JP2009242431A - Prophylactic-ameliorative-therapeutic agent for dysbolism caused by aging - Google Patents
Prophylactic-ameliorative-therapeutic agent for dysbolism caused by aging Download PDFInfo
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- JP2009242431A JP2009242431A JP2009168431A JP2009168431A JP2009242431A JP 2009242431 A JP2009242431 A JP 2009242431A JP 2009168431 A JP2009168431 A JP 2009168431A JP 2009168431 A JP2009168431 A JP 2009168431A JP 2009242431 A JP2009242431 A JP 2009242431A
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- lactobacillus gasseri
- aging
- lactic acid
- strain
- culture
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Abstract
Description
本発明は、加齢に伴って発生する代謝異常症の予防・改善・治療剤及び／または加齢に伴って発生する代謝異常症の予防・改善・治療作用を有する飲食品に関する。 The present invention relates to a preventive / ameliorating / treating agent for metabolic disorders occurring with aging and / or a food / beverage product having an effect of preventing / ameliorating / treating metabolic disorders occurring with aging.
老化は生物にとって避けることのできない生命現象である。老化の原因として種々の要因が仮説として挙げられている。例えば、細胞レベルではプログラム説や、エラー破綻説等がある。いずれの説をとっても、細胞内に生じた老化機構による変化が生体全般の老化現象にどのような形で関連しているか不明である。しかし、それらの変化が中枢的な細胞群で生じ、全般に波及効果を及ぼすという考え方や、末梢的に個々の細胞で生じた変化が影響し合って全般的に老化現象に反映するという考え方もある。これらの変化を老化という現象の指標とするために種々の指標が提案されているが、まだ確定的な指標はない。
近年、加齢に伴って発生する種々の代謝障害、代謝異常症、あるいは機能障害を改善することで、寿命の延長が実現され、ひいては種々の老化指標が低下するといわれている。欧米化された食生活の定着に伴い、加齢に伴う日本人の代謝異常は変化している。
Aging is an unavoidable life phenomenon for organisms. Various factors have been cited as hypotheses as causes of aging. For example, there are a program theory and an error failure theory at the cell level. Whichever theories are taken, it is unclear how changes caused by the aging mechanism in the cells are related to the aging phenomenon in the whole organism. However, there is also an idea that these changes occur in central cell groups and have a ripple effect in general, and changes that occur in individual cells in the periphery influence each other and reflect them in the aging phenomenon in general. is there. Various indicators have been proposed to use these changes as indicators of the phenomenon of aging, but there is no definite indicator yet.
In recent years, it has been said that by improving various metabolic disorders, metabolic disorders, or dysfunctions that occur with aging, life extension is realized, and various aging indices are lowered. With the establishment of a Westernized diet, the metabolic abnormalities of Japanese people with aging are changing.
近年特に問題となっている加齢にともなって発生する代謝異常が原因と考えられる各種疾患としては、肥満による高脂血症・脳内アミロイド蓄積を伴う老人性痴呆・免疫異常・腸管機能低下・腸内微生物の交代に由来する大腸がん・***などの腎臓機能障害等である。
肥満には種々の原因が挙げられるが、食餌療法や運動療法以上の効果を示す抜本的な治療策は見出されていない。これまで食餌療法以外に加齢に伴う体脂肪の蓄積抑制剤としては、バラ科植物の果実又はエッセンスを投与する方法（特許文献１）、そば粉由来の組成物を投与する方法（特許文献２）、プロシアニジンを投与する方法（特許文献３）、冬瓜果皮と茄子果皮を投与する方法（特許文献４）、特定の脂肪酸を投与してエネルギー代謝効率を変える方法（特許文献５）等さまざまな方法や剤が提案されている。しかし、本発明で以下に説明する腸内定着性を有するラクトバチルス・ガセリによる脂肪蓄積を抑制させるような提案はない。
老人性痴呆には脳血管性痴呆とアルツハイマー型痴呆の２タイプがあるが、特に近年になり脳内アミロイドの蓄積（アミロイドーシス）を伴うアルツハイマー型痴呆の発生が増加している。アミロイドの蓄積症（アミロイドーシス）を抑制する物質としては、アミロイドβ蛋白質を投与する方法（特許文献６）、アミロイド蛋白質の断片を投与する方法（特許文献７）、アニオンで置換された特定構造を有する糖組成物を投与する方法（特許文献８）等が提案されている。しかし、本発明で以下に説明する腸内定着性を有するラクトバチルス・ガセリによる脳内アミロイド蓄積症を抑制させるような提案はない。
Various diseases that are thought to be caused by metabolic abnormalities that occur with aging, which have been particularly problematic in recent years, include hyperlipidemia due to obesity, senile dementia with cerebral amyloid accumulation, immune abnormalities, decreased intestinal function, These include renal dysfunction such as colon cancer and uremia resulting from the change of intestinal microorganisms.
There are various causes of obesity, but no radical treatment has been found that is more effective than diet or exercise. Conventionally, as a body fat accumulation inhibitor with aging other than dietary therapy, a method of administering a fruit or essence of a rose family plant (Patent Document 1), a method of administering a composition derived from buckwheat (Patent Document 2) ), A method of administering procyanidins (Patent Document 3), a method of administering winter pericarp and coconut pericarp (Patent Document 4), a method of changing energy metabolism efficiency by administering a specific fatty acid (Patent Document 5), etc. And agents have been proposed. However, there is no proposal to suppress fat accumulation by Lactobacillus gasseri having intestinal colonization described below in the present invention.
There are two types of senile dementia, cerebrovascular dementia and Alzheimer-type dementia. In particular, the occurrence of Alzheimer-type dementia accompanied by accumulation of amyloid in the brain (amyloidosis) has increased in recent years. Examples of substances that suppress amyloid accumulation disease (amyloidosis) include a method of administering amyloid β protein (Patent Document 6), a method of administering fragments of amyloid protein (Patent Document 7), and a specific structure substituted with an anion. A method of administering a saccharide composition (Patent Document 8) and the like have been proposed. However, there is no proposal to suppress cerebral amyloid accumulation caused by Lactobacillus gasseri having intestinal colonization described below in the present invention.
加齢に伴う腎臓機能低下は、老化による糸球体の機能低下やメサンジュウム細胞の機能低下、あるいは老廃物・IgAの蓄積など種々の原因が挙げられている。加齢に伴う腎臓機能の低下を抑制するために、IGF-1またはIGF-3を投与する方法、IPレセプター作動薬を投与する方法（特許文献９）等、新規な治療剤や治療方法が提案されている。しかし、本発明で以下に説明する腸内定着性を有するラクトバチルス・ガセリによる腎臓機能や代謝の低下を抑制させるような提案はない。
上記の疾患はいずれも高齢者の思考や行動を大幅に制限するものであり、その結果、高齢者の生活の質（クオリティー・オブ・ライフ：QOL）を低下させている。
これらの疾患の症状を改善するための治療薬は種々提案され実用化されているが、高齢者のQOLを抜本的に改善するものではない。
The decline in kidney function associated with aging has been attributed to various causes such as a decrease in glomerular function due to aging, a decrease in mesangium cell function, and accumulation of waste products and IgA. Proposed new therapeutic agents and methods, such as a method of administering IGF-1 or IGF-3, a method of administering an IP receptor agonist (Patent Document 9), etc., in order to suppress a decrease in kidney function associated with aging Has been. However, there is no proposal to suppress the decrease in kidney function and metabolism due to Lactobacillus gasseri having intestinal colonization described below in the present invention.
