JP2001169760A - Fermented and concentrated beverage derived from microorganism having disinfection/infection protection action on vancomycin-resistant enterococcus - Google Patents
Fermented and concentrated beverage derived from microorganism having disinfection/infection protection action on vancomycin-resistant enterococcusInfo
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- JP2001169760A JP2001169760A JP2000150125A JP2000150125A JP2001169760A JP 2001169760 A JP2001169760 A JP 2001169760A JP 2000150125 A JP2000150125 A JP 2000150125A JP 2000150125 A JP2000150125 A JP 2000150125A JP 2001169760 A JP2001169760 A JP 2001169760A
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- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Non-Alcoholic Beverages (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、バンコマイシン耐
性腸球菌に対して殺菌・感染防御作用のある濃縮飲料、
さらに詳しくは、桿菌、酵母菌および乳酸菌の共生培養
により製造されるバンコマイシン耐性腸球菌に対して殺
菌・感染防御作用のある濃縮飲料に関するものである。The present invention relates to a concentrated beverage having a bactericidal and protective action against vancomycin-resistant enterococci,
More specifically, the present invention relates to a concentrated beverage having a bactericidal / infective protective action against vancomycin-resistant enterococci produced by co-cultivation of bacilli, yeasts and lactic acid bacteria.
【０００２】[0002]
【従来の技術】グリコペプチド抗生物質、バンコマイシ
ンは、他の抗生剤が効かない疾病に対する治療薬として
用いられてきた。BACKGROUND OF THE INVENTION The glycopeptide antibiotic vancomycin has been used as a remedy for diseases in which other antibiotics do not work.
【０００３】[0003]
【発明が解決しようとする課題】抗生物質が効かない
「耐性菌」が出現しない唯一の薬と考えられてきたバン
コマイシンは、抗生物質の「最後の切り札」とされてき
た。しかし、１９８０年代後半にフランスで、また、日
本でも１９９６年にバンコマイシン耐性腸球菌（ＶＲ
Ｅ）が見付かっている。院内感染も海外では多数報告さ
れ、また、日本でも報告例がある。SUMMARY OF THE INVENTION Vancomycin, which has been considered the only drug in which "resistant bacteria" in which antibiotics do not work and does not appear, has been regarded as the "last resort" of antibiotics. However, vancomycin-resistant enterococci (VR) were introduced in France in the late 1980s and in Japan in 1996.
E) is found. A number of hospital-acquired infections have been reported overseas, and there are also cases reported in Japan.
【０００４】健康な人の体内にバンコマイシン耐性腸球
菌が存在していても病気を起こす力は非常に弱く問題は
ないが、抗癌剤を使用していたり、高齢で体力が落ちて
いて免疫力が低下していると、バンコマイシン耐性腸球
菌によって敗血症などを起こして死亡することもある。[0004] Even if vancomycin-resistant enterococci exist in the body of a healthy person, the ability to cause illness is very weak, and there is no problem. However, immunity is reduced due to the use of anticancer drugs or the decline of physical strength in the elderly. If they do, vancomycin-resistant enterococci may cause sepsis and death.
【０００５】バンコマイシン耐性腸球菌に対して抗生物
質が効かないため薬による治療は難しいが、免疫力を高
めるなどの対処法も一つの方法として考えられている。
このような背景下、本発明者は、かねてより微生物醗酵
生産物による飲料を提供することにつき、鋭意研究を重
ねてきた。[0005] Although antibiotics are not effective against vancomycin-resistant enterococci, it is difficult to treat them with drugs, but measures such as enhancing immunity are also considered as one method.
Against this background, the present inventor has been enthusiastically studying the provision of beverages produced by microbial fermentation.
【０００６】[0006]
【課題を解決するための手段】その結果、桿菌、酵母菌
および乳酸菌から選ばれた複数種の有益菌を特定の組み
合せで共生培養して得られた培養液のろ液から、濃縮法
によってアミノ酸、ビタミン及びミネラルなどの有効成
分をバランス良く含有し栄養価が高い濃縮液が得られる
こと、及び、この濃縮液が健康飲料として適するもので
あることを見出した。そして、さらに研究を重ねて行く
うちに、この濃縮飲料にバンコマイシン耐性腸球菌に対
して殺菌・感染防御作用があることを見出した。本発明
は、かかる知見に基づくものである。As a result, amino acids are concentrated by a concentration method from a filtrate of a culture solution obtained by co-cultivating a plurality of beneficial bacteria selected from bacilli, yeasts and lactic acid bacteria in a specific combination. It has been found that a concentrated solution having a high nutritional value containing active ingredients such as vitamins and minerals in a well-balanced manner can be obtained, and that the concentrated solution is suitable as a health drink. Through further research, they have found that this concentrated beverage has a bactericidal and protective action against vancomycin-resistant enterococci. The present invention is based on such findings.
【０００７】すなわち、本発明に係るバンコマイシン耐
性腸球菌に対して殺菌・感染防御作用がある濃縮飲料
は、桿菌、酵母菌および乳酸菌からなるものである。さ
らに詳しくは、桿菌、酵母菌および乳酸菌から選ばれた
複数種の有益菌を特定の組み合せで共生培養して得られ
た培養液のろ液の濃縮液からなるものである。そして、
本発明に係る濃縮飲料には含有成分としてのアミノ酸、
ビタミンおよびミネラルなどの他に、少なくとも下記構
造式からなる化合物Ａ〜Ｆが１つ以上含まれている。[0007] That is, the concentrated beverage according to the present invention which has a bactericidal and protective action against vancomycin-resistant enterococci is composed of bacilli, yeasts and lactic acid bacteria. More specifically, it comprises a concentrated solution of a filtrate of a culture solution obtained by co-cultivating a plurality of beneficial bacteria selected from bacilli, yeasts and lactic acid bacteria in a specific combination. And
Amino acid as an ingredient in the concentrated beverage according to the present invention,
In addition to vitamins and minerals, at least one compound A to F having the following structural formula is contained.
