JPWO2015056770A1 - New lactic acid bacteria, innate immunity activator containing new lactic acid bacteria as active ingredients, and food and drink containing new lactic acid bacteria - Google Patents
New lactic acid bacteria, innate immunity activator containing new lactic acid bacteria as active ingredients, and food and drink containing new lactic acid bacteria Download PDFInfo
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- JPWO2015056770A1 JPWO2015056770A1 JP2015542676A JP2015542676A JPWO2015056770A1 JP WO2015056770 A1 JPWO2015056770 A1 JP WO2015056770A1 JP 2015542676 A JP2015542676 A JP 2015542676A JP 2015542676 A JP2015542676 A JP 2015542676A JP WO2015056770 A1 JPWO2015056770 A1 JP WO2015056770A1
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- acid bacteria
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- innate immunity
- acid bacterium
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Abstract
本発明は、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)における受領番号がNITE ABP−01694であるラクトコッカス(Lactococcus)属に属する乳酸菌、該乳酸菌を有効成分とする自然免疫活性化剤、該乳酸菌又は該自然免疫活性化剤を含有する飲食品、並びに、乳酸菌を含有する発酵乳であり、該発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して抵抗性を有する発酵乳に関する。The present invention is a lactic acid bacterium belonging to the genus Lactococcus having a receipt number of NITE ABP-01694 in the Patent Microorganism Deposit Center (NPMD) of the National Institute for Product Evaluation and Technology (NITE), and the lactic acid bacterium as an active ingredient. A natural immunity activator, a food or drink containing the lactic acid bacterium or the natural immunity activator, and a fermented milk containing the lactic acid bacterium, the fermented milk comprising methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, green The present invention relates to fermented milk having resistance to at least one bacterium selected from the group consisting of Pseudomonas aeruginosa and Enterococcus mundidi.
Description
本発明は、新規乳酸菌、新規乳酸菌を有効成分とする自然免疫活性化剤、及び新規乳酸菌を含有する飲食品に関する。 The present invention relates to a novel lactic acid bacterium, an innate immune activator containing the novel lactic acid bacterium as an active ingredient, and a food or drink containing the novel lactic acid bacterium.
乳酸菌は古くから発酵食品に利用され、食品や医薬品、プロバイオティクスの生産に産業的に利用されている。乳酸菌はグラム陽性、カタラーゼ陰性、内生胞子を形成しない、運動性がないという特徴がある。 Lactic acid bacteria have long been used for fermented foods, and industrially used for the production of foods, pharmaceuticals and probiotics. Lactic acid bacteria are characterized by Gram-positive, catalase-negative, no endospore formation and no motility.
Lactococcus lactis(L.lactis)は、非病原性のグラム陽性の乳酸菌で、ヒトの腸内フローラに属せず、口腔や腸管でコロニー形成をしないことが知られている。また、全ゲノムが解読されているほか、遺伝学、ベクター系、遺伝子発現系の解析がなされている。最近では、組換えL.lactisが動物の腸表皮を通じたサイトカインや特異的抗原のin situ合成、in vivoデリバリーに利用されていることが報告されている(非特許文献1〜4)。
Lactococcus lactis (L. lactis) is a non-pathogenic gram-positive lactic acid bacterium that does not belong to human intestinal flora and is known not to form colonies in the oral cavity or intestinal tract. In addition, the entire genome has been decoded, and genetics, vector systems, and gene expression systems have been analyzed. Recently, recombinant L. It has been reported that lactis is used for in situ synthesis and in vivo delivery of cytokines and specific antigens through the intestinal epidermis of animals (Non-Patent
自然免疫反応では、樹状細胞やマクロファージといった免疫細胞が細菌やウイルスに由来する自然免疫活性化物質に応答してサイトカインを産生し、その後の免疫反応が起こることが知られている。自然免疫機構は、生物が共通に有する感染防御機構であり、非特異的であるために反応が素早く、多くの感染源に対して有効に機能することが特徴である。
ヒト等の高等な脊椎動物においても、感染初期の抵抗性、癌や生活習慣病の予防、組織修復等の観点からは、感染源に特異的な獲得免疫よりも、非特異的な自然免疫の方がより重要な位置を占めていると考えられる。In the innate immune reaction, it is known that immune cells such as dendritic cells and macrophages produce cytokines in response to innate immune activators derived from bacteria and viruses, and subsequent immune reactions occur. The innate immunity mechanism is an infection defense mechanism common to living organisms, and is characterized by a non-specific reaction and a quick reaction that effectively functions against many infection sources.
Even in higher vertebrates such as humans, nonspecific innate immunity is more important than acquired immunity specific to the source of infection from the viewpoint of early infection resistance, prevention of cancer and lifestyle-related diseases, and tissue repair. Seems to occupy a more important position.
これまでに、本発明者により、カイコにおいて、自然免疫活性化反応を簡便に測定できる方法が開発されている(特許文献1)。また、本発明者により、自然免疫機構のみを有する生物を利用した、獲得免疫機構を有する生物に対する病原微生物感染のモデルが開発されている(特許文献2)。 So far, the present inventor has developed a method capable of simply measuring the innate immune activation reaction in silkworms (Patent Document 1). In addition, the present inventor has developed a model of pathogenic microorganism infection for an organism having an acquired immune mechanism using an organism having only an innate immune mechanism (Patent Document 2).
自然免疫機構の異常は、様々な疾患を引き起こす原因となり、従って、このような自然免疫機構を所望に調節することが可能な、優れた自然免疫活性化剤や自然免疫を活性化させる飲食品の開発が望まれている。 Abnormal innate immunity mechanisms cause various diseases, and therefore, innate immunity activators and food / beverages that activate innate immunity that can regulate such innate immunity mechanisms as desired. Development is desired.
また、食品としてのラクトバチルス属やビフィドバクテリウム属を用いたヨーグルトについては整腸効果が報告されてきたが、ヨーグルトとして食用したときの自然免疫の活性化については確認されていない。乳酸菌L.burgaliticsが分泌する多糖に自然免疫の活性化作用があるという報告があるが、ヨーグルトを食用する実験ではない(非特許文献5)。 In addition, intestinal effects have been reported for yogurts using Lactobacillus or Bifidobacterium as food, but the activation of innate immunity when used as yogurt has not been confirmed. Lactic acid bacteria L. Although there is a report that polysaccharides secreted by burgalitics have an innate immunity activating effect, it is not an experiment in which yogurt is edible (Non-patent Document 5).
また、自然免疫活性化のメカニズム研究として乳酸菌が持つ二本鎖RNAがTLR3経路を介して樹状細胞のIFNβ産生を促進していることが言われている(非特許文献6)。二本鎖RNAはCRISPR−Cas9経路で形成されていると考えられているが、L.lactisのゲノム塩基配列からはCRISPR−Cas9が見出されない。しかし、L.lactisではCpGDNAがTLR9経路を介して樹状細胞のIFNβ産生を活性化しているという報告がある(非特許文献7)。 In addition, as a mechanism study of innate immunity activation, it is said that double-stranded RNA possessed by lactic acid bacteria promotes IFNβ production of dendritic cells via the TLR3 pathway (Non-patent Document 6). Double-stranded RNA is thought to be formed by the CRISPR-Cas9 pathway. CRISPR-Cas9 is not found from the genomic base sequence of lactis. However, L. In lactis, there is a report that CpG DNA activates IFNβ production of dendritic cells via the TLR9 pathway (Non-patent Document 7).
本発明の課題は、高い自然免疫活性化能を有する乳酸菌を提供することであり、また、該乳酸菌、該乳酸菌の死菌若しくは該乳酸菌の処理物を有効成分とする自然免疫活性化剤、及び、該乳酸菌若しくは該自然免疫活性化剤を含有する飲食品を提供することにある。 An object of the present invention is to provide a lactic acid bacterium having high innate immunity activation ability, and an innate immunity activator comprising as an active ingredient the lactic acid bacterium, a killed bacterium of the lactic acid bacterium, or a processed product of the lactic acid bacterium, and An object of the present invention is to provide a food or drink containing the lactic acid bacteria or the innate immunity activator.
本発明者は、上記の課題を解決すべく鋭意検討を重ねた結果、キウイフルーツから新規の乳酸菌を分離した。そして、特許文献1に開示されている、自然免疫活性化反応を簡便に測定できる方法を用いて検討した結果、これまでに知られている乳酸菌より高い自然免疫活性化能を有していることが確認された。
As a result of intensive studies to solve the above-mentioned problems, the present inventor has isolated a novel lactic acid bacterium from kiwifruit. And as a result of examining using the method disclosed in
上記の自然免疫活性化能を有する乳酸菌は、その性状の分析や16S rRNAの塩基配列等の解析結果、ラクトコッカス(Lactococcus)属に属する新規乳酸菌株(以下、「11/19−B1株」と略記する場合がある)であることが判明した。 The above-mentioned lactic acid bacteria having the ability to activate innate immunity are characterized by analysis of their properties and analysis of the base sequence of 16S rRNA, etc. (It may be abbreviated in some cases).
また、上記の乳酸菌を含有するヨーグルトを食用したカイコに、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、又は、エンテロコッカス・ムンディディを注射した結果、該菌に感染したカイコは、高い抵抗性を示すことを見出して、本発明を完成するに至った。 In addition, as a result of injecting methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, or Enterococcus mundidi into silkworms edible with yogurt containing the above lactic acid bacteria, silkworms infected with the bacteria are: It has been found that it exhibits high resistance, and the present invention has been completed.
すなわち、本発明は、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)における受領番号がNITE ABP−01694であるラクトコッカス(Lactococcus)属に属する乳酸菌を提供するものである。
以下、この発明の態様を「態様1」とする。That is, the present invention provides a lactic acid bacterium belonging to the genus Lactococcus having a receipt number of NITE ABP-01694 at the Patent Microorganism Deposit Center (NPMD) of the National Institute for Product Evaluation and Technology (NITE). .
