JP2008063289A - Promoter of increase in adiponectin level in blood and/or reduction inhibitor - Google Patents

Promoter of increase in adiponectin level in blood and/or reduction inhibitor Download PDF

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JP2008063289A
JP2008063289A JP2006244377A JP2006244377A JP2008063289A JP 2008063289 A JP2008063289 A JP 2008063289A JP 2006244377 A JP2006244377 A JP 2006244377A JP 2006244377 A JP2006244377 A JP 2006244377A JP 2008063289 A JP2008063289 A JP 2008063289A
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lactobacillus
blood
lactic acid
increase
adiponectin concentration
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JP5229977B2 (en
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Hiroshi Kawakami
浩 川上
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Snow Brand Milk Products Co Ltd
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Snow Brand Milk Products Co Ltd
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Priority to NZ575469A priority patent/NZ575469A/en
Priority to KR1020097005375A priority patent/KR101492650B1/en
Priority to EP07805787.4A priority patent/EP2062587A4/en
Priority to AU2007292786A priority patent/AU2007292786B2/en
Priority to US12/439,728 priority patent/US20100021444A1/en
Priority to CN2007800327825A priority patent/CN101678051B/en
Priority to NZ597178A priority patent/NZ597178A/en
Priority to PCT/JP2007/000932 priority patent/WO2008029505A1/en
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an increase promoter and/or a reduction inhibitor of adiponectin level in blood and a food and drink and a feed for promoting an increase and/or inhibiting a reduction in the adiponectin level in blood. <P>SOLUTION: The increase promoter and/or reduction inhibitor of the adiponectin level in blood comprise a cultured product of a lactic acid bacterium of the genus Lactobacillus, above all, Lactobacillus gasseri and Lactobacillus helveticus or a bacterial cell itself thereof as an active ingredient. The food and drink and feed for promoting the increase and/or inhibiting the reduction in the adiponectin level in blood comprise the cultured product of the lactic acid bacterium of the genus Lactobacillus and/or bacterial cell thereof as the active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

本発明は、ラクトバチラス(Lactobacillus)属乳酸菌、その中でも特にラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制剤、血中アディポネクチン濃度増加促進及び/又は減少抑制作用を賦与した新規な飲食品、及び、血中アディポネクチン濃度増加促進及び/又は減少抑制作用を賦与した新規な飼料に関する。本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤は、摂取することで血中アディポネクチン濃度の増加を促進及び/又は減少を抑制することができる。血中アディポネクチン濃度の低下は、血栓症、インスリン抵抗性、糖代謝異常、高血圧など、将来的な循環器系疾患の発症に関連するといわれているメタボリックシンドロームの原因とされており、本発明はその予防・治療に有効である。   The present invention relates to the promotion of an increase in the concentration of adiponectin in the blood comprising, as an active ingredient, a Lactobacillus gasseri or Lactobacillus helveticus culture and / or cell body, among others, Lactobacillus lactic acid bacteria. The present invention relates to a reduction inhibitor, a novel food / beverage product imparted with a blood adiponectin concentration increase promotion and / or a decrease suppression effect, and a novel feed that imparted a blood adiponectin concentration increase promotion and / or a decrease suppression effect. The blood adiponectin concentration increase promoting and / or decreasing inhibitor of the present invention can promote and / or suppress the increase of blood adiponectin concentration by ingestion. The decrease in blood adiponectin concentration is considered to be the cause of metabolic syndrome that is said to be related to the development of future cardiovascular diseases such as thrombosis, insulin resistance, abnormal glucose metabolism, and hypertension. Effective for prevention and treatment.

近年、生活習慣の欧米化に伴い、生活習慣病である糖尿病、高血圧、高脂血症、動脈硬化症といった病態を呈する人口が増加している。特に、心血管疾患と脳血管疾患による死亡は死因の約3分の1を占めており、その数が年々増加していることから、この対策は大きな課題となっている。これら動脈硬化性疾患は、高血圧、高脂血症、耐糖能障害などのリスク因子の集積によって、発症の危険度が著しく上昇する。このリスク因子が集積した状態はメタボリックシンドロームと呼ばれ、広く認識されてきている。日本の企業労働者12万人の調査では、軽症であっても「肥満」、「高血圧」、「高血糖」、「高トリグリセリド(中性脂肪)血症」、又は「高コレステロール血症」の危険因子を1つ持つ人は心臓病の発症リスクが5倍、2つ持つ人は10倍、3〜4つ併せ持つ人では31倍にもなるといわれている。また、厚生労働省の調査では、高血圧患者数は3,900万人、高脂血症は2,200万人、糖尿病(予備軍を含め)は1,620万人、肥満症は468万人と報告されており、これらの患者は年々増加している。   In recent years, with the shift of lifestyle habits to Europe and the United States, the population exhibiting pathological conditions such as diabetes, hypertension, hyperlipidemia, and arteriosclerosis, which are lifestyle-related diseases, is increasing. In particular, deaths due to cardiovascular and cerebrovascular diseases account for about one-third of the causes of death, and the number of deaths is increasing year by year. These arteriosclerotic diseases are significantly increased in risk of onset due to accumulation of risk factors such as hypertension, hyperlipidemia and impaired glucose tolerance. This state of accumulation of risk factors is called metabolic syndrome and has been widely recognized. According to a survey of 120,000 Japanese corporate workers, “obesity”, “hypertension”, “hyperglycemia”, “high triglyceride (triglyceridemia)” or “hypercholesterolemia” People who have one risk factor are said to be five times as likely to develop heart disease, people who have two have 10 times the risk, and people who have three or four have 31 times the risk. According to a survey by the Ministry of Health, Labor and Welfare, the number of hypertensive patients was 39 million, hyperlipidemia was 22 million, diabetes (including the reserve army) was 16.2 million, and obesity was 4.68 million. The number of patients is increasing year by year.

メタボリックシンドロームとは、「内臓脂肪の蓄積と、それを基盤にしたインスリン抵抗性及び糖代謝異常、脂質代謝異常、高血圧を複数合併するマルチプルリスクファクター症候群で、動脈硬化になりやすい病態」であり、内臓脂肪の蓄積にともなう血中アディポネクチン濃度の低下は、まさしくメタボリックシンドロームや動脈硬化の根本的な要因である。生体最大の分泌組織である脂肪組織は、種々の内分泌因子を産生し、生体における恒常性の維持に関わっている。しかし、内臓脂肪の過剰な蓄積は、内分泌因子の分泌バランスを崩し、種々の病態を引き起こすことが分ってきた。特に、プラスミノーゲンアクチベーターインヒビター(PAI-1)、腫瘍壊死因子(TNF-α)、レプチンなどの内分泌因子は、内臓脂肪の蓄積に伴って分泌量が増加し、血栓症、インスリン抵抗性、糖代謝異常、高血圧などを引き起こす。一方、脂肪組織が特異的に分泌するアディポネクチンは通常血中に高濃度で存在するが、内臓脂肪の蓄積に伴い、その濃度が減少することが知られている。アディポネクチンは、抗糖尿病、抗動脈硬化、抗炎症作用、抗高血圧など様々な生理機能を持つことが知られており、血中において、アディポネクチン濃度の増加を促進すること、もしくはアディポネクチン濃度の減少を抑制することは、メタボリックシンドロームの予防・治療において非常に重要である。   Metabolic syndrome is `` a pathological condition that tends to cause arteriosclerosis in multiple risk factor syndrome, which is a combination of insulin resistance and glucose metabolism abnormality, lipid metabolism abnormality, hypertension based on the accumulation of visceral fat, and on the basis of it. '' The decrease in blood adiponectin concentration associated with the accumulation of visceral fat is a fundamental factor in metabolic syndrome and arteriosclerosis. Adipose tissue, the largest secretory tissue in the living body, produces various endocrine factors and is involved in maintaining homeostasis in the living body. However, it has been found that excessive accumulation of visceral fat disrupts the secretion balance of endocrine factors and causes various pathological conditions. In particular, endocrine factors such as plasminogen activator inhibitor (PAI-1), tumor necrosis factor (TNF-α), and leptin increase in secretion amount as visceral fat accumulates, resulting in thrombosis, insulin resistance, Causes abnormal glucose metabolism, high blood pressure, etc. On the other hand, adiponectin, which is secreted specifically by adipose tissue, is usually present in a high concentration in the blood, but it is known that its concentration decreases with the accumulation of visceral fat. Adiponectin is known to have various physiological functions such as anti-diabetes, anti-arteriosclerosis, anti-inflammatory action, and anti-hypertension, and promotes increase of adiponectin concentration or suppresses decrease of adiponectin concentration in blood It is very important to prevent and treat metabolic syndrome.