【０００８】[0008]
【化１】 Embedded image
【０００９】[0009]
【化２】 Embedded image
【００１０】[0010]
【化３】 Embedded image
【００１１】[0011]
【化４】 Embedded image
【００１２】[0012]
【化５】 Embedded image
【００１３】[0013]
【化６】 Embedded image
【００１４】本発明に係る濃縮飲料の製造に際し用いら
れる有益菌（桿菌、酵母菌、乳酸菌）としては、表１に
示すものなどを挙げることができる。The beneficial bacteria (rods, yeasts, lactic acid bacteria) used in the production of the concentrated beverage according to the present invention include those shown in Table 1.
【００１５】[0015]
【表１】 [Table 1]
【００１６】本発明に係る濃縮飲料は、桿菌、酵母菌お
よび乳酸菌から選ばれた複数種の有益菌を特定の組み合
せで共生培養して得られた培養液のろ液を濃縮すること
により得られるが、複数種の有益菌のグループ分けとし
ては、例えば表２に示すような場合を挙げることができ
る。The concentrated beverage according to the present invention is obtained by concentrating a filtrate of a culture solution obtained by co-culturing a plurality of beneficial bacteria selected from bacilli, yeasts and lactic acid bacteria in a specific combination. However, examples of the grouping of a plurality of types of beneficial bacteria include the cases shown in Table 2.
【００１７】[0017]
【表２】 [Table 2]
【００１８】本発明に係る濃縮飲料を分析すると、タン
パク質、リン、鉄、カルシウム、サイアミン（ビタミン
B1）、リボフラビン（ビタミンB2）などが含まれている
ことが判明した。分析結果の一例を表３に示す。Analysis of the concentrated beverage according to the present invention shows that protein, phosphorus, iron, calcium, thiamine (vitamin
B 1 ), riboflavin (vitamin B 2 ) and so on. Table 3 shows an example of the analysis result.
【００１９】[0019]
【表３】 [Table 3]
【００２０】また、本発明に係る濃縮飲料中には、アミ
ノ酸として、スレオニン、バリン、リジン、ロイシンな
どの必須アミノ酸のほか、グルタミン酸、アスパラギン
酸、アルギニンなど20種近いアミノ酸を確認することが
できた。In the concentrated beverage according to the present invention, as amino acids, in addition to essential amino acids such as threonine, valine, lysine and leucine, nearly 20 kinds of amino acids such as glutamic acid, aspartic acid and arginine could be confirmed. .
【００２１】また、本発明に係る濃縮飲料に含まれてい
る有機化合物（アミノ酸及び糖類を除く）を抽出し、さ
らに、酢酸エチル層中に溶けている物質を分離してそれ
らの構造式を特定することができた。なお、有機化合物
の抽出には逆抽出法を用いる液−液抽出の手法を用い、
また、酢酸エチル層中に溶けている物質の分離には液性
を変化させ再度液−液抽出を行う手法を用いた。Further, the organic compounds (excluding amino acids and saccharides) contained in the concentrated beverage according to the present invention are extracted, and the substances dissolved in the ethyl acetate layer are separated to specify their structural formulas. We were able to. In addition, the method of liquid-liquid extraction using the back extraction method is used for the extraction of the organic compound,
For the separation of the substance dissolved in the ethyl acetate layer, a method of changing the liquid property and performing liquid-liquid extraction again was used.
【００２２】本発明に係る濃縮飲料から有機化合物（ア
ミノ酸及び糖類を除く）を抽出する方法を図解すると、
図１のようになる。そして、酢酸エチル層中に溶けてい
る物質から分離された各化合物Ａ〜Ｆの構造式並びに物
質名は次の通りである。The method for extracting an organic compound (excluding amino acids and saccharides) from the concentrated beverage according to the present invention is as follows.
As shown in FIG. The structural formulas and substance names of the compounds A to F separated from the substance dissolved in the ethyl acetate layer are as follows.
【００２３】化合物Ａ（Daidzein）Compound A (Daidzein)
【化１】 上記構造式の化合物Ａは中性画分より単離、精製された
ものであり、大豆に含まれているイソフラボン配糖体で
あるdaidzin から糖がとれたdaidzeinと同定することが
できる。Embedded image Compound A of the above structural formula is isolated and purified from the neutral fraction, and can be identified as daidzein obtained by removing sugar from daidzin, an isoflavone glycoside contained in soybean.
【００２４】化合物Ｂ（2,3,5-Trihydroxybenzaldehyd
e）Compound B (2,3,5-Trihydroxybenzaldehyd
e)
【化２】 上記構造式の化合物Ｂは中性画分より単離、精製された
ものであり、３個の水酸基を有する2,3,5-Trihydroxybe
nzaldehydeと同定することができる。文献にも未記載の
新規な物質である。Embedded image Compound B of the above structural formula is isolated and purified from a neutral fraction, and has 2,3,5-trihydroxybe having three hydroxyl groups.
It can be identified as nzaldehyde. It is a new substance not described in the literature.
【００２５】化合物Ｃ（2-furoic acid ）Compound C (2-furoic acid)
【化３】 上記構造式の化合物Ｃは酸性画分より単離、精製された
ものであり、2-furoic acid と同定することができる。Embedded image Compound C of the above structural formula is isolated and purified from the acidic fraction, and can be identified as 2-furoic acid.
【００２６】化合物Ｄ〔4-hydroxy-3-methoxybenzoic a
cid(Vanillic Acid)〕Compound D [4-hydroxy-3-methoxybenzoic a
cid (Vanillic Acid))
【化４】 上記構造式の化合物Ｄは酸性画分より単離、精製された
ものであり、バニリン酸と同定することができる。Embedded image Compound D of the above structural formula is isolated and purified from the acidic fraction and can be identified as vanillic acid.
