JP2003253262A - Antioxidant - Google Patents
AntioxidantInfo
- Publication number
- JP2003253262A JP2003253262A JP2002054730A JP2002054730A JP2003253262A JP 2003253262 A JP2003253262 A JP 2003253262A JP 2002054730 A JP2002054730 A JP 2002054730A JP 2002054730 A JP2002054730 A JP 2002054730A JP 2003253262 A JP2003253262 A JP 2003253262A
- Authority
- JP
- Japan
- Prior art keywords
- antioxidant
- lactobacillus
- gasseri
- foods
- vitamin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】食品、飼料、化粧品またはこ
れらの原料等の酸化による品質低下を防ぐのに有効な抗
酸化活性を有し、食品、飼料、化粧品に添加することに
より、それを利用するヒトまたは動物の生体内酸化によ
り発生する活性酸素やフリーラジカルを消去もしくは低
減、またはそれらによる過酸化脂質の発生を低減するの
に有効な抗酸化活性を有する、天然物由来の抗酸化剤に
関する。本発明はまた、天然物由来の抗酸化剤を含有す
る、食品または飼料に関する。本発明はまた、食品、飼
料、化粧品に添加することにより、それを利用するヒト
または動物の生体内で発生する活性酸素やフリーラジカ
ルを消去もしくは低減、またはそれらによる過酸化脂質
の発生を低減するための治療剤に関する。TECHNICAL FIELD The present invention has an antioxidant activity effective for preventing deterioration of quality of foods, feeds, cosmetics or raw materials thereof due to oxidation, and it is utilized by adding to foods, feeds or cosmetics. The present invention relates to an antioxidant derived from a natural product, which has an antioxidant activity effective for eliminating or reducing active oxygen and free radicals generated by in vivo oxidation of humans or animals, or for reducing the generation of lipid peroxide by them. The present invention also relates to foods or feeds containing antioxidants of natural origin. The present invention also eliminates or reduces active oxygen and free radicals generated in the living body of humans or animals using them by adding them to foods, feeds, and cosmetics, or reduces the generation of lipid peroxides by them. For therapeutic agents.
【０００２】[0002]
【従来の技術】近年、食生活の欧風化に伴い、高脂肪食
品を摂取する機会が増え、高脂血症、動脈硬化症等の成
人病が増加している。この現象は、中高年層のみなら
ず、若年層にまで及んでいる。その結果、生体内脂質の
酸化によってさまざまな疾病が招来されることとなっ
た。抗酸化剤には、食品、飼料及び化粧品に添加し、そ
の品質を保持する目的で使用されるものと、その抗酸化
剤を生体に投与することにより、生体内酸化により発生
する活性酸素、フリーラジカル及び過酸化脂質を消去ま
たは低減し、つまり生体内酸化を防止または低減する目
的で使用されるものがある。2. Description of the Related Art In recent years, with the westernization of eating habits, the chances of ingesting high-fat foods have increased, and adult diseases such as hyperlipidemia and arteriosclerosis have increased. This phenomenon extends not only to middle-aged and older people, but also to younger people. As a result, various diseases have been caused by the oxidation of lipids in the body. Antioxidants are added to foods, feeds and cosmetics and used for the purpose of maintaining their quality, as well as active oxygen generated by in vivo oxidation by administering the antioxidant to the living body, free Some are used for the purpose of eliminating or reducing radicals and lipid peroxides, that is, for preventing or reducing in vivo oxidation.
【０００３】食品、飼料または化粧品に含まれる油脂
類、色素、その他の有効成分が保存中に酸化されると、
製品の樹脂化、異臭発生、着色、変色、毒性物質の生成
または栄養価の低下を引き起こす。このため、食品、飼
料及び化粧品には品質保持のための抗酸化剤が含有され
ていることが多い。このような抗酸化効果は、油脂の酸
化抑制効果および色素退色抑制効果を試験することによ
り測定される。When oils and fats, pigments and other active ingredients contained in food, feed or cosmetics are oxidized during storage,
It causes resinification of products, generation of off-flavor, coloration, discoloration, generation of toxic substances, or deterioration of nutritional value. Therefore, foods, feeds and cosmetics often contain antioxidants for maintaining quality. Such antioxidative effect is measured by testing the antioxidative effect of oil and fat and the antifading effect of dye.
【０００４】このような目的で、従来主として食品、化
粧品あるいは医薬品などの分野で用いられている抗酸化
剤としては、例えば、トコフェロール（ビタミンＥ）、
アスコルビン酸（ビタミンＣ）等の天然抗酸化剤や、ブ
チルヒドロキシアニソール（BHA）、ジブチルヒドロキ
シトルエン（BHT）などのフェノール系合成抗酸化剤が
知られている。トコフェロールは油脂の抗酸化剤として
よく用いられるが、水に溶けにくいため用途が限られ、
また肝心の抗酸化力があまり高くないためほかの抗酸化
剤と併用するなどの必要があった。アスコルビン酸は、
水溶性の抗酸化剤として用いられ油脂へは使用しにく
く、また食品に用いる場合にその酸味が付与されること
から食品の味を変えてしまい、また合成抗酸化剤と比較
してその抗酸化力が劣るという欠点があった。一方、BH
AやBHTのような合成抗酸化剤は、その抗酸化力は強い
が、その発ガン性や肺・肝臓への悪影響が指摘されてい
ること等、安全性が疑問視されるようになった。このよ
うなことから、抗酸化力の強い、汎用性の高い、天然の
抗酸化剤の開発が望まれてきた。Toxiferol (vitamin E), for example, is used as an antioxidant conventionally used mainly in the fields of foods, cosmetics or pharmaceuticals for such purpose.
Natural antioxidants such as ascorbic acid (vitamin C) and phenolic synthetic antioxidants such as butylhydroxyanisole (BHA) and dibutylhydroxytoluene (BHT) are known. Tocopherol is often used as an antioxidant for fats and oils, but its use is limited because it is difficult to dissolve in water.
Also, since the antioxidant power of the core is not so high, it was necessary to use it in combination with other antioxidants. Ascorbic acid is
It is used as a water-soluble antioxidant that is difficult to use in oils and fats, and when used in foods, it changes the taste of foods because it imparts its sour taste. It had the drawback of being less powerful. On the other hand, BH
Synthetic antioxidants such as A and BHT have strong antioxidant power, but their safety has been questioned because of their carcinogenicity and adverse effects on lungs and liver. . For these reasons, it has been desired to develop a highly versatile, natural antioxidant having a strong antioxidant power.
【０００５】従来、天然の抗酸化剤として以下のような
ものが報告されている。ミカン科植物果皮の水または含
水アルコール抽出物を有効成分として含有する抗酸化性
組成物（特開平８−259945号公報）、ミカン科コブミカ
ンの葉の抽出物を有効成分とする抗酸化剤組成物（特開
平11−199427号公報）、緑色植物の緑葉から抽出した抗
酸化活性画分を配合した飲食品類（特開平11−123071号
公報）、成熟前期の麦類の緑葉に水に可溶性またはｎ−
ヘキサンに不溶性で且つ含水率が80％以下の含水エタノ
ールに可溶性の画分であって、2-O-グルコシル−イソビ
テキシンを含有することを特徴とする麦類の緑葉の抗酸
化活性画分（特開平５−65480号公報）、ヤマモモ科ヤ
マモモ属植物から炭素数１から５までの脂肪族アルコー
ル系有機溶媒および／またはその他の有機溶媒の１種以
上を用いて抽出した抗酸化剤（特開平５−156249号公
報）、冬葵子の溶媒抽出物を含む食品および化粧品（特
開平９−59127号公報）、クフェア属植物に含有される
抗酸化性物質を極性溶媒で抽出、採取することを特徴と
する抗酸化性物質の製造法（特開平６−212154号公
報）、オリーブ植物溶媒抽出物の加水分解物を有効成分
としてなる抗酸化剤（特開平９−78061号公報）等が報
告されている。また、乳酸菌の抽出物にも抗酸化効果が
見出されており、本出願人は特開平４−264034号、特開
平５−276912号公報に技術を開示している。この技術
は、乳酸菌の中のラクトバチルス・デルブルッキー及び
ラクトバチルス・ブルガリクスに属する乳酸菌に由来す
るものである。この乳酸菌はヒト腸管に定着性を有しな
い。Conventionally, the followings have been reported as natural antioxidants. Antioxidant composition containing water or hydroalcoholic extract of citrus peel as an active ingredient (Japanese Patent Application Laid-Open No. 8-259945), antioxidant composition containing an extract of Rutaceae Kobumikan leaf as an active ingredient (JP-A No. 11-199427), foods and drinks containing an antioxidant activity fraction extracted from green leaves of green plants (JP-A-11-123071), soluble in water or n −
Fractions insoluble in hexane and soluble in water-containing ethanol having a water content of 80% or less and containing 2-O-glucosyl-isovitexin, the antioxidant activity fraction of green leaves of barley (specifically, (Kaihei 5-65480), an antioxidant extracted from a plant of the genus Yammeridae with a carbon number of 1 to 5 and / or one or more other organic solvents (JP-A-5-65480). No. 156249), foods and cosmetics containing a solvent extract of Aoi fuchu (Japanese Patent Laid-Open No. 9-59127), and antioxidants contained in plants of the genus Cuphea are extracted and collected with a polar solvent. Has been reported (JP-A-6-212154), an antioxidant comprising a hydrolyzate of olive plant solvent extract as an active ingredient (JP-A-9-78061), and the like. There is. In addition, an antioxidant effect has been found in the extract of lactic acid bacteria, and the applicant of the present invention discloses the technique in JP-A-4-264034 and JP-A-5-276912. This technique is derived from lactic acid bacteria belonging to Lactobacillus delbruckey and Lactobacillus bulgaricus among lactic acid bacteria. This lactic acid bacterium does not have colonization properties in the human intestinal tract.