従来、メタボリックシンドロームの個々の病態への対策としては薬物療法も行われているが、処方が必要なことや副作用を伴うことなどが問題となっている。さらに、一つの病態に対する治療を行っても、その他の病態がきっかけとなって重篤な病態へと発展することが分っており、これらの状態の上流に存在する脂肪細胞由来の内分泌因子の分泌バランスを整えることが必要となってくる。このため、内臓脂肪の蓄積に起因するメタボリックシンドロームの予防・治療には、薬物療法よりも運動療法や食事療法など日々の生活を見直すことがより重要とされている。そこで、日常的に摂取でき、長期にわたって摂取しても安全性の高い、内臓脂肪の蓄積に起因するメタボリックシンドロームの予防・治療に有効な飲食品が望まれている。   Conventionally, pharmacotherapy is also used as a countermeasure for individual pathological conditions of metabolic syndrome, but there are problems such as the need for prescription and side effects. Furthermore, it has been found that even if treatment for one pathological condition is performed, other pathological conditions lead to development of serious pathological conditions, and endocrine factors derived from adipocytes existing upstream of these conditions It becomes necessary to adjust the secretion balance. For this reason, reviewing daily life such as exercise therapy and diet therapy is more important than drug therapy for the prevention and treatment of metabolic syndrome caused by visceral fat accumulation. Therefore, a food and drink that can be ingested on a daily basis and is highly safe even when ingested over a long period of time and effective for the prevention and treatment of metabolic syndrome caused by the accumulation of visceral fat is desired.

血中において、アディポネクチン濃度の増加を促進する物質についてはりんご抽出物(例えば、特許文献1参照。)、ホップ苞抽出物(例えば、特許文献2参照。)、緑茶カテキン(例えば、特許文献3参照。)、米ぬか抽出物(例えば、特許文献4参照。)、ウコン根茎抽出物(例えば、特許文献5参照。)など植物由来の抽出物が多く開示されている。しかし、これらは抽出条件が複雑なものもあり、また抽出原料の入手に制約があるものもあり、製剤や飲食品配合原料としての安定な供給に懸念がある。菌の培養物や菌体自体がアディポネクチン濃度の増加を促進及び/又は減少を抑制する効果があることについては知られていない。   For substances that promote the increase in adiponectin concentration in blood, apple extract (see, for example, Patent Document 1), hop koji extract (for example, see Patent Document 2), green tea catechin (see, for example, Patent Document 3). ), Rice bran extract (for example, see Patent Document 4), and turmeric rhizome extract (for example, see Patent Document 5), many plant-derived extracts are disclosed. However, some of these have complicated extraction conditions, and some have restrictions on the availability of extraction raw materials, and there is a concern about stable supply as a formulation or a food and beverage blending raw material. It is not known that the culture of bacteria or the cells themselves have an effect of promoting an increase in adiponectin concentration and / or suppressing a decrease.

ラクトバチラス・ガセリ(Lactobacillus gasseri)には、病原体感染防御作用(例えば、特許文献6参照。)、炎症性腸疾患及び過敏性腸症候群予防作用(例えば、特許文献7参照。)、糖尿病合併症予防作用(例えば、特許文献8参照。)、血清コレステロール上昇抑制作用(例えば、特許文献9参照。)、骨吸収抑制作用(例えば、特許文献10参照。)、免疫増強作用(例えば、特許文献11参照。)などが知られている。しかしながら、ラクトバチラス・ガセリ(Lactobacillus gasseri)の発酵物、あるいはその菌体自体が、血中アディポネクチン濃度増加促進作用及び減少抑制作用を有することは全く知られていない。   Lactobacillus gasseri has a pathogen infection protective action (for example, see Patent Document 6), an inflammatory bowel disease and irritable bowel syndrome preventive action (for example, Patent Document 7), and a diabetic complication preventive action. (See, for example, Patent Document 8), serum cholesterol elevation-inhibiting action (for example, see Patent Document 9), bone resorption-inhibiting action (for example, see Patent Document 10), immune enhancing action (for example, see Patent Document 11). ) Etc. are known. However, it is not known at all that the fermented product of Lactobacillus gasseri, or the microbial cell itself, has a blood adiponectin concentration increase promoting action and a decrease suppressing action.

ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)は、古くから代表的な酪農乳製品用乳酸菌スターターとして用いられている。ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)は強い蛋白分解活性を有し、特に高い活性を有する菌体外プロティナーゼは、乳の発酵性に対して重要な働きをする。即ち、菌体外プロティナーゼは乳蛋白質を分解し各種のペプチド断片を生成する。生成されたペプチドはペプチダーゼ群の作用を受けて、さらに低分子のペプチドになる。蛋白質分解酵素群の作用により培地中に生成したペプチドの一部は、乳酸菌の菌体内へ取り込まれて、窒素源として利用されることが知られている。一方、培地中に生成したペプチドには、血圧上昇作用の原因物質であるアンギオテンシン変換酵素(Angiotensin Converting Enzyme、以下ACEと称す)に対して阻害活性を有するものが存在することが報告されている(例えば、非特許文献1参照。)。ACEの酵素活性を阻害し、血圧上昇を抑制することを目的としたペプチドについては、既に乳蛋白質、大豆蛋白質あるいは魚肉蛋白質分解物等から、多くの有効ペプチドが報告されているが、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)を使用した発酵乳中のACE阻害活性を有するペプチドは、Val-Pro-ProとIle-Pro-Proであること、さらにこれらラクトトリペプチドは強い血圧降下作用を有することが自然発症高血圧ラット(SHR)を用いた実験により確認されている(例えば、非特許文献2参照。)。さらに、ラクトトリペプチドは、血圧降下活性に加え、ストレス緩和作用を有することが示唆されている(例えば、特許文献12、13参照。)。また、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)には、免疫賦活作用のあることが知られている(例えば、特許文献14参照。)。しかしながら、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の発酵物、あるいはその菌体自体が、血中アディポネクチン濃度増加促進作用及び減少抑制作用を有することは全く知られていない。
特開2006-193502号公報 特開2006-193501号公報 特開2006-131512号公報 特開2005-68132号公報 特開2005-60308号公報 特開平8-268899号公報 特開2003-95963号公報 特開2003-252770号公報 特開2003-306436号公報 特開2004-315477号公報 特開2006-69993号公報 特開平10-45610号公報 特開平11-98978号公報 特開2006-76961号公報 J. Dairy Sci., 78:777-783(1995) J. Dairy Sci., 78:1253-1257(1995)
Lactobacillus helveticus (Lactobacillus helveticus) has long been used as a typical lactic acid bacteria starter for dairy dairy products. Lactobacillus helveticus has a strong proteolytic activity, and an extracellular proteinase having a particularly high activity plays an important role on the fermentability of milk. That is, extracellular proteinase degrades milk protein to produce various peptide fragments. The generated peptide is subjected to the action of the peptidase group to become a peptide having a lower molecular weight. It is known that a part of the peptide produced in the medium by the action of the proteolytic enzyme group is taken into the lactic acid bacteria and used as a nitrogen source. On the other hand, it has been reported that peptides produced in the medium have an inhibitory activity against angiotensin converting enzyme (hereinafter referred to as ACE), which is a causative substance of blood pressure raising action ( For example, refer nonpatent literature 1.). As for peptides aimed at inhibiting the enzyme activity of ACE and suppressing the increase in blood pressure, many effective peptides have already been reported from milk protein, soybean protein, fish protein degradation products, etc., but Lactobacillus helvetica It is natural that peptides having ACE inhibitory activity in fermented milk using Lactobacillus helveticus are Val-Pro-Pro and Ile-Pro-Pro, and that these lactotripeptides have a strong antihypertensive action. It has been confirmed by experiments using onset hypertensive rats (SHR) (see, for example, Non-Patent Document 2). Furthermore, it has been suggested that lactotripeptide has a stress relieving action in addition to blood pressure lowering activity (see, for example, Patent Documents 12 and 13). Lactobacillus helveticus is known to have an immunostimulatory effect (see, for example, Patent Document 14). However, it is not known at all that the fermented product of Lactobacillus helveticus, or the fungus body itself, has a blood adiponectin concentration increase promoting action and a decrease suppressing action.
JP 2006-193502 A JP 2006-193501 A JP 2006-131512 A JP 2005-68132 A JP 2005-60308 A JP-A-8-268899 JP 2003-95963 A Japanese Patent Laid-Open No. 2003-252770 Japanese Patent Laid-Open No. 2003-306436 Japanese Patent Laid-Open No. 2004-315477 JP 2006-69993 A Japanese Patent Laid-Open No. 10-45610 Japanese Patent Laid-Open No. 11-98978 JP 2006-76961 A J. Dairy Sci., 78: 777-783 (1995) J. Dairy Sci., 78: 1253-1257 (1995)