【００２７】化合物Ｅ（4-hydroxy-3,5-dimethoxybenzo
ic acid ）Compound E (4-hydroxy-3,5-dimethoxybenzo
ic acid)
【化５】 上記構造式の化合物Ｅも酸性画分より単離、精製された
ものであり、4-hydroxy-3,5-dimethoxybenzoic acid と
同定することができる。本化合物Ｅは既知物質であり、
文献によると植物から抽出されている。Embedded image Compound E of the above structural formula is also isolated and purified from the acidic fraction, and can be identified as 4-hydroxy-3,5-dimethoxybenzoic acid. This compound E is a known substance,
According to literature, it is extracted from plants.
【００２８】化合物Ｆ（2-methyl-4-hydroxy-4H-pyran-
4-one ）Compound F (2-methyl-4-hydroxy-4H-pyran-
4-one)
【化６】 上記構造式の化合物Ｆは塩基性画分より単離、精製され
たものであり、2-methyl-4-hydroxy-4H-pyran-4-one と
同定することができる。Embedded image Compound F of the above structural formula is isolated and purified from the basic fraction, and can be identified as 2-methyl-4-hydroxy-4H-pyran-4-one.
【００２９】ところで、本発明に係る濃縮飲料にはバン
コマイシン耐性腸球菌に対して殺菌・感染防御作用があ
ることが認められる。その試験方法等をデータとともに
詳細に説明する。 〔バンコマイシン耐性腸球菌（ＶＲＥ）に対する試験方
法（その１）〕本発明に係る濃縮飲料を任意濃度添加し
た感受性測定用平板に、バンコマイシン耐性腸球菌（Ｖ
ＲＥ）の菌液を塗抹・培養後、発育が阻止された最小濃
度をもって、バンコマイシン耐性腸球菌（ＶＲＥ）に対
する最小発育阻止濃度を求めた。ここに、感受性測定用
平板、菌液、塗抹・培養とは、次のようなものをいう。The concentrated beverage according to the present invention is found to have a bactericidal and protective action against vancomycin-resistant enterococci. The test method and the like will be described in detail with data. [Test Method for Vancomycin-Resistant Enterococcus (VRE) (Part 1)] Vancomycin-resistant enterococcus (VRE) was added to a sensitivity measurement plate to which the concentrated beverage of the present invention was added at an arbitrary concentration.
After smearing and culturing the bacterial solution of RE), the minimum growth inhibitory concentration for vancomycin-resistant enterococcus (VRE) was determined from the minimum concentration at which growth was inhibited. Here, the plate for sensitivity measurement, the bacterial solution, the smear and the culture refer to the following.
【００３０】（感受性測定用平板）滅菌精製水を用いて
本発明に係る濃縮飲料を順次２倍希釈し、２倍希釈系列
溶液を調製した。次に、滅菌、溶解後、50〜60℃に保っ
た感受性測定用培地〔HeartInfusion Agar(DIFCO LABOR
ATORIES INCORPORATED)〕に、本発明に係る濃縮飲料及
び前記希釈系列溶液を任意量添加し、十分に混合後、シ
ャーレに分注、固化させた。これが本試験にいう感受性
測定用平板である。(Plate for Sensitivity Measurement) The concentrated beverage according to the present invention was sequentially diluted 2-fold with sterile purified water to prepare a 2-fold dilution series solution. Next, after sterilization and dissolution, a sensitivity measurement medium [Heart Infusion Agar (DIFCO LABOR
ATORIES INCORPORATED)], an arbitrary amount of the concentrated beverage according to the present invention and the above-mentioned diluted series solution were added, mixed well, dispensed into a petri dish, and solidified. This is the sensitivity measurement plate referred to in this test.
【００３１】（接種用菌液の調製）継代培養した試験菌
〔Enterococcus faecium NCTC 12204(VRE)〕を増菌用培
地〔Heart Infusion Broth (DIFCO LABORATORIES INCOR
PORATED)〕に接種し、35℃、18〜20時間培養後、菌数が
約106CFU／mlとなるように前記増菌用培地で希釈し、接
種用菌液とした。(Preparation of bacterial solution for inoculation) A subcultured test bacterium [Enterococcus faecium NCTC 12204 (VRE)] was enriched with a culture medium for enrichment [Heart Infusion Broth (DIFCO LABORATORIES INCOR.).
PORATED)], and after culturing at 35 ° C. for 18 to 20 hours, the mixture was diluted with the enrichment medium so that the number of bacteria was about 10 6 CFU / ml, to obtain a bacterial solution for inoculation.
【００３２】（塗抹・培養）感受性測定用平板に、前記
接種用の菌液をニクロム線ループ（内径約１mm）を用い
て１〜２cm程度画線塗抹し、35℃、18〜20時間培養し
た。これが本試験にいう塗抹・培養である。そして、こ
の培養後、発育が阻止された最小濃度を測定した。その
結果を表４に示す。(Smearing / Culture) The bacteria solution for inoculation was streaked about 1-2 cm on a plate for sensitivity measurement using a nichrome wire loop (inner diameter: about 1 mm) and cultured at 35 ° C. for 18-20 hours. . This is the smearing and culture referred to in this test. After this culture, the minimum concentration at which growth was inhibited was measured. Table 4 shows the results.
【００３３】[0033]
【表４】 [Table 4]
【００３４】表４から明らかなように、本発明に係る濃
縮飲料を用いるとバンコマイシン耐性腸球菌の成長を阻
害することができ、少なくともバンコマイシン耐性腸球
菌に対して殺菌作用があることが認められる。なお、バ
ンコマイシン耐性腸球菌に対して殺菌作用のない場合、
最小発育阻止濃度（Ｗ／Ｖ％）は 100となることから、
本発明に係る濃縮飲料にはバンコマイシン耐性腸球菌に
対して明らかに殺菌作用があることが分かる。As is clear from Table 4, the use of the concentrated beverage according to the present invention can inhibit the growth of vancomycin-resistant enterococci, and it is confirmed that the beverage has a bactericidal action on at least vancomycin-resistant enterococci. In addition, when there is no bactericidal action against vancomycin-resistant enterococci,
Since the minimum growth inhibitory concentration (W / V%) is 100,
It can be seen that the concentrated beverage according to the present invention clearly has a bactericidal action against vancomycin-resistant enterococci.