All of the above-mentioned diseases greatly limit the thinking and behavior of the elderly, and as a result, the quality of life (QOL) of the elderly is reduced.
Various therapeutic agents for improving the symptoms of these diseases have been proposed and put into practical use, but do not drastically improve the QOL of the elderly.
本発明者らは、ヒト腸管内に定着性を有する乳酸菌の研究を行っていたところ、腸管内定着性を有する乳酸菌、特にラクトバチルス・ガセリ（Lactobacillusgasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を投与すると、これらの微生物は腸管内に定着することによって宿主に作用し、実験動物においては顕著な寿命延長をもたらすことを見出した。さらに研究を進めた結果、ラクトバチルス・ガセリ（Lactobacillus gasseri)を加齢動物に投与すると、腸管内に定着したラクトバチルス・ガセリ（Lactobacillus gasseri)が宿主に作用して、加齢に伴う代謝異常を改善し、腎臓機能の低下や悪化を抑制し、肥満の原因となる脂質代謝を改善し、さらに脳内アミロイドの蓄積を抑制するという驚くべき効果を有することを見出した。その結果、加齢に伴うQOLは明らかに向上することを見出し、本発明を完成するに到った。
従って本発明は、ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を有効成分とする代謝異常症の予防・改善・治療剤を提供することを課題とする。
さらにまた本発明は、ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を添加した加齢に伴う代謝異常症の予防・改善・治療作用を有する飲食品を提供することを課題とする。
The inventors of the present invention have been researching lactic acid bacteria having colonization in the human intestinal tract. A culture obtained by culturing lactic acid bacteria having colonization in the intestinal tract, particularly lactic acid bacteria belonging to Lactobacillus gasseri It was found that when administered and / or microbial cells, these microorganisms act on the host by colonizing in the intestinal tract, resulting in a significant increase in life span in experimental animals. As a result of further investigation, when administered Lactobacillus gasseri the (Lactobacillus gasseri) aging animals, Lactobacillus gasseri that is fixed to the intestinal tract (Lactobacillus gasseri) acts on the host, the metabolic abnormalities associated with aging It has been found that it has a surprising effect of improving, suppressing a decrease or worsening of kidney function, improving lipid metabolism causing obesity, and further suppressing accumulation of amyloid in the brain. As a result, it was found that QOL accompanying aging was clearly improved, and the present invention was completed.
Accordingly, an object of the present invention is to provide a culture product obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri and / or a preventive / ameliorating / treating agent for metabolic disorders containing the bacterial cells as active ingredients. And
Furthermore, the present invention provides a culture obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri and / or a food and drink having a preventive, ameliorating, and / or therapeutic action on metabolic disorders associated with aging by adding bacterial cells. The issue is to provide goods.
本発明者らは、従来から種々の発酵乳の研究を行っていたところ、これらの発酵乳から分離された乳酸菌やヒト由来の乳酸菌の中で特にラクトバチルス・ガセリ（Lactobacillus gasseri)が従来に見られない高いヒト腸管内定着性を有していることを見出し、さらにこのラクトバチルス・ガセリ（Lactobacillus gasseri)が、従来知られていなかった腸管定着性によって加齢に伴う代謝異常を改善し、その結果、腎臓機能の低下や悪化を抑制し、肥満の原因となる脂質の蓄積を低下させ、さらに脳内アミロイドの蓄積を抑制し、寿命を延長させることを見出し、上記課題の解決に成功した。 The inventors of the present invention have been researching various fermented milks. Lactobacillus gasseri ( Lactobacillus gasseri ), in particular, among lactic acid bacteria isolated from these fermented milks and human-derived lactic acid bacteria, has been found in the past. It has been found that it has high intestinal colonization, and this Lactobacillus gasseri has improved the metabolic abnormalities associated with aging by the previously unknown intestinal colonization. As a result, the inventors have found that the decrease or deterioration of kidney function is suppressed, the accumulation of lipids causing obesity is decreased, the accumulation of amyloid in the brain is suppressed, and the life span is extended, and the above problems have been successfully solved.
本発明は、ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を有効成分とする加齢に伴う代謝異常症の予防・改善・治療剤に関する。
また本発明は、このような有効成分を添加した加齢に伴う代謝異常症の予防・改善・治療作用を有する飲食品に関する。
即ち本発明は、特許請求範囲に記載した下記の構成からなる発明である。
The present invention relates to a culture obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri and / or a prophylactic, ameliorating, or therapeutic agent for metabolic disorders associated with aging, which comprises microbial cells as active ingredients.
Moreover, this invention relates to the food-drinks which have the prevention, improvement, and treatment effect | action of the metabolic disorder accompanying aging which added such an active ingredient.
That is, this invention is invention which consists of the following structure described in the claim.
（１）ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を有効成分とする代謝異常症の予防・改善・治療剤。
（２）ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌がヒト腸管内定着性を有するラクトバチルス・ガセリ（Lactobacillus gasseri)である（１）記載の代謝異常症の予防・改善・治療剤。
（３）代謝異常症が腎臓機能異常症、脳内アミロイドーシス、脂質代謝異常症である（１）または（２）記載の代謝異常症の予防・改善・治療剤。
（４）ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物が発酵乳である（１）〜（３）のいずれかに記載の代謝異常症の予防・改善・治療剤。
（５）ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌がラクトバチルス・ガセリ（Lactobacillus gasseri)・SBT2055（FERM P-15535）である（１）〜（４）のいずれかに記載の代謝異常症の予防・改善・治療剤。
（６）ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を添加した代謝異常症の予防・改善・治療作用を有する飲食品。
(1) A preventive, ameliorating, or therapeutic agent for metabolic disorders comprising as an active ingredient a culture obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri and / or bacterial cells.
(2) a Lactobacillus gasseri (Lactobacillus gasseri) Lactobacillus lactic acid bacteria belongs with human intestinal fixability gasseri (Lactobacillus gasseri) (1) preventing or ameliorating or therapeutic agent for metabolic disorders described.
(3) The preventive / improving / treating agent for metabolic disorders according to (1) or (2), wherein the metabolic disorders are renal dysfunction, cerebral amyloidosis, and lipid metabolism disorders.
(4) The preventive / ameliorating / treating agent for metabolic disorders according to any one of (1) to (3), wherein the culture obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri is fermented milk .
(5) lactic acid bacterium belonging to Lactobacillus gasseri (Lactobacillus gasseri) is Lactobacillus gasseri (Lactobacillus gasseri) · SBT2055 (FERM P-15535) (1) ~ metabolic disorder according to any one of (4) Prevention / improvement / therapeutic agent.
(6) A culture obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri and / or a food or drink having a preventive, ameliorating, or therapeutic effect on metabolic disorders with the addition of bacterial cells.
本発明によれば、ラクトバチルス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を培養して得られる培養物及び／または菌体を有効成分とする代謝異常症の予防・改善・治療剤と代謝異常症の予防・改善・治療作用を有する飲食品を提供することができる。
本発明によって提供される代謝異常症の予防・改善・治療剤は、毒性および副作用が極めて少なく、また、食品素材としても有用である。
INDUSTRIAL APPLICABILITY According to the present invention, a preventive / improving / therapeutic agent for metabolic disorders comprising a culture obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri and / or bacterial cells as an active ingredient, and metabolic disorders. A food or drink having a preventive, ameliorating, or therapeutic effect can be provided.