本発明は、日常的な摂取が可能であり、なおかつ摂取することで、血中アディポネクチン濃度の増加を促進及び/又は減少を抑制する、メタボリックシンドロームの予防・治療に有効な血中アディポネクチン濃度増加促進及び/又は減少抑制剤、これらの機能を賦与した飲食品及び飼料を提供することを課題とする。   The present invention can be taken daily and promotes an increase in blood adiponectin concentration effective for prevention and treatment of metabolic syndrome that promotes and / or suppresses an increase in blood adiponectin concentration. An object of the present invention is to provide a decrease inhibitor, a food and drink and a feed provided with these functions.

本発明者らは、乳成分の中から血液中の濃度が低下すると循環器系疾患のリスクが高まるといわれているアディポネクチンの濃度を低下させない成分の探索を鋭意進めてきた。その結果、ラクトバチラス(Lactobacillus)属乳酸菌、その中でも特にラクトバチラス・ガセリ(Lactobacillus gasseri)及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の培養物、あるいは菌体自体が、極めて高い血中アディポネクチン濃度増加促進及び/又は減少抑制作用を有することを見出し、本発明を完成させるに至った。   The present inventors have been diligently searching for a component that does not decrease the concentration of adiponectin, which is said to increase the risk of cardiovascular disease when the concentration in the blood is reduced from among the milk components. As a result, Lactobacillus genus lactic acid bacteria, in particular, Lactobacillus gasseri and Lactobacillus helveticus cultures, or the cells themselves, have a very high blood adiponectin concentration increase promotion and / or It has been found that it has a decrease-inhibiting action, and the present invention has been completed.

したがって、本発明は、下記の構成からなる発明である。
(1)ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制剤。
(2)ラクトバチラス(Lactobacillus)属乳酸菌が、ラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)である(1)記載の血中アディポネクチン濃度増加促進及び/又は減少抑制剤。
(3)ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制用飲食品。
(4)ラクトバチラス(Lactobacillus)属乳酸菌が、ラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)である(3)記載の血中アディポネクチン濃度増加促進及び/又は減少抑制用飲食品。
(5)ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制用飼料。
(6)ラクトバチラス(Lactobacillus)属乳酸菌が、ラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)である(5)記載の血中アディポネクチン濃度増加促進及び/又は減少抑制用飼料。
Accordingly, the present invention is an invention having the following configuration.
(1) A blood adiponectin concentration increase promoter and / or a decrease inhibitor comprising a culture of Lactobacillus lactic acid bacteria and / or bacterial cells as an active ingredient.
(2) Lactobacillus lactic acid bacteria are Lactobacillus gasseri or Lactobacillus helveticus, (1) The blood adiponectin concentration increase promotion and / or decrease inhibitor.
(3) A food / beverage product for promoting and / or suppressing decrease in blood adiponectin concentration, comprising a culture of Lactobacillus genus lactic acid bacteria and / or bacterial cells as an active ingredient.
(4) Lactobacillus lactic acid bacterium is Lactobacillus gasseri or Lactobacillus helveticus, (3) The blood adiponectin concentration increase promotion and / or decrease suppression food / beverage products.
(5) A feed for promoting and / or suppressing decrease in blood adiponectin concentration, comprising a culture of Lactobacillus genus lactic acid bacteria and / or bacterial cells as active ingredients.
(6) Lactobacillus lactic acid bacteria is Lactobacillus gasseri or Lactobacillus helveticus, (5) The blood adiponectin concentration increase promotion and / or decrease suppression feed.

本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤、及び血中アディポネクチン濃度増加促進及び/又は減少抑制作用を賦与した飲食品、飼料は、血中アディポネクチンの低下により発症するといわれるメタボリックシンドロームの予防・治療に有効である。また、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤、及び血中アディポネクチン濃度増加促進及び/又は減少抑制作用を賦与した飲食品、飼料は、ラクトバチラス(Lactobacillus)属乳酸菌、その中でも特にラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の培養物、あるいはその菌体自体を使用するので、比較的安価に大量供給が可能であり、なおかつ極めて安全性が高いという特徴を有している。   The blood adiponectin concentration increase promoting and / or decreasing inhibitor of the present invention, and the food and drink and feed imparted with the blood adiponectin concentration increasing promoting and / or decreasing suppressing action are said to be metabolic syndrome, which is said to develop due to a decrease in blood adiponectin It is effective for prevention and treatment. Further, the blood adiponectin concentration increase promoting and / or decreasing inhibitor of the present invention, and the food and drink and the feed imparted with the blood adiponectin concentration increasing promotion and / or decrease inhibiting action are Lactobacillus lactic acid bacteria, among others Lactobacillus gasseri (Lactobacillus helveticus) culture, or its cell itself is used, so it can be supplied in large quantities at a relatively low cost and is extremely safe. Have.