【００３５】〔バンコマイシン耐性腸球菌（ＶＲＥ）に
対する試験方法（その２）〕本発明に係る濃縮飲料及び
対照としての培地10mlを滅菌Ｌ字管に入れ、108CFU／ml
に調製したバンコマイシン耐性腸球菌（ＶＲＥ）液 0.1
mlを加え、室温で振とうした。その後、時間ごと（０、
60分、120 分及び24時間）にサンプリングして菌数計算
を行った。その結果を表５に示す。なお、試験菌株に
は、Enterococcus feacalis Ku1856株を用いた。[Test Method for Vancomycin-Resistant Enterococcus (VRE) (Part 2)] 10 ml of the concentrated beverage according to the present invention and a medium as a control were placed in a sterile L-shaped tube, and 10 8 CFU / ml.
Vancomycin-resistant enterococcus (VRE) solution 0.1
ml was added and shaken at room temperature. Then every hour (0,
Sampling was performed at 60 minutes, 120 minutes and 24 hours) to calculate the bacterial count. Table 5 shows the results. In addition, Enterococcus feacalis Ku1856 strain was used as the test strain.
【００３６】[0036]
【表５】 [Table 5]
【００３７】表５から明らかなように、本発明に係る濃
縮飲料では、腸球菌数が０時間で 1.5×106CFU／mlであ
ったのに対し、24時間後では検出限界以下であり、少な
くともバンコマイシン耐性腸球菌に対して殺菌ないし抗
菌作用があることが認められる。その結果、本発明に係
る濃縮飲料にはバンコマイシン耐性腸球菌（ＶＲＥ）に
対して明らかに殺菌作用があることが分かる。なお、表
５に示すように、本発明に係る濃縮飲料の抗菌作用は抗
生物質あるいは合成抗菌剤に見られる即効性の殺菌作用
ではなく、徐々に作用するタイプであるから、抗生剤等
に見られる副作用がないと考えられる。As is clear from Table 5, in the concentrated beverage according to the present invention, the number of enterococci was 1.5 × 10 6 CFU / ml at 0 hour, but it was below the detection limit after 24 hours. It is recognized that it has a bactericidal or antibacterial effect on at least vancomycin-resistant enterococci. As a result, it can be seen that the concentrated beverage according to the present invention clearly has a bactericidal action against vancomycin-resistant enterococcus (VRE). As shown in Table 5, the antibacterial action of the concentrated beverage according to the present invention is not a quick-acting bactericidal action found in antibiotics or synthetic antibacterial agents, but is a type that gradually acts. It is considered that there is no side effect.
【００３８】〔バンコマイシン耐性腸球菌（ＶＲＥ）に
対する試験方法（その３）〕次に、本発明に係る濃縮飲
料及び対照としての培地をマウスに連続経口投与した
後、バンコマイシン耐性腸球菌（ＶＲＥ）を腹腔内に投
与し、マウスの生死を観察した。以下に、この試験方法
をさらに詳細に示す。[Test Method for Vancomycin-Resistant Enterococcus (VRE) (Part 3)] Next, the concentrated beverage of the present invention and a medium as a control were continuously orally administered to mice. After intraperitoneal administration, the mice were observed for life and death. Hereinafter, this test method will be described in more detail.
【００３９】（バンコマイシン耐性腸球菌（ＶＲＥ）の
調製）ブレーンハートインフュウジョン寒天培地に37℃
24時間培養後、標準白金耳で10mg集菌し、それを滅菌生
理食塩水に浮遊させ、109CFU／mlに調製した。この菌液
を10倍段階希釈し、10％ムチン溶液で107 及び106CFU／
mlに調製した。(Preparation of vancomycin-resistant enterococcus (VRE)) On a Brainheart infusion agar medium at 37 ° C.
After culturing for 24 hours, 10 mg of bacteria were collected using a standard platinum loop, suspended in sterile physiological saline, and adjusted to 10 9 CFU / ml. This bacterial solution was serially diluted 10-fold, and 10 7 and 10 6 CFU /
It was adjusted to ml.
【００４０】（試験動物）６週齢のBALB／c 雌マウス
（ＳＰＦ）を使用した。試験動物はマウス用ポリカーボ
ネート製のケージ（24×17×12cm）に５匹づつ収容し、
室温23±2 ℃、相対湿度55±15％に設定した飼育室にお
いて飼育した。飼料〔マウス・ラット用固形飼料；ラボ
MRストック、日本農産工業株式会社〕を自由に摂取させ
た。飲料水（水道水）は吸水びんに入れて吸水した。(Test Animal) A 6-week-old BALB / c female mouse (SPF) was used. The test animals were housed five by five in polycarbonate cages for mice (24 x 17 x 12 cm),
They were bred in a breeding room set at room temperature 23 ± 2 ° C. and relative humidity 55 ± 15%. Feed [mouse / rat solid feed; laboratory
MR Stock, Nihon Nosan Kogyo Co., Ltd.]. Drinking water (tap water) was placed in a water absorption bottle to absorb water.
【００４１】（被験物質及びバンコマイシン耐性腸球菌
（ＶＲＥ）の投与方法）上記マウスを１週間予備飼育し
た後、被験物質0.3 mlをゾンデを用いて１日１回５日間
連続して強制経口投与し、２日間（土・日）は投与を休
止し、さらに、２日間連続して投与した。エンドキサン
200 mg／kgは被験物質投与開始５日目に腹腔内に投与し
た。上述したように調製したバンコマイシン耐性腸球菌
（ＶＲＥ）を、最後の被験物質投与４時間後に0.5 ml／
マウスづつ腹腔内に投与した。(Method of Administration of Test Substance and Vancomycin-Resistant Enterococcus (VRE)) After preliminarily breeding the above mice for one week, 0.3 ml of the test substance was orally administered once a day for 5 consecutive days using a sonde. The administration was stopped for two days (Saturday and Sunday), and the administration was continued for two consecutive days. Endoxane
200 mg / kg was intraperitoneally administered on the 5th day from the start of test substance administration. The vancomycin-resistant enterococci (VRE) prepared as described above were mixed with 0.5 ml /
Each mouse was administered intraperitoneally.