【０００６】従来一般に、抗酸化剤とは食品、飼料、化
粧品などの酸化を防止する保存料であるととらえられて
いた。しかし、近年になって、これまで食品に用いられ
てきた抗酸化剤に、生体内酸化により発生するフリーラ
ジカル、活性酸素及び過酸化脂質を消去または低減する
抗酸化効果を有するものがあることが明らかになり、ま
た生体内抗酸化力が強い天然抽出物の探索（Food &
Food Ingredients Journal of Japan, 163, 19-29 (19
95)、New Food Industry, 39(3), 17-24 (1997)、月刊
フードケミカル1998-8, P.33-41）が行われるようにな
った。[0006] In the past, antioxidants have generally been regarded as preservatives that prevent the oxidation of foods, feeds, cosmetics and the like. However, in recent years, some of the antioxidants used so far in foods have an antioxidant effect of eliminating or reducing free radicals, active oxygen and lipid peroxides generated by in vivo oxidation. Search for natural extracts that have become clear and have strong antioxidant activity in vivo (Food &
Food Ingredients Journal of Japan, 163, 19-29 (19
95), New Food Industry, 39 (3), 17-24 (1997), and monthly food chemicals 1998-8, P.33-41).
【０００７】生体内酸化により生成するフリーラジカル
や活性酸素には様々なものが知られている。フリーラジ
カルは不対電子を持つ分子種の総称であるため、様々な
生体内フリーラジカルが存在するが、活性酸素でもある
フリーラジカルとしてスーパーオキシドアニオン、ヒド
ロキシルラジカルが知られている。また、フリーラジカ
ルではない活性酸素には、過酸化水素および一重項酸素
が知られている。これらの中で一般に生体内抗酸化効果
の指標として測定されるものは、1,1-ジフェニル-2-ピ
クリルヒドラジル（DPPH）を用いたラジカル消去活性、
スーパーオキシドアニオン消去活性、ヒドロキシルラジ
カルの消去活性および過酸化脂質生成抑制活性であり、
一般にこれらの活性を有するものを生体内抗酸化力のあ
る抗酸化剤と位置づけている（月刊フードケミカル1998
-8, P.33-41）。Various free radicals and active oxygen generated by in-vivo oxidation are known. Since free radicals are a general term for molecular species having unpaired electrons, various in-vivo free radicals exist, and superoxide anion and hydroxyl radicals are known as free radicals that are also active oxygen. Hydrogen peroxide and singlet oxygen are known as active oxygen that is not a free radical. Among these, those generally measured as an index of in vivo antioxidant effect are radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH),
Superoxide anion scavenging activity, hydroxyl radical scavenging activity and lipid peroxide production inhibitory activity,
Generally, those having these activities are classified as antioxidants having in-vivo antioxidant power (Monthly Food Chemical 1998
-8, P.33-41).
【０００８】最近では、臨床レベルで食品による老化防
止の可能性を評価する際に、遺伝子レベルにおける酸化
的障害を測定する方法が研究されている。なかでも、生
体内脂質過酸化反応の結果生じた活性酸素によるDNA中
の核酸塩基（デオキシグアノシン）に対する攻撃の結
果、8-ヒドロキシデオキシグアノシン（8-OHdG）が生成
し、このDNA中に生じた8-OhdGは、通常はDNA修復酵素に
より切り取られ、血中を経て最終的には尿中に排出され
ることが明らかになった。従って、血液や尿中の8-OHdG
量を測定することにより老化防止効果を測定することが
できるが、この測定には免疫化学的な手法であるELISA
法を用い、この方法はまだコストが高く、一般的な方法
として確立されているわけではない。従って、現状で
は、生体内抗酸化効果の指標として、通常は前述のフリ
ーラジカル消去活性および活性酸素消去活性等の測定を
行っている。Recently, a method for measuring oxidative damage at the genetic level has been studied in evaluating the possibility of food-induced aging prevention at the clinical level. Among them, 8-hydroxydeoxyguanosine (8-OHdG) was generated in the DNA as a result of attacking the nucleobase (deoxyguanosine) in DNA by active oxygen generated as a result of lipid peroxidation in vivo. It was revealed that 8-OhdG is usually excised by a DNA repair enzyme, passed through the blood, and finally excreted in the urine. Therefore, 8-OHdG in blood and urine
The anti-aging effect can be measured by measuring the amount, and this measurement is performed by ELISA, which is an immunochemical technique.
This method is still expensive and is not established as a general method. Therefore, under the present circumstances, the above-mentioned free radical scavenging activity and active oxygen scavenging activity are usually measured as indicators of in vivo antioxidant effect.
【０００９】現在、生体内酸化により引き起こされると
考えられている疾患として、以下のものが知られてい
る。脳・神経系疾患としては、脳浮腫、外傷性てんか
ん、脳虚血、パーキンソン病、脊髄損傷等が、目の疾患
としては、白内障、網膜変性、未熟児網膜症等が、呼吸
器系疾患としては、気管支喘息、肺気腫、肺繊維症、成
人呼吸窮迫症候群（ARDS）、未熟児呼吸窮迫症候群（IR
DS）等が、循環器系疾患としては、動脈硬化、心筋梗塞
等が、消化器系疾患としては、潰瘍性大腸炎、ストレス
性胃潰瘍、すい炎、消化管粘膜障害等が、皮膚疾患とし
ては、紫外線障害、アトピー性皮膚炎、火傷、凍傷、床
ずれ等が、腎臓疾患としては、腎炎、腎不全等が、その
他の疾患としては、ガン、糖尿病、膠原病、リウマチ、
アルツハイマー病、自己免疫疾患、ベーチェット病等が
挙げられる。また、老化、老化による皮膚のしわや痴呆
症も、生体内酸化によると考えられている。生体内酸化
を防止又は低減する抗酸化剤は、このような疾患の予防
・治療につながると考えられ、機能性食品あるいは健康
食品として注目されるようになった。At present, the following are known as diseases which are considered to be caused by in vivo oxidation. Brain / nervous system diseases include cerebral edema, traumatic epilepsy, cerebral ischemia, Parkinson's disease, spinal cord injury, and eye diseases include cataract, retinal degeneration, retinopathy of prematurity, etc. Bronchial asthma, emphysema, pulmonary fibrosis, adult respiratory distress syndrome (ARDS), respiratory distress syndrome of premature infants (IR
DS), etc., cardiovascular diseases include arteriosclerosis, myocardial infarction, etc., and gastrointestinal diseases include ulcerative colitis, stress gastric ulcer, pancreatitis, gastrointestinal mucosal disorders, etc. , UV damage, atopic dermatitis, burns, frostbite, bed sores, etc., renal diseases include nephritis, renal failure, etc., and other diseases include cancer, diabetes, collagen disease, rheumatism,
Examples include Alzheimer's disease, autoimmune diseases, Behcet's disease and the like. Aging, skin wrinkles and dementia due to aging are also considered to be caused by in-vivo oxidation. Antioxidants that prevent or reduce in-vivo oxidation are considered to lead to the prevention and treatment of such diseases, and have been attracting attention as functional foods or health foods.