本発明者らは、発酵乳やヒト由来の数多くの乳酸菌のうち、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、食品に適用した際に生残性が高く、香味、物性も優れている菌株の選定を進めてきた。次に、ヒト腸管へ高い定着性を示す乳酸菌の中で、血中アディポネクチン濃度増加促進及び/又は減少抑制するという条件を設定して選定を進め、ラクトバチラス(Lactobacillus)属乳酸菌、その中でもラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)に属する乳酸菌が、血中アディポネクチン濃度増加促進、及び/又は減少抑制効果を有することを見出した。上記の条件に合致する菌株として、ラクトバチラス・ガセリに属する乳酸菌のうち、ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055株、ラクトバチラス・ガセリ(Lactobacillus gasseri)JCM1131株、およびラクトバチラス・ガセリ(Lactobacillus gasseri)ATCC19992株を選択することができた。なお、SBT2055株は、寄託番号FERM P-15535として、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。また、JCM1131株は独立行政法人理化学研究所の公開菌株、ATCC19992株はAmerican Type Culture Collectionの公開菌株である。   Among the many lactic acid bacteria derived from fermented milk and humans, the present inventors have high gastric acid tolerance, good growth under low pH conditions, high human intestinal cell affinity and high human intestinal tract affinity. The selection of strains that are resistant to bile acids, colonize in the intestinal tract, have high survival when applied to foods, and have excellent flavor and physical properties has been promoted. Next, among the lactic acid bacteria showing high colonization in the human intestinal tract, the selection is made under the condition of promoting and / or suppressing the decrease of blood adiponectin concentration, and the lactic acid bacteria belonging to the genus Lactobacillus, especially Lactobacillus gasseri It has been found that lactic acid bacteria belonging to (Lactobacillus gasseri) or Lactobacillus helveticus have a blood adiponectin concentration increase promotion and / or a decrease suppression effect. Lactobacillus gasseri SBT2055 strain, Lactobacillus gasseri JCM1131 strain, and Lactobacillus gasseri ATCC19992 strain are selected from lactic acid bacteria belonging to Lactobacillus gaselli as strains meeting the above conditions We were able to. The SBT2055 strain has been deposited at the National Institute of Advanced Industrial Science and Technology Patent Microorganism Deposit Center under the deposit number FERM P-15535. The JCM1131 strain is a public strain of RIKEN, and the ATCC19992 strain is a public strain of the American Type Culture Collection.

また、先の条件に合致する菌株として、ラクトバチラス・ヘルベチカスに属する乳酸菌のうち、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)SBT2171株、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)ATCC10386株およびラクトバチラス・ヘルベチカス(Lactobacillus helveticus)ATCC10797株を選択することができた。この場合、生菌及び死菌のいずれにおいても本発明による効果を期待できた。なお、SBT2171株は、寄託番号FERM P-14381として、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。また、ATCC10386株及びATCC10797株はAmerican Type Culture Collectionの公開菌株である。   Moreover, among the lactic acid bacteria belonging to Lactobacillus helveticus as strains meeting the above conditions, Lactobacillus helveticus (Lactobacillus helveticus) SBT2171 strain, Lactobacillus helveticus (Lactobacillus helveticus) ATCC10386 strain and Lactobacillus helveticus (Lactobacillus helveticus) ) The ATCC10797 strain could be selected. In this case, the effects of the present invention could be expected for both live and dead bacteria. The SBT2171 strain has been deposited at the National Institute of Advanced Industrial Science and Technology Patent Microorganism Deposit Center under the deposit number FERM P-14381. The ATCC 10386 strain and ATCC 10797 strain are public strains of the American Type Culture Collection.

特に、ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055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、また、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、血中アディポネクチン濃度増加促進、及び/又は減少抑制効果を有する活性が高い。体外から投与したラクトバチラス・ガセリ(Lactobacillus gasseri)に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初めて明らかにされた。さらに本発明では、上記の菌株に限らずヒトや発酵乳から分離されるラクトバチラス・ガセリ(Lactobacillus gasseri)であっても、生菌のみならず死菌体であっても、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。また、ラクトバチラス・ガセリ(Lactobacillus gasseri)の変異株であって、上記の作用を示すものも使用することができる。本発明のラクトバチラス・ガセリ(Lactobacillus gasseri)の培地には、乳培地又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。   In particular, Lactobacillus gasseri strain SBT2055 has a high affinity for human intestinal cells, and can survive and reach the intestinal tract when administered orally. It has a high activity that acts on the host by growing in the intestinal tract and has an effect of promoting an increase in blood adiponectin concentration and / or a decrease in decrease. Lactobacillus gasseri (Lactobacillus gasseri) administered from outside the body has been established in the intestine and exhibits no such physiological effect, and has been revealed for the first time by the present inventors. Furthermore, in the present invention, not only the above-mentioned strains but also Lactobacillus gasseri isolated from humans and fermented milk, and not only live bacteria but also dead cells, exhibit the above action Any one can be used. In addition, a mutant strain of Lactobacillus gasseri that exhibits the above action can also be used. As the Lactobacillus gasseri medium of the present invention, various media such as a milk medium or a medium containing a milk component, and a semi-synthetic medium not containing this can be used. An example of such a medium is a reduced skim milk medium obtained by reducing skim milk and then heat sterilizing.

これらラクトバチラス属乳酸菌の培養法は、静置培養又は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。菌体は、乳酸菌培養の常法に従って培養し、得られた培養物から遠心分離等の集菌手段によって分離されたものをそのまま本発明の有効成分として用いることができる。また、菌体として純粋に分離された菌体だけでなく、培養物、発酵物、懸濁物、その他の菌体含有物や、菌体を酵素や物理的手段を用いて処理した細胞質や細胞壁画分も用いることができる。   These Lactobacillus lactic acid bacteria are cultured by static culture or neutralized culture with a constant pH, but the culture method is not particularly limited as long as the bacteria grow well. Bacteria are cultured according to a conventional method for lactic acid bacteria culture, and those isolated from the obtained culture by means of collection such as centrifugation can be used as they are as the active ingredient of the present invention. In addition to cells that have been purely isolated as cells, cultures, fermented products, suspensions, other cell-containing materials, and cytoplasm and cells that have been processed using enzymes or physical means Wall fractions can also be used.

本発明の血中アディポネクチン濃度増加促進、及び/又は減少抑制剤は、ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又はその菌体自体を有効成分としたものである。さらに、製剤化に際しては製剤上許可されている賦形剤、安定剤、矯味剤等を適宜混合して濃縮、凍結乾燥するほか、加熱乾燥して死菌体にしてもよい。これらの乾燥物、濃縮物、ペースト状物も包含される。また、菌体や培養物の作用を妨げない範囲で、賦型剤、結合剤、崩壊剤、滑沢剤、矯味矯臭剤、懸濁剤、コーティング剤、その他の任意の薬剤を混合して製剤化することもできる。剤形としては、錠剤、丸剤、カプセル剤、顆粒剤、散剤、粉剤、シロップ剤等が可能であり、これらを経口的に投与することが望ましい。   The blood adiponectin concentration increase promoting and / or decreasing inhibitor of the present invention comprises a culture of Lactobacillus lactic acid bacteria and / or the cells themselves as active ingredients. Furthermore, in formulating, excipients, stabilizers, flavoring agents, and the like that are permitted in the formulation are appropriately mixed and concentrated, freeze-dried, or heat-dried to form dead cells. These dried products, concentrates, and pastes are also included. In addition, it is formulated by mixing excipients, binders, disintegrants, lubricants, flavoring agents, suspending agents, coating agents, and other optional agents as long as they do not interfere with the action of the cells or culture. It can also be converted. The dosage form can be tablets, pills, capsules, granules, powders, powders, syrups, etc., and these are preferably administered orally.