【００４２】なお、被験物質、エンドキサン及びバンコ
マイシン耐性腸球菌（ＶＲＥ）の投与状態を図表に表わ
すと、次のようになる。投与した場合を矢印で示す。 The administration state of the test substance, endoxan and vancomycin-resistant enterococcus (VRE) is shown in the following chart. The case of administration is indicated by an arrow.
【００４３】（群分け） １群：バンコマイシン耐性腸球菌（ＶＲＥ） ２群：培地＋バンコマイシン耐性腸球菌（ＶＲＥ） ３群：本発明に係る濃縮飲料＋バンコマイシン耐性腸球
菌（ＶＲＥ）(Grouping) Group 1: Vancomycin-resistant enterococcus (VRE) Group 2: Medium + vancomycin-resistant enterococcus (VRE) Group 3: Concentrated beverage according to the present invention + Vancomycin-resistant enterococcus (VRE)
【００４４】（観察）マウスの生死の観察は毎日行った
（但し、土、日は除く）。この試験結果を表６に示す。(Observation) The observation of the life and death of the mice was performed every day (however, except for soil and day). Table 6 shows the test results.
【００４５】[0045]
【表６】 [Table 6]
【００４６】表６から分かるように、バンコマイシン耐
性腸球菌（ＶＲＥ）107CFU／ml投与に対しては、本発明
に係る濃縮飲料及び非投与群では１例づつ生存が認めら
れ、培地投与群では全例斃死した。一方、バンコマイシ
ン耐性腸球菌（ＶＲＥ）106CFU／ml投与に対しては、非
投与群及び培地投与群では全例斃死が認められた（100
％の死亡率であった）が、本発明に係る濃縮飲料投与群
では２例の斃死が認められたのみで、40％の低い死亡率
であった。その結果、本発明に係る濃縮飲料にはバンコ
マイシン耐性腸球菌（ＶＲＥ）に対して明らかに感染防
御作用があることが分かる。以上のような結果から見
て、本発明に係る濃縮飲料にはバンコマイシン耐性腸球
菌（ＶＲＥ）に対して明らかに殺菌ないし抗菌作用と感
染防御作用とがあることが分かる。[0046] As can be seen from Table 6, for vancomycin-resistant enterococci (VRE) 10 7 CFU / ml dose, one case at a time survival observed in the beverage concentrate and non-administered group according to the present invention, the medium administration group Then all died. On the other hand, when vancomycin-resistant enterococci (VRE) was administered at 10 6 CFU / ml, all the animals died in the non-administration group and the medium administration group (100).
Mortality rate), but only two deaths were observed in the concentrated beverage administration group according to the present invention, and the mortality rate was as low as 40%. As a result, it can be seen that the concentrated beverage according to the present invention has a clear protective effect against vancomycin-resistant enterococcus (VRE). From the above results, it can be seen that the concentrated beverage according to the present invention clearly has a bactericidal or antibacterial action and a protective action against vancomycin-resistant enterococcus (VRE).
【００４７】一方、本発明に係る濃縮飲料には毒性は認
められない。その試験方法、試験結果等をデータととも
に示す。On the other hand, the concentrated beverage according to the present invention has no toxicity. The test method, test results, etc. are shown together with the data.
【００４８】（毒性試験）本発明に係る濃縮飲料につい
て、OECD化学物質毒性試験指針(1987)に準拠し、マウス
における急性経口毒性を調べる。(Toxicity test) The concentrated beverage according to the present invention is examined for acute oral toxicity in mice according to the OECD Guideline for Toxicity on Chemical Substances (1987).
【００４９】（試験液の調製）本発明に係る濃縮飲料を
精製水で５倍希釈し、試験液とする。(Preparation of Test Solution) The concentrated beverage according to the present invention is diluted 5-fold with purified water to prepare a test solution.
【００５０】（試験動物）４週齢の ICR系雌雄マウス
（日本エスエルシー株式会社）を約１週間の予備飼育を
行って一般状態に異常のないことを確認した後、試験に
使用した。試験動物はポリカーボネート製ケージに各５
匹収容し、室温23±2 ℃、照明時間12時間／日に設定し
た飼育室において飼育した。飼料〔マウス・ラット用固
形飼料；ラボMRストック、日本農産工業株式会社〕及び
飲料水（水道水）は自由に摂取させた。(Test Animals) Four-week-old ICR male and female mice (Nippon SLC Co., Ltd.) were preliminarily reared for about one week to confirm that there was no abnormality in their general condition, and then used in the test. Test animals were placed in polycarbonate cages for 5
The animals were housed and reared in a breeding room set at a room temperature of 23 ± 2 ° C. and an illumination time of 12 hours / day. Feed (solid feed for mice / rats; Lab MR Stock, Nippon Agricultural Industry Co., Ltd.) and drinking water (tap water) were freely available.
【００５１】（試験方法）試験群及び対称群ともに雌雄
それぞれ10匹を用いた。投与前に約４時間試験動物を絶
食させた。体重を測定した後、試験群には雌雄ともに検
体投与量として4.4mL/Kg用量の本発明に係る濃縮飲料を
胃ゾンデを用いて強制単回経口投与した。対照群には雄
では 0.8mL、雌では 0.7mLの精製水を同様に投与した。
観察期間は14日間とし、投与日は頻回、翌日から１日１
回の観察を行った。投与後７日目及び14日目に体重を測
定し、ｔ−検定により有意水準５％で群間の比較を行っ
た。観察期間終了時に動物すべてを剖検した。(Test Method) In each of the test group and the symmetric group, 10 males and 10 females were used. The test animals were fasted for approximately 4 hours before dosing. After measuring the body weight, the test group was administered a 4.4 mL / Kg dose of the concentrated beverage according to the present invention as a test dose to both males and females by oral gavage using a gastric tube. The control group received 0.8 mL of purified water in males and 0.7 mL in females in the same manner.
