a unique blue odor suppressed.
実施例５（ラクトバチルス・ペントーサスＴＪ５１５の配合錠剤の製造）
第１５改正日本薬局方解説書製剤総則「錠剤」の規定に準拠し、実施例１で調製したラクトバチルス・ペントーサスＴＪ５１５乾燥菌末２ｍｇ（菌数、５×１０８ 相当）と乳糖（日局）６１ｍｇ、澱粉（日局）１６．２ｍｇ、結合剤としてポリビニルピロリドンＫ２５（日局）２０ｍｇ、滑沢剤としてステアリン酸マグネシウム（日局）０．８ｍｇを加えて均一に混合し、打錠機で圧縮成型し１錠当たり３００ｍｇの素錠を作り、さらに、ヒドロキシプロピルセルロース（ＨＰＣ）を用いてフィルムコーティングを施して白色のフィルムコーティングされた錠剤を製造した。
Example 5 (Production of Lactobacillus pentosus TJ515 Combination Tablet)
In accordance with the provisions of the 15th revised Japanese Pharmacopoeia Guideline General Formulation “Tablets”, Lactobacillus pentosas TJ515 dry bacteria powder 2 mg (number of bacteria, equivalent to 5 × 10 8) prepared in Example 1 and lactose (JP) 61 mg , Starch (JP) 16.2 mg, Polyvinylpyrrolidone K25 (JP) 20 mg as binder, Magnesium stearate (JP) 0.8 mg as lubricant and mixed uniformly, compression molding with tablet press Then, 300 mg of uncoated tablets were made per tablet, and further, film coating was performed using hydroxypropylcellulose (HPC) to produce white film-coated tablets.
本発明の菌株は、ＩＬ−１０の産生不足による疾患、例えばＩＢＤ、アレルギー疾患、リウマチや膠原病などの自己免疫疾患、細菌感染による炎症疾患、乾癬、臓器移植時の拒絶反応等の予防・治療に有用であり、かつ日常的に安全な食品及び医薬品として利用できる。 The strain of the present invention prevents or treats diseases caused by insufficient production of IL-10, such as IBD, allergic diseases, autoimmune diseases such as rheumatism and collagen disease, inflammatory diseases caused by bacterial infection, psoriasis, rejection during organ transplantation, etc. It can be used as a food and medicine that is useful for daily use and is safe on a daily basis.
Claims (5)
（１）グラム陽性
（２）桿菌
（３）運動性なし
（４）無胞子
（５）通性嫌気性
（６）カタラーゼ陰性
（７）生育温度 １５〜４０℃ （至適生育温度 ３７℃）
（８）生育ｐＨ ３．６〜８．６
（９）Ｄ−キシロース、Ｄ−アラビトール、Ｄ−ラフィノース、ズルシトールおよびＤ−メレジトースを資化する。 Strains having the following mycological properties (1) to (9):
(1) Gram positive (2) Neisseria gonorrhoeae (3) No motility (4) No spores (5) facultative anaerobic (6) Catalase negative (7) Growth temperature 15-40 ° C (optimum growth temperature 37 ° C)
(8) Growth pH 3.6-8.6
(9) Assimilate D-xylose, D-arabitol, D-raffinose, dulcitol and D-melezitose.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2017026620A1 (en) * | 2015-08-13 | 2017-02-16 | 한국식품연구원 | Composition for preventing, alleviating, or treating th1-mediated immune diseases, th17-mediated immune diseases, or th2-mediated immune diseases, containing, as active ingredient, lactobacillus pentosus |
| KR101761506B1 (en) | 2015-08-13 | 2017-07-25 | 한국식품연구원 | Composition for Preventing, Improving, or Treating of Th1-mediated Immune Disease, Th17-mediated Immune Disease, or Th2-mediated Immune Disease Comprising Extracts from Lactobacillus pentosus as an Active Ingredients |
| JP6298912B1 (en) * | 2017-04-10 | 2018-03-20 | 有限会社バイオ研 | Method for producing lactic acid bacteria and composition for immunomodulation |
| CN109486700A (en) * | 2018-08-31 | 2019-03-19 | 石家庄君乐宝乳业有限公司 | Lactobacillus paracasei N1115 prevents application and the corresponding probiotic powder, application of colitis |
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| JP2022033444A (en) * | 2020-08-17 | 2022-03-02 | 株式会社バイオジェノミクス | Germ, il10 gene expression promoting agent, and pharmaceutical preparation |
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| KR20220011937A (en) | 2020-07-22 | 2022-02-03 | (주)지에프씨생명과학 | Lactobacillus paracasei GFC_GFV5 for removing hangover and food composition comprising the same as an effective ingredient |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2017026620A1 (en) * | 2015-08-13 | 2017-02-16 | 한국식품연구원 | Composition for preventing, alleviating, or treating th1-mediated immune diseases, th17-mediated immune diseases, or th2-mediated immune diseases, containing, as active ingredient, lactobacillus pentosus |
| KR101761506B1 (en) | 2015-08-13 | 2017-07-25 | 한국식품연구원 | Composition for Preventing, Improving, or Treating of Th1-mediated Immune Disease, Th17-mediated Immune Disease, or Th2-mediated Immune Disease Comprising Extracts from Lactobacillus pentosus as an Active Ingredients |
| JP6298912B1 (en) * | 2017-04-10 | 2018-03-20 | 有限会社バイオ研 | Method for producing lactic acid bacteria and composition for immunomodulation |
| JP2018174772A (en) * | 2017-04-10 | 2018-11-15 | 有限会社バイオ研 | Methods for producing lactic acid bacteria, and compositions for immunity modulation |
| CN109486700A (en) * | 2018-08-31 | 2019-03-19 | 石家庄君乐宝乳业有限公司 | Lactobacillus paracasei N1115 prevents application and the corresponding probiotic powder, application of colitis |
| JP2021069289A (en) * | 2019-10-29 | 2021-05-06 | 大塚製薬株式会社 | Anti-i type allergy agent |
| JP7372112B2 (en) | 2019-10-29 | 2023-10-31 | 大塚製薬株式会社 | Anti-type I allergy agent |
| JP2022033444A (en) * | 2020-08-17 | 2022-03-02 | 株式会社バイオジェノミクス | Germ, il10 gene expression promoting agent, and pharmaceutical preparation |
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