JP6654639B2 - 血中トリプトファン濃度上昇抑制剤 - Google Patents
血中トリプトファン濃度上昇抑制剤 Download PDFInfo
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- JP6654639B2 JP6654639B2 JP2017540017A JP2017540017A JP6654639B2 JP 6654639 B2 JP6654639 B2 JP 6654639B2 JP 2017540017 A JP2017540017 A JP 2017540017A JP 2017540017 A JP2017540017 A JP 2017540017A JP 6654639 B2 JP6654639 B2 JP 6654639B2
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- blood
- lactobacillus casei
- lactic acid
- tryptophan concentration
- increase
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Description
ニコチン酸欠乏症の予防には、ニコチン酸を含むビタミンB群を摂取することが行われているが、トリプトファンの代謝を改善するアプローチは行われていない。
〔1〕ラクトバチルス属乳酸菌の菌体若しくはその処理物又はこれらを含有する発酵物を有効成分とする血中トリプトファン濃度上昇抑制剤。
〔2〕ラクトバチルス属乳酸菌が、ラクトバチルス・カゼイである〔1〕記載の血中トリプトファン濃度上昇抑制剤。
〔3〕ラクトバチルス属乳酸菌が、ラクトバチルス・カゼイ YIT9029(FERM BP−1366)である〔1〕又は〔2〕記載の血中トリプトファン濃度上昇抑制剤。
〔4〕1日摂取量が、ラクトバチルス属乳酸菌の生菌数として1011cfu以上である〔1〕〜〔3〕いずれかに記載の血中トリプトファン濃度上昇抑制剤。
〔5〕ラクトバチルス属乳酸菌の菌体若しくはその処理物又はこれらを含有する発酵物を有効成分とする血中トリプトファン濃度上昇抑制用食品。
〔6〕血中トリプトファン濃度上昇抑制剤を製造するための、ラクトバチルス属乳酸菌の菌体若しくはその処理物又はこれらを含有する発酵物の使用。
〔7〕血中トリプトファン濃度上昇抑制に使用するための、ラクトバチルス属乳酸菌の菌体若しくはその処理物又はこれらを含有する発酵物。
〔8〕ラクトバチルス属乳酸菌の菌体若しくはその処理物又はこれらを含有する発酵物の有効量を投与又は摂取する血中トリプトファン濃度上昇抑制方法。
斯かる乳酸菌は、自然界から分離可能なもの、又はATCC等の細胞バンクから入手可能なものであってもよいが、好適な乳酸菌株としては、例えば、ラクトバチルス・カゼイ YIT 9018(FERM BP−665)、ラクトバチルス・カゼイ YIT 9029(FERM BP−1366)、ラクトバチルス・カゼイ YIT 10003(FERM BP−7707)が挙げられ、このうちラクトバチルス・カゼイ YIT9029(FERM BP−1366)が特に好ましい。
本発明において、上記乳酸菌は、1種単独で用いてもよく、2種以上を組み合わせて用いてもよい。
菌体は、生菌体を培養することにより大量に生産することができる。培地は、液体培地及び固体培地のいずれでもよいが、窒素源及び炭素源を含有するものが好ましい。窒素源としては、肉エキス、ペプトン、グルテン、カゼイン、酵母エキス、アミノ酸等を、また、炭素源としては、グルコース、キシロース、フルクトース、イノシトール、マルトース、水アメ、麹汁、デンプン、バカス、フスマ、糖蜜、グリセリン等を用いることができる。また、無機質として、硫酸アンモニウム、リン酸カリウム、塩化マグネシウム、食塩、鉄、マンガン、モリブデン等を添加することができ、さらにビタミン等を添加することができる。好適な培地としては、MRS培地、LBS培地、Rogosa培地、WYP培地、GYP培地等が挙げられる。
また、死菌体を用いる場合は、例えば、加熱処理、抗生物質などの薬物による処理、ホルマリンなどの化学物質による処理、紫外線による処理、γ線などの放射線による処理により得ることができる。これらの処理のうち、特に超音波処理、酵素処理、加熱処理が好ましい。
血中トリプトファン濃度は、内因的または外因的に上昇し得、血中トリプトファン濃度上昇の原因は、例えば、精神的ストレス、肉体的ストレス、持久的な運動、トリプトファンを多く含む食材の摂取等であり得る。本発明において、血中トリプトファン濃度の上昇抑制作用は、血中トリプトファン濃度の上昇を抑制する作用(予防作用)、または、上昇した血中トリプトファン濃度