The preventive / ameliorating / treating agent for metabolic disorders provided by the present invention has extremely low toxicity and side effects, and is also useful as a food material.
本発明は、上記した課題を解決するためになされたものであって、本発明者らは、目的とする乳酸菌をスクリーニングするに際し、次のような基準を新たに設定し目的に合致する株を選定した。すなわち、本発明者らは、発酵乳やヒト由来の数多くのラクトバチルス・ガセリのうち、胃酸耐性が高い、低ｐＨ条件下での生育が良好である、ヒト腸管へ高い定着性を示す、ヒト腸管細胞親和性を示す、胆汁酸耐性がある、腸管内に定着することによって加齢に伴う種々の代謝異常を予防・改善・治療する効果を有する、食品に適用した際に生残性が高く、香味、物性も優れている等々の条件を設定し、菌株の選定につき鋭意研究を重ねた。本条件によってスクリーニングした結果、これらの条件に合致する菌株として以下菌株を選択することができた。なお、この菌株は、下記の寄託番号により独立行政法人産業技術総合研究所特許微生物寄託センターに寄託されている。 The present invention has been made in order to solve the above-mentioned problems, and the present inventors newly set the following criteria and screened strains that meet the purpose when screening the target lactic acid bacteria. Selected. That is, the present inventors, among fermented milk and many Lactobacillus gasseri derived from humans, have high gastric acid resistance, good growth under low pH conditions, and exhibit high colonization in the human intestinal tract. It has the ability to prevent, improve, and treat various metabolic abnormalities associated with aging by colonizing in the intestinal tract, showing intestinal cell affinity, bile acid resistance, and high survival when applied to food. We set various conditions such as excellent flavor, physical properties, etc., and conducted extensive research on the selection of strains. As a result of screening under these conditions, the following strains could be selected as strains meeting these conditions. This strain is deposited at the Patent Microorganism Depositary, National Institute of Advanced Industrial Science and Technology under the following deposit number.
菌株
ラクトバチルス・ガセリ Lactobacillus gasseri SBT2055 FERM P-15535
この菌株は、ヒト腸管細胞に高い親和性を有し、経口で投与した時、生存して腸管内に到達することができ長期間腸管内に常在することが可能であり、腸管内生育することで宿主に作用し加齢に伴う代謝異常を予防・改善・治療する。体外から投与したラクトバチルス・ガセリに（Lactobacillus gasseri)属する乳酸菌が腸内に定着し、このような生理効果を示すことは全く知られておらず、本発明者らによって始めて明らかにされた。
Strain Lactobacillus gasseri SBT2055 FERM P-15535
This strain has a high affinity for human intestinal cells, and when orally administered, it can survive and reach the intestinal tract and can be resident in the intestinal tract for a long period of time, and grows in the intestinal tract It acts on the host to prevent, ameliorate, and treat metabolic disorders associated with aging. Lactobacillus gasseri ( Lactobacillus gasseri ), which is administered from outside the body, is established in the intestine and exhibits such a physiological effect, and has been clarified for the first time by the present inventors.
さらに本発明では、上記寄託菌株に限らずヒトや発酵乳から分離されるラクトバチルス・ガセリ（Lactobacillus gasseri)であって、上記の作用を示すものであれば、いずれのものでも使用できる。
次にこれらの乳酸菌の培養方法を記す。
本発明のラクトバチルス・ガセリ（Lactobacillus gasseri)の培地には、乳培地または乳成分を含む培地、これを含まない半合成培地等、種々の培地を用いることができる。このような培地としては、脱脂乳を還元して加熱殺菌した還元脱脂乳培地を例示することができる。
培養法は、静置培養またはｐＨを一定にコントロールした中和培養で行うが、菌が良好に生育する条件であれば特に培養法に制限はない。
Furthermore, in the present invention, not only the deposited strain but also Lactobacillus gasseri isolated from humans or fermented milk and any of the above-described actions can be used.
Next, the culture method of these lactic acid bacteria is described.
As the Lactobacillus gasseri culture medium of the present invention, various media such as a milk medium or a medium containing milk components, a semi-synthetic medium not containing this, or the like can be used. An example of such a medium is a reduced skim milk medium obtained by reducing skim milk and then heat sterilizing.
The culture method is a static culture or a neutralization culture in which pH is controlled to be constant. However, the culture method is not particularly limited as long as the bacteria grow well.
本発明は、上述のようにして得られる培養物及び／または菌体を有効成分とする。また乾燥した粉末を有効成分としてもよい。これらの乾燥は凍結乾燥で行なうことが菌体を変質させることなく乾燥することができるので好ましい。
これらの有効成分は経口摂取することが望ましい。また、これらの粉末は乳糖等の適当な賦形剤と混合し、粉剤、錠剤、丸剤、カプセル剤または粒剤等として経口投与することができる。投与量は、投与対象者の症状、年齢等を考慮してそれぞれ個別に適宜決定されるが、通常成人１日当たり乾燥物として0.5〜10ｇであり、これを１日数回に分けて投与するとよい。特に好ましくは、それぞれの株を生菌として、成人一人当たり108〜1012cfu／日投与することで本発明の目的とする効果を発揮させることが可能となる。このようにして摂取することによって腸管内に定着し所望の効果を発揮する。
In the present invention, the culture and / or cells obtained as described above are used as active ingredients. A dried powder may be used as the active ingredient. These drying operations are preferably performed by freeze-drying because the cells can be dried without deteriorating the cells.
These active ingredients are preferably taken orally. These powders can be mixed with an appropriate excipient such as lactose and orally administered as a powder, tablet, pill, capsule, granule or the like. The dosage is appropriately determined individually in consideration of the symptom, age, etc. of the administration subject, but is usually 0.5 to 10 g as a dry product per day for an adult, and this may be divided into several times a day. Particularly preferably, administration of 10 8 to 10 12 cfu / day per adult as the respective strains as viable bacteria makes it possible to exert the intended effect of the present invention. By taking in this way, it settles in the intestinal tract and exhibits the desired effect.
また、本発明の有効成分は、飲食品の製造工程中に原料に添加してもよい。飲食品としてはどのような飲食品でもよく、その例として、乳飲料、発酵乳、果汁飲料、ゼリー、キャンディー、乳製品、マヨネーズ等の卵加工品、バターケーキ等の菓子パン類等の食品を挙げることができる。但し、本発明の特性として乳酸菌が生存した状態で腸管に定着することが必要であり、過度の加熱を避けることが好ましい。また、マイクロカプセル等の従来技術を採用して、加熱を避ける手段を講じてもよい。
さらにまた、本発明における飲食品は、前述したラクトバチルス・ガセリ（Lactobacillus gasseri)の菌株を使用して乳酸発酵を行なって製造されたヨーグルト等であっても良い。
以下に本発明に用いる乳酸菌株として、ラクトバチルス・ガセリ（Lactobacillus gasseri)・SBT2055(LG2055)を用いた試験例を示し、菌学的性質及びインビトロ、インビボによる効果を具体的に説明する。しかし、本発明はこの記載内容に限定されるものではない。
[試験例]
Moreover, you may add the active ingredient of this invention to a raw material during the manufacturing process of food-drinks. As the food and drink, any food and drink may be used. Examples thereof include milk drinks, fermented milk, fruit juice drinks, jelly, candy, dairy products, processed eggs such as mayonnaise, and foods such as butter cakes and other confectionery breads. be able to. However, as a characteristic of the present invention, it is necessary to settle in the intestinal tract while the lactic acid bacteria are alive, and it is preferable to avoid excessive heating. In addition, conventional techniques such as microcapsules may be employed to take measures to avoid heating.