Hereinafter, this aspect of the present invention is referred to as “
また、本発明は、受領番号NITE ABP−01694で寄託されているラクトコッカス属に属する乳酸菌、該乳酸菌の死菌、又は、該乳酸菌の処理物を有効成分とする自然免疫活性化剤であって、上記乳酸菌の処理物は、乳酸菌の培養物;濃縮物;ペースト化物;噴霧乾燥物、凍結乾燥物、真空乾燥物、ドラム乾燥物等の乾燥物;液状化物;希釈物;破砕物;殺菌加工物、及び、該培養物からの抽出物よりなる群から選ばれる少なくとも1つの処理物であることを特徴とする自然免疫活性化剤を提供するものである。
以下、この発明の態様を「態様2」とする。The present invention also relates to an innate immunity activator comprising as an active ingredient a lactic acid bacterium belonging to the genus Lactococcus deposited under the receipt number NITE ABP-01694, a killed bacterium of the lactic acid bacterium, or a processed product of the lactic acid bacterium. The processed product of lactic acid bacteria is a culture of lactic acid bacteria; a concentrate; a paste product; a dry product such as a spray-dried product, a freeze-dried product, a vacuum-dried product, or a drum-dried product; a liquefied product; a diluted product; And an innate immunity activator characterized in that it is at least one processed product selected from the group consisting of a product and an extract from the culture.
Hereinafter, this embodiment is referred to as “embodiment 2”.
また、本発明は、受領番号NITE ABP−01694で寄託されているラクトコッカス属に属する乳酸菌を含有する飲食品を提供するものであり、また、上記自然免疫活性化剤を含有する飲食品を提供するものである。また、該乳酸菌を用いて発酵する工程を用いて製造された飲食品を提供するものである。
以下、この発明の態様を「態様3」とする。Moreover, this invention provides the food / beverage products containing the lactic acid bacteria which belong to the Lactococcus genus deposited by receipt number NITE ABP-01694, and provides the food / beverage products containing the said innate immune activator. To do. Moreover, the food / beverage products manufactured using the process fermented using this lactic acid bacteria are provided.
Hereinafter, this aspect of the invention is referred to as "Aspect 3".
また、本発明は、受領番号NITE ABP−01694で寄託されているラクトコッカス属に属する乳酸菌を含有する発酵乳であり、該発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して抵抗性を有する発酵乳を提供するものである。
以下、この発明の態様を「態様4」とする。Further, the present invention is a fermented milk containing a lactic acid bacterium belonging to the genus Lactococcus deposited under the receipt number NITE ABP-01694, the fermented milk comprising methicillin-sensitive S. aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa. The present invention provides fermented milk having resistance to at least one bacterium selected from the group consisting of bacterium and Enterococcus mundidi.
Hereinafter, this embodiment is referred to as “embodiment 4”.
本発明によれば、これまでに知られている乳酸菌より高い自然免疫活性化能を有する新規の乳酸菌を提供することができる。
更には、該乳酸菌を有効成分とする自然免疫活性化剤、及び、該乳酸菌又は該自然免疫活性化剤を含有する飲食品を提供することができる。ADVANTAGE OF THE INVENTION According to this invention, the novel lactic acid bacterium which has a higher innate immunity activation ability than the lactic acid bacterium known until now can be provided.
Furthermore, the innate immunity activator which uses this lactic acid bacterium as an active ingredient, and the food-drinks containing this lactic acid bacterium or this innate immunity activator can be provided.
また、本発明の乳酸菌又は乳酸菌を含有する発酵乳を食用することにより、メチシリン感受性黄色ブドウ球菌(MSSA)、メチシリン耐性黄色ブドウ球菌(MRSA)、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して高い抵抗性を得ることができる。
これらの菌は院内感染を引き起こす原因菌であり、該発酵乳を食用することにより、これらの菌による感染を予防又は治療することができる。In addition, the group consisting of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Enterococcus mundidi by edible lactic acid bacteria or fermented milk containing lactic acid bacteria of the present invention High resistance to at least one bacterium selected from
These bacteria are causative bacteria that cause nosocomial infections, and by using the fermented milk, infection by these bacteria can be prevented or treated.
以下、本発明について説明するが、本発明は、以下の具体的態様に限定されるものではなく、技術的思想の範囲内で任意に変形することができる。 Hereinafter, the present invention will be described, but the present invention is not limited to the following specific embodiments, and can be arbitrarily modified within the scope of the technical idea.
<態様1>
本発明の態様1は、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)における受領番号がNITE ABP−01694であるラクトコッカス(Lactococcus)属に属する乳酸菌である。<
以下、この新規乳酸菌株(11/19−B1株)について詳述する。
形態:本11/19−B1株は、グラム陽性の桿菌であり、鞭毛は認められず、運動性がない。本株は、果実を分離源として分離された。Hereinafter, this novel lactic acid strain (11 / 19-B1 strain) will be described in detail.
Form: This 11 / 19-B1 strain is a Gram-positive rod and has no flagella and no motility. This strain was isolated using fruit as a source of separation.
培地における生育状況:
(1)GAM及びMRS寒天培地上では白色のコロニーを形成する。拡散性の色素は認められない。
(2)炭酸カルシウム入りMRS寒天培地上では乳酸の生成に伴う透明帯の形成が認められる。Growth status in medium:
(1) White colonies are formed on GAM and MRS agar medium. Diffusible dyes are not observed.
(2) Formation of a zona pellucida accompanying the production of lactic acid is observed on the MRS agar medium containing calcium carbonate.
生理学的性質:本11/19−B1株の生理学的、化学分類学的性質は以下の通りである。
(1)酸素に対する態度:嫌気的
(2)カタラーゼ:−
(3)アルカリフォスファターゼ:−
(4)エステラーゼ:−
(5)エステラーゼリパーゼ:−
(6)リパーゼ:−
(7)ロイシンアリルアミダーゼ:−
(8)バリンアリルアミダーゼ:−
(9)シスチンアリルアミダーゼ:−
(10)トリプシン:−
(11)α−キモトリプシン:−
(12)酸性フォスファターゼ:+
(13)ナフトール−AS−BI−フォスフォヒトロラーゼ:+
(14)α−ガラクトシダーゼ:−
(15)β−ガラクトシダーゼ:−
(16)β−グルクロニダーゼ:−
(17)α−グルコシダーゼ:−
(18)β−グルコシダーゼ:−
(19)N−アセチル−β−グルコサミニダーゼ:−
(20)α−マンノシダーゼ:−
(21)α−フコシダーゼ:−Physiological properties: The physiological and chemical taxonomic properties of this 11 / 19-B1 strain are as follows.
(1) Attitude toward oxygen: Anaerobic (2) Catalase:-
(3) Alkaline phosphatase:-
(4) Esterase:-
(5) Esterase lipase:-
(6) Lipase:-
(7) Leucine allylamidase:-
(8) Valine allylamidase:-
(9) Cystine allylamidase:-
(10) Trypsin: −
(11) α-chymotrypsin: −
(12) Acid phosphatase: +
(13) Naphthol-AS-BI-phosphohumanlorase: +
(14) α-galactosidase: −
(15) β-galactosidase: −
(16) β-glucuronidase: −
(17) α-Glucosidase:-
(18) β-glucosidase: −
(19) N-acetyl-β-glucosaminidase:-
(20) α-mannosidase: −
(21) α-fucosidase: −
(22)下記の糖類等からの酸及びガスの生成能
グリセロール(Glycerol):−
エリトリトール(Erythritol):−
D−アラビノース(D−Arabinose):−
L−アラビノース(L−Arabinose):+
D−リボース(D−Ribose):+
D−キシロース(D−Xylose):+
L−キシロース(L−Xylose):−
D−アドニトール(D−Adonitol):−
メチル−β−D−キシロピラノサイド(methyl−β−D−xylopyranoside):−
D−ガラクトース(D−Galactose):±
D−グルコース(D−Glucose):+
D−フルクトース(D−Fructose):+
D−マンノース(D−Mannose):+
L−ソルボース(D−Sorbose):−
L−ラムノース(L−Rhamnose):−
ズルシトール(Dulcitol):−
イノシトール(Inositol):−
D−マンニトール(D−Mannitol):+
D−ソルビトール(D−Sorbitol):−
メチル−α−D−マンノピラノサイド(methyl−α−D−mannopyranoside):−
メチル−α−D−グルコピラノサイド(methyl−α−D−glucopyranoside):−
N−アセチルグルコサミン(N−Acetyl glucosamine):+
アミグダリン(Amygdalin):±
アルブチン(Arbutin):+
エスクリン(Esculin):+
サリシン(Salicin):+
D−セロビオース(D−Cellobiose):−
D−マルトース(D−Maltose):+
D−ラクトース(D−Lactose):+
D−メリビオース(D−Melibiose):−
D−スクロース(D−Sucrose):+
D−トレハロース(D−Trehalose):+
インスリン(Insulin):−
D−メレジトース(D−Melezitose):−
D−ラフィノース(D−Raffinose):−
スターチ(Starch):−
グリコーゲン(Glycogen):−
キシリトール(Xylitol):−
ゲンチオビオース(Gentiobiose):+
D−ツラノース(D−Turanose):−
D−リキソース(D−Lyxose):−
D−タガトース(D−Tagatose):−
D−フコース(D−Fucose):−
L−フコース(L−Fucose):−
D−アラビトール(D−Arabitol):−
L−アラビトール(L−Arabitol):−
グルコネート(Gluconate):±
2−ケト−グルコネート(2−Keto−gluconate):−
5−ケト−グルコネート(5−Keto−gluconate):−(22) Acid and gas production ability from the following saccharides etc. Glycerol: −
Erythritol:-
D-arabinose:-
L-arabinose: +
D-Ribose: +
D-Xylose: +
L-Xylose:-
D-Adonitol:-
Methyl-β-D-xylopyranoside:-
D-galactose: ±
D-glucose: +
D-fructose: +
D-Mannose: +
L-Sorbose:-
L-Rhamnose:-
Dulcitol:-
Inositol:-
D-Mannitol: +
D-sorbitol:-
Methyl-α-D-mannopyranoside:-
Methyl-α-D-glucopyranoside (methyl-α-D-glucopyranoside):
N-acetylglucosamine: +
Amygdalin: ±
Arbutin: +
Esculin: +
Salicin: +
D-Cellobiose:-
D-Maltose: +
D-Lactose: +
D-Melibiose:-
D-Sucrose: +
D-trehalose: +
Insulin:-
D-melezitose:-
D-Raffinose:-
Starch:-
Glycogen:-
Xylitol:-
Gentiobiose: +
D-Turanose:-
D-lyxose:-
D-Tagatose:-
D-Fucose:-
L-Fucose:-
D-Arabitol:-
L-Arabitol:-
Gluconate: ±
2-Keto-gluconate:-
5-Keto-gluconate:-
分子生物学的解析結果:分子生物学的な系統分類の指標として用いられている16S rRNAに関する11/19−B1株の解析結果は以下の通りである。
11/19−B1株のゲノムDNAから、PCRにより、16S rRNA領域の塩基配列を増幅し、シーケンサーによる解析を行った結果、5’末端側、3’末端側のいくつかの塩基を除く16S rRNAのほぼ全長に当たる塩基配列が見出された。この塩基配列を配列表の配列番号1に示す。配列表の配列番号1の塩基配列は、16S rRNAの全長ではないため、16S rRNA「領域」とした。
この塩基配列をNCBIのBLASTで相同性検索を行ったところ、11/19−B1株の16S rRNA領域の塩基配列は、ラクトコッカス属であるLactococcus lactis subsp.lactis IL1403、Lactococcus lactis subsp.hordniae NCDO 2181、Lactococcus lactis subsp.lactis NCDO 604株の塩基配列(NR_103918,NR_040956,NR_040955)と相同率99%を示した。しかしながら、完全には一致していないので、11/19−B1株とは異なるものである。Molecular biological analysis result: The analysis result of 11 / 19-B1 strain on 16S rRNA used as an index of molecular biological phylogeny is as follows.