【００１０】このような用途の抗酸化剤としては、ハン
タイカイを水または含水有機溶媒で抽出して得られる抽
出物を有効成分として含有する活性酸素消去剤（特開平
８−20544号公報）、植物種子又は胚芽類を焙煎した
後、酵素処理したものに植物種子を加えて得られる組成
物を非極性溶媒で洗浄し、その後不溶物を極性溶媒で抽
出してなることを特徴とする抗活性酸素作用組成物（特
開平４−139132号公報）、オウギより抽出したアスチル
ビンを含有することを特徴とする活性酸素消去剤（特開
平６−65074号公報）、キハダ果実を水、メタノール等
の溶媒で抽出してなる抗酸化作用を有するエキス（特開
平10−17485号公報）、新規ミント交配種のエッセンス
からなる、活性酸素消去剤（特開平10−66465号公
報）、植物繊維成分を含有する培地を用いて担子菌及び
／又は子嚢菌の菌糸体を培養し、この培養物から抽出し
て得られた糖質、蛋白質、水溶性リグニンを主成分とす
ることを特徴とする生体の抗酸化機能増強剤（特開平11
−228441号公報）、アカミノキ、ウヤク、ウワウルシ、
ジコッピ、シソ、テンチャ、ハス、ラベンダーから選ば
れる１種以上の植物抽出物を含有することを特徴とする
活性酸素消去剤（特開平11−279069号公報）、カプサン
チン又はその脂肪酸エステルを有効成分とする抗酸化剤
（特開平10−195433号公報）、ごまの植物体から誘導さ
れた増殖性細胞の培養物の溶媒抽出由来のスーパーオキ
シドディスムターゼ様活性物質（特開平４−275226号公
報）等が報告されている。また、ルイボスティー抽出
物、イチョウ葉乾燥エキス等が上市されている。As an antioxidant for such use, an active oxygen scavenger (JP-A-8-20544) containing an extract obtained by extracting Hantaikai with water or a water-containing organic solvent as an active ingredient, plants After roasting seeds or germs, the composition obtained by adding the plant seeds to the enzyme-treated product is washed with a non-polar solvent, and then the insoluble matter is extracted with a polar solvent. Oxygen-acting composition (Japanese Unexamined Patent Publication No. 4-139132), active oxygen scavenger characterized by containing astilbin extracted from Japanese cedar (Japanese Unexamined Patent Publication No. 6-65074), yellowfin fruit in water, solvent such as methanol An extract having an antioxidant effect (Japanese Patent Application Laid-Open No. 10-17485), an active oxygen scavenger (Japanese Patent Application Laid-Open No. 10-66465) composed of an essence of a novel mint hybrid, and a plant fiber component For medium An antioxidant function enhancer for a living body, which comprises saccharides, proteins, and water-soluble lignin obtained by culturing mycelium of basidiomycete and / or ascomycete, and extracting from the culture. (JP-A-11
-228441 gazette), red cypress, oyster, oak,
Active oxygen scavenger characterized by containing one or more kinds of plant extracts selected from Zicoppi, perilla, tencha, lotus and lavender (JP-A-11-279069), capsanthin or a fatty acid ester thereof as an active ingredient. Antioxidants (JP-A-10-195433), superoxide dismutase-like active substances derived from solvent extraction of a culture of proliferating cells derived from sesame plants (JP-A-4-275226), etc. It has been reported. Rooibos tea extract, dried ginkgo biloba extract, etc. are also on the market.
【００１１】また、品質保持用の抗酸化効果と生体内抗
酸化効果の両方を持つ抗酸化剤としては、香辛料植物の
一種であるフェンネルの葉と茎から極性溶媒で抽出して
得られた物質を有効成分とする抗酸化剤（特開平６−29
9151号公報）、ユキノシタ科のユキノシタ植物抽出物を
有効成分とすることを特徴とする抗酸化剤（特開平10−
46142号公報）等が開示されている。また、茶抽出物、
ブドウ種子抽出物等が生体内酸化を抑制することが知ら
れている。しかし、ヒト腸管内定着性を示す乳酸菌が生
体内酸化を抑制することは知られていない。Further, as an antioxidant having both an antioxidant effect for maintaining quality and an in-vivo antioxidant effect, a substance obtained by extracting with a polar solvent from leaves and stems of fennel, which is a kind of spice plant, Antioxidant containing as an active ingredient (JP-A-6-29)
9151), and an antioxidant characterized by using an extract of a Yukinoshita plant of the family Yukinoshita as an active ingredient.
No. 46142) is disclosed. Also, tea extract,
Grape seed extract and the like are known to suppress in vivo oxidation. However, it has not been known that lactic acid bacteria exhibiting colonization in the human intestinal tract suppress in vivo oxidation.
【００１２】[0012]
【発明が解決しようとする課題】従来報告されてきた品
質保持用の抗酸化剤には、合成品と天然抽出物がある。
合成品は安全性に問題があることから、天然で安全性の
高い抗酸化剤が求められているが、天然の抗酸化剤にも
様々な問題点があり、改善が求められている。The antioxidants for quality preservation that have hitherto been reported include synthetic products and natural extracts.
Since synthetic products have a safety problem, natural and highly safe antioxidants are required, but natural antioxidants also have various problems, and improvement is required.
【００１３】例えば、トコフェロール、ゴマの抽出物、
ヒマワリ種子抽出物のように基本的に脂溶性である抗酸
化剤は、水溶系の製品に用いる場合にそのままでは使用
しにくく、水溶性の抗酸化剤は油脂類には使用しにくい
という欠点があった。また、特有の味や風味を有する抗
酸化剤は、製品の味や風味に影響を与えるため使用範囲
が限られていた。従って、広範囲の食品、飼料及び化粧
品に付与される味や臭いが許容される範囲内であり、わ
ずかな投与量で酸化防止効果を示す天然の抗酸化剤が望
まれている。For example, tocopherol, sesame extract,
Antioxidants that are basically fat-soluble, such as sunflower seed extract, are difficult to use as they are when used in water-based products, and water-soluble antioxidants have the drawback that they are difficult to use in oils and fats. there were. In addition, antioxidants having a specific taste and flavor have a limited range of use because they affect the taste and flavor of the product. Therefore, a natural antioxidant having a taste and an odor imparted to a wide range of foods, feeds, and cosmetics is acceptable, and a natural antioxidant showing an antioxidant effect with a small dose is desired.
【００１４】また、これまで知られている生体内抗酸化
剤に関しても、様々な問題が存在する。従来、漢方やハ
ーブまたは民間薬として知られているような植物の抽出
物は、抗酸化効果以外の薬効を有し、その薬効による副
作用が発現することがあった。このようなことから、従
来より食品として扱われてきた、安全な植物由来の天然
抗酸化剤が望まれている。また、従来の天然抗酸化剤
は、抗酸化剤の抽出目的で栽培され、使用されるため、
コストが高いという問題もあった。There are also various problems with the known antioxidants in vivo. Conventionally, plant extracts known as Chinese herbs, herbs or folk medicines have medicinal effects other than the antioxidant effect, and side effects due to the medicinal effects may occur. Therefore, safe plant-derived natural antioxidants that have been treated as foods have been desired. Also, conventional natural antioxidants are cultivated and used for the purpose of extracting antioxidants,
There was also the problem of high costs.