Furthermore, the food and drink in the present invention may be yogurt produced by lactic acid fermentation using the aforementioned strain of Lactobacillus gasseri .
Test examples using Lactobacillus gasseri ( Lactobacillus gasseri ) / SBT2055 (LG2055) as the lactic acid strain used in the present invention are shown below, and the bacteriological properties and in vitro and in vivo effects are specifically described. However, the present invention is not limited to this description.
[Test example]
LG2055株の性状
１．菌学的性状
（１）菌形
LBS寒天平板培地を用いて37℃、48時間嫌気培養後の結果を示す。
形状：桿菌
大きさ：0.5-1×3-4μm
連鎖したもの多数
（２）グラム染色性 陽性
（３）コロニー形態
形状：円形
周縁：波状
大きさ：直径2-3mm
色調：白色
表面：円滑
（４）芽胞形成 陰性
（５）ガス産生 なし
（６）運動性 なし
（７）カタラーゼ活性 陰性
（８）脱脂乳凝固性 凝固
（９）ゼラチン液化性 なし
（１０）硝酸塩還元性 なし
（１１）インドール産性 なし
（１２）硫化水素産性 なし
Properties of LG2055 stock Mycological properties (1) Fungal form
The result after anaerobic culture at 37 ° C. for 48 hours using LBS agar plate medium is shown.
Shape: Aspergillus Size: 0.5-1 × 3-4μm
Many linked (2) Gram stain positive (3) Colony shape Shape: Circular Perimeter: Wave Size: Diameter 2-3mm
Color: White Surface: Smooth (4) Spore formation Negative (5) Gas production None (6) Motility None (7) Catalase activity Negative (8) Nonfat milk coagulability Coagulation (9) Gelatin liquefaction None (10) Nitrate reduction None (11) Indole productivity None (12) Hydrogen sulfide productivity None
２．糖の発酵性
市販の細菌同定用キット（アピ50CH、ビオメリュー社）他にて糖の発酵性を検討した結果を以下に記載する。
グリセロール −
エリスリトール −
D-アラビノース −
L-アラビノース ＋
リボース −
D−キシロース −
L−キシロース −
アド二トール −
β−メチル−D−キシロシド −
ガラクト-ス ＋
D−グルコース ＋
L-フルクト-ス ＋
D-マンノース ＋
L-ソルボース −
ラムノース −
ダルシトール −
イノシトール −
マンニトール −
ソルビトール −
α−メチル− D−マンノシド −
α−メチル− D−グルコシド −
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 ＋
セロビオース ＋
マルトース ＋
ラクト-ス ＋
メリビオース −
サッカロース ＋
トレハロース ＋
イヌリン −
メレジトース −
D-ラフィノース −
アミドン −
グリコーゲン −
キシリトール −
β−ゲンチオビオース ＋
D-ツラノース −
D-リキソース −
D-タガトース ＋
D-アラビトール −
L-アラビトール −
グルコネート −
２−ケトーグルコネート −
５−ケトーグルコネート −
（＋は発酵性有りを示し、−は発酵性なしを示す。）
2. Fermentability of sugars The results of examining the fermentability of sugars with commercially available bacteria identification kits (Api 50CH, Biomeryu) and others are described below.
Glycerol −
Erythritol −
D-arabinose −
L-arabinose +
Ribose −
D-xylose-
L-xylose-
Aditol-
β-methyl-D-xyloside −
Galactose +
D-glucose +
L-Fructose +
D-Mannose +
L-sorbose −
Rhamnose −
Dulcitol −
Inositol −
Mannitol −
Sorbitol −
α-methyl-D-mannoside −
α-methyl-D-glucoside −
N-acetyl-glucosamine +
Amygdalin +
Arbutin +
Esclin +
Salicin +
Cellobiose +
Maltose +
Lactose +
Melibiose −
Sucrose +
Trehalose +
Inulin −
Merezitose −
D-Raffinose −
Amidon −
Glycogen −
Xylitol −
β-gentiobiose +
D-Tulanose −
D-lyxose −
D-Tagatose +
D-arabitol −
L-arabitol −
Gluconate −
2-Kethogluconate −
5-ketotogluconate −
(+ Indicates that there is fermentability, − indicates that there is no fermentability.)
上記の分類学的性状と糖の発酵性は、典型的なラクトバチルス・アシドフィルス複合菌種（Lactobacillus acidophilus complex）の性状を示した。 The taxonomic properties and sugar fermentability indicated the properties of a typical Lactobacillus acidophilus complex.
次いで、以下の通りDNA相同性試験による確認試験を実施した。
DNA相同性試験
以下に記載したラクトバチルスの基準株、被験菌LG2055株 、そしてコントロールとして、大腸菌（Escherichia. coli）のDNAを抽出、精製した。
DNA homology test The DNA of Escherichia coli was extracted and purified as a reference strain of Lactobacillus described below, the test strain LG2055, and as a control.
胃酸耐性
胃酸耐性試験は瀧口らの方法（腸内細菌学雑誌 14.11-18．2000）に従ってｐＨ2.0の人工胃液を調製し胃酸耐性試験を行ったところLG2055株は３時間以上生残した。
Gastric acid resistance In the gastric acid resistance test, an artificial gastric fluid having a pH of 2.0 was prepared according to the method of Higuchi et al. (Intestinal Bacteriology Journal 14.11-18.2000), and a gastric acid resistance test was conducted. The LG2055 strain survived for 3 hours or more.
人工腸液耐性
瀧口らの方法（腸内細菌学雑誌 14.11-18．2000）に従って胆汁末を含む人工腸液を調製し、これに前記の人工胃液処理を行ったLG2055株を加えて耐性を試験したところ、20時間以上の生存性を示した。LG2055株は、消化管を通過し、大腸まで生存して到達することが確認された。
Artificial intestinal juice resistance Artificial intestinal fluid containing bile powder was prepared according to the method of Higuchi et al. (Intestinal Bacteriology Journal 14.11-18.2000), and the resistance was tested by adding LG2055 strain that had been treated with artificial gastric juice to this. , Showed viability of more than 20 hours. The LG2055 strain was confirmed to pass through the gastrointestinal tract and survive to reach the large intestine.
ヒトの腸管通過能と腸内定着性
無脂乳固形9.5％、乳脂肪3.0％の乳にLG2055のスターターを４％接種して39度で４時間発酵させた発酵乳を健康な成人ボランティア42名に４週間、毎日100ｇを１日１回食させて腸内菌の変化を観察した。試験期間中は腸内菌に影響のある食品やオリゴ糖、薬品の摂取を禁ずる以外は自由に食事をさせて評価を行った。試験前は検出されなかったLG2055株がすべての被験者から４週間後には検出され、両株が高い腸管内定着性を有することがわかった。
Human intestinal transit ability and intestinal colonization 42 healthy adult volunteers with fermented milk fermented with 39% non-fat milk solid 9.5%, milk fat 3.0% fermented milk fermented at 39 degrees for 4 hours For 4 weeks, 100 g was eaten once a day, and changes in the intestinal bacteria were observed. During the test period, evaluation was performed by eating freely except forbidding foods, oligosaccharides, and drugs that affect enterobacteria. The LG2055 strain, which was not detected before the test, was detected in all subjects after 4 weeks, indicating that both strains have high intestinal colonization.