As a result of amplification of the base sequence of the 16S rRNA region by PCR from the genomic DNA of the 11 / 19-B1 strain and analysis by a sequencer, 16S rRNA excluding some bases on the 5 ′ end side and 3 ′ end side The base sequence corresponding to almost the entire length of was found. This base sequence is shown in SEQ ID NO: 1 in the sequence listing. Since the base sequence of SEQ ID NO: 1 in the sequence listing is not the full length of 16S rRNA, it was designated as a 16S rRNA “region”.
When this base sequence was subjected to homology search with BLAST of NCBI, the base sequence of 16S rRNA region of 11 / 19-B1 strain was found to be Lactococcus lactis subsp. lactis IL1403, Lactococcus lactis subsp. hordniae NCDO 2181, Lactococcus lactis subsp. The base sequence (NR_103918, NR_040956, NR_040955) of lactis NCDO 604 strain and a homology of 99% were shown. However, it is different from the 11 / 19-B1 strain because it is not completely consistent.
以上の11/19−B1株の性質を、バージース・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.3 1989)による分類及びその他の文献の記載内容に照らし合わせ、更に、16S rRNA解析の結果を考慮して総合的に判断した結果、11/19−B1株は、ラクトコッカス(Lactococcus)属に属する微生物であると判断した。 The properties of the 11 / 19-B1 strain described above were compared with the classification according to Bergey's Manual of Systematic Bacteriology (vol. 3 1989) and the contents of other documents, and further, 16S rRNA. As a result of comprehensive determination in consideration of the analysis results, the 11 / 19-B1 strain was determined to be a microorganism belonging to the genus Lactococcus.
また、11/19−B1株の16S rRNA領域の塩基配列に一致する16S rRNA領域の塩基配列を有する微生物が存在しないこと、ラクトコッカス・ラクティスに属する既知の株と比べて、高い自然免疫活性化能を示すこと等を含め総合的に判断した結果、11/19−B1株は、新規な微生物株であると判断した。 In addition, there is no microorganism having a 16S rRNA region base sequence that matches the base sequence of the 16S rRNA region of the 11 / 19-B1 strain, and higher innate immunity activation compared to known strains belonging to Lactococcus lactis As a result of comprehensive judgment including showing performance, etc., the 11 / 19-B1 strain was judged to be a novel microbial strain.
11/19−B1株は、千葉県木更津市かずさ鎌足2−5−8、独立行政法人製品評価技術基盤機構(Natural Institute of Technology and Evaluation、以下、「NITE」と略記する)の特許微生物寄託センター(NPMD)に国内寄託され、受託番号:NITE P−01694(寄託日:2013年8月20日)として受託された微生物である。
「11/19−B1」は、その後、千葉県木更津市かずさ鎌足2−5−8、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)に、原寄託申請書を提出して、国内寄託(原寄託日:2013年8月20日)から、ブタペスト条約に基づく寄託への移管申請を行った(受領日:2014年10月15日、受領番号「NITE ABP−01694」)。11 / 19-B1 strain is a patent microorganism deposit of 2-5-8 Kazusa-Kamashita, Kisarazu City, Chiba Prefecture, National Institute of Technology and Evaluation (hereinafter abbreviated as “NITE”) It is a microorganism deposited in Japan at the Center (NPMD) and deposited under the deposit number: NITE P-01694 (deposit date: August 20, 2013).
“11 / 19-B1” will then be submitted to the patent microorganisms deposit center (NPMD) of Kazusa Kamashichi 2-5-8, Kisarazu City, Chiba Prefecture, and National Institute for Product Evaluation and Technology (NITE). Application for transfer from domestic deposit (original deposit date: August 20, 2013) to deposit under the Budapest Treaty (reception date: October 15, 2014, receipt number “NITE ABP-01694”) ").
バクテリアの一般的な性状として、その菌株としての性質は変異し易いため、11/19−B1株は、先に示した生理学的性状の範囲内に留まらない可能性も有している。また、かかる「変異」には、自然的な変異と人工的な変異の両方を含むことは言うまでもない。 As a general property of bacteria, since its properties as a strain are easily mutated, the 11 / 19-B1 strain may not be within the range of the physiological properties shown above. Needless to say, such “mutation” includes both natural and artificial mutations.
以下に、11/19−B1株の培養方法について記載する。11/19−B1株の培養方法は、ラクトコッカス属の微生物に対して行われる一般的な培養方法に準じて行えばよい。
培養は嫌気条件下で行うことが好ましい。培地中の炭素源としては、例えば、L−アラビノース、D−リボース、D−キシロース、D−ガラクトース、D−マンノース、D−マンニトール、N−アセチルグルコサミン、アミグダリン、アルブチン、エスクリン、サリシン、D−セロビオース、D−マルトース、D−ラクトース、D−トレハロース、ゲンチオビオース、グルコネート、D−グルコース、D−フラクトース、シュクロース、糖蜜、水飴、油脂類等の有機炭素化合物が用いられ、窒素源としては、肉エキス、カゼイン、ペプトン、酵母エキス、乾燥酵母、胚芽、大豆粉、尿素、アミノ酸、アンモニウム塩等の有機・無機窒素化合物を用いることができる。
また、塩類は、ナトリウム塩、カリウム塩、カルシウム塩、マグネシウム塩、リン酸塩、鉄塩、銅塩、亜鉛塩、コバルト塩等の無機塩類を必要に応じて適宜添加する。更に、ビオチン、ビタミンB1、シスチン、オレイン酸メチル、ラード油等の生育促進物質を添加することが、目的物の産生量を増加させる点で好ましい。
また、シリコン油、界面活性剤等の消泡剤を添加してもよい。調製済みの培地としては、例えば、MRS培地、GAM培地等を用いることが好ましい。Below, it describes about the culture | cultivation method of 11 / 19-B1 strain | stump | stock. What is necessary is just to perform the culture method of 11 / 19-B1 stock | strain according to the general culture method performed with respect to the microorganisms of the genus Lactococcus.
The culture is preferably performed under anaerobic conditions. Examples of the carbon source in the medium include L-arabinose, D-ribose, D-xylose, D-galactose, D-mannose, D-mannitol, N-acetylglucosamine, amygdalin, arbutin, esculin, salicin, D-cellobiose. Organic carbon compounds such as D-maltose, D-lactose, D-trehalose, gentiobiose, gluconate, D-glucose, D-fructose, sucrose, molasses, starch syrup, and fats and oils are used as the nitrogen source. Organic / inorganic nitrogen compounds such as casein, peptone, yeast extract, dry yeast, germ, soybean powder, urea, amino acid, ammonium salt can be used.
Further, as the salts, inorganic salts such as sodium salt, potassium salt, calcium salt, magnesium salt, phosphate, iron salt, copper salt, zinc salt, cobalt salt and the like are appropriately added as necessary. Furthermore, it is preferable to add a growth promoting substance such as biotin, vitamin B1, cystine, methyl oleate, lard oil or the like in terms of increasing the production amount of the target product.
Moreover, you may add antifoamers, such as a silicone oil and surfactant. As the prepared medium, for example, an MRS medium, a GAM medium or the like is preferably used.
培養条件は、先に記したようにラクトコッカス属の微生物に対して行われる一般的な培養条件に準じて行えばよい。液体培養法であれば静置培養が望ましい。小規模であれば蓋付きガラス瓶による静置培養法を用いてもよい。培養温度は、25℃〜37℃間に保つことが好ましく、37℃近辺で行うことがより好ましい。培養pHは、7付近で行うことが好ましい。培養期間は、用いた培地組成、培養温度等により変動するファクターであるが、11/19−B1株の場合、通常は12〜48時間程度、好ましくは12〜24時間程度の短期間に充分な量の目的物を確保することができる。 The culture conditions may be performed according to the general culture conditions performed for microorganisms belonging to the genus Lactococcus as described above. If it is a liquid culture method, stationary culture is desirable. If it is a small scale, you may use the stationary culture method by the glass bottle with a lid | cover. The culture temperature is preferably maintained between 25 ° C. and 37 ° C., more preferably around 37 ° C. The culture pH is preferably performed in the vicinity of 7. The culture period is a factor that varies depending on the composition of the medium used, the culture temperature, etc. In the case of the 11 / 19-B1 strain, it is usually sufficient for a short period of about 12 to 48 hours, preferably about 12 to 24 hours. A certain amount of objects can be secured.