【００１５】[0015]
【課題を解決するための手段】本発明者らは、以上の問
題点に鑑み、ヒトあるいは動物に安全な、低コストで製
造できる、用途の広い抗酸化剤について鋭意検討を重ね
てきた。本発明者らは、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・ガセリに従来
に見られない高いヒト腸管内定着性を有しており、さら
にこのラクトバチルス・ガセリ乳酸菌及び、その変異株
の培養物および菌体が生体内抗酸化効果をもたらすこと
を見出し、上記課題の解決に成功した。In view of the above problems, the present inventors have conducted extensive studies on a versatile antioxidant which is safe for humans or animals and can be produced at low cost. The inventors of the present invention have conducted various studies on fermented milk and found that among the lactic acid bacteria and human-derived lactic acid bacteria isolated from these fermented milks, a particularly high human intestinal tract content not found in Lactobacillus gasseri. The present inventors have found that the lactobacillus Lactobacillus gasseri lactobacillus and its mutant strain cultures and cells have an in vivo antioxidative effect, and have succeeded in solving the above problems.
【００１６】本明細書において、「抗酸化効果」とは、
食品、飼料をヒトあるいは動物に投与した際に、生体内
で発生するフリーラジカルや活性酸素を消去または低減
して細胞膜の安定化効果を発揮する、生体内酸化防止効
果を包含する。「抗酸化剤」とはこのような抗酸化効果
を有する剤である。すなわち、本発明は、ラクトバチル
ス・ガセリ（Lactobacillus gasseri)に属する乳酸菌を
培養して得られる菌体、その培養物を有効成分とする抗
酸化剤に関する。さらに、本発明は、このような有効成
分を含有してなる抗酸化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。In the present specification, the "antioxidant effect" means
When a food or feed is administered to humans or animals, it includes an in vivo antioxidant effect that eliminates or reduces free radicals and active oxygen generated in the body to exert a cell membrane stabilizing effect. The "antioxidant" is an agent having such an antioxidant effect. That is, the present invention relates to a microbial cell obtained by culturing a lactic acid bacterium belonging to Lactobacillus gasseri , and an antioxidant containing the culture as an active ingredient. Furthermore, the present invention relates to foods and drinks containing such an active ingredient and having an antioxidant effect.
That is, the present invention is an invention having the following configurations described in the claims.
【００１７】（１）ラクトバチルス・ガセリ（Lactobac
illus 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抗酸化剤。
（２）ラクトバチルス・ガセリ（Lactobacillus gasser
i)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）記載の抗酸化剤。
（３）ラクトバチルス・ガセリ（Lactobacillus gasser
i)に属する乳酸菌を培養して得られる培養物が醗酵乳で
ある、（１）又は（２）のいずれかに記載の抗酸化剤。
（４）ラクトバチルス・ガセリ（Lactobacillus gasser
i)に属する乳酸菌がLG2055（FERM P-15535）である
（１）〜（３）のいずれかに記載の抗酸化剤。
（５）ラクトバチルス・ガセリ（Lactobacillus gasser
i)属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抗酸化作用を有する飲食品又は飼
料。(1) Lactobacillus gasseri ( Lactobac
illus gasseri ) cultivated lactic acid bacteria and / or an antioxidant containing a bacterial cell as an active ingredient. (2) Lactobacillus gasser
The antioxidant according to (1), wherein the lactic acid bacterium belonging to i ) is Lactobacillus gasseri having human intestinal colonization. (3) Lactobacillus gasser
The antioxidant according to (1) or (2), wherein the culture obtained by culturing the lactic acid bacterium belonging to i ) is fermented milk. (4) Lactobacillus gasser
The antioxidant according to any one of (1) to (3), wherein the lactic acid bacterium belonging to i ) is LG2055 (FERM P-15535). (5) Lactobacillus gasser
i ) A food or drink or feed having an antioxidant effect, which is obtained by culturing a lactic acid bacterium belonging to the genus and / or cells.
【００１８】[0018]
【発明の実施の形態】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、醗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、血清コレステロールの上昇を
抑制する、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、生体内酸化を強く抑
制する、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。このような条件を満足するラクトバチ
ルス・ガセリ菌については全く知られていなかった。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の菌株を選択することができ
た。なお、これらの菌株は、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生物寄託センターに寄
託されている。BEST MODE FOR CARRYING OUT THE INVENTION The present invention has been made in order to solve the above-mentioned problems, and the present inventors newly set the following criteria when screening a target lactic acid bacterium. Then, a strain that matches the purpose was selected. That is, the present inventors, among many fermented milk and human-derived Lactobacillus gasseri, high gastric acid resistance, good growth under low pH conditions, suppress the elevation of serum cholesterol, human intestinal tract It has high colonization ability, shows affinity for human intestinal cells, has bile acid resistance, strongly suppresses in vivo oxidation, has high survival rate when applied to foods, has excellent flavor and physical properties, etc. The conditions were set and intensive research was conducted on the selection of strains. Lactobacillus gasseri that satisfies such conditions has not been known at all. As a result of screening under these conditions, the following strains could be selected as strains that meet these conditions. Note that these strains have been deposited at the Patent Biological Depositary Center, National Institute of Advanced Industrial Science and Technology, with the following deposit numbers.
【００１９】菌株ラクトハ゛チルス・カ゛セリ
（Lactobacillus gasseri) SBT10801 FE
RM P-18137ラクトハ゛チルス・カ゛セリ
(Lactobacillus gasseri) SBT1703 FE
RM P-17785ラクトハ゛チルス・カ゛セリ
(Lactobacillus gasseri) SBT10241 FE
RM P-17786ラクトハ゛チルス・カ゛セリ
(Lactobacillus gasseri) SBT0274 F
ERM P-17784ラクトハ゛チルス・カ゛セリ
(Lactobacillus gasseri) SBT10239 F
ERM P-16639ラクトハ゛チルス・カ゛セリ
(Lactobacillus gasseri) SBT2055 F
ERM P-15535
さらにこれらの菌株は、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る。そし
てラクトバチルス・ガセリに属する乳酸菌が腸内に定着
し、生体内酸化を防止する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。
さらに本発明では、上記寄託菌に限らずヒトや醗酵乳か
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。Strain Lactobacillus gasseri SBT10801 FE
RM P-18137 Lactobacillus gasseri SBT1703 FE
RM P-17785 Lactobacillus gasseri SBT10241 FE
RM P-17786 Lactobacillus gasseri SBT0274 F
ERM P-17784 Lactobacillus gasseri SBT10239 F
ERM P-16639 Lactobacillus gasseri SBT2055 F
ERM P-15535 Furthermore, these strains have a high affinity for human intestinal cells, and when orally administered, they can survive and reach the intestinal tract and remain resident in the intestine for a long time. is there. The fact that lactic acid bacteria belonging to Lactobacillus gasseri settle in the intestine and exhibit an effect of preventing in-vivo oxidation is not known at all, and was first clarified by the present inventors.
Furthermore, in the present invention, not only the deposited bacteria but also Lactobacillus gasseri ( Lactobacillus) isolated from humans and fermented milk.
gasseri ), any of which exhibits the above-mentioned action can be used.
【００２０】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 gasser
i)の培養基には、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。Next, the method for culturing these lactic acid bacteria will be described. The Lactobacillus gasser of the present invention
As the culture medium of i ), various media such as a milk medium or a medium containing a milk component and a semi-synthetic medium not containing it can be used. Examples of such a medium include a reduced skim milk medium obtained by reducing skim milk and sterilizing by heating. The culture method is static culture or neutralization culture in which the pH is controlled at a constant level, but the culture method is not particularly limited as long as the bacteria grow well.
【００２１】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。その摂取に際しては、高コレステロール
含有食品に添加して同時に摂取するか、それ自体を高コ
レステロール食品の摂取の前後に摂取してもよい。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0.5〜50ｇであり、これを
１日数回に分けて投与するとよい。本発明においては、
ヒト腸管内にラクトバチルス・ガセリが定着することに
よってより強い効果を発揮する。このため特に好ましく
は、生菌として成人一人当たり108〜1012cuf／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。The present invention uses the culture and / or cells obtained as described above as an active ingredient. Further, dried powder may be used as an active ingredient. It is preferable that these are dried by freeze-drying because they can be dried without degrading the cells. It is desirable to ingest these active ingredients orally. At the time of ingestion, it may be added to a high-cholesterol-containing food and ingested at the same time, or it may be ingested before or after ingestion of the high-cholesterol food. Further, these powders can be orally administered as powders, tablets, pills, capsules or granules by mixing with a suitable excipient such as lactose. The dose is appropriately determined individually in consideration of the subject's symptoms, age, etc., but is usually 0.5 to 50 g as a dry substance per day for an adult, and this may be administered in several divided doses per day. In the present invention,
It exerts a stronger effect by the establishment of Lactobacillus gasseri in the human intestinal tract. For this reason, it is particularly preferable to administer 10 8 to 10 12 cuf / day per adult as a viable bacterium so that the intended effect of the present invention can be exhibited. By ingesting in this way, it colonizes the intestinal tract and exerts the desired effect.