また、本発明は、ラクトバチラス(Lactobacillus)属乳酸菌、その中でもラクトバチラス・ガセリ(Lactobacillus gasseri)及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の発酵物、あるいはその菌体自体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制の機能を賦与した飲食品である。本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制作用を賦与した飲食品としては、ラクトバチラス(Lactobacillus)属乳酸菌、その中でもラクトバチラス・ガセリ(Lactobacillus gasseri)及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の培養物又は発酵物、あるいはその菌体自体であっても良いし、菌体や培養物又は発酵物自体を配合した飲食品としても良い。培養物又は発酵物の形態としてヨーグルトやチーズなどの発酵食品が好適である。菌体や培養物又は発酵物は、どのような飲食品に配合しても良く、飲食品の製造工程中に原料に添加しても良い。飲食品の例として、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。また、各種粉乳の他、乳児、幼児及び低出生体重児等を対象とする栄養組成物に配合したものを例示することができる。生菌体として利用する場合には、ラクトバチラス(Lactobacillus)属乳酸菌、その中でもラクトバチラス・ガセリ(Lactobacillus gasseri)及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の菌株自体、および上記乳酸菌の菌体を発酵して得られた発酵乳やチーズを素材として使用し、血中アディポネクチン濃度増加促進及び/又は減少抑制用のパンやスナック菓子、ケーキ、プリン等にしてもよい。これらは日常的に摂取することが可能であり、血中アディポネクチン濃度増加促進及び/又は減少抑制作用を有するので、血中アディポネクチンの低下を原因とするメタボリックシンドロームの予防・治療に有効である。
さらに、本発明は、ラクトバチラス(Lactobacillus)属乳酸菌、その中でもラクトバチラス・ガセリ(Lactobacillus gasseri)及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の発酵物、あるいはその菌体自体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制の機能を賦与した飼料である。家畜用飼料として、前記飲食品と同様に、菌体や培養物又は発酵物は、どのような飼料に配合しても良く、飲食品の製造工程中に原料に添加しても良い。
In addition, the present invention provides an increased concentration of adiponectin in the blood containing, as an active ingredient, a lactobacillus genus lactic acid bacterium, in particular, a fermented product of Lactobacillus gasseri and Lactobacillus helveticus, or the cell itself. It is the food / beverage product which provided the function of promotion and / or reduction suppression. The food and drink provided with the blood adiponectin concentration increase accelerating and / or suppressing effect of the present invention include lactic acid bacteria belonging to the genus Lactobacillus, among others, Lactobacillus gasseri and Lactobacillus helveticus (Lactobacillus helveticus). Product or fermented product, or the microbial cell itself, or a food or drink containing the microbial cell, culture, or fermented product itself. Fermented foods such as yogurt and cheese are suitable as the form of the culture or fermented product. The microbial cells, culture or fermented product may be blended in any food or drink, and may be added to the raw material during the production process of the food or drink. Examples of foods and drinks include milk drinks, fermented milk, fruit juice drinks, jelly, candy, dairy products, processed egg products such as mayonnaise, and foods such as confectionery and breads such as butter cake. Moreover, what was mix | blended with the nutritional composition intended for infants, an infant, a low birth weight infant, etc. other than various milk powder can be illustrated. When used as a living cell, it is obtained by fermenting a Lactobacillus genus lactic acid bacterium, in particular, a Lactobacillus gasseri and Lactobacillus helveticus strain itself, and the lactic acid bacterium. The obtained fermented milk or cheese may be used as a raw material to make bread, snacks, cakes, puddings, etc. for promoting and / or suppressing decrease in blood adiponectin concentration. These can be ingested on a daily basis and have the effect of promoting the increase in blood adiponectin concentration and / or suppressing the decrease in blood adiponectin, and thus are effective in the prevention and treatment of metabolic syndrome caused by a decrease in blood adiponectin.
Furthermore, the present invention provides an increase in the concentration of adiponectin in the blood comprising as an active ingredient a lactic acid bacterium belonging to the genus Lactobacillus, in particular, a fermented product of Lactobacillus gasseri and Lactobacillus helveticus, or the cell itself. It is a feed provided with a function of promoting and / or suppressing decrease. As a feed for livestock, as in the case of the above-mentioned food and drink, the fungus body, culture or fermented product may be blended in any feed, and may be added to the raw material during the production process of the food or drink.

本発明において、血中アディポネクチン濃度増加促進及び/又は減少抑制作用を発揮させるためには、成人の場合、ラクトバチラス・ガセリ(Lactobacillus gasseri)及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の培養物を10〜200g、あるいはその菌体自体を1日当たり0.1〜 5,000mg摂取できるように配合量等を調整すれば良い。乳酸菌の含有割合は特に限定されず、製造の容易性や好ましい一日投与量等に合わせて適宜調節すれば良い。例えば剤型が液体の場合には、1×105cells/ml〜1×1010cells/mlとすることが好ましく、固体の場合には、1×105cells/g〜1×1010cells/gとすることが好ましい。生菌として投与する場合は、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, 10 to 200 g of a culture of Lactobacillus gasseri and Lactobacillus helveticus is used in the case of an adult in order to exert a blood adiponectin concentration increase promoting and / or suppressing effect. Alternatively, the blending amount and the like may be adjusted so that 0.1 to 5,000 mg of the cells per day can be ingested. The content ratio of lactic acid bacteria is not particularly limited, and may be appropriately adjusted in accordance with ease of production, a preferable daily dose, and the like. For example, when the dosage form is liquid, it is preferably 1 × 10 5 cells / ml to 1 × 10 10 cells / ml, and when solid, 1 × 10 5 cells / g to 1 × 10 10 cells / g is preferable. When administered as a living bacterium, the intended effect of the present invention can be exhibited by administering 10 8 to 10 12 cfu / day per adult. By taking in this way, it settles in the intestinal tract and exhibits the desired effect.

これらの血中アディポネクチン濃度増加促進及び/又は減少抑制剤、あるいは血中アディポネクチン濃度増加促進及び/又は減少抑制用飲食品、飼料は、血中アディポネクチン濃度の増加促進及び/又は減少抑制効果を有するので、前述した血中アディポネクチン濃度の低下により引き起こされるさまざまな病態の予防、治療、改善に非常に有益となり得る。
本発明で用いる乳酸菌菌体は、古来、発酵乳やチーズの製造に用いられており、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤、あるいは血中アディポネクチン濃度増加促進及び/又は減少抑制用飲食品、飼料は安全性に問題はないという特徴がある。
以下に、実施例及び試験例を示し、本発明についてより詳細に説明するが、これらは単に例示するのみであり、本発明はこれらによって何ら限定されるものではない。
Since these blood adiponectin concentration increase promoting and / or decreasing inhibitor, or blood adiponectin concentration increasing and / or decreasing suppressing food and drink, feed has an effect of increasing blood adiponectin concentration and / or decreasing decrease. It can be very useful for the prevention, treatment, and improvement of various pathologies caused by the aforementioned decrease in blood adiponectin concentration.
The lactic acid bacteria used in the present invention have been used for the production of fermented milk and cheese since ancient times, and the blood adiponectin concentration increase promotion and / or decrease inhibitor of the present invention, or the blood adiponectin concentration increase promotion and / or decrease. Inhibitory foods and drinks and feeds are characterized by no safety issues.
Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples. However, these are merely illustrative and the present invention is not limited thereto.

(ラクトバチラス・ガセリ培養物粉末の調製1)
還元脱脂乳培地(13重量%脱脂粉乳、0.5重量%酵母エキス含有)を95℃で30分間殺菌した後、ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055を接種し、37℃で16時間培養し、得られた培養物を凍結乾燥してラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055の培養物粉末を得た。これは、そのまま本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤として使用し得る。
(Preparation of Lactobacillus gasseri culture powder 1)
Reduced skim milk medium (13 wt% skim milk powder, containing 0.5 wt% yeast extract) is sterilized at 95 ° C for 30 minutes, then inoculated with Lactobacillus gasseri SBT2055, and cultured at 37 ° C for 16 hours. The culture was freeze-dried to obtain a culture powder of Lactobacillus gasseri SBT2055. This can be used as it is as an agent for promoting and / or suppressing the increase in blood adiponectin concentration of the present invention.

(ラクトバチラス・ガセリ培養物粉末の調製2)
還元脱脂乳培地(13重量%脱脂粉乳、0.5重量%酵母エキス含有)を95℃で30分間殺菌した後、ラクトバチラス・ガセリ(Lactobacillus gasseri)JCM1131を接種し、37℃で16時間培養し、得られた培養物を凍結乾燥してラクトバチラス・ガセリ(Lactobacillus gasseri)JCM1131の培養物粉末を得た。これは、そのまま本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤として使用し得る。
(Preparation of Lactobacillus gasseri culture powder 2)
Reduced skim milk medium (13 wt% skim milk powder, containing 0.5 wt% yeast extract) was sterilized at 95 ° C for 30 minutes, then inoculated with Lactobacillus gasseri JCM1131 and cultured at 37 ° C for 16 hours. The culture was freeze-dried to obtain a culture powder of Lactobacillus gasseri JCM1131. This can be used as it is as an agent for promoting and / or suppressing the increase in blood adiponectin concentration of the present invention.