動物試験
Ａ.インビボでの実験動物の寿命に与える影響試験
１．乳酸菌脱脂乳培養の調製
LG2055株を用いた。乳酸菌は、115℃、20分間の滅菌処理をした0.5％酵母エキス（アサヒビール食品社製）添加11.55％脱脂乳培地にて、37℃、16時間培養した。得られた培養物は凍結乾燥後、乳鉢で粉砕した。
Animal test A. Effect test on the life span of experimental animals in vivo Preparation of lactic acid bacteria skim milk culture
LG2055 strain was used. Lactic acid bacteria were cultured at 37 ° C. for 16 hours in a 11.55% skim milk medium supplemented with 0.5% yeast extract (manufactured by Asahi Beer Foods) sterilized at 115 ° C. for 20 minutes. The obtained culture was freeze-dried and then ground in a mortar.
２．試験飼料の調製
表１にAIN-93M（オリエンタル酵母工業社製）に準拠した食餌組成を示した。この飼料に５％脱脂乳または上記脱脂乳乳酸菌培養物を添加した。
2. Preparation of test feed Table 1 shows the diet composition based on AIN-93M (Oriental Yeast Co., Ltd.). To this feed, 5% skim milk or the above skim milk lactic acid bacteria culture was added.
３．試験動物
５週齢の老化促進モデルであるSenescence-Accelerated Mouse（SAM）P8系雌マウス（日本SLC社より入手）を２群、各群30とした。AIN-93Mにて１週間予備飼育後、上記の試験飼料で死亡するまで飼育した。この間、イオン交換水及び飼料（７ｇから８ｇ以内で）は自由摂取させた。
3. Test animals Two groups of Senescence-Accelerated Mouse (SAM) P8 female mice (obtained from SLC, Japan), which are 5-week-old aging promotion models, were divided into 30 groups. After pre-breeding for 1 week in AIN-93M, the breeding was continued until the above test feed died. During this time, ion-exchanged water and feed (within 7 to 8 g) were ad libitum.
４．体重測定
飼育期間中、週１回体重を測定した。５週齢から60週齢までの体重について分割区法による分散分析を行った。
4). Body weight measurement The body weight was measured once a week during the breeding period. Analysis of variance was performed for the body weight from the age of 5 to 60 weeks of age by the division method.
５．食餌摂取量測定法
食餌摂取量は約４週間に１回測定した。予め秤量した飼料を与え、翌日同時間帯に容器中にある餌残量を測定し、１日当たりの食餌摂取量を算出した。
5. Dietary intake measurement method Dietary intake was measured about once every 4 weeks. A pre-weighed feed was given, and the remaining amount of food in the container was measured at the same time zone the next day, and the amount of food intake per day was calculated.
６．フローラ解析
新鮮な糞便を採取し、「嫌気性菌の分離と同定法」（菜根出版）に記載されている光岡らの方法に準拠し、５週齢（初発値）、３ヶ月齢、５ヶ月齢、７ヶ月齢、10ヶ月齢、さらに12ヶ月齢において、腸内フローラ解析を行った。得られたデータについては、分割区法による分散分析を行った。
6). Flora analysis Fresh stool was collected, and 5 weeks old (initial value), 3 months old, 5 months in accordance with the method of Mitsuoka et al. Intestinal flora analysis was performed at age 7, 7 months, 10 months, and 12 months. About the obtained data, analysis of variance by the division method was performed.
Ｂ．老化指標に与える影響についての試験（40週齢時の生体機能）
１．乳酸菌脱脂乳培養物の調製
前記Ａと同様にLG2055株を用いた。乳酸菌は、115℃、20分間の滅菌処理をした0.5％酵母エキス（アサヒビール食品社製）添加11.55％脱脂乳培地にて、37℃、16時間培養した。得られた培養物は凍結乾燥後、乳鉢で粉砕した。
B. Test on effects on aging index (biological function at 40 weeks of age)
1. Preparation of lactic acid bacteria skim milk culture LG2055 strain was used in the same manner as A described above. Lactic acid bacteria were cultured at 37 ° C. for 16 hours in a 11.55% skim milk medium supplemented with 0.5% yeast extract (manufactured by Asahi Beer Foods) sterilized at 115 ° C. for 20 minutes. The obtained culture was freeze-dried and then ground in a mortar.
２．試験飼料
前記と同様にAIN-93M（オリエンタル酵母工業社製）に準拠した食餌を調整し、この飼料に５％脱脂乳または上記脱脂乳乳酸菌培養物を添加した。
2. Test feed As described above, a diet based on AIN-93M (manufactured by Oriental Yeast Co., Ltd.) was prepared, and 5% skim milk or the above skim milk lactic acid bacteria culture was added to this feed.
３．実験動物
５週齢のSAM P8系雌マウス（日本SLC社より入手）を２群、各群10匹として用いた。AIN-93Mにて1週間予備飼育後、上記の試験飼料で36週飼育した。この間、イオン交換水及び飼料は自由摂取させた。40週齢まで飼育した後、約16時間絶食させ、ネンブタール（大日本製薬社製）麻酔下に開腹し、下大静脈採血によって屠殺した。
3. Experimental animals Five-week-old SAM P8 female mice (obtained from Japan SLC) were used as 2 groups, 10 mice each. After preliminarily raised in AIN-93M for 1 week, it was raised for 36 weeks with the above test feed. During this time, ion-exchanged water and feed were ingested freely. After raising to 40 weeks of age, the animals were fasted for about 16 hours, opened under anesthesia with Nembutal (Dainippon Pharmaceutical Co., Ltd.), and sacrificed by inferior vena cava blood sampling.
４．体重測定
飼育期間中、週1回体重を測定した。得られたデータについては、分割区法による分散分析を行った。
4). Body weight measurement The body weight was measured once a week during the breeding period. About the obtained data, analysis of variance by the division method was performed.
５．食餌摂取量測定法
食餌摂取量の測定は、幼若時においては毎週、後に約１ヶ月に１回（１週）の割合で測定した。予め秤量した飼料を与え、翌日同時間帯に容器中にある餌残量を測定し、１日当たりの食餌摂取量を算出した。
5. Dietary intake measurement method Dietary intake was measured at a rate of once a week (after 1 week) every week when young. A pre-weighed feed was given, and the remaining amount of food in the container was measured at the same time zone the next day, and the amount of food intake per day was calculated.
６．代謝ケージ
飼育期間中、４回代謝ケージにて飼育し、採尿、採糞を行った。代謝ケージでの飼育は、14週齢、22週齢、29週齢及び38週齢において行った。２日間の慣らし飼育の後、３日目から４日目にかけて約24時間、糞便ならびに尿を採取した。期間中は、飲料水、飼料摂取量ならびに体重もモニターした。
6). Metabolic cages During the breeding period, the animals were raised four times in a metabolic cage, and urine collection and feces were collected. Rearing in metabolic cages was carried out at 14, 22, 29 and 38 weeks of age. After two days of breeding, feces and urine were collected for approximately 24 hours from the 3rd to 4th day. Drinking water, feed intake and body weight were also monitored during the period.