<態様2>
本発明の態様2は、態様1の乳酸菌、該乳酸菌の死菌、又は、該乳酸菌の処理物を有効成分とする自然免疫活性化剤であって、
上記乳酸菌の処理物は、乳酸菌の培養物、濃縮物、ペースト化物、噴霧乾燥物、凍結乾燥物、真空乾燥物、ドラム乾燥物等の乾燥物、液状化物、希釈物、破砕物、殺菌加工物及び該培養物からの抽出物よりなる群から選ばれる少なくとも1つの処理物であることを特徴とする自然免疫活性化剤である。
すなわち、本発明の態様2は、態様1の乳酸菌、該乳酸菌の死菌、又は、該乳酸菌の処理物を有効成分とする自然免疫活性化剤である。<Aspect 2>
Aspect 2 of the present invention is an innate immunity activator comprising as an active ingredient the lactic acid bacterium of
The above processed products of lactic acid bacteria are lactic acid bacteria cultures, concentrates, pasted products, spray-dried products, freeze-dried products, vacuum-dried products, drum-dried products, etc., liquefied products, diluted products, crushed products, and sterilized products. And an innate immunity activator characterized by being at least one processed product selected from the group consisting of an extract from the culture.
That is, Aspect 2 of the present invention is an innate immunity activator comprising as an active ingredient the lactic acid bacteria of
本発明の自然免疫活性化剤は、態様1の乳酸菌を種々の状態で含むことができ、例えば、乳酸菌懸濁液、乳酸菌培養物(菌体、培養上清液(培地成分を含む))が挙げられる。
The innate immunity activator of the present invention can contain the lactic acid bacteria of
本発明の自然免疫活性化剤は、態様1の乳酸菌をそのまま含んでもよく、又は、態様1の乳酸菌に何らかの処理を施した乳酸菌処理物として含んでもよい。
本発明の自然免疫活性化剤に用いられる乳酸菌の処理物としては、具体的には、例えば、乳酸菌の培養物;濃縮物;ペースト化物;噴霧乾燥物、凍結乾燥物、真空乾燥物、ドラム乾燥物等の乾燥物;液状化物;希釈物;破砕物;殺菌加工物;該培養物からの抽出物;等が挙げられる。The innate immunity activator of the present invention may include the lactic acid bacterium of
Specific examples of the treated product of lactic acid bacteria used in the innate immunity activator of the present invention include, for example, a culture of lactic acid bacteria; a concentrate; a paste; a spray-dried product, a freeze-dried product, a vacuum-dried product, and a drum-dried product. A dried product such as a product; a liquefied product; a diluted product; a crushed product; a sterilized processed product; an extract from the culture product;
乳酸菌としては、生菌体、湿潤菌、乾燥菌等が適宜使用可能である。
また、殺菌、すなわち、加熱殺菌処理、放射線殺菌処理、破砕処理等を施した死菌であってもよい。As lactic acid bacteria, viable cells, wet bacteria, dry bacteria and the like can be used as appropriate.
Moreover, the killed bacteria which performed sterilization, ie, a heat sterilization process, a radiation sterilization process, a crushing process, etc. may be sufficient.
本発明の自然免疫活性化剤中の有効成分である、乳酸菌、該乳酸菌の死菌、該乳酸菌の処理物の、自然免疫活性化剤全体に対する含有量は、特に制限がなく、目的に応じて適宜選択することができるが、自然免疫活性化剤全体を100質量部としたときに、乳酸菌、該乳酸菌の死菌、該乳酸菌の処理物の合計量として、0.001〜100質量部の含量で配合することが好ましく、より好ましくは0.01〜99質量部、特に好ましくは0.1〜95質量部、更に好ましくは1〜90質量部の含量で配合することができる。 The content of the lactic acid bacterium, the killed lactic acid bacterium, and the processed product of the lactic acid bacterium, which is an active ingredient in the innate immunity activator of the present invention, with respect to the entire innate immunity activator is not particularly limited, depending on the purpose. Although it can select suitably, when the innate immunity activation agent is 100 mass parts as a whole, 0.001-100 mass parts content as a total amount of lactic acid bacteria, killed bacteria of the lactic acid bacteria, and processed products of the lactic acid bacteria It is preferable to mix | blend by 0.1-99 mass parts, More preferably, it is 0.1-95 mass parts, More preferably, it can mix | blend with the content of 1-90 mass parts.
また、前記有効成分は、何れか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。2種以上を併用する場合の、前記自然免疫活性化剤中の各々の有効成分の含有比についても、特に制限はなく、目的に応じて適宜選択することができる。 Moreover, the said active ingredient may be used individually by 1 type, and may use 2 or more types together. The content ratio of each active ingredient in the innate immunity activator when two or more are used in combination is not particularly limited and can be appropriately selected according to the purpose.
本発明の自然免疫活性化剤は、粉ミルク等、生物学的規格を有する医薬品及び/又は飲食品においても添加することも可能であり、医薬品及び/又は飲食品の形態等によらず様々な医薬品及び/又は飲食品に応用できる。 The innate immunity activator of the present invention can also be added to pharmaceuticals and / or foods and drinks having biological standards such as milk powder, and various pharmaceuticals regardless of the form of the pharmaceuticals and / or foods and drinks. And / or can be applied to food and drink.
また、本発明の自然免疫活性化剤は、有効成分である、乳酸菌、該乳酸菌の死菌、該乳酸菌の処理物に加えて、「その他の成分」を含有することができる。 Further, the innate immunity activator of the present invention can contain “other components” in addition to lactic acid bacteria, killed bacteria of the lactic acid bacteria, and processed products of the lactic acid bacteria, which are active ingredients.
前記自然免疫活性化剤における、上記「その他の成分」としては、特に制限はなく、本発明の効果を損なわない範囲内で、目的に応じて適宜選択することができ、例えば、薬学的に許容され得る担体等が挙げられる。
かかる担体としては、特に制限はなく、例えば、後述する剤型等に応じて適宜選択することができる。また、前記自然免疫活性化剤中の前記「その他の成分」の含有量としても、特に制限はなく、目的に応じて適宜選択することができる。The “other components” in the innate immunity activator are not particularly limited and can be appropriately selected according to the purpose within a range not impairing the effects of the present invention. For example, pharmaceutically acceptable And a carrier that can be used.
There is no restriction | limiting in particular as this support | carrier, For example, according to the dosage form etc. which are mentioned later, it can select suitably. Further, the content of the “other components” in the innate immunity activator is not particularly limited and can be appropriately selected according to the purpose.
本発明の自然免疫活性化剤の剤型としては、特に制限はなく、例えば、後述するような所望の投与方法に応じて適宜選択することができる。
具体的には、例えば、経口固形剤(錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等)、経口液剤(内服液剤、シロップ剤、エリキシル剤等)、注射剤(溶剤、懸濁剤等)、軟膏剤、貼付剤、ゲル剤、クリーム剤、外用散剤、スプレー剤、吸入散布剤等が挙げられる。There is no restriction | limiting in particular as a dosage form of the innate immunity activation agent of this invention, For example, it can select suitably according to the desired administration method as mentioned later.
Specifically, for example, oral solids (tablets, coated tablets, granules, powders, capsules, etc.), oral liquids (internal solutions, syrups, elixirs, etc.), injections (solvents, suspensions, etc.) , Ointments, patches, gels, creams, powders for external use, sprays, inhalation sprays and the like.
前記経口固形剤としては、例えば、前記有効成分に、賦形剤、更には必要に応じて結合剤、崩壊剤、滑沢剤、着色剤、矯味・矯臭剤等の添加剤を加え、常法により製造することができる。
前記賦形剤としては、例えば、乳糖、白糖、塩化ナトリウム、ブドウ糖、デンプン、炭酸カルシウム、カオリン、微結晶セルロース、珪酸等が挙げられる。
前記結合剤としては、例えば、水、エタノール、プロパノール、単シロップ、ブドウ糖液、デンプン液、ゼラチン液、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルスターチ、メチルセルロース、エチルセルロース、シェラック、リン酸カルシウム、ポリビニルピロリドン等が挙げられる。
前記崩壊剤としては、例えば、乾燥デンプン、アルギン酸ナトリウム、カンテン末、炭酸水素ナトリウム、炭酸カルシウム、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド、乳糖等が挙げられる。
前記滑沢剤としては、例えば、精製タルク、ステアリン酸塩、ホウ砂、ポリエチレングリコール等が挙げられる。
前記着色剤としては、例えば、酸化チタン、酸化鉄等が挙げられる。
前記矯味・矯臭剤としては、例えば、白糖、橙皮、クエン酸、酒石酸等が挙げられる。Examples of the oral solid preparation include, for example, excipients and further additives such as binders, disintegrants, lubricants, colorants, flavoring and flavoring agents as necessary, in addition to the active ingredients. Can be manufactured.
Examples of the excipient include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid and the like.
Examples of the binder include water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, shellac, calcium phosphate, polyvinylpyrrolidone and the like. It is done.
Examples of the disintegrant include dry starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, and lactose.
Examples of the lubricant include purified talc, stearate, borax, and polyethylene glycol.
Examples of the colorant include titanium oxide and iron oxide.
Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.
前記経口液剤としては、例えば、前記有効成分に、矯味・矯臭剤、緩衝剤、安定化剤等の添加剤を加え、常法により製造することができる。
前記矯味・矯臭剤としては、例えば、白糖、橙皮、クエン酸、酒石酸等が挙げられる。前記緩衝剤としては、例えば、クエン酸ナトリウム等が挙げられる。前記安定化剤としては、例えば、トラガント、アラビアゴム、ゼラチン等が挙げられる。The oral solution can be produced by a conventional method, for example, by adding additives such as a flavoring / flavoring agent, a buffering agent, and a stabilizer to the active ingredient.
Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like. Examples of the buffer include sodium citrate. Examples of the stabilizer include tragacanth, gum arabic, and gelatin.
前記注射剤としては、例えば、前記有効成分に、pH調節剤、緩衝剤、安定化剤、等張化剤、局所麻酔剤等を添加し、常法により皮下用、筋肉内用、静脈内用等の注射剤を製造することができる。
前記pH調節剤及び前記緩衝剤としては、例えば、クエン酸ナトリウム、酢酸ナトリウム、リン酸ナトリウム等が挙げられる。前記安定化剤としては、例えば、ピロ亜硫酸ナトリウム、EDTA、チオグリコール酸、チオ乳酸等が挙げられる。前記等張化剤としては、例えば、塩化ナトリウム、ブドウ糖等が挙げられる。前記局所麻酔剤としては、例えば、塩酸プロカイン、塩酸リドカイン等が挙げられる。As the injection, for example, a pH adjuster, a buffer, a stabilizer, a tonicity agent, a local anesthetic, etc. are added to the active ingredient, and subcutaneous, intramuscular, intravenous use are performed by a conventional method. Etc. can be manufactured.
Examples of the pH adjusting agent and the buffering agent include sodium citrate, sodium acetate, sodium phosphate and the like. Examples of the stabilizer include sodium pyrosulfite, EDTA, thioglycolic acid, thiolactic acid, and the like. Examples of the isotonic agent include sodium chloride and glucose. Examples of the local anesthetic include procaine hydrochloride and lidocaine hydrochloride.
前記軟膏剤としては、例えば、前記有効成分に、公知の基剤、安定剤、湿潤剤、保存剤等を配合し、常法により混合し、製造することができる。
前記基剤としては、例えば、流動パラフィン、白色ワセリン、サラシミツロウ、オクチルドデシルアルコール、パラフィン等が挙げられる。前記保存剤としては、例えば、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル等が挙げられる。As the ointment, for example, a known base, stabilizer, wetting agent, preservative and the like may be blended with the active ingredient and mixed by a conventional method.
Examples of the base include liquid paraffin, white petrolatum, white beeswax, octyldodecyl alcohol, and paraffin. Examples of the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and the like.
前記貼付剤としては、例えば、公知の支持体に前記軟膏剤としてのクリーム剤、ゲル剤、ペースト剤等を、常法により塗布し、製造することができる。前記支持体としては、例えば、綿、スフ、化学繊維からなる織布、不織布、軟質塩化ビニル、ポリエチレン、ポリウレタン等のフィルム、発泡体シート等が挙げられる。 As the patch, for example, a cream, gel or paste as the ointment can be applied to a known support by a conventional method. Examples of the support include woven fabric, nonwoven fabric, soft vinyl chloride, polyethylene, polyurethane and other films made of cotton, suf, and chemical fibers, and foam sheets.
本発明の自然免疫活性化剤は、例えば、自然免疫機構の活性化を必要とする個体(例えば、健康維持や疲労回復を必要とする個体;癌や生活習慣病の予防や治療を必要とする個体;細菌、真菌、ウイルス等に感染した個体;等)に投与することにより使用することができる。 The innate immunity activator of the present invention is, for example, an individual who requires activation of the innate immune mechanism (for example, an individual who needs to maintain health or recover from fatigue; needs prevention or treatment of cancer or lifestyle-related diseases) Individual; individuals infected with bacteria, fungi, viruses, etc .; etc.).
本発明の自然免疫活性化剤の投与対象動物としては、特に制限はないが、例えば、ヒト;マウス;ラット;サル;ウマ;ウシ、ブタ、ヤギ、ニワトリ等の家畜;ネコ、イヌ等のペット;等が挙げられる。 There are no particular restrictions on the animal to which the innate immunity activator of the present invention is administered. For example, humans; mice; rats; monkeys; horses; domestic animals such as cows, pigs, goats and chickens; And the like.
また、前記自然免疫活性化剤の投与方法としては、特に制限はなく、例えば、前記自然免疫活性化剤の剤型等に応じ、適宜選択することができ、経口投与、腹腔内投与、血液中への注射、腸内への注入等が挙げられる。
また、前記自然免疫活性化剤の投与量としては、特に制限はなく、投与対象である個体の年齢、体重、所望の効果の程度等に応じて適宜選択することができるが、例えば、成人への1日の投与量は、有効成分の量として、1mg〜30gが好ましく、10mg〜10gがより好ましく、100mg〜3gが特に好ましい。
また、前記自然免疫活性化剤の投与時期としても、特に制限はなく、目的に応じて適宜選択することができ、例えば、予防的に投与されてもよいし、治療的に投与されてもよい。In addition, the method for administering the innate immunity activator is not particularly limited, and can be appropriately selected according to, for example, the dosage form of the innate immunity activator. Oral administration, intraperitoneal administration, blood Injection, intestinal injection and the like.
The dose of the innate immunity activator is not particularly limited and may be appropriately selected depending on the age, weight, desired degree of effect, etc. of the individual to be administered. The daily dose is preferably from 1 mg to 30 g, more preferably from 10 mg to 10 g, particularly preferably from 100 mg to 3 g as the amount of the active ingredient.
Moreover, there is no restriction | limiting in particular also as an administration time of the said innate immunity activation agent, According to the objective, it can select suitably, For example, you may administer prophylactically and may administer therapeutically. .
<態様3>
本発明の態様3は、上記本発明の乳酸菌又は上記本発明の自然免疫活性化剤を含有する飲食品である。<Aspect 3>
Aspect 3 of the present invention is a food or drink containing the lactic acid bacterium of the present invention or the innate immunity activator of the present invention.
上記乳酸菌又は上記自然免疫活性化剤を含有する飲食品(以下、「本発明の飲食品」と略記する場合がある)中の、乳酸菌又は自然免疫活性化剤の含有量は、特に制限がなく、目的や飲食品の態様(種類)に応じて、適宜選択することができるが、飲食品全体を100質量部としたときに、上記自然免疫活性化剤の合計量で、0.001〜100質量部で含有することが好ましく、より好ましくは0.01〜100質量部、特に好ましくは0.1〜100質量部の含量である。 The content of the lactic acid bacterium or the innate immunity activator in the food or drink containing the lactic acid bacterium or the innate immunity activator (hereinafter sometimes abbreviated as “the food or drink of the present invention”) is not particularly limited. Depending on the purpose and the form (type) of the food or drink, it can be selected as appropriate, but when the total food and drink is 100 parts by mass, the total amount of the innate immune activator is 0.001 to 100. It is preferable to contain by mass part, More preferably, it is 0.01-100 mass part, Most preferably, it is 0.1-100 mass part.
また、乳酸菌又は自然免疫活性化剤の何れか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。2種以上を併用する場合の、前記飲食品中の各々の物質の含有量比には、特に制限はなく、目的に応じて適宜選択することができる。 In addition, any one of lactic acid bacteria and innate immunity activators may be used alone, or two or more may be used in combination. There is no restriction | limiting in particular in content ratio of each substance in the said food / beverage products in the case of using 2 or more types together, According to the objective, it can select suitably.
本発明の態様3の飲食品は、自然免疫活性化作用を有する。
本発明の飲食品は、本発明の態様2の自然免疫活性化剤に加えて、更に、「その他の成分」を含有することができる。The food / beverage products of aspect 3 of this invention have an innate immunity activation effect.
In addition to the innate immunity activator of aspect 2 of the present invention, the food and beverage product of the present invention can further contain “other components”.
かかる自然免疫活性化作用を有する本発明の飲食品における、前記「その他の成分」としては、特に制限はなく、本発明の効果を損なわない範囲内で目的に応じて適宜選択することができ、例えば、各種食品原料等が挙げられる。また、「その他の成分」の含有量は、特に制限はなく、目的に応じて適宜選択することができる。 In the food and drink of the present invention having such an innate immunity activation action, the `` other ingredients '' are not particularly limited and can be appropriately selected according to the purpose within a range not impairing the effects of the present invention. For example, various food raw materials are mentioned. Further, the content of “other components” is not particularly limited and can be appropriately selected depending on the purpose.
前記飲食品の種類としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、ゼリー、キャンディー、チョコレート、ビスケット等の菓子類;緑茶、紅茶、コーヒー、清涼飲料等の嗜好飲料;発酵乳、ヨーグルト、アイスクリーム等の乳製品;野菜飲料、果実飲料、ジャム類等の野菜・果実加工品;スープ等の液体食品;パン類、麺類等の穀物加工品;各種調味料;等が挙げられる。中でも、ヨーグルト、発酵乳等の乳製品が好ましい。
これらの飲食品の製造方法としては、特に制限はなく、例えば、通常の各種飲食品の製造方法に応じて、適宜製造することができる。There is no restriction | limiting in particular as the kind of said food / beverage products, According to the objective, it can select suitably, For example, confectionery, such as jelly, a candy, chocolate, a biscuit; Taste drinks, such as green tea, tea, coffee, a soft drink ; Dairy products such as fermented milk, yogurt and ice cream; Vegetable and fruit processed products such as vegetable drinks, fruit drinks and jams; Liquid foods such as soup; Grain processed products such as breads and noodles; Various seasonings; etc. Is mentioned. Of these, dairy products such as yogurt and fermented milk are preferred.
There is no restriction | limiting in particular as a manufacturing method of these food / beverage products, For example, according to the manufacturing method of various normal food / beverage products, it can manufacture suitably.
また、前記飲食品は、例えば、錠剤、顆粒剤、カプセル剤等の経口固形剤や、内服液剤、シロップ剤等の経口液剤として製造されたものであってもよい。前記経口固形剤、経口液剤の製造方法は、特に制限はなく、目的に応じて適宜選択することができ、例えば、前記した薬剤の経口固形剤、経口液剤の製造方法にならい、製造することができる。 Moreover, the said food / beverage products may be manufactured as oral liquid preparations, such as oral solid preparations, such as a tablet, a granule, a capsule, and an internal use liquid preparation, a syrup preparation, for example. The method for producing the oral solid preparation and oral liquid preparation is not particularly limited and can be appropriately selected according to the purpose. For example, the preparation can be produced in accordance with the method for producing the oral solid preparation or oral liquid preparation described above. it can.