〔試験例1〕
(ラクトバチラス・ガセリ培養物の投与と血中アディポネクチンの測定)
4週令Fischer系雄ラット50匹に、コントロール食を自由に摂取させて1週間飼育した後、10匹ずつ各群に分け、1群は引き続きコントロール食を、別の群にはラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055、ラクトバチラス・ガセリ(Lactobacillus gasseri)JCM1131、ラクトバチラス・ガセリ(Lactobacillus gasseri)ATCC19992、ラクトバチラス・カゼイ(Lactobacillus casei)ATCC11578を配合した試験食を自由に摂取させてさらに4週間飼育した後、血中アディポネクチン濃度を測定した。なお、5群に体重、摂食量、糞重量の差は認められなかった。
血中アディポネクチン濃度を測定して得られた結果を表1に示す。これによると血中アディポネクチン濃度は、コントロール食摂取群と比較してラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055、ラクトバチラス・ガセリ(Lactobacillus gasseri)JCM1131、ラクトバチラス・ガセリ(Lactobacillus gasseri)ATCC19992、ラクトバチラス・カゼイ(Lactobacillus casei)ATCC11578食摂取群は有意に高値を維持していた。すなわち、ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055、ラクトバチラス・ガセリ(Lactobacillus gasseri)JCM1131、ラクトバチラス・ガセリ(Lactobacillus gasseri)ATCC19992、ラクトバチラス・カゼイ(Lactobacillus casei)ATCC11578の培養物粉末を添加した食品は、血中アディポネクチン濃度を一定に維持することが確認された。
[Test Example 1]
(Lactobacillus gasseri culture administration and blood adiponectin measurement)
50 4-week-old Fischer male rats were allowed to freely receive a control diet and bred for 1 week, then divided into groups of 10 each, one group continued to receive the control diet, the other group contained Lactobacillus gasseri ( Lactobacillus gasseri) SBT2055, Lactobacillus gasseri JCM1131, Lactobacillus gasseri ATCC 19992, Lactobacillus casei Lactobacillus casei ATCC11578 and fed for a further 4 weeks Medium adiponectin concentration was measured. There were no differences in body weight, food intake, or fecal weight among the five groups.
Table 1 shows the results obtained by measuring the blood adiponectin concentration. According to this, the concentration of adiponectin in the blood was compared with that in the control food intake group. ) The ATCC11578 diet group maintained a significantly high value. That is, Lactobacillus gasseri SBT2055, Lactobacillus gasseri JCM1131, Lactobacillus gasseri ATCC19992, Lactobacillus casei Lactobacillus casei in a food powder with the addition of Lactobacillus casei ATCC11578 It was confirmed that the concentration was kept constant.

Figure 2008063289
Figure 2008063289

以上の結果から、ラクトバチラス・ガセリ(Lactobacillus gasseri)の培養物粉末を添加した食品は、循環器系疾患のリスクが高まることが示されている血中アディポネクチン濃度の低下を抑制し、適切な値に維持させる効果があることが明らかとなった。   Based on the above results, foods supplemented with Lactobacillus gasseri culture powder suppressed the decrease in blood adiponectin concentration, which has been shown to increase the risk of cardiovascular disease, and reached an appropriate value. It became clear that there was an effect to maintain.

(錠剤の製造)
ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055の液体培養物を4℃、7,000rpm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部に脱脂粉乳4部を混合し、この混合粉末を打錠機により1gずつ定法により打錠して、本発明のラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055の菌体200mgを含む錠剤を調製した。
(Manufacture of tablets)
A liquid culture of Lactobacillus gasseri SBT2055 was centrifuged at 7,000 rpm for 15 minutes at 4 ° C. and washed with sterilized water, and this was repeated three times to obtain washed cells. This was freeze-dried to obtain cell powder. Tablets containing 200 mg of Lactobacillus gasseri SBT2055 cells of the present invention are prepared by mixing 1 part of this powder with 4 parts of skim milk powder, and tableting this mixed powder 1 g at a time using a tableting machine. Was prepared.

(発酵乳の製造)
ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055をMRS液体培地(Difco社)にて培養した。対数増殖期にある各培養液を、0.3%の酵母エキスを添加した10%還元脱脂乳(115℃、20分滅菌)に1%接種し、マザーカルチャーを作成した。これに10%の還元脱脂乳を添加して、100℃にて10分間加熱したヨーグルトミックスに2.5%添加して調製した。37℃で発酵を行い、乳酸酸度0.85に到達した時点で冷却し、発酵を終了させ、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制剤用発酵乳を得た。
(Manufacturing fermented milk)
Lactobacillus gasseri SBT2055 was cultured in MRS liquid medium (Difco). 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 0.3% yeast extract to prepare a mother culture. 10% reduced skim milk was added thereto, and 2.5% was added to the yogurt mix heated at 100 ° C. for 10 minutes. Fermentation was performed at 37 ° C., cooling was performed when the lactic acid acidity reached 0.85, the fermentation was terminated, and the fermented milk for blood adiponectin concentration increase and / or decrease inhibitor of the present invention was obtained.

(散剤の製造)
ラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055をMRS液体培地(Difco社)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、凍結乾燥菌末を製造した。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、この凍結乾燥菌末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、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用散剤を得た。
(Manufacture of powder)
After inoculating 5 L of MRS liquid medium (Difco) with Lactobacillus gasseri (Lactobacillus gasseri) SBT2055, 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 concentrated cells in the culture solution. Next, the concentrated cells were mixed with the same amount of a dispersion medium containing 10% by weight of skim milk powder and 1% by weight of sodium glutamate, adjusted to pH 7, and then freeze-dried. The obtained lyophilized product was sized with a 60 mesh sieve to produce a lyophilized bacterial powder. In accordance with the provisions of the 13th revised Japanese Pharmacopoeia General Rules for Preparations, “Powder”, 1 g of this freeze-dried bacterial powder is added with 400 g of lactose (JP) and 600 g of potato starch (JP), and mixed uniformly. A powder for promoting and / or suppressing decrease in blood adiponectin concentration was obtained.

(スティック状健康食品の製造)
実施例1で得られたラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055の培養物粉末30gに、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を加えて混合した。混合物をスティック状袋に詰め、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用スティック状健康食品を製造した。
(Manufacture of stick health food)
Lactobacillus gasseri SBT2055 culture powder obtained in Example 1 was mixed with 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. . The mixture was packed in a stick-shaped bag to produce a stick-shaped health food for promoting and / or suppressing decrease in blood adiponectin concentration of the present invention.

(ナチュラルチーズの製造)
脂肪率を調整した原料乳を75℃で15秒間のプレート加熱殺菌を行った後、30℃まで冷却し、0.01%塩化カルシウムを添加した。次に、これらの原料乳に市販の乳酸菌スターター(クリスチャン・ハンセン社製) 0.7%及びラクトバチラス・ガセリ(Lactobacillus gasseri)SBT2055 1%を添加し、レンネット0.003 %を添加して乳を凝固させた後、カッテングしてpHが 6.2〜6.1 となるまで撹拌し、ホエーを排出し、カード粒を得た。さらに、このカード粒を型詰めして圧搾し、さらに加塩して、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用ナチュラルチーズを製造した。
(Manufacture of natural cheese)
The raw milk with adjusted fat percentage was sterilized by heating at 75 ° C. for 15 seconds, then cooled to 30 ° C., and 0.01% calcium chloride was added. Next, after adding 0.7% of commercially available lactic acid bacteria starter (made by Christian Hansen) and 1% of Lactobacillus gasseri SBT2055 to these raw milk, and adding rennet 0.003% to coagulate the milk Then, the mixture was cut and stirred until the pH reached 6.2 to 6.1, and whey was discharged to obtain curd grains. Furthermore, this curd grain was mold-packed, squeezed, and further salted to produce a natural cheese for promoting and / or suppressing decrease in blood adiponectin concentration of the present invention.