７．尿8-ヒドロキシデオキシグアノシンの測定
代謝ケージ飼育にて得られた尿について、8-OHDG測定用ELISAキット（日本老化制御研究所製）を用いて測定した。
7). Measurement of urinary 8-hydroxydeoxyguanosine The urine obtained in metabolic cage breeding was measured using an ELISA kit for 8-OHDG measurement (manufactured by Japan Aging Control Laboratory).
８．脳内アミロイド蓄積量の測定
屠殺直後に解剖し、大脳を摘出した。得られた大脳をプロテインインヒビターミクスチャー（SIGMA社製）0.5％添加PBSを用い、テフロン（登録商標）ホモジナイザーにて均質化し、アミロイドベータ（1-42）測定キット（免疫生物研究所製）を用いて測定した。
8). Measurement of amyloid accumulation in the brain Dissection was performed immediately after sacrifice and the cerebrum was removed. The obtained cerebrum was homogenized with a Teflon (registered trademark) homogenizer using PBS containing 0.5% protein inhibitor mixture (manufactured by SIGMA), and using an amyloid beta (1-42) measurement kit (manufactured by Immunobiological Research Institute). It was measured.
９．後腹壁脂肪重量
屠殺直後に解剖し、後腹壁脂肪を左右各々摘出し、精密天秤METTLER AE240（日本シイベルヘグナー社製）にて重量を測定した。
9. The weight of the abdominal wall fat was dissected immediately after slaughtering, and the left and right abdominal wall fats were excised respectively, and the weight was measured with a precision balance METTLER AE240 (manufactured by Siebel Hegner, Japan).
１０．起立運動ならびに自発運動測定法
40週齢において、マウスの自発運動ならびに起立運動を測定した。30分間におけるコイル間移動回数、ならびに起立回数を計測した。計測には、実験動物運動量測定装置（室町機械社製）を用いた。
10. Standing and spontaneous movement measurement method
At 40 weeks of age, spontaneous movements and standing movements of mice were measured. The number of movements between coils in 30 minutes and the number of standing were measured. For the measurement, an experimental animal momentum measuring device (Muromachi Kikai Co., Ltd.) was used.
１１．血漿分析
約16時間絶食させた後、ネンブタール麻酔下にて、下大静脈から全採血後、抗凝固剤処理（ヘパリン10単位／ml）後、遠心分離により血漿を得た。その後、生化学自動分析装置FDC5500（富士フィルムメディカル社製）を用いて測定した。
11. Plasma analysis After fasting for about 16 hours, the whole blood was collected from the inferior vena cava under Nembutal anesthesia, and after anticoagulant treatment (
１２．糞便中IgAの測定
代謝ケージ飼育にて得られた糞便について、遠心エバポレーターCVE-200D（EYELA社製）にて乾燥した後、重量を測定し、プロテインインヒビター（SIGMA社製）0.5％添加PBSを加え、糞便を0.05g／ml濃度に分散し、ホモジナイザー（池本理化工業社製）にて均質化した。この分散液を、４℃、15,000rpmにて10分間遠心し、上清をマウスIgA測定に供した。マウスIgA測定用ELISAキット（BETHYL社製）を用いて測定した。
12 Measurement of fecal IgA The feces obtained from metabolic cages were dried with a centrifugal evaporator CVE-200D (EYELA), weighed, and added with PBS containing 0.5% protein inhibitor (SIGMA) Feces were dispersed at a concentration of 0.05 g / ml and homogenized with a homogenizer (Ikemoto Rika Kogyo Co., Ltd.). This dispersion was centrifuged at 4 ° C. and 15,000 rpm for 10 minutes, and the supernatant was subjected to mouse IgA measurement. Measurement was performed using an ELISA kit for mouse IgA measurement (manufactured by BETHYL).
１３．血球分析
マウスを約16時間絶食させた後、ネンブタール麻酔下、抗凝固剤処理（ヘパリン10単位／ml）をしたシリンジを用い、下大静脈から全採血後、全自動血球計数器MEK−6158（日本光電社製）を用いて測定した。
13. Blood cell analysis After mice were fasted for about 16 hours, a whole blood sample was collected from the inferior vena cava using an anticoagulant-treated (
１４． Th１／Th２細胞比の測定
脾臓を摘出したのち無菌的につぶし、25mMHEPES-RPMIを加えながら、脾臓細胞懸濁液を調製する。この脾臓細胞懸濁液を定法に従い、セルストレイナーを通して単細胞懸濁液とした。EPICS Application Note８の方法に従い、脾臓リンパ球の細胞表面CD３、細胞内IL４、細胞内INF-gammaの蛍光染色を行った。この後、Coulter EPICS XL にて解析を行い、CD３陽性細胞比、Th１／Th２細胞比を算出した。
14 Measurement of Th1 / Th2 cell ratio After removing the spleen, it is crushed aseptically, and a spleen cell suspension is prepared while adding 25 mM HEPES-RPMI. This spleen cell suspension was made into a single cell suspension through a cell strainer according to a conventional method. According to the method of
試験結果
Ａ．インビボでの実験動物の寿命に与える影響についての試験結果
図１に実験に用いたマウスの寿命を示した。コントロールに比べ本発明の発酵乳（LG2055）投与群が寿命延長に効果を示すことが明らかになった。
また体重増加曲線を比較した場合（図２）も大きな相違は認められなかった。
Test results A. Test results on effects on the life span of experimental animals in vivo FIG. 1 shows the life span of mice used in the experiment. It was revealed that the fermented milk (LG2055) administration group of the present invention showed an effect on life extension compared to the control.
In addition, when the weight gain curves were compared (FIG. 2), no significant difference was observed.
Ｂ．老化指標に与える影響についての試験結果
表２に、12ヶ月齢に達するまでの腸内フローラ変化の解析結果を示した。本発明の発酵乳（LG2055）投与群による糞便内ビフィドバクテリウム属の有意な増加ならびにレシチナーゼ陰性クロストリディウム属の著しい減少を示した。両菌群共に時間依存性の変化が認められた。
B. Test results on effects on aging index Table 2 shows the analysis results of changes in intestinal flora up to 12 months of age. The fermented milk (LG2055) administration group of the present invention showed a significant increase in fecal Bifidobacterium and a significant decrease in lecithinase-negative Clostridium. Time-dependent changes were observed in both fungal groups.
本発明の発酵乳（LG2055）投与群では生活齢に伴ってビフィドバクテリウム属の菌数が増加することが明らかになった（図３）。一方、クロストリディウム属の菌数は、本発明の発酵乳（LG2055）投与群において著しく低下することが確認された（図４）。 In the fermented milk (LG2055) administration group of the present invention, it became clear that the number of Bifidobacterium spp. Increased with the age of life (FIG. 3). On the other hand, it was confirmed that the number of Clostridium bacteria significantly decreased in the fermented milk (LG2055) administration group of the present invention (FIG. 4).
図５に、実験期間を通して観察した尿の***量の解析結果を示した。本発明の発酵乳（LG2055株）投与群では、尿の***量が増加した。 FIG. 5 shows the analysis results of the urinary excretion observed throughout the experimental period. In the fermented milk (LG2055 strain) administration group of the present invention, urinary excretion increased.