The observation period was 14 days, with frequent administration on one day, one day from the next day.
Observations were made. The body weight was measured on the 7th and 14th days after the administration, and comparison between groups was performed at a significance level of 5% by a t-test. All animals were necropsied at the end of the observation period.
【００５２】この試験結果を考察とともに以下に示す。The test results are shown below with consideration.
【００５３】（死亡例及び死亡率）雌雄ともに観察期間
中に死亡は認められなかった。(Deaths and mortality) No mortality was observed during the observation period for both males and females.
【００５４】（一般状態）試験群の雄では、観察期間中
に異常は認められなかった。雌では、投与後一時間以内
に接触刺激により発声する動物が２例に見られたが、５
時間には回復し、その後異常は見られなかった。対照群
では、雌雄ともに観察期間中に異常は認められなかっ
た。(General condition) No abnormality was observed in the males of the test group during the observation period. In females, two animals uttered by contact stimulation within one hour after administration, but 5
He recovered in time, after which no abnormalities were seen. In the control group, no abnormalities were observed during the observation period for both males and females.
【００５５】（体重変化）投与後７日目及び14日目に体
重測定した。雌雄ともに各群間で体重増加に差は見られ
なかった。雄群についての体重変化を表７に示す。ま
た、雌群についての体重変化を表８に示す。表７、表８
における体重は、平均値±標準偏差で表した（単位：
ｇ）。なお、括弧内に動物数を示した。(Change in body weight) Body weight was measured on the 7th and 14th days after administration. There was no difference in weight gain between the groups for both sexes. Table 7 shows the change in body weight for the male group. Table 8 shows changes in body weight for the female group. Table 7, Table 8
Are expressed as mean ± standard deviation (unit:
g). The number of animals is shown in parentheses.
【００５６】[0056]
【表７】 [Table 7]
【００５７】[0057]
【表８】 [Table 8]
【００５８】（剖検所見）観察期間終了後の剖検では、
雌雄ともにすべての試験動物の主要臓器に異常は見られ
なかった。(Necropsy findings) At the necropsy after the observation period,
No abnormalities were found in the major organs of all test animals in both sexes.
【００５９】（考察）本発明に係る濃縮飲料を4.4mL/Kg
の用量で雌雄マウスに単回経口投与した結果、死亡例は
見られず、剖検時にも異常は見られなかった。従って、
表７、表８から明らかなように、本発明に係る濃縮飲料
には毒性は認められないことが分かる。なお、この場合
におけるLD50値は、雌雄ともに4.4mL/Kg以上であるもの
と考えられる。(Consideration) 4.4 mL / Kg of the concentrated beverage according to the present invention
As a result of a single oral administration to male and female mice at the above dose, no deaths were observed and no abnormalities were observed at necropsy. Therefore,
As is clear from Tables 7 and 8, no toxicity is recognized in the concentrated beverage according to the present invention. The LD50 value in this case is considered to be 4.4 mL / Kg or more for both sexes.
【００６０】以上から明らかなように、本発明に係る濃
縮飲料には、少なくともバンコマイシン耐性腸球菌に対
する殺菌・感染防御作用があることが分かる。本発明に
係る濃縮飲料は、桿菌、酵母菌および乳酸菌から選ばれ
た複数種の有益菌を特定の組み合せで共生培養して得ら
れた培養液である微生物醗酵生産物のろ液を濃縮するこ
とにより得られたものであるから、健康飲料として適し
ている。As is clear from the above, it can be seen that the concentrated beverage according to the present invention has at least a bactericidal / infective protective action against vancomycin-resistant enterococci. The concentrated beverage according to the present invention comprises concentrating a filtrate of a microorganism fermentation product, which is a culture solution obtained by co-cultivating a plurality of beneficial bacteria selected from bacilli, yeasts, and lactic acid bacteria in a specific combination. Thus, it is suitable as a health drink.
【００６１】[0061]
【発明の実施の形態】以下、具体例を挙げて本発明に係
る濃縮飲料をさらに詳細に説明する。本発明に係る濃縮
飲料は桿菌、酵母菌および乳酸菌からなるものであり、
さらに詳しくは、桿菌、酵母菌および乳酸菌から選ばれ
た複数種の有益菌を特定の組み合せで共生培養して得ら
れた培養液のろ液を濃縮することにより生成される。培
養基として、大豆からの豆乳を使用するのが最適であ
る。乳酸菌の培養には一般に牛乳が多く用いられている
が、牛乳の不均一性、経時変化性、その生産過程におけ
る薬剤等の使用混入等を考慮し、さらに、人工添加物を
一切使用しない自然飲料という観点から、培養基とし
て、自然食品であって、かつ、完全無農薬保証大豆（ア
イオワ州産）からの豆乳を使用するのが最適である。ま
た、本発明に係る濃縮飲料は、培養完了後において生菌
を加熱殺菌して菌体を除去し、この菌体を分離した培養
液のろ液を約15分の１に濃縮することにより生成するの
が好ましい。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the concentrated beverage according to the present invention will be described in more detail with reference to specific examples. The concentrated beverage according to the present invention is composed of bacilli, yeasts and lactic acid bacteria,
More specifically, it is produced by concentrating a filtrate of a culture solution obtained by co-culturing a plurality of beneficial bacteria selected from bacilli, yeasts and lactic acid bacteria in a specific combination. Optimally, soymilk from soybeans is used as the culture medium. Milk is commonly used for cultivation of lactic acid bacteria. In view of this, it is most preferable to use soymilk, which is a natural food and completely pesticide-free soybean (from Iowa), as a culture medium. Further, the concentrated beverage according to the present invention is produced by heating and sterilizing live bacteria after culture is completed to remove the cells, and concentrating the filtrate of the culture solution from which the cells were separated to about 1/15. Is preferred.