前記飲食品は、自然免疫機構の活性化を目的とした、機能性食品、健康食品等として、特に有用であると考えられる。 The foods and drinks are considered to be particularly useful as functional foods, health foods and the like for the purpose of activating the innate immune mechanism.
上記11/19−B1株は、キウイフルーツから人為的に分離された、新規の乳酸菌である。キウイフルーツ以外には、自然界において、11/19−B1株は単離された形では存在しない。従って、人為的に分離された11/19−B1株は自然界に存在する物質そのものでない。従って、該11/19−B1株を含有する自然免疫活性化剤も、該11/19−B1株を含有する飲食品も、何れも自然産物には該当しない。
況や、自然界では、上記11/19−B1株と乳とが接触することはなく、上記菌株が飲食品として存在することもないので、本発明の発酵乳と飲食品は自然界に存在していたことはなく、従ってこれらは何れも自然産物には該当しない。The 11 / 19-B1 strain is a novel lactic acid bacterium that has been artificially isolated from kiwifruit. Other than kiwifruit, the 11 / 19-B1 strain does not exist in an isolated form in nature. Therefore, the artificially isolated 11 / 19-B1 strain is not a substance that exists in nature. Therefore, neither the innate immune activator containing the 11 / 19-B1 strain nor the food or drink containing the 11 / 19-B1 strain correspond to natural products.
In the current situation and the natural world, the 11 / 19-B1 strain does not come into contact with milk, and the bacterial strain does not exist as a food or drink, so the fermented milk and the food or drink of the present invention existed in the natural world. Therefore, none of these are natural products.
本発明の乳酸菌又は自然免疫活性化剤を飲食品の製造に使用する場合、製造方法は当業者に周知の方法によって行うことができる。当業者であれば、本発明の乳酸菌の菌体又は処理物を他の成分と混合する工程、成形工程、殺菌工程、発酵工程、焼成工程、乾燥工程、冷却工程、造粒工程、包装工程等を適宜組み合わせ、目的の飲食品を作ることが可能である。 When the lactic acid bacteria or innate immunity activator of the present invention is used for the production of food and drink, the production method can be carried out by methods well known to those skilled in the art. If it is an expert, the process which mixes the microbial cell or processed material of the lactic acid bacteria of this invention with another component, a formation process, a sterilization process, a fermentation process, a baking process, a drying process, a cooling process, a granulation process, a packaging process, etc. Can be combined as appropriate to produce the desired food or drink.
また、本発明の乳酸菌を各種発酵乳の製造に使用する場合、当業者に周知の方法を用いて製造することができる。例えば、本発明の乳酸菌を発酵乳に死菌として所要量添加する工程を用いて製造された飲食品や、乳酸菌スターターとして本発明の乳酸菌を用いて発酵する工程を用いて製造された飲食品が挙げられる。
乳酸菌スターターとして本発明の乳酸菌を用いて発酵を行う場合、本発明の乳酸菌の培養条件と同様の条件等で行うことができる。Moreover, when using the lactic acid bacteria of this invention for manufacture of various fermented milk, it can manufacture using a method well-known to those skilled in the art. For example, a food or drink manufactured using the process of adding a required amount of the lactic acid bacteria of the present invention as dead bacteria to fermented milk, or a food or drink manufactured using the process of fermenting using the lactic acid bacteria of the present invention as a lactic acid bacteria starter Can be mentioned.
When fermentation is performed using the lactic acid bacteria of the present invention as a lactic acid bacteria starter, the fermentation can be performed under the same conditions as the culture conditions of the lactic acid bacteria of the present invention.
<態様4>
本発明の態様4は、上記本発明の乳酸菌を含有する発酵乳であり、該発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して抵抗性を有することを特徴とする発酵乳である。<Aspect 4>
Aspect 4 of the present invention is a fermented milk containing the lactic acid bacterium of the present invention, wherein the fermented milk is a group consisting of methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus mundidi. It is fermented milk characterized by having resistance to at least one bacterium selected from.
発酵乳とは、牛等の乳を、乳酸菌や酵母で発酵させた乳製品であり、例えば、ヨーグルト、等が挙げられる。 Fermented milk is a dairy product obtained by fermenting milk such as cows with lactic acid bacteria or yeast, and examples thereof include yogurt.
上記本発明の乳酸菌を含有する発酵乳が、メチシリン感受性黄色ブドウ球菌(Methicillin−sensitive Staphylococcus aureus(MSSA))、メチシリン耐性黄色ブドウ球菌(Methicillin−resistant Staphylococcus aureus(MRSA))、緑膿菌(Pseudomonas aeruginosa)、及び、エンテロコッカス・ムンディディ(Enterococcus mundtii)の何れの菌についても抵抗性を有することは、実施例4〜6の結果に示されている。 Fermented milk containing the above lactic acid bacteria of the present invention is methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus MRaureus (MRSA), It is shown in the results of Examples 4 to 6 that there is resistance to any fungus of Enterococcus munditi.
上記発酵乳の接種対象者は、健常者も種々の感染症に対する抵抗力を高めるという意味でもちろん摂取対象者であり、各種の感染症を有する者も自然免疫機能の低下に伴う疾患者に限定することなく、全身の自然免疫機能の活性化を目的としてほとんどの疾患を有する者に使用することができる。更に動物に対しても、飼料や動物用薬品等種々の形態で適用することができる。
上記発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディによる感染の予防又は治療に用いられることが好ましく、特に緑膿菌感染の予防又は治療に用いられることが好ましい。Of course, the subject of vaccination with fermented milk is a person who is ingested in the sense of increasing resistance to various infectious diseases, and those who have various infectious diseases are also limited to those with a decrease in innate immune function. Without being used, it can be used for those who have most diseases for the purpose of activating the systemic innate immune function. Furthermore, it can be applied to animals in various forms such as feed and veterinary drugs.
The fermented milk is preferably used for prevention or treatment of infection caused by methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus mundidi, particularly for prevention or treatment of Pseudomonas aeruginosa infection. It is preferable to be used.
以下、実施例及び検討例に基づき本発明を更に詳細に説明するが、本発明は以下の実施例等の具体的範囲に限定されるものではない。 EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example and a study example, this invention is not limited to specific ranges, such as a following example.
実施例において使用する「11/19−B1株」は、上述の如く、キウイフルーツから分離されたものである。ラクトコッカス・ラクティス(Lactococcus lactis)に属する乳酸菌11/19−B1株として、独立行政法人製品評価技術基盤機構特許微生物寄託センター(NPMD)(千葉県木更津市かずさ鎌足2−5−8)に寄託されている(受託番号:NITE P−01694、寄託日:2013年8月20日)。
「11/19−B1」は、その後、千葉県木更津市かずさ鎌足2−5−8、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)に、原寄託申請書を提出して、国内寄託(原寄託日:2013年8月20日)から、ブタペスト条約に基づく寄託への移管申請を行った(受領日:2014年10月15日、受領番号「NITE ABP−01694」)。The “11 / 19-B1 strain” used in the examples is isolated from kiwifruit as described above. Deposited as
“11 / 19-B1” will then be submitted to the patent microorganisms deposit center (NPMD) of Kazusa Kamashichi 2-5-8, Kisarazu City, Chiba Prefecture, and National Institute for Product Evaluation and Technology (NITE). Application for transfer from domestic deposit (original deposit date: August 20, 2013) to deposit under the Budapest Treaty (reception date: October 15, 2014, receipt number “NITE ABP-01694”) ").
実施例1
<自然免疫活性化活性の測定>
GAM培地で一晩培養した11/19−B1株を、121℃、20分で滅菌処理後、50μLを5齢カイコの断頭筋肉標本に注射し、緩行性筋収縮により自然免疫活性化活性を測定した。
緩行性筋収縮による自然免疫活性化活性の測定は、Ishii K.,Hamamoto H., Kamimura M., Sekimizu K., J.Biol.Chem. Jan.25;283(4):2185-91(2008)に記載の方法に従って行った。
すなわち、5齢カイコの断頭筋肉標本に、上記試料0.05mLを血液内投与し、C値が最大となったとき(約10分後)に体長を測定して、注射前の体長から注射後の体長を引き算し、その値を注射前の体長で割り算した値であるC値(Contraction Value)を測定した。Example 1
<Measurement of innate immunity activation activity>
The 11 / 19-B1 strain cultured overnight in GAM medium is sterilized at 121 ° C for 20 minutes, and then 50 μL is injected into a decapitation muscle specimen of a 5-year-old silkworm, and the innate immune activation activity is measured by slowing muscle contraction. did.
Measurement of innate immunity activation activity by slowing muscle contraction is performed by Ishii K., Hamamoto H., Kamimura M., Sekimizu K., J. Biol. Chem. Jan. 25; 283 (4): 2185-91 (2008) ).
That is, 0.05 mL of the above sample was administered into blood to a decapitation muscle specimen of a 5-year-old silkworm, and the body length was measured when the C value reached the maximum (after about 10 minutes). The body length was subtracted, and the C value (Contraction Value), which was a value obtained by dividing the value by the body length before injection, was measured.
比較例1
GAM培地で一晩培養した培養したラクトバチルス・ブルガリクス OLL1073株を、121℃、20分で滅菌処理後、50μLを断頭カイコに注射し、筋収縮により自然免疫活性化活性を測定した。Comparative Example 1
The cultured Lactobacillus bulgaricus OLL1073 strain cultured overnight in GAM medium was sterilized at 121 ° C. for 20 minutes, and 50 μL was injected into a decapitated silkworm, and the innate immunity activation activity was measured by muscle contraction.
比較例2
GAM培地で一晩培養した培養したラクトバチルス・カゼイ YIT9029株を、121℃、20分で滅菌処理後、50μLを断頭カイコに注射し、筋収縮により自然免疫活性化活性を測定した。Comparative Example 2
The cultured Lactobacillus casei strain YIT9029 cultured overnight in GAM medium was sterilized at 121 ° C. for 20 minutes, and 50 μL was injected into a decapitated silkworm, and the innate immunity activation activity was measured by muscle contraction.