図６に、尿中に***される酸化マーカー（8-OHDG）の***量を示した。代謝の盛んな時期には両群とも***が盛んになるが、全試験期間を通して本発明の発酵乳（LG2055株）投与群の***量が高いことが明かとなった。
以上の尿***量と8-OHDG***量の測定結果から、本発明の発酵乳（LG2055株含有）は、加齢に伴う腎臓の機能の低下を予防・改善することが明らかとなった。
FIG. 6 shows the excretion amount of the oxidation marker (8-OHDG) excreted in urine. Although excretion was active in both groups during the period of high metabolism, it was revealed that the excretion amount of the fermented milk (LG2055 strain) administration group of the present invention was high throughout the entire test period.
From the above measurement results of urinary excretion and 8-OHDG excretion, it was revealed that the fermented milk of the present invention (containing LG2055 strain) prevents / improves the decrease in kidney function with aging.
図７に、大脳のアミロイド蓄積量の測定結果を示す。本発明の発酵乳（LG2055株）投与群において、加齢に伴うアミロイド蓄積の抑制が確認され、アミロイドーシスの予防・改善効果が確認できた。
また、以下に示す起立運動試験の結果と合わせて痴呆症の予防・改善効果を確認できた。
FIG. 7 shows the measurement results of the cerebral amyloid accumulation amount. In the fermented milk (LG2055 strain) administration group of the present invention, inhibition of amyloid accumulation accompanying aging was confirmed, and the prevention / amelioration effect of amyloidosis could be confirmed.
In addition, the prevention / improvement effect of dementia was confirmed together with the results of the standing exercise test shown below.
図８に、後腹壁脂肪蓄積量の比較結果を示す。本発明の発酵乳（LG2055株）投与群において、著しく低下することが確認され、加齢に伴う脂質代謝異常を改善することが明かとなった。 FIG. 8 shows a comparison result of the abdominal wall fat accumulation amount. In the fermented milk (LG2055 strain) administration group of the present invention, it was confirmed that it decreased significantly, and it became clear that lipid metabolism abnormality accompanying aging was improved.
図９に、マウスの自発運動の観察結果を示す。コントロール群で異常な動きが観察され、本発明の発酵乳（LG2055株）投与群ではこのような異常な行動は少なかった。本発明の発酵乳（LG2055株含有）により、脳内アミロイド蓄積が低下し、加齢に伴う痴呆抑制に効果があることが判明した。 FIG. 9 shows the observation result of the spontaneous movement of the mouse. Abnormal movements were observed in the control group, and there were few such abnormal behaviors in the fermented milk (LG2055 strain) administration group of the present invention. It was found that fermented milk of the present invention (containing LG2055 strain) reduced amyloid accumulation in the brain and was effective in suppressing dementia associated with aging.
図１０に、血糖値の測定結果を示す。本発明の発酵乳（LG2055株）投与群により、加齢に伴う高血糖の発生を抑制できた。 FIG. 10 shows the blood glucose level measurement results. By the fermented milk (LG2055 strain) administration group of the present invention, the occurrence of hyperglycemia accompanying aging could be suppressed.
図１１に、脾臓ヘルパーＴ細胞レパートリーの解析結果を示す。本発明の発酵乳（LG2055株）投与群において、細胞性免疫機能の活性化が生じていることが確認された。同時に脾臓内CD3陽性細胞比率（Ｔ細胞）も高くなっていることが確認された。 FIG. 11 shows the analysis result of the spleen helper T cell repertoire. In the fermented milk (LG2055 strain) administration group of the present invention, it was confirmed that cellular immune function was activated. At the same time, it was confirmed that the ratio of CD3-positive cells (T cells) in the spleen was also increased.
図１２に、盲腸内容ｐＨ測定結果を示す。本発明の発酵乳（LG2055投与群）により、腸内ｐＨを低下させ、腸内代謝を改善することが確認された。 FIG. 12 shows the cecal content pH measurement results. It was confirmed that the fermented milk of the present invention (LG2055 administration group) lowered the intestinal pH and improved intestinal metabolism.
図１３に、糞便IgAの***量を示す。糞便IgAの***量は、本発明の発酵乳（LG2055株）投与群において抑制された。 FIG. 13 shows the excretion amount of fecal IgA. Fecal IgA excretion was suppressed in the fermented milk (LG2055 strain) administration group of the present invention.
図１４に、試験期間を通した飼料効率を示す。試験期間を通した飼料効率は、本発明の発酵乳（LG2055株）投与群が有意に高いことが確認された。一方、図14から加齢による飼料効率のマイナス化が抑制されていることが判明した。この結果は、「元気に生きてぽくっりなくなる」ことを立証するものであり、QOLの維持・改善効果を確認することができた。 FIG. 14 shows the feed efficiency throughout the test period. It was confirmed that the feed efficiency throughout the test period was significantly higher in the fermented milk (LG2055 strain) administration group of the present invention. On the other hand, it was found from FIG. 14 that the negative effect on feed efficiency due to aging was suppressed. This result proves that “we live well and become chubby”, and we were able to confirm the effect of maintaining and improving QOL.
１．乾燥粉末
LG2055株を10％還元脱脂乳培地（121℃、10分加熱）で培養し、本培養物を凍結乾燥し粉末化し、本発明の予防改善治療剤を調製した（Ａ）。
1. Dry powder
The LG2055 strain was cultured in a 10% reduced skim milk medium (heated at 121 ° C. for 10 minutes), and this culture was freeze-dried and powdered to prepare the preventive / ameliorating therapeutic agent of the present invention (A).
２．発酵乳
LG2055株をMRS液体培地にて培養した。対数増殖期にある各培養液を、0.35％の酵母エキスを添加した10％還元脱脂乳（115℃、20分間滅菌）に１％接種し、個々マザーカルチャーを作成した。
これをヨーグルトミックス（10％の還元脱脂乳を添加し、100℃にて10分間加熱したもの）に各2.5％添加して調製した。発酵は37℃で行い、乳酸酸度0.85に到達した時点で冷却し、発酵を終了させ、本発明の予防改善治療作用を有する発酵乳を調製した（Ｂ）。
2. Fermented milk
LG2055 strain was cultured in MRS liquid medium. Each culture solution in the logarithmic growth phase was inoculated with 1% in 10% reduced skim milk (115 ° C., sterilized for 20 minutes) supplemented with 0.35% yeast extract to prepare individual mother cultures.
This was prepared by adding 2.5% each to yogurt mix (10% reduced skim milk was added and heated at 100 ° C. for 10 minutes). Fermentation was performed at 37 ° C., and when the lactic acid acidity reached 0.85, the mixture was cooled, the fermentation was terminated, and fermented milk having the preventive improvement therapeutic action of the present invention was prepared (B).