【００２２】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、果汁、乳飲料、清
涼飲料等の飲料、菓子類、或いは脂質含量の高いバター
等の乳製品、マヨネーズ等の卵加工品、バターケーキ等
の食品をあげることができる。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、過度の加熱は避けなければならない。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
段を講じることも必要であろう。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（La
ctobacillus 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等であっても良い。Further, the active ingredient of the present invention may be added to the raw material during the manufacturing process of food or drink. As the food and drink, any food and drink may be used, and examples thereof include beverages such as fruit juice, dairy drinks and soft drinks, confectionery, or dairy products such as butter having a high lipid content, processed egg products such as mayonnaise, and butter cake. And so on. However, as a characteristic of the present invention, it is necessary for lactic acid bacteria to settle in the intestinal tract in a living state, and excessive heating must be avoided. It would also be necessary to employ conventional techniques such as microcapsules to take measures to avoid heating. Furthermore, the food and drink according to the present invention is the above-mentioned Lactobacillus gasseri (La
It may be yogurt produced by lactic acid fermentation using a strain of Ctobacillus gasseri).
【００２３】以下に本発明に用いる乳酸菌株としてLG20
55（FERM P-15535）を用いた試験例を示し、菌学的性状
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。
乳酸菌の性状LG20 as a lactic acid bacterium strain used in the present invention is described below.
A test example using 55 (FERM P-15535) is shown to specifically explain the mycological properties and the in vitro and in vivo effects. However, the present invention is not limited to this description. Properties of lactic acid bacteria
【００２４】[0024]
【表1】 【table 1】
【００２５】遺伝学的特性
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LG20
55株 、そしてコントロールとして、大腸菌（Escherich
ia. coli）のDNAを抽出、精製した。
LG2055株のDNA同士の相同性を100％、LG2055株と大腸菌
とのDNA相同性を0％としたときの、LG2055株と各基準株
のDNA相同性をDNAハイブリダイゼーション法により検討
した。その結果、LG2055株はラクトバチルス・ガセリJC
M1131株と90％以上の相同性を有していたため、LG2055
株はラクトバチルス・ガセリと同定された。Genetic Characteristics DNA Homology Test Lactobacillus reference strain, test strain LG20, described below
55 strains and, as a control, Escherichia coli (Escherich
ia. coli) DNA was extracted and purified. The DNA homology between the LG2055 strain and each reference strain was examined by the DNA hybridization method when the homology between the DNAs of the LG2055 strain was 100% and the DNA homology between the LG2055 strain and E. coli was 0%. As a result, the LG2055 strain is Lactobacillus gasseri JC
LG2055 has more than 90% homology with M1131 strain.
The strain was identified as Lactobacillus gasseri.
【００２６】胃酸耐性
胃酸耐性試験は瀧口らの方法（腸内細菌学雑誌 14.11-1
8．2000）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 gastric acid resistance test is the method of Takiguchi et al. (Journal of Enterobacteriaceae 14.11-1
8.2000), an artificial gastric juice having a pH of 2.0 was prepared and a gastric acid resistance test was conducted, and the LG2055 strain survived for 3 hours or more.
【００２７】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 fluid resistance According to the method of Takiguchi et al. (Journal of Enterobacteriaceae 14.11-18.2000), an artificial intestinal fluid containing bile powder was prepared, and the LG2055 strain treated with the above-mentioned artificial gastric juice was added thereto for resistance. When tested, it showed a viability of 20 hours or more. It was confirmed that the LG2055 strain passed through the digestive tract and survived and reached the large intestine.
【００２８】インビトロでの抗酸化作用
B. Halliwellらのデオキシリボース法（Analytical Bio
chemistry，Vol.165,pp.215-219 (1987)）によりLG2055
株の培養産物を用いて調べたところヒドロキシルラジカ
ル消去効果を示した。また、SOD様活性をSODテストワコ
ー（和光純薬工業社製）を用いて測定したところSOD様
活性を示した。In vitro antioxidant effect B. Halliwell et al. Deoxyribose method (Analytical Bio
Chemistry, Vol.165, pp.215-219 (1987)) LG2055
When examined using the culture product of the strain, it showed a hydroxyl radical scavenging effect. Moreover, when the SOD-like activity was measured using SOD Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.), the SOD-like activity was shown.
【００２９】
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時間醗酵させた醗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、LG2055株が高
い腸内定着性を有することがわかった。Human intestinal transit ability and intestinal colonization non-fat milk solid 9.5%, milk fat 3.0% milk 4% LG2055 starter was inoculated and fermented at 39 degrees for 4 hours. Volunteer 42
The name was fed with 100 g of once daily for 4 weeks, and the change of intestinal bacteria was observed. During the test period, evaluation was conducted by freely eating except for prohibiting the intake of foods, oligosaccharides, and drugs that affect the intestinal bacteria. The LG2055 strain, which was not detected before the test, was detected in all the subjects after 4 weeks, and it was found that the LG2055 strain has high intestinal colonization.
【００３０】インビボでの生体内抗酸化効果試験
１. 乳酸菌脱脂乳培養物の調製
LG2055を用い、115℃、20分間の滅菌処理をした0.5％酵
母エキス（アサヒビール社製）添加11.55％脱脂乳培地
にて、37℃、16時間の培養を３代以上行って賦活させ
た。これを同培地に3％接種し、37℃で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。In vivo anti-oxidant effect test 1. Preparation of lactic acid bacterium skim milk culture 11.25% skim milk added with 0.5% yeast extract (manufactured by Asahi Breweries) sterilized with LG2055 at 115 ° C. for 20 minutes Incubation was carried out in a medium at 37 ° C. for 16 hours for three or more generations to activate. 3% of this was inoculated into the same medium and cultured at 37 ° C for 16 hours. The obtained culture was freeze-dried and then ground in a mortar.
【００３１】２．試験飼料
食餌組成
表２にAIN-76TM（オリエンタル酵母社製）に準拠した食
餌組成を示した。この飼料に10％脱脂粉乳、又は上記脱
脂粉乳乳酸菌培養物を添加し、さらに、添加物に含まれ
るタンパク質量を考慮してガゼインを添加した。2. Test feed diet composition Table 2 shows the diet composition based on AIN-76TM (manufactured by Oriental Yeast Co., Ltd.). To this feed, 10% skim milk powder or the above skimmed milk powder lactic acid bacterium culture was added, and further, casein was added in consideration of the amount of protein contained in the additive.
【００３２】[0032]
【表２】 [Table 2]
【００３３】脱脂粉乳培養物と脱脂粉乳の粗タンパク質
含量(％)は35.0と34.1で、アミノ酸組成に差異は認めら
れなかった。抗酸化性成分の効果の評価を容易にするた
めに、齧歯類用飼料中の通常のビタミンＥレベルよりも
低いビタミンＥを含む飼料に調製を行った。この目的の
ために、ビタミンＥフリーのビタミン混合物を用いた。
また、油脂源として市販のサフラワー油(9.4mgα−トコ
フェロール)を用いた(それぞれの油脂を含む飼料を高ビ
タミンＥ及び低ビタミンＥ飼料とした)。ビタミンＥは
両乳製品で検出されなかった。なお、脱脂粉乳培養物は
脱脂乳と比較してコハク酸、乳酸、ギ酸、酪酸を高濃度
含んでいた。脱脂乳とサフラワー油あるいは活性炭処理
とサフラワー油を含む飼料群をそれぞれ、１、３群とし
た。脱脂粉乳培養物とサフラワー油あるいは活性炭処理
とサフラワー油を含む飼料群をそれぞれ、２、４群とし
た。The crude protein content (%) of the skim milk culture and skim milk powder was 35.0 and 34.1, and no difference was observed in the amino acid composition. In order to facilitate the evaluation of the effects of antioxidants, preparations were made on diets containing vitamin E below the usual levels of vitamin E in rodent diets. A vitamin E-free vitamin mixture was used for this purpose.