比較例3
GAM培地で一晩培養した培養したラクトコッカス・ラクティス JCM5805株を、121℃、20分で滅菌処理後、50μLを断頭カイコに注射し、筋収縮により自然免疫活性化活性を測定した。Comparative Example 3
The cultured Lactococcus lactis JCM5805 strain cultured overnight in GAM medium was sterilized at 121 ° C. for 20 minutes, and 50 μL was injected into a decapitated silkworm, and the innate immunity activation activity was measured by muscle contraction.
実施例1及び比較例1〜3の結果を表1に示す。C値=0.15を、1(U)ユニットと定義する。 The results of Example 1 and Comparative Examples 1 to 3 are shown in Table 1. C value = 0.15 is defined as 1 (U) unit.
比較例1〜3の乳酸菌は、実際に市販の発酵乳の製造に用いられている乳酸菌である。
表1に示されるように、実施例1の乳酸菌は、比較例1〜3に比べてより高い自然免疫活性化能を有することが分かった。
11/19−B1株、及び、その死菌は、自然免疫活性化能が高いことから、11/19−B1株は、自然免疫を活性化させる「発酵乳等の飲食品」の生産菌として有望であることが示唆された。The lactic acid bacteria of Comparative Examples 1 to 3 are actually lactic acid bacteria that are used in the production of commercially available fermented milk.
As shown in Table 1, it was found that the lactic acid bacteria of Example 1 had higher innate immunity activation ability than Comparative Examples 1 to 3.
Since the 11 / 19-B1 strain and its killed bacteria have high innate immunity activation ability, the 11 / 19-B1 strain is a production strain of “food and drinks such as fermented milk” that activates innate immunity. It was suggested that it was promising.
検討例1
<16S rRNA解析>
11/19−B1株の16S rDNAの塩基をゲノムDNAからPCR法によって増幅し、増幅できたDNA断片についてシーケンサーによって解析し、5’末端側、3’末端側のいくつかの塩基を除く配列番号1に示すほぼ16S rRNA領域全長に相当する塩基配列を決定した。
この塩基配列を元に、NCBIのBLASTを用いて既存の菌株との相同性検索を行った。その結果、11/19−B1株は、既存のLactococcus lactis IL1403株と99%の相同性を示したことから、ラクトコッカス(Lactococcus)属に属する微生物であると考えられた。Study example 1
<16S rRNA analysis>
The 16S rDNA base of 11 / 19-B1 strain was amplified from genomic DNA by PCR, the amplified DNA fragment was analyzed by a sequencer, and SEQ ID NO: excluding some bases on the 5 ′ end side and 3 ′ end side The base sequence corresponding to almost the entire 16S rRNA region shown in Fig. 1 was determined.
Based on this nucleotide sequence, homology search with existing strains was performed using NCBI BLAST. As a result, the 11 / 19-B1 strain showed 99% homology with the existing Lactococcus lactis IL1403 strain, and thus was considered to be a microorganism belonging to the genus Lactococcus.
<11/19−B1株の新規性について>
11/19−B1株は、糖の発酵能と化学的性質について既存のLactococcus lactisに相似する点が多く、細菌944株のapi web v5.1 database(シスメックス・ビオメリュー)による解析では、Lactococcus lactis ssp lactis 1と77.2%の同一性を示し、Lactobacillus brevis 1と21.9%の同一性を示した点で全く異なっている。この点は、既存の菌株との大きな相違点である。尚、Lactobacillus brevisである可能性は11/19−B1株のグラム染色像がグラム陽性球菌であることから排除される。よって、以上の結果から、11/19−B1株は、ラクトコッカス(Lactococcus)属に属する新規な微生物であると判定した。<Novelty of 11 / 19-B1 strain>
The 11 / 19-B1 strain has many similarities to the existing Lactococcus lactis in terms of sugar fermentability and chemical properties. Lactococcus lactis ssps ssp was found in the analysis by api web v5.1 database (Sysmex Biomelie) of the 944 strain of bacteria. It is completely different in that it shows 77.2% identity with
実施例2
<自然免疫活性化剤の製造>
<<錠剤>>
培養した11/19−B1株を、121℃、20分で滅菌処理後、濃縮した。該濃縮させた11/19−B1株の培養液20.0mg、ラクトース40mg、デンプン20mg、及び、低置換度ヒドロキシプロピルセルロース5mgを均一に混合した後、ヒドロキシプロピルメチルセルロース8質量%水溶液を結合剤として湿式造粒法で打錠用顆粒を製造した。これに、滑沢性を与えるのに必要なステアリン酸マグネシウムを0.5mg〜1mg加えてから打錠機を用いて打錠し、錠剤とした。Example 2
<Manufacture of innate immunity activation agent>
<< Tablet >>
The cultured 11 / 19-B1 strain was sterilized at 121 ° C. for 20 minutes and then concentrated. After uniformly mixing the concentrated culture solution of 11 / 19-B1 strain 20.0 mg,
<<液剤>>
上記濃縮させた11/19−B1株の培養液10.0mgを、2質量%の2−ヒドロキシプロピル−β−サイクロデキストリン水溶液10mLに溶解し、注射用液剤とした。<< Liquid >>
10.0 mg of the concentrated culture solution of 11 / 19-B1 strain was dissolved in 10 mL of a 2% by mass 2-hydroxypropyl-β-cyclodextrin aqueous solution to prepare an injection solution.
実施例3
<発酵乳の製造>
牛乳を95℃で5分間殺菌した後、40℃に冷却し、11/19−B1株を0.001質量部加えた。そして、37℃、72時間で発酵して、発酵乳を得た。該発酵乳を10℃以下で冷却してから、風味と物性を確認した。
その結果、風味と物性は何れも極めて良好であった。Example 3
<Manufacture of fermented milk>
The milk was sterilized at 95 ° C. for 5 minutes, cooled to 40 ° C., and 0.001 part by mass of 11 / 19-B1 strain was added. And it fermented at 37 degreeC and 72 hours, and fermented milk was obtained. After cooling this fermented milk at 10 degrees C or less, the flavor and physical property were confirmed.
As a result, both flavor and physical properties were extremely good.
実施例4
<11/19−B1ヨーグルトのプロバイオティクス効果>
生体外の実験では、11/19−B1株の培養液、培養上清、及び、11/19−B1株を用いて製造されたヨーグルトには抗菌活性が見られなかった(図示せず)。
11/19−B1株を用いて製造されたヨーグルトのプロバイオティクス効果(生菌を利用して腸内バランスを改善し、抵抗力や免疫力を高める効果)を検証した。Example 4
<Probiotic effect of 11 / 19-B1 yogurt>
In an in vitro experiment, antibacterial activity was not observed in the culture solution, culture supernatant of the 11 / 19-B1 strain, and yogurt produced using the 11 / 19-B1 strain (not shown).
The probiotic effect of yogurt produced using the 11 / 19-B1 strain (effect of improving intestinal balance and enhancing resistance and immunity using live bacteria) was verified.
<<カイコ菌感染モデルの作製>>
LB培地で一晩培養した緑膿菌(Pseudomonas aeruginosa PAO1)又はメチシリン感受性黄色ブドウ球菌(Staphylococcus aureus MSSA1)の培養液を、滅菌した0.9質量%NaCl溶液で希釈し、5齢2日目のカイコ幼虫(平均体重2g)に50μLずつ血液内注射した。<< Preparation of silkworm infection model >>
A culture solution of Pseudomonas aeruginosa PAO1 or methicillin-sensitive Staphylococcus aureus (SAPH1) cultured overnight in LB medium was diluted with a sterilized 0.9 mass% NaCl solution, and the second day of
<<ヨーグルトの作製>>
乳酸菌(11/19−B1株)末50mgを生理食塩水(滅菌済み0.9質量%NaCl溶液)1mLに懸濁し、懸濁液50μLを、0.267質量%グルコース及び0.025質量%カザミノ酸を含む牛乳200mL中に混ぜ、滅菌したガラス瓶中で、37℃、3日間保温した。以下、作製したヨーグルトを、「11/19−B1ヨーグルト」と略記する。<< Preparation of yogurt >>
50 mg of lactic acid bacteria (11 / 19-B1 strain) powder is suspended in 1 mL of physiological saline (sterilized 0.9 mass% NaCl solution), and 50 μL of the suspension is 0.267 mass% glucose and 0.025 mass% casamino. The mixture was mixed with 200 mL of acid-containing milk and kept at 37 ° C. for 3 days in a sterilized glass bottle. Hereinafter, the produced yogurt is abbreviated as “11 / 19-B1 yogurt”.
<<検証方法>>
11/19−B1ヨーグルトを含有する餌、又は、対照として通常の餌をカイコに一晩与えた後、カイコに菌を感染させた。通常の餌として、人工飼料シルクメイト2S(日本農産工業)を用いた。ここで、「11/19−B1ヨーグルトを含有する餌」とは、通常の餌に、11/19−B1ヨーグルトを混合させた餌である。
1群当たりのカイコの総数は7匹とし、緑膿菌又はメチシリン感受性黄色ブドウ球菌の接種2日後に生死を判定し、生存曲線からLD50(50%半数致死量)を算出した。ネガティブコントロールには0.9質量%NaCl溶液を用いた。結果を図1に示す。
図1中、縦軸は生存率(Survival%)、横軸は感染2日後の生存率における菌の用量依存性を表す(OD600)。<< Verification method >>
Silkworms were infected overnight with bait containing 11 / 19-B1 yogurt, or normal bait as a control, and then infected with the fungus. Artificial feed silk mate 2S (Nippon Agricultural Industries) was used as a normal bait. Here, the “bait containing 11 / 19-B1 yogurt” is a bait obtained by mixing 11 / 19-B1 yogurt with normal bait.