３．製剤例１
LG2055株の液体培養物から対数増殖期にある菌体を４℃、7,000 rpmで15分間遠心分離して滅菌水による洗浄を行い、これを３回繰り返して洗浄菌体を得た。これを凍結乾燥処理して菌体粉末を得た。この菌体粉末１部に脱脂乳４部を混合し、この粉末を打錠機により１ｇずつ定法により打錠して、菌体200ｍｇを含む錠剤を調製した。また、上記のLG2055株を含有する発酵乳を凍結乾燥し、得られた粉末を用いて直接打錠した。
3. Formulation Example 1
Cells in the logarithmic growth phase were centrifuged at 4 ° C. and 7,000 rpm for 15 minutes from a liquid culture of the LG2055 strain, washed with sterilized water, and this was repeated three times to obtain washed cells. This was freeze-dried to obtain cell powder. 4 parts of skimmed milk was mixed with 1 part of this bacterial cell powder, and 1 g of this powder was tableted by a conventional method with a tableting machine to prepare a tablet containing 200 mg of bacterial cell. Further, the fermented milk containing the above LG2055 strain was freeze-dried and directly compressed using the obtained powder.
４．カプセル化剤
凍結乾燥粉末を散剤化した後、造粒により顆粒状とした後、空カプセルに10mgづつ充填しカプセル剤とした。
4). Encapsulating agent After freeze-dried powder was powdered, it was granulated by granulation, and 10 mg each was filled into empty capsules to form capsules.
５．製剤例２
LG2055株をMRS液体培地（Difco社製）５Ｌに接種後、37℃、18時間静置培養を行った。LG2055株を脱脂乳５Ｌに接種後、37℃、18時間静置培養を行った。培養終了後、7,000rpmで15分間遠心分離を行い、培養液の１／50量のそれぞれの濃縮菌体を得た。次いで、この濃縮菌体を脱脂粉乳10重量％、グルタミン酸ソーダ１重量％を含む分散媒と同量混合し、ｐＨ７に調整後、凍結乾燥を行った。得られた凍結乾燥物を60メッシュのフルイで整粒化し、凍結乾燥菌末を得た。
第13改正日本薬局方解説書製剤総則「散剤」の規定に準拠し、上記５で得られた凍結乾燥菌末１ｇにラクトース（日局）400ｇ、バレイショデンプン（日局）600ｇを加えて均一に混合し、散剤を製造した。
5. Formulation Example 2
The LG2055 strain was inoculated into 5 L of MRS liquid medium (Difco), followed by static culture at 37 ° C. for 18 hours. After inoculating the LG2055 strain in 5 L of skim milk, static culture was performed at 37 ° C. for 18 hours. After completion of the culture, centrifugation was performed at 7,000 rpm for 15 minutes to obtain 1/50 amount of each concentrated bacterial cell of the culture solution. Next, the concentrated cells were mixed in the same amount with a dispersion medium containing 10% by weight of skim milk powder and 1% by weight of sodium glutamate, adjusted to pH 7, and then lyophilized. The obtained freeze-dried product was sized with a 60-mesh sieve to obtain a freeze-dried bacterial powder.
In accordance with the provisions of the 13th revised Japanese Pharmacopoeia General Rules for Preparations, “Powder”, add 1 g of freeze-dried bacteria obtained in 5 above to 400 g of lactose (Japan Pharmacopoeia) and 600 g of potato starch (Japan Pharmacopoeia) to evenly Mixed to produce a powder.
６．製剤例３
次の配合により錠剤を製造した。
（１）LG2055株の脱脂粉乳培地における培養物の凍結乾燥物50ｇ、
（２）ラクトース90ｇ、
（３）コーンスターチ29ｇ、
（４）ステアリン酸マグネシウム１ｇ、
この混合物を圧縮錠剤機により圧縮して、１錠あたり有効成分を40ｍｇ含有する錠剤100個を製造した。
6). Formulation Example 3
Tablets were produced with the following formulation.
(1) 50 g freeze-dried culture of LG2055 strain nonfat dry milk medium,
(2) 90 g lactose,
(3) Corn starch 29g,
(4) Magnesium stearate 1 g,
This mixture was compressed by a compression tablet machine to produce 100 tablets containing 40 mg of active ingredient per tablet.
７．製剤例４
LG2055株をホエー培地（0.5％酵母エキス、0.1％トリプチケースペプトン添加）で培養後遠心分離で菌体を回収した。この培養物１ｇを乳糖５ｇと混合し顆粒状に成形して顆粒剤を得た。
7). Formulation Example 4
The LG2055 strain was cultured in whey medium (0.5% yeast extract and 0.1% trypticase peptone added), and the cells were collected by centrifugation. 1 g of this culture was mixed with 5 g of lactose and formed into granules to obtain granules.
８．LG2055を含む食品
（１）飲料
洗浄菌体の凍結乾燥粉末をLG2055株が各々108個以上含まれるように200 mlの牛乳と混合して、本発明の予防改善治療剤入り飲料を得た。良好な風味を有していた。
（２）醗酵乳
LG2055株をヨーグルトミックス（生乳に２％脱脂乳を添加し、100℃、10分加熱した）に接種し、20℃で24時間培養した。紙カップに充填し冷却後、ヨーグルトとした製品中のLG2055株の生菌数濃度は、100ｇ当たり108個以上であった。
8). Food (1) Beverage Containing LG2055 The freeze-dried powder of the washed cells was mixed with 200 ml of milk so that each of the LG2055 strains contained 10 8 or more to obtain a beverage containing the preventive / ameliorating treatment agent of the present invention. It had a good flavor.
(2) Fermented milk
The LG2055 strain was inoculated into a yogurt mix (2% skim milk was added to raw milk and heated at 100 ° C. for 10 minutes) and cultured at 20 ° C. for 24 hours. After filling into a paper cup and cooling, the viable cell count concentration of LG2055 strain in the product made into yogurt was 10 8 or more per 100 g.
（３）発酵バター
発酵バター （ｗｔ／ｗｔ）
乳脂肪 ９６．８％
食塩 １．２
１．で得られた試料(Ａ) ２
(3) Fermented butter Fermented butter (wt / wt)
Milk fat 96.8%
Salt 1.2
1. Sample (A) obtained in 2
（４） バターケーキ
バターケーキ （ｗｔ／ｗｔ）
バター ２４％
薄力粉 ２４
砂糖 ２４
全卵 ２４
２．で得られた試料（Ｂ） ４
香料 少々
(4) Butter cake Butter cake (wt / wt)
Butter 24%
Light flour 24
Sugar 24
Whole egg 24
2. Sample (B) obtained in 4
Fragrance a little
（５） マヨネーズ
マヨネーズ （ｗｔ／ｗｔ）
サラダ油 ６５％
卵黄 １７
食酢 １０
１．で得られた試料（Ａ） ３
香辛料 ４．４
グルタミン酸モノナトリウム ０．６
(5) Mayonnaise Mayonnaise (wt / wt)
Salad oil 65%
Egg yolk 17
1. Sample (A) obtained in 3
Spice 4.4
Monosodium glutamate 0.6
Claims (6)
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| JP2012020974A (en) * | 2010-07-15 | 2012-02-02 | Yasutomo Arashima | Lactobacillus-cocultivated extract |
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| JP2015526085A (en) * | 2012-08-16 | 2015-09-10 | ユニバーシティ−インダストリー コオペレーション グループ オブ キョン ヒ ユニバーシティＵｎｉｖｅｒｓｉｔｙ−Ｉｎｄｕｓｔｒｙ Ｃｏｏｐｅｒａｔｉｏｎ Ｇｒｏｕｐ Ｏｆ Ｋｙｕｎｇ Ｈｅｅ Ｕｎｉｖｅｒｓｉｔｙ | Lactic acid bacteria having preventive and / or therapeutic activity for aging and dementia |
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