(カプセル剤の製造)
表2に示した配合により原料を混合し、造粒した後、カプセルに充填して、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用カプセル剤を製造した。
(Manufacture of capsules)
The raw materials were mixed according to the formulation shown in Table 2, granulated and then filled into capsules to produce capsules for promoting and / or suppressing decrease in blood adiponectin concentration of the present invention.

[表2]
──────────────────────────
SBT2055(実施例1) 20.0 (重量%)
ラクトース 24.5
可溶性デンプン 55.0
ステアリン酸マグネシウム 0.5
──────────────────────────
[Table 2]
──────────────────────────
SBT2055 (Example 1) 20.0 (wt%)
Lactose 24.5
Soluble starch 55.0
Magnesium stearate 0.5
──────────────────────────

(飲料の製造)
表3に示した配合により原料を混合し、容器に充填した後、加熱殺菌して、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用飲料を製造した。
(Manufacture of beverages)
The ingredients shown in Table 3 were mixed and filled into a container, and then heat sterilized to produce a blood adiponectin concentration increase promotion and / or decrease suppression beverage of the present invention.

[表3]
──────────────────────────
SBT2055(実施例2) 2.5 (重量%)
砂糖 7.5
クエン酸 0.6
リンゴ果汁 10.0
水 79.4
──────────────────────────
[Table 3]
──────────────────────────
SBT2055 (Example 2) 2.5 (wt%)
Sugar 7.5
Citric acid 0.6
Apple juice 10.0
Water 79.4
──────────────────────────

(低脂肪硬質ナチュラルチーズの製造)
チーズ中の脂肪率が12〜30%となるように調整した原料乳を使用して、数種類の低脂肪硬質ナチュラルチーズを製造した。すなわち、脂肪率を調整した原料乳を75℃で15秒間のプレート加熱殺菌を行った後、30℃まで冷却し、0.01%塩化カルシウムを添加した。次に、これらの原料乳に乳酸菌スターター(クリスチャン・ハンセン社製) 0.7%及びラクトバチラス・ヘルベチカス(Lactobacillus helveticus)SBT2171 1%を添加し、レンネット0.003 %を添加して乳を凝固させた後、カッテングしてpHが6.2〜6.1となるまで撹拌し、ホエーを排出し、カード粒を得た。さらに、このカード粒を型詰めして圧搾し、さらに加塩して、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用ゴーダチーズタイプ低脂肪硬質ナチュラルチーズを製造した。
(Manufacture of low fat hard natural cheese)
Several kinds of low-fat hard natural cheeses were produced using raw milk adjusted so that the fat percentage in cheese was 12 to 30%. That is, the raw milk with adjusted fat percentage was sterilized by heating at 75 ° C. for 15 seconds, then cooled to 30 ° C., and 0.01% calcium chloride was added. Next, after adding 0.7% lactic acid bacteria starter (manufactured by Christian Hansen) and 1% Lactobacillus helveticus SBT2171 to these raw milk, and adding rennet 0.003% to coagulate the milk, The mixture was cut and stirred until the pH reached 6.2 to 6.1, and whey was discharged to obtain curd grains. Further, the curd grains were molded, squeezed, and further salted to produce a gouda cheese type low-fat hard natural cheese for increasing and / or suppressing blood adiponectin concentration according to the present invention.

(発酵乳の製造)
ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)SBT2171を用いて発酵乳の製造を行った。ラクトバチラス・ヘルベチカス(Lactobacillus helveticus) SBT2171を、脱脂乳100gを用いて37℃、12時間培養したものを、新しい同培地3kgに接種し、37℃、12時間培養した。培養終了した乳全量をスターターとして用い、脱脂乳100kgを32℃、20時間発酵させ本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用発酵乳を得た。ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)SBT2171の生菌数は8.2×108cells/gであった。
(Manufacturing fermented milk)
Fermented milk was produced using Lactobacillus helveticus SBT2171. Lactobacillus helveticus (Lactobacillus helveticus) SBT2171 cultured in 100 g of skim milk at 37 ° C. for 12 hours was inoculated into 3 kg of the same medium and cultured at 37 ° C. for 12 hours. Using the total amount of milk after culturing as a starter, 100 kg of skimmed milk was fermented at 32 ° C. for 20 hours to obtain fermented milk for promoting and / or suppressing decrease in blood adiponectin concentration of the present invention. The viable count of Lactobacillus helveticus SBT2171 was 8.2 × 10 8 cells / g.

(ドリンクヨーグルトの製造)
実施例11で得られた発酵乳43kgにグラニュー糖4kg、水3kg、ペクチン0.15kgを加えた後に均質化して、ドリンクヨーグルト50kgを得た。このドリンクヨーグルトはマイルドな好ましい風味を有し、pH3.6で、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)SBT2171の生菌数は4.6×108cells/gであった。
(Manufacture of drink yogurt)
To 43 kg of fermented milk obtained in Example 11, 4 kg of granulated sugar, 3 kg of water and 0.15 kg of pectin were added and homogenized to obtain 50 kg of drink yogurt. This drink yogurt had a mild and favorable flavor, was pH 3.6, and the viable cell count of Lactobacillus helveticus SBT2171 was 4.6 × 10 8 cells / g.

実施例11と同様にして得られた発酵物5kgに同量の水を添加した後、連続遠心分離機で3,500×g、20分間の遠心分離を行い、菌体のみを分離回収した。沈殿物の中に含まれる非菌体成分を除去するため、水を1kg添加した後、遠心分離を再度行い、これを3回繰り返した。最終的にラクトバチラス・ヘルベチカス(Lactobacillus helveticus)SBT2171の菌体20gを回収した。   After adding the same amount of water to 5 kg of the fermented product obtained in the same manner as in Example 11, it was centrifuged at 3,500 × g for 20 minutes with a continuous centrifuge to separate and recover only the cells. In order to remove the non-bacterial components contained in the precipitate, 1 kg of water was added, followed by centrifugation again, and this was repeated three times. Finally, 20 g of Lactobacillus helveticus SBT2171 cells were collected.

〔試験例2〕
(血中アディポネクチン濃度増加促進及び/又は減少抑制作用の確認)
ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)の菌体を使用して、血中アディポネクチン濃度増加促進及び/又は減少抑制作用を確認した。動物実験は4週令Fischer系雄ラット1群8匹とし、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)を配合した飼料を投与した群(菌体食群)、菌体を配合しない飼料を投与した群(対照食群)として行った。動物実験は、飼育後4週目までは対照飼料を与え、その後8週目まで対照飼料、あるいはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)を配合した菌体飼料を与えた。4週目、8週目に採血を行い、マウス/ラットアディポネクチンELISAキット(大塚製薬社)を用いて血中アディポネクチン濃度を測定した。
結果を表4に示す。これによると対照食群の血中アディポネクチン濃度は時間の経過によって減少しているのに対し、菌体食群では増加することが明らかとなった。つまり、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)を摂取することにより、血中アディポネクチン濃度の増加が促進、あるいは減少が抑制されることが分った。
[Test Example 2]
(Confirmation of blood adiponectin concentration increase promotion and / or decrease suppression effect)
Using Lactobacillus helveticus cells, the effect of promoting and / or suppressing the decrease of blood adiponectin concentration was confirmed. Animal experiments consisted of 8 4-week-old Fischer male rats per group, a group administered with a diet containing Lactobacillus helveticus (a fungal diet group), and a group administered with a diet not containing a bacterial cell ( Control diet group). In the animal experiment, a control feed was given until the 4th week after breeding, and then a control feed or a fungal feed containing Lactobacillus helveticus was given until the 8th week. Blood was collected at 4th and 8th weeks, and the blood adiponectin concentration was measured using a mouse / rat adiponectin ELISA kit (Otsuka Pharmaceutical Co., Ltd.).
The results are shown in Table 4. According to this, it was clarified that the blood adiponectin concentration in the control diet group decreased with time, whereas that in the fungal diet group increased. That is, it was found that by ingesting Lactobacillus helveticus, the increase in blood adiponectin concentration was promoted or decreased.