In addition, commercially available safflower oil (9.4 mg α-tocopherol) was used as a source of fats and oils (the feeds containing the respective fats and oils were high vitamin E and low vitamin E feeds). Vitamin E was not detected in both dairy products. The skim milk powder culture contained a higher concentration of succinic acid, lactic acid, formic acid, and butyric acid than skim milk. Feed groups containing skim milk and safflower oil or activated carbon treatment and safflower oil were respectively set as groups 1 and 3. Feed groups containing nonfat dry milk culture and safflower oil or activated carbon treatment and safflower oil were divided into groups 2 and 4, respectively.
【００３４】実験動物
５週齢のSprague-Dawley系雄ラット(各群12匹)を用い
た。表２の飼料で４週間飼育した。この間水を自由に与
えた。飼育終了後、エーテル麻酔下で大動脈採血によっ
てと殺した。Experimental Animal Five-week-old Sprague-Dawley male rats (12 animals in each group) were used. The diet shown in Table 2 was bred for 4 weeks. During this time he was given water ad libitum. After the rearing, the mice were killed by aortic blood sampling under ether anesthesia.
【００３５】分析
常法に従って、赤血球の溶血反応抑制活性、血清、肝臓
と赤血球のthiobarbituric acid reactive substance(T
BARS)濃度、血漿と肝臓のα−トコフェロール濃度およ
び肝臓のグルタチオン濃度をそれぞれ測定した。血漿と
肝臓のホモジネート(0.25ml)について、FeSO4とCumene
hydoroperoxideを添加し一定時間インキュベーション
し、過酸化物の生成を、TBARSを指標にして測定した。Analysis According to the usual method, the hemolytic reaction inhibitory activity of red blood cells, thiobarbituric acid reactive substance (T) of serum, liver and red blood cells
BARS) concentration, plasma and liver α-tocopherol concentration, and liver glutathione concentration were measured, respectively. FeSO4 and Cumene were added to plasma and liver homogenate (0.25 ml).
Hydoroperoxide was added and incubated for a certain period of time, and the production of peroxide was measured using TBARS as an index.
【００３６】統計処理
結果は平均値と標準誤差で表し、Duncanの多重比較検定
法およびANOVA検定を行った。The statistical processing results were represented by the mean value and standard error, and Duncan's multiple comparison test method and ANOVA test were performed.
【００３７】実験結果
表３から明かなように、Sprague-Dawley系ラットの体重
増加量、摂食量は食事の影響を受けなかったが、高ビタ
ミンＥ食−脱脂乳群で肝臓重量がやや低下した。Experimental Results As is clear from Table 3, the weight gain and food intake of Sprague-Dawley rats were not affected by diet, but the liver weight was slightly reduced in the high vitamin E diet-fat milk group. .
【００３８】[0038]
【表３】 [Table 3]
【００３９】赤血球の溶血阻害活性に対する食事の影響
を図 1に示した。低ビタミンＥー脱脂乳群(３)で、僅か
ではあるが赤血球の溶血阻害活性が低下した。一方、低
ビタミンＥ−発酵脱脂乳群では溶血阻害活性の低下は見
られなかった。The effect of diet on the hemolytic inhibitory activity of red blood cells is shown in FIG. In the low vitamin E-skim milk group (3), the hemolytic inhibitory activity of erythrocytes was slightly reduced. On the other hand, in the low vitamin E-fermented skim milk group, no decrease in hemolytic inhibition activity was observed.
【００４０】赤血球のTBARS濃度は、低ビタミンＥ食ラ
ット(3,4)で高ビタミンＥ食ラット(1,2)よりも低下した
(図２)。赤血球の場合と類似して、Cumene hydoroperox
ideで処理してない血漿のTBARS濃度も低ビタミンＥ食ラ
ット(3,4)で低下した(図３)。この場合のTBARS濃度は、
発酵脱脂乳群(2,4)で対応する脱脂乳群(1,3)と比較して
低い傾向にあり、特に、高ビタミンＥ−発酵脱脂乳群の
TBARS濃度は相当する脱脂乳群と比較して有意に低下し
た(図３)。ヒドロペルオキシド処理によって血漿TBARS
濃度はいずれも増加したが、その増加は低ビタミンＥ食
ラット(3,4)で顕著であり、発酵脱脂乳群(4)でその上昇
は脱脂乳添加群(3)よりも抑制された。Erythrocyte TBARS levels were lower in low-vitamin E-fed rats (3,4) than in high-vitamin E-fed rats (1,2).
(Figure 2). Similar to the case of red blood cells, Cumene hydoroperox
TBARS levels in plasma not treated with ide were also reduced in low vitamin E-fed rats (3,4) (Fig. 3). The TBARS concentration in this case is
The fermented skim milk group (2,4) tends to be lower than the corresponding skim milk group (1,3), and particularly, in the high vitamin E-fermented skim milk group.
TBARS concentrations were significantly reduced compared to the corresponding skim milk group (Figure 3). Plasma TBARS by hydroperoxide treatment
Although the concentration increased in all cases, the increase was remarkable in the low vitamin E diet rats (3, 4), and the increase was suppressed in the fermented skim milk group (4) as compared with the skim milk added group (3).
【００４１】図４に肝臓のTBARS濃度を示した。赤血球
や血漿の場合と異なり、ヒドロペルオキシド処理を行っ
ていない肝臓ホモジネートのTBARS濃度は低ビタミンＥ
食ラット(3,4)で、高ビタミンＥ食ラット(1,2)よりも低
かった。ヒドロペルオキシド処理によって肝臓ホモジネ
ートのTBARS濃度増加し、特に、低ビタミンＥ食ラット
(3,4)で顕著であった。この場合、発酵脱脂乳添加の影
響は見られなかった。FIG. 4 shows the TBARS concentration in the liver. Unlike erythrocytes and plasma, liver homogenates without hydroperoxide treatment have low levels of vitamin E.
It was lower in the diet rats (3,4) than in the high vitamin E diet rats (1,2). Hydroperoxide treatment increased TBARS levels in liver homogenates, especially in low vitamin E-fed rats
It was remarkable in (3,4). In this case, the effect of adding fermented skim milk was not seen.
【００４２】図５に肝臓のグルタチオン濃度を示した。
還元型グルタチオン濃度は高ビタミンＥ食ラット(1,2)
と比較して低ビタミンＥ食ラット(3,4)で高かった。還
元型グルタチオン濃度に対する発酵脱脂乳添加の影響は
見られなかった。酸化型グルタチオン濃度は高ビタミン
Ｅ−脱脂乳群(1)で相当する発酵脱脂乳群(2)や他群(3,
4)よりも高値を示した。FIG. 5 shows the glutathione concentration in the liver.
Reduced glutathione concentration is high in vitamin E-fed rats (1,2)
It was higher in rats fed a low-vitamin E diet (3,4) compared to. No effect of the addition of fermented skim milk on the concentration of reduced glutathione was observed. Oxidized glutathione concentration is equivalent to the high vitamin E-skim milk group (1) in the fermented skim milk group (2) and other groups (3,
It was higher than 4).
【００４３】血漿、赤血球、肝臓のα−トコフェロール
濃度を図６に示した。これらのα−トコフェロール濃度
は、予想されるように、低ビタミンＥ食ラット(3,4)で
高ビタミンＥ食ラット(1,2)と比較して顕著に低かっ
た。血漿のα−トコフェロール濃度は、発酵脱脂乳群
(2,4)で対応する脱脂乳群(1,3)よりも高い傾向にあり、
特に、低ビタミンＥラット飼料−発酵脱脂乳群(4)で相
当する脱脂乳群(3)と比較して有意に高かった。赤血球
α−トコフェロール濃度には発酵脱脂乳添加の影響は見
られなかった。肝臓では、高ビタミンＥー発酵脱脂乳群
(2)で相当する脱脂乳群(1)よりもα−トコフェロール濃
度は、高かった。The α-tocopherol concentrations in plasma, erythrocytes and liver are shown in FIG. These α-tocopherol concentrations were, as expected, significantly lower in low vitamin E-fed rats (3,4) compared to high vitamin E-fed rats (1,2). Plasma α-tocopherol concentration was determined by the fermented skim milk group.