【００６２】次に、本発明に係る濃縮飲料の製造方法の
一例を挙げる。その一例として、特許第１９６２５１２
号（特公平６−９５９１４号）を挙げることができる。 (1) 第１工程（特殊寒天培養基の製造） 精製された天然の寒天に、蒸留水により湯煎された牛
肉、昆布から得られたスープと塩分と有益菌培養液とを
加えて特殊寒天培養基を製造する。 (2) 第２工程（有益菌の純粋培養） 第１工程で製造された特殊寒天培養基に有益菌を各種類
ごと移植し、これを恒温器に入れて39℃で48〜50時間培
養する。 (3) 第３工程（特殊豆乳培養基の製造） 大豆より脂肪を除き、蒸留水を加えたものを70〜110 分
煮沸後、ろ過した豆乳のろ液に、塩、三温糖および有益
菌培養液を加えて特殊豆乳培養基を製造する。 (4) 第４工程（有益菌の特殊豆乳培養基による純粋培
養） 第３工程で製造された特殊豆乳培養基に第２工程で純粋
培養された有益菌を各種類ごとに移植し、恒温器に入れ
て39℃で48〜50時間培養する。 (5) 第５工程（有益菌の中量馴化培養） 第３工程で得られた特殊豆乳培養基に第４工程で製造さ
れた純粋培養された有益菌をグループにより分け、その
グループごとに移植して39℃で48〜50時間馴化培養す
る。 (6) 第６工程（有益菌の工業共生培養） 第３工程で得られた特殊豆乳培養基13リットルの中に、
第５工程で製造されたグループに従って、馴化培養した
生菌を一括移植し、40℃で100 〜120 時間一括共生培養
を行う。 (7) 第７工程（培養の停止と濃縮） 第６工程で製造された共生培養液を100 ℃で30分加熱す
ることによって生菌の繁殖を止め、次に、生菌を分離除
去し、得られたろ液を約15分の１（93〜96％の水分を除
去する）にまで濃縮する。 (8) 第８工程（熟成） 第７工程により得られた濃縮液を、17℃に３ケ月以上静
置して熟成させる。以上 (1)〜(8) の工程により得られ
た生産物を容器に封入し、法定加熱を経て濃縮飲料製品
とする。Next, an example of a method for producing a concentrated beverage according to the present invention will be described. As one example, Japanese Patent No. 1962512
No. (Japanese Patent Publication No. 6-95914). (1) 1st step (manufacture of special agar culture medium) A special agar culture medium is added to purified natural agar by adding soup, salt and beneficial bacteria culture solution obtained from beef and kelp that have been roasted with distilled water. To manufacture. (2) Second step (pure cultivation of beneficial bacteria) Beneficial bacteria of each kind are transplanted to the special agar culture medium produced in the first step, which is placed in a thermostat and cultured at 39 ° C for 48 to 50 hours. (3) 3rd step (manufacture of special soymilk culture medium) After removing fat from soybeans, adding distilled water and boiling for 70-110 minutes, add salt, trisaccharide and beneficial bacteria to the filtered soymilk filtrate. The liquid is added to produce a special soymilk culture medium. (4) Fourth step (pure cultivation of beneficial bacteria in special soymilk culture medium) The beneficial bacteria purely cultured in the second step are transplanted for each type into the special soymilk culture medium produced in the third step, and placed in a thermostat. And culture at 39 ° C for 48-50 hours. (5) Fifth step (medium volume adaptation culture of beneficial bacteria) Purely cultured beneficial bacteria produced in the fourth step are divided into groups on the special soymilk culture medium obtained in the third step, and transplanted for each group. For 48-50 hours at 39 ° C. (6) Sixth step (industrial symbiotic culture of beneficial bacteria) In 13 liters of special soymilk culture medium obtained in the third step,
According to the group produced in the fifth step, the conditioned culture live cells are collectively transplanted and co-cultivated at 40 ° C. for 100 to 120 hours. (7) Step 7 (Stopping and Concentrating Culture) The probiotic culture solution produced in Step 6 is heated at 100 ° C. for 30 minutes to stop the growth of viable bacteria, and then the viable bacteria are separated and removed. The filtrate obtained is concentrated to about 1/15 (removing 93-96% of water). (8) Eighth Step (Aging) The concentrated solution obtained in the seventh step is allowed to stand at 17 ° C. for 3 months or more to mature. The product obtained by the above steps (1) to (8) is sealed in a container and subjected to legal heating to obtain a concentrated beverage product.
【００６３】本発明に係る濃縮飲料はこのような工程を
経て製造することができ、要約すると桿菌、酵母菌およ
び乳酸菌との醗酵生産物であるということができる。人
工添加物無添加の自然健康飲料であるということもでき
る。The concentrated beverage according to the present invention can be produced through such steps, and can be summarized as a fermentation product of bacilli, yeasts and lactic acid bacteria. It can also be said that it is a natural health drink without artificial additives.
【００６４】[0064]
【発明の効果】本発明に係る濃縮飲料には、少なくとも
バンコマイシン耐性腸球菌に対して殺菌・感染防御作用
があってその成長を阻害するから、これを飲用すること
によりこれらの細菌による感染症を改善又は予防するこ
とができる。The concentrated beverage according to the present invention has a bactericidal / infective protective action against vancomycin-resistant enterococci and inhibits the growth thereof. Can be improved or prevented.
【図１】本発明に係る濃縮飲料から有機化合物を抽出す
る方法の一例を示すフローチャートである。FIG. 1 is a flowchart showing an example of a method for extracting an organic compound from a concentrated beverage according to the present invention.
フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｋ 31/341 Ａ６１Ｋ 31/351 ４Ｃ０８７ 31/351 31/352 ４Ｃ２０６ 31/352 35/66 35/66 35/72 35/72 Ａ６１Ｐ 31/00 Ａ６１Ｐ 31/00 31/04 31/04 Ｃ１２Ｎ 1/20 Ｅ Ｃ１２Ｎ 1/20 Ｃ１２Ｐ 7/24 // Ｃ１２Ｐ 7/24 7/42 7/42 17/04 17/04 17/06 17/06 Ａ２３Ｌ 2/00 Ｆ Ｆターム(参考） 4B017 LC03 LK21 LP02 LP05 4B018 LB08 MD07 MD79 MD81 ME09 MF13 4B064 AC26 AD46 AE45 AE46 CA02 CA06 CC01 DA10 4B065 AA30X AA34X AA72X BC50 CA08 CA10 CA18 CA42 4C086 AA01 AA02 AA04 BA03 BA07 BA08 MA01 MA04 MA16 MA52 NA14 ZB35 4C087 AA01 AA02 AA03 BC11 BC55 BC60 MA16 MA52 NA14 ZB35 4C206 AA01 AA02 AA04 DA19 MA01 MA04 MA36 MA72 ZB35 Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat II (reference) A61K 31/341 A61K 31/351 4C087 31/351 31/352 4C206 31/352 35/66 35/66 35/72 35 / 72 A61P 31/00 A61P 31/00 31/04 31/04 C12N 1/20 E C12N 1/20 C12P 7/24 // C12P 7/24 7/42 7/42 17/04 17/04 17/06 17 / 06 A23L 2/00 FF term (reference) 4B017 LC03 LK21 LP02 LP05 4B018 LB08 MD07 MD79 MD81 ME09 MF13 4B064 AC26 AD46 AE45 AE46 CA02 CA06 CC01 DA10 4B065 AA30X AA34X AA72X BC50 CA08 CA10 BA18 A04 A02 A08 A02 MA04 MA16 MA52 NA14 ZB35 4C087 AA01 AA02 AA03 BC11 BC55 BC60 MA16 MA52 NA14 ZB35 4C206 AA01 AA02 AA04 DA19 MA01 MA04 MA36 MA72 ZB35
Claims (3)
り製造されることを特徴とするバンコマイシン耐性腸球
菌に対して殺菌・感染防御作用のある微生物由来の醗酵
濃縮飲料。1. A fermented concentrated beverage derived from a microorganism having a bactericidal and protective action against vancomycin-resistant enterococci, which is produced by co-cultivation of bacilli, yeasts and lactic acid bacteria.
数種の有益菌を特定の組み合せで共生培養して得られた
培養液のろ液の濃縮液である請求項１記載のバンコマイ
シン耐性腸球菌に対して殺菌・感染防御作用のある微生
物由来の醗酵濃縮飲料。2. The vancomycin-resistant intestine according to claim 1, which is a concentrate of a filtrate of a culture solution obtained by co-culturing a plurality of beneficial bacteria selected from bacilli, yeasts and lactic acid bacteria in a specific combination. Fermented concentrated beverages derived from microorganisms that have a bactericidal and protective action against cocci.
Ｆを１つ以上含んでいることを特徴とする請求項１又は
２記載のバンコマイシン耐性腸球菌に対して殺菌・感染
防御作用のある微生物由来の醗酵濃縮飲料。 【化１】 【化２】 【化３】 【化４】 【化５】 【化６】 3. A compound having at least the following structural formula:
3. The concentrated fermented beverage derived from a microorganism having a bactericidal and protective action against vancomycin-resistant enterococci according to claim 1 or 2, wherein the beverage contains one or more Fs. Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000150125A JP3417904B2 (en) | 1999-10-08 | 2000-05-22 | Fermentation-concentrated beverage derived from microorganisms that have antibacterial and infection-protective effects against vancomycin-resistant enterococci |
| TW089112771A TWI243649B (en) | 1999-10-08 | 2000-06-28 | Fermented and concentrated beverage derived from microorganism having disinfection/infection protection action on vancomycin-resistant enterococcus |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11-288526 | 1999-10-08 | ||
| JP28852699 | 1999-10-08 | ||
| JP2000150125A JP3417904B2 (en) | 1999-10-08 | 2000-05-22 | Fermentation-concentrated beverage derived from microorganisms that have antibacterial and infection-protective effects against vancomycin-resistant enterococci |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001169760A true JP2001169760A (en) | 2001-06-26 |
| JP3417904B2 JP3417904B2 (en) | 2003-06-16 |
Family
ID=26557215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000150125A Expired - Fee Related JP3417904B2 (en) | 1999-10-08 | 2000-05-22 | Fermentation-concentrated beverage derived from microorganisms that have antibacterial and infection-protective effects against vancomycin-resistant enterococci |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP3417904B2 (en) |
| TW (1) | TWI243649B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005032568A1 (en) * | 2003-10-03 | 2005-04-14 | Nihon Baio Kabushiki Kaisha | Immunopotentiator, antiulcer agent and processed foods comprising fermented soybean product and process for producing fermented soybean product |
| EP1721526A4 (en) * | 2003-12-04 | 2012-11-14 | Fuji Oil Co Ltd | Bread improving agent and breads containing the same |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113194971A (en) * | 2018-09-10 | 2021-07-30 | 拉克托拜欧有限公司 | Method for reducing the transfer of pathogenic microorganisms |
| CN118102881A (en) * | 2021-07-29 | 2024-05-28 | 微生物发现集团有限责任公司 | Method for treating dermatitis of feet |
-
2000
- 2000-05-22 JP JP2000150125A patent/JP3417904B2/en not_active Expired - Fee Related
- 2000-06-28 TW TW089112771A patent/TWI243649B/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005032568A1 (en) * | 2003-10-03 | 2005-04-14 | Nihon Baio Kabushiki Kaisha | Immunopotentiator, antiulcer agent and processed foods comprising fermented soybean product and process for producing fermented soybean product |
| EP1721526A4 (en) * | 2003-12-04 | 2012-11-14 | Fuji Oil Co Ltd | Bread improving agent and breads containing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3417904B2 (en) | 2003-06-16 |
| TWI243649B (en) | 2005-11-21 |
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