The total number of silkworms per group was 7, and the viability was determined 2 days after inoculation with Pseudomonas aeruginosa or methicillin-sensitive Staphylococcus aureus, and the LD 50 (50% half lethal dose) was calculated from the survival curve. As a negative control, a 0.9 mass% NaCl solution was used. The results are shown in FIG.
In FIG. 1, the vertical axis represents the survival rate (Survival%), and the horizontal axis represents the dose dependency of bacteria in the survival rate 2 days after infection (OD 600 ).
また、同様の手法を用い、グラム陽性細菌である、メチシリン感受性黄色ブドウ球菌(S.aureus MSSA1)、メチシリン耐性黄色ブドウ球菌(S.aureus MRSA4)、又は、エンテロコッカス・ムンディディ(Enterococcus mundtii 12/5−1)をカイコに感染させ、プロバイオティクス効果を検証した。結果を図2に示す。 In addition, using the same technique, gram-positive bacteria such as methicillin-sensitive S. aureus (S. aureus MSSA1), methicillin-resistant S. aureus (S. aureus MRSA4), or Enterococcus munditi 12/5 -1) was infected with silkworm and the probiotic effect was verified. The results are shown in FIG.
図1及び図2の結果より、カイコに感染させたP.aeruginosa PAO1、S.aureus MSSA1、S.aureus MRSA4及びエンテロコッカス・ムンディディについて、11/19−B1ヨーグルトを含有させた餌を食用させることにより、カイコは何れの菌についても高い抵抗性を示した。 From the results of FIG. 1 and FIG. aeruginosa PAO1, S. aeruginosa. aureus MSSA1, S. About aureus MRSA4 and Enterococcus mundidi, the silkworm showed high resistance with respect to any microbe by feeding the food containing 11 / 19-B1 yogurt.
以上の結果から、11/19−B1ヨーグルトのプロバイオティクス効果が認められた。特に、緑膿菌を感染させたとき(図1(A))に強い効果が認められたことより、緑膿菌感染の予防の可能性が示唆された。 From the above results, the probiotic effect of 11 / 19-B1 yogurt was recognized. In particular, when a strong effect was observed when Pseudomonas aeruginosa was infected (FIG. 1 (A)), the possibility of prevention of Pseudomonas aeruginosa infection was suggested.
実施例5
<カイコ緑膿菌感染モデルでの11/19−B1ヨーグルト及び11/19−B1生菌粉末の効果の比較>
次に、緑膿菌を感染させたときに強い効果を示した要因を検証した。
10リットルスケールで11/19−B1株を培養し、生菌粉末を作製した。以下、作製した生菌粉末を、「11/19−B1生菌粉末」と略記する。
実施例4と同様の手法により、11/19−B1ヨーグルト(8×107 cfu/g、0.5g/個体)を含有する餌、11/19−B1生菌粉末(4×108 cfu/g、0.1g/個体)を含有する餌、又は、通常の餌をカイコに一晩与えた後、カイコに緑膿菌(P.aeruginosa PAO1)を感染させた。
結果を図3及び表2に示す。Example 5
<Comparison of effects of 11 / 19-B1 yogurt and 11 / 19-B1 live powder in silkworm Pseudomonas aeruginosa infection model>
Next, we examined the factors that showed a strong effect when infected with Pseudomonas aeruginosa.
The 11 / 19-B1 strain was cultured on a 10 liter scale to produce viable powder. Hereinafter, the produced viable powder is abbreviated as “11 / 19-B1 viable powder”.
In the same manner as in Example 4, a feed containing 11 / 19-B1 yogurt (8 × 10 7 cfu / g, 0.5 g / individual), 11 / 19-B1 viable powder (4 × 10 8 cfu / g, 0.1 g / individual) or normal food was given to the silkworm overnight, and then the silkworm was infected with P. aeruginosa PAO1.
The results are shown in FIG.
また、図3及び表2の結果より、カイコに感染させた緑膿菌(P.aeruginosa PAO1)について、11/19−B1生菌粉末によるプロバイオティクス効果が認められた。
また、11/19−B1ヨーグルト及び11/19−B1生菌粉末は同等の効果であったから、11/19−B1による緑膿菌感染死の予防効果は、菌自体に含まれる成分によるプロバイオティクス効果であるものではないかと示唆された。From the results shown in FIG. 3 and Table 2, the probiotic effect of 11 / 19-B1 viable powder was observed for P. aeruginosa PAO1 infected with silkworm.
Moreover, since 11 / 19-B1 yogurt and 11 / 19-B1 viable powder had the same effect, the preventive effect of 11 / 19-B1 on death caused by Pseudomonas aeruginosa infection is probiotic due to components contained in the bacterium itself. It was suggested that it might be a tics effect.
実施例6
<カイコ緑膿菌感染モデルでの11/19−B1ヨーグルト摂取量とLD50との相関性>
実施例4と同様の手法により、餌全体に対して、11/19−B1ヨーグルトを6質量%、11質量%、20質量%、33質量%をそれぞれ含有する餌、又は、対照として通常の餌をカイコに一晩与えた後、カイコに緑膿菌(P.aeruginosa PAO1)を感染させた。Example 6
<Relationship between 11 / 19-B1 yogurt intake and LD 50 in silkworm Pseudomonas aeruginosa infection model>
In the same manner as in Example 4, the bait containing 6% by mass, 11% by mass, 20% by mass, and 33% by mass of 11 / 19-B1 yogurt with respect to the entire bait, or a normal bait as a control Was given to silkworms overnight, and the silkworms were infected with P. aeruginosa PAO1.
結果を図4に示す。図4Bは、ヨーグルト摂食量と、(P.aeruginosa PAO1)のLD50との相関性を示したグラフである。図4B中、縦軸は、LD50比((11/19−B1ヨーグルトを含有する餌を与えた場合のLD50値)/(11/19−B1ヨーグルトを含有していない通常の餌を与えた場合のLD50値))であり、横軸は、餌全体に対するヨーグルトの割合(質量%)である。The results are shown in FIG. FIG. 4B is a graph showing the correlation between the amount of yogurt food intake and the LD 50 of (P. aeruginosa PAO1). In FIG. 4B, the vertical axis represents the LD 50 ratio ((LD 50 value when feeding containing 11 / 19-B1 yogurt) / (ordinary feeding without 11 / 19-B1 yogurt). LD 50 value))), and the horizontal axis represents the ratio (mass%) of yogurt to the whole bait.
図4の結果、ヨーグルト摂食量とLD50とは相関性があることがわかった。 As a result of FIG. 4, it was found that there was a correlation between the amount of yogurt consumed and LD50.
本発明の新規乳酸菌は、高い自然免疫活性化能を有する。よって、本発明の乳酸菌を利用した、自然免疫を活性化させる自然免疫活性化剤又は飲食品を提供することができ、食品業界や医薬品業界等で広く利用可能である。 The novel lactic acid bacteria of the present invention have high innate immunity activation ability. Therefore, the innate immunity activation agent or food / beverage product which activates innate immunity using the lactic acid bacteria of this invention can be provided, and it can use widely in the food industry, the pharmaceutical industry, etc.
本願は、2013年10月17日に出願した日本の特許出願である特願2013−216517に基づくものであり、その出願の全ての内容はここに引用し、本発明の明細書の開示として取り込まれるものである。 This application is based on Japanese Patent Application No. 2013-216517 filed on Oct. 17, 2013, the entire contents of which are hereby incorporated by reference as the disclosure of the present specification. It is what
NITE ABP−01694 NITE ABP-01694
配列番号1は、ラクトコッカス(Lactococcus)属に属する未知の菌株の、16S rRNAのほぼ全長にあたる塩基配列である。 SEQ ID NO: 1 is a base sequence corresponding to almost the entire length of 16S rRNA of an unknown strain belonging to the genus Lactococcus.
Claims (9)
上記乳酸菌の処理物は、乳酸菌の培養物、濃縮物、ペースト化物、乾燥物、液状化物、希釈物、破砕物、殺菌加工物、及び、該培養物からの抽出物よりなる群から選ばれる少なくとも1つの処理物であることを特徴とする自然免疫活性化剤。An innate immunity activator comprising as an active ingredient the lactic acid bacterium according to any one of claims 1 to 3, a killed bacterium of the lactic acid bacterium, or a processed product of the lactic acid bacterium,
The treated product of lactic acid bacteria is at least selected from the group consisting of cultures, concentrates, pasted products, dried products, liquefied products, diluted products, crushed products, sterilized processed products, and extracts from the cultured products of lactic acid bacteria. An innate immunity activator characterized by being one processed product.
該発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して抵抗性を有することを特徴とする発酵乳。A fermented milk containing the lactic acid bacterium according to any one of claims 1 to 3,
The fermented milk is resistant to at least one bacterium selected from the group consisting of methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus mundidi. milk.
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JP6576890B2 (en) * | 2016-08-30 | 2019-09-18 | 株式会社ゲノム創薬研究所 | Method for reducing sugar concentration in vegetable or fruit juice, and method for producing lactic acid bacteria-containing vegetable or fruit juice using the method |
CN107802659B (en) * | 2016-09-08 | 2020-08-25 | 潍坊华英生物科技有限公司 | Intravenous injection for enhancing immunologic function |
US11213555B2 (en) | 2016-09-08 | 2022-01-04 | Weifang Huaying Biotechnology Co., Ltd. | Intravenous injection for enhancing immune function |
JP7267536B2 (en) * | 2017-10-11 | 2023-05-02 | 株式会社ゲノム創薬研究所 | Method for producing lactic acid-fermented carrot |
WO2020204615A1 (en) * | 2019-04-05 | 2020-10-08 | 에스케이바이오랜드 주식회사 | Method for producing lava seawater-derived natural mineral-coated probiotics and lava seawater-derived natural mineral-coated probiotics using same |
KR102154254B1 (en) * | 2020-04-29 | 2020-09-09 | (주)녹십자웰빙 | Novel Lactic Acid Bacteria with Excellent Immune function enhancing effect and Food Composition Containing the Same and Health Functional Food Composition Containing the Same and Probiotics comprising the Same |
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