(2,4) tends to be higher than the corresponding skim milk group (1,3),
In particular, the low vitamin E rat feed-fermented skim milk group (4) was significantly higher than the corresponding skim milk group (3). No effect of addition of fermented skim milk was observed on erythrocyte α-tocopherol concentration. In the liver, high vitamin E-fermented skim milk group
The α-tocopherol concentration was higher than that of the skim milk group (1) corresponding to (2).
【００４４】表４に血漿と肝臓の脂質濃度を示した。低
ビタミンＥ食ラット(3,4)で高ビタミンＥ食ラット(1,2)
と比較して血清トリグリセリド濃度は高く、また、発酵
脱脂乳群(2,4)で脱脂乳群(1,3)よりも高い傾向にあっ
た。血漿のコレステロールとリン脂質、肝臓のトリグリ
セリド濃度には食事の影響は見られなかった。肝臓のコ
レステロールとリン脂質濃度は低ビタミンＥ食ラット
(3,4)で高ビタミンＥ食ラット(1,2)と比較して低下し
た。Table 4 shows the lipid concentrations in plasma and liver. Low-vitamin E-fed rats (3,4) and high-vitamin E-fed rats (1,2)
The serum triglyceride concentration was higher than that in the fermented skimmed milk group (2,4) and higher than that in the skim milk group (1,3). There were no effects of diet on plasma cholesterol and phospholipids and liver triglyceride levels. Liver cholesterol and phospholipid levels are low in vitamin E-fed rats
(3,4) decreased compared to high vitamin E-fed rats (1,2).
【００４５】[0045]
【表４】 [Table 4]
【００４６】以上の結果以下のことが判明した。本実験
では、ラット食餌のビタミンＥレベルを調整することに
よって生体内の酸化的ストレスが異なる条件を設定し
た。そのために、食事のビタミン混合からビタミンＥを
除いた。また、市販の植物油にはビタミンＥが含まれて
いることから、飼料に用いる植物油を活性炭処理するこ
とでビタミンＥを除いた。そして、飼料中のビタミンＥ
のレベルが、AIN-76食のビタミン混合を用いて調製され
た標準食から供給される量の約98.8%(高ビタミンＥ食)
と18.8％(低ビタミンＥ食)の２段階となるように設定し
た。その結果、低ビタミン食を与えた場合には、血漿の
Cumene hydoroperoxideによる過酸化反応の亢進に対し
て、本発明の発酵乳は抗酸化作用を示した。また、赤血
球の溶血阻害活性に対しても、本発明の発酵乳は有効で
あった。低ビタミンＥ食ラットにおける血漿ビタミンＥ
レベルの低下は脱脂乳群で本発明の発酵脱脂乳群よりも
高かった。As a result of the above, the following has been found. In the present experiment, conditions under which oxidative stress in vivo was different were set by adjusting the vitamin E level of rat diet. Therefore, vitamin E was removed from the dietary vitamin mix. Further, since commercially available vegetable oil contains vitamin E, vitamin E was removed by treating the vegetable oil used for feed with activated carbon. And vitamin E in the feed
The level of about 98.8% of the amount provided by the standard diet prepared using the vitamin mixture of the AIN-76 diet (high vitamin E diet)
And 18.8% (low vitamin E diet). As a result, when given a low vitamin diet, plasma
The fermented milk of the present invention exhibited an antioxidant effect against the enhancement of the peroxidation reaction by cumene hydoroperoxide. Further, the fermented milk of the present invention was also effective against the hemolytic inhibition activity of red blood cells. Plasma vitamin E in low vitamin E-fed rats
The level reduction was higher in the skim milk group than in the fermented skim milk group of the present invention.
【００４７】したがって、本発明の発酵脱脂乳はビタミ
ンＥ消耗の抑制を介して、生体内の酸化的ストレス上昇
に伴う過酸化物の上昇や溶血阻害活性の低下に対して作
用したものと判断できる。以上のインビボ実験の結果本
発明が生体内抗酸化効果を有していることが確認され
た。Therefore, it can be judged that the fermented skim milk of the present invention acts on the increase of peroxide and the decrease of hemolytic inhibitory activity associated with the increase of oxidative stress in the body through the suppression of vitamin E consumption. . As a result of the above in vivo experiments, it was confirmed that the present invention has an in vivo antioxidant effect.
【００４８】以下に実施例を示して本発明を具体的に説
明する。しかし、本発明はこの実施例に限定されるもの
ではない。The present invention will be specifically described below with reference to examples. However, the present invention is not limited to this embodiment.
【実施例】実施例１
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、抗酸化剤を調
製した（Ａ）。Example 1 The LG2055 strain was cultured in a 10% reduced skim milk medium (121 ° C., heated for 10 minutes), and the main culture was freeze-dried and powdered to prepare an antioxidant (A).
【００４９】実施例２
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、抗酸化ヨーグルト
とした（Ｂ）。Example 2 The LG2055 strain was inoculated into 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 a paper cup and cooling, it was made into antioxidant yogurt (B).
【００５０】実施例３
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。この菌体１ｇを乳糖５ｇと混合し顆粒状に成形し
て顆粒剤を得た。Example 3 The LG2055 strain was cultured in whey medium (added with 0.5% yeast extract and 0.1% trypticase peptone) and then centrifuged to collect the cells. 1 g of the cells was mixed with 5 g of lactose and molded into a granule to obtain a granule.
【００５１】実施例４ 高コレステロール含有食品に配合した例を示す。 発酵バター （ｗｔ／ｗｔ） 乳脂肪 ９６．８％ 食塩 １．２ 実施例１で得られた抗酸化剤（Ａ） ２Example 4 An example of blending with a high cholesterol content food is shown. Fermented butter (wt / wt) Milk fat 96.8% Salt 1.2 Antioxidant (A) 2 obtained in Example 1
【００５２】バターケーキ （ｗｔ／
ｗｔ）
バター ２４％
薄力粉 ２４
砂糖 ２４
全卵 ２４
実施例２で得られた抗酸化剤（Ｂ） ４
香料 少々Butter cake (wt /
wt) Butter 24% Soft flour 24 Sugar 24 Whole egg 24 Antioxidant (B) 4 obtained in Example 2 4 Fragrance
【００５３】マヨネーズ （ｗｔ／
ｗｔ）
サラダ油 ６５．４％
卵黄 １７
食酢 １０
実施例１で得られた抗酸化剤（Ａ） ３
香辛料 ４．４
グルタミン酸モノナトリウム ０．６Mayonnaise (wt /
wt) Salad oil 65.4% Egg yolk 17 Vinegar 10 Antioxidant (A) 3 obtained in Example 1 Spice 4.4 Monosodium glutamate 0.6
【００５４】実施例５
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。培養終了後、7,000rpm、
15分間遠心分離を行い、培養液の1／50量の濃縮菌体を
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粉体化し、凍結乾燥菌
末を得た。Example 5 The LG2055 strain was inoculated in 5 L of MRS liquid medium (manufactured by Difco), and then 37
C., static culture was performed for 18 hours. After completion of culturing, 7,000 rpm,
Centrifugation was performed for 15 minutes to obtain concentrated bacterial cells in 1/50 volume of the culture solution. Next, the concentrated bacterial cells were mixed with skim milk powder 10% (by weight),
The same amount of the dispersion medium containing 1% (by weight) of sodium glutamate was mixed, adjusted to pH 7, and then freeze-dried. The freeze-dried product obtained was powdered with a 60-mesh sieve to obtain freeze-dried bacterial powder.
【００５５】実施例６
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、上記実施例で得られたLG2055株の凍結乾燥菌末１
ｇ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。Example 6 Freeze-dried bacterial powder 1 of the LG2055 strain obtained in the above-mentioned example, in accordance with the provisions of "Powder" in the 13th revised Japanese Pharmacopoeia
To g, 400 g of lactose (JP) and 600 g of potato starch (JP) were added and uniformly mixed to prepare a powder.