Figure 2008063289
Figure 2008063289

〔試験例3〕
(アディポネクチン増加促進及び/又は減少抑制作用の確認)
実施例10で得られたチーズを使用して、アディポネクチン増加促進及び/又は減少抑制作用を確認した。動物実験は4 週齢のFischer系ラットを1群8匹とし、チーズを配合した飼料を投与した群(チーズ食群)、チーズを配合しない対照飼料を投与した群(対照食群)として行った。対照飼料は、タンパク質源としてミルクカゼイン、脂質源としてバターオイルを用い、チーズの成分分析の結果(表5)をもとに、一般成分、主要ミネラル、ビタミンE(α―トコフェロール)の含有量がチーズを配合した飼料と同じになるように配合した。チーズを配合した飼料では、タンパク質、脂質とも、チーズ成分のみでまかなった。
動物実験は、飼育後4週目までは対照飼料を与え、その後2群に分けて8週目まで対照飼料、チーズ飼料を与えた。4週目、8週目に採血を行い、マウス/ラットアディポネクチンELISAキット(大塚製薬社)を用いて血中アディポネクチン濃度を測定した。
[Test Example 3]
(Confirmation of adiponectin increase promotion and / or suppression effect)
Using the cheese obtained in Example 10, the adiponectin increase promotion and / or the decrease suppression action was confirmed. The animal experiment was carried out as 8 groups of 4 week-old Fischer rats, a group to which a diet containing cheese was administered (cheese diet group), and a group to which a control diet without cheese was administered (control diet group). . The control feed uses milk casein as the protein source and butter oil as the lipid source. Based on the results of cheese component analysis (Table 5), the content of general ingredients, major minerals, and vitamin E (α-tocopherol) It mix | blended so that it might become the same as the feed which mix | blended cheese. In the feed mixed with cheese, both protein and lipid were covered only with cheese components.
In the animal experiment, a control feed was given up to 4 weeks after breeding, and then divided into two groups, and a control feed and a cheese feed were given up to 8 weeks. Blood was collected at 4th and 8th weeks, and the blood adiponectin concentration was measured using a mouse / rat adiponectin ELISA kit (Otsuka Pharmaceutical Co., Ltd.).

Figure 2008063289
Figure 2008063289

結果を表6に示す。これによると対照食群の血中アディポネクチン濃度は時間の経過によって減少しているのに対し、チーズ食群ではむしろ増加することが明らかとなった。つまり、ラクトバチラス・ヘルベチカス(Lactobacillus helveticus)で製造したチーズを摂取することにより、血中アディポネクチン濃度が増加若しくは低下抑制されることが分った。   The results are shown in Table 6. According to this, it was clarified that the blood adiponectin concentration in the control diet group decreased with time, whereas the cheese diet group increased rather. That is, it was found that the blood adiponectin concentration was increased or decreased by ingesting cheese produced with Lactobacillus helveticus.

Figure 2008063289
Figure 2008063289

表7に示した配合により原料を混合し、本発明の血中アディポネクチン濃度増加促進及び/又は減少抑制用イヌ飼育用飼料を製造した。   The raw materials were mixed according to the formulation shown in Table 7, and the feed for breeding dogs for promoting and / or suppressing the increase in blood adiponectin concentration of the present invention was produced.

[表 7]
──────────────────────────
SBT2171菌体 2.5 (重量%)
脱脂粉乳 13.5
大豆粕 12.0
大豆油 4.0
コーン油 2.0
パーム油 27.0
トウモロコシでんぷん 14.0
小麦粉 9.0
ふすま 2.0
ビタミン混合物 9.0
ミネラル混合物 2.0
セルロース 3.0
──────────────────────────
[Table 7]
──────────────────────────
SBT2171 cells 2.5 (wt%)
Nonfat dry milk 13.5
Soybean cake 12.0
Soybean oil 4.0
Corn oil 2.0
Palm oil 27.0
Corn starch 14.0
Flour 9.0
Bran 2.0
Vitamin mixture 9.0
Mineral mixture 2.0
Cellulose 3.0
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Claims (6)

ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制剤。   Lactobacillus lactic acid bacteria culture and / or blood adiponectin concentration increase promotion and / or reduction inhibitor comprising as an active ingredient. ラクトバチラス(Lactobacillus)属乳酸菌が、ラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)である請求項1記載の血中アディポネクチン濃度増加促進及び/又は減少抑制剤。   The Lactobacillus lactic acid bacterium is Lactobacillus gasseri or Lactobacillus helveticus, The blood adiponectin concentration increase promotion and / or decrease inhibitor according to claim 1. ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制用飲食品。   A food and drink for promoting and / or suppressing decrease in blood adiponectin concentration, comprising a culture of Lactobacillus lactic acid bacteria and / or bacterial cells as active ingredients. ラクトバチラス(Lactobacillus)属乳酸菌が、ラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)である請求項3記載の血中アディポネクチン濃度増加促進及び/又は減少抑制用飲食品。   Lactobacillus lactic acid bacteria are Lactobacillus gasseri or Lactobacillus helveticus, The food / beverage product for blood-adiponectin density | concentration increase promotion and / or suppression suppression of Claim 3. ラクトバチラス(Lactobacillus)属乳酸菌の培養物及び/又は菌体を有効成分とする血中アディポネクチン濃度増加促進及び/又は減少抑制用飼料。   A feed for promoting and / or suppressing decrease in blood adiponectin concentration, comprising a lactobacillus lactic acid bacteria culture and / or cells as active ingredients. ラクトバチラス(Lactobacillus)属乳酸菌が、ラクトバチラス・ガセリ(Lactobacillus gasseri)もしくはラクトバチラス・ヘルベチカス(Lactobacillus helveticus)である請求項5記載の血中アディポネクチン濃度増加促進及び/又は減少抑制用飼料。   The feed for promoting and / or suppressing decrease in blood adiponectin concentration according to claim 5, wherein the Lactobacillus lactic acid bacterium is Lactobacillus gasseri or Lactobacillus helveticus.
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PCT/JP2007/000932 WO2008029505A1 (en) 2006-09-04 2007-08-30 Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
EP07805787.4A EP2062587A4 (en) 2006-09-04 2007-08-30 Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
AU2007292786A AU2007292786B2 (en) 2006-09-04 2007-08-30 Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
US12/439,728 US20100021444A1 (en) 2006-09-04 2007-08-30 Blood-adiponectin-concentration increase-accelerator and/or decrease-inhibitor thereof and visceral fat accumulation inhibitor
CN2007800327825A CN101678051B (en) 2006-09-04 2007-08-30 Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
NZ575469A NZ575469A (en) 2006-09-04 2007-08-30 Agent comprising lactobacillus for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
KR1020097005375A KR101492650B1 (en) 2006-09-04 2007-08-30 Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
NZ597178A NZ597178A (en) 2006-09-04 2007-08-30 Agent comprising Lactobacillus helveticus for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
US13/236,034 US20120009165A1 (en) 2006-09-04 2011-09-19 Blood-adiponectin-concentration increase-accelerator and/or decrease-inhibitor thereof and visceral fat accumulation inhibitor

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