【００５６】実施例７
脱脂乳を80〜85℃で20〜30分間殺菌した後、ホモゲナイ
ズし、冷却した。これにスターターとして本菌株LG2055
株の純培養物を２〜５％加え、37〜40℃で16時間発酵さ
せ、乳酸含量２％の酸乳（脱脂乳培地における培養物）
を得た。ついで、生じたカードを砕きながら、５℃に冷
却し、これを酸乳とした。別に、しょ糖15％のほかに適
量の酸味料、香料、色素を含有する糖液を調合し、ホモ
ジナイズし、70〜80℃で20〜30分間殺菌した後、５℃に
冷却し、糖液とした。このようにして得た酸乳35に対し
て糖液65の割合で混合して酸乳飲料を得た。Example 7 Skim milk was sterilized at 80 to 85 ° C. for 20 to 30 minutes, then homogenized and cooled. This strain LG2055 as a starter
2-5% of pure culture of the strain was added and fermented at 37-40 ° C for 16 hours, sour milk with lactic acid content of 2% (culture in skim milk medium)
Got Then, the resulting curd was crushed and cooled to 5 ° C. to obtain sour milk. Separately, in addition to sucrose 15%, prepare a sugar solution containing an appropriate amount of acidulant, flavor, and pigment, homogenize, sterilize at 70 to 80 ° C for 20 to 30 minutes, and then cool to 5 ° C to prepare sugar solution. did. The sour milk 35 thus obtained was mixed at a ratio of a sugar liquid 65 to obtain a sour milk drink.
【００５７】実施例８
ビタミンＣ40ｇまたはビタミンＣとクエン酸の等量混合
物40ｇ、グラニュー糖100ｇ、コーンスターチと乳糖の
等量混合物60ｇに、上記実施例１で得た本菌株の脱脂乳
培地における培養物の凍結乾燥物を40ｇ加えて十分に混
合した。混合物を袋に詰め、１袋1.5ｇのステック状栄
養健康食品を150袋製造した。Example 8 40 g of vitamin C or 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar and 60 g of an equal mixture of corn starch and lactose were added to a culture of the strain obtained in Example 1 in a skim milk medium. 40 g of the freeze-dried product of was added and thoroughly mixed. The mixture was packed in a bag and 150 bags of 1.5 g of stick-like nutritional health food were produced.
【００５８】実施例９
次の配合により生体内抗酸化剤を製造した。
（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。Example 9 An in vivo antioxidant was produced by the following formulation. (1) 50 g of freeze-dried product of culture of non-fat dry milk medium of LG2055 strain, (2) 90 g of lactose, (3) 29 g of corn starch, (4) 1 g of magnesium stearate, this mixture was compressed by a compression tablet machine to give 1 100 tablets were prepared containing 40 mg of active ingredient per tablet.
【００５９】[0059]
【発明の効果】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
得られる菌体、その培養物を有効成分とする抗酸化剤に
乳酸菌及び／またはその変異株を主成分とする抗酸化剤
が提供することができる。本発明の抗酸化剤は、毒性及
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, bacterial cells obtained by culturing lactic acid bacteria belonging to Lactobacillus gasseri , lactic acid bacteria containing the culture as an active ingredient, and / or mutants thereof It is possible to provide an antioxidant containing as a main component. The antioxidant of the present invention has extremely little toxicity and side effects, and is also useful as a food material.
【図１】飼育ラットの赤血球溶血阻害活性を示す。FIG. 1 shows the erythrocyte hemolysis inhibitory activity of breeding rats.
【図２】飼育ラットの赤血球チオバルビツール酸反応物
質量を示す。FIG. 2 shows the amount of erythrocyte thiobarbituric acid-reactive substance in reared rats.
【図３】血漿中のチオバルビツール酸反応物質量を示
す。FIG. 3 shows the amount of thiobarbituric acid reactive substance in plasma.
【図４】肝臓中のチオバルビツール酸反応物質量を示
す。FIG. 4 shows the amount of thiobarbituric acid reactive substance in the liver.
【図５】肝臓中のグルタチオン濃度を示す。FIG. 5 shows the concentration of glutathione in the liver.
【図６】血漿中、赤血球、肝臓のビタミンＥ濃度を示
す。FIG. 6 shows vitamin E concentrations in plasma, red blood cells, and liver.
───────────────────────────────────────────────────── 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 35/20 Ａ６１Ｋ 35/74 Ａ ４Ｈ０２５ 35/74 Ａ６１Ｐ 39/06 Ａ６１Ｐ 39/06 Ａ２３Ｌ 2/00 Ｆ Ｆターム(参考） 2B150 AC05 AC06 DD12 DD26 4B001 AC31 BC14 EC05 4B017 LC03 LK18 LK21 4B018 LB07 MD86 ME06 MF13 4C087 AA01 AA02 AA03 BB39 BC56 CA09 CA10 MA35 MA36 MA37 MA41 MA43 MA52 NA14 ZC37 4H025 BA00 ─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 7 Identification code FI theme code (reference) A61K 35/20 A61K 35/74 A 4H025 35/74 A61P 39/06 A61P 39/06 A23L 2/00 F F Term (reference) 2B150 AC05 AC06 DD12 DD26 4B001 AC31 BC14 EC05 4B017 LC03 LK18 LK21 4B018 LB07 MD86 ME06 MF13 4C087 AA01 AA02 AA03 BB39 BC56 CA09 CA10 MA35 MA36 MA37 MA41 MA43 MA52 NA14 ZC37 4H025 BA00
Claims (5)
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抗酸化剤。1. Lactobacillus Lactobacillus
A antioxidant obtained by culturing a lactic acid bacterium belonging to gasseri ) and / or containing a bacterial cell as an active ingredient.
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
る請求項１記載の抗酸化剤。2. Lactobacillus
lactic acid bacteria belonging to gasseri) is an antioxidant according to claim 1, wherein the Lactobacillus gasseri (Lactobacillus gasseri) with human intestinal fixability.
gasseri)に属する乳酸菌を培養して得られる培養物が醗
酵乳である、請求項１又は２記載の抗酸化剤。3. Lactobacillus Lactobacillus
The antioxidant according to claim 1 or 2, wherein the culture obtained by culturing a lactic acid bacterium belonging to gasseri ) is fermented milk.
gasseri)に属する乳酸菌がラクトバチルス・ガセリ（La
ctobacillus gasseri)・SBT2055（以下LG2055という）
（FERM P-15535）である請求項１〜３のいずれかに記載
の抗酸化剤。4. Lactobacillus Lactobacillus
Lactobacillus belonging to gasseri is Lactobacillus gasseri ( La
ctobacillus gasseri ) ・ SBT2055 (hereinafter referred to as LG2055)
(FERM P-15535), The antioxidant according to any one of claims 1 to 3.
s 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抗酸化作用を有する飲食品又
は飼料。5. Lactobacillu ( Lactobacillu)
s gasseri ) cultivated lactic acid bacteria, and / or foods and drinks or feed having an antioxidant effect, to which cultures and / or bacterial cells have been added.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002054730A JP4119656B2 (en) | 2002-02-28 | 2002-02-28 | Antioxidant |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002054730A JP4119656B2 (en) | 2002-02-28 | 2002-02-28 | Antioxidant |
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| Publication Number | Publication Date |
|---|---|
| JP2003253262A true JP2003253262A (en) | 2003-09-10 |
| JP4119656B2 JP4119656B2 (en) | 2008-07-16 |
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ID=28665807
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002054730A Expired - Fee Related JP4119656B2 (en) | 2002-02-28 | 2002-02-28 | Antioxidant |
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| Country | Link |
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| JP (1) | JP4119656B2 (en) |
Cited By (12)
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| WO2004089109A1 (en) * | 2003-04-08 | 2004-10-21 | Meiji Feed Co., Ltd. | Feed composition |
| WO2006093022A1 (en) * | 2005-03-03 | 2006-09-08 | Meiji Dairies Corporation | Immune function modulating agent |
| JP2006271219A (en) * | 2005-03-28 | 2006-10-12 | Yonezawa Biru System Service:Kk | Cultured microorganism obtained from medium consisting mainly of green tea and black tea and product using the same |
| KR100801556B1 (en) | 2005-04-04 | 2008-02-11 | 대한민국 | 312Antioxidant Lactobacillus gasseri NLRI 312 |
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| WO2011105403A1 (en) * | 2010-02-26 | 2011-09-01 | コンビ株式会社 | Composition having bedsore-relieving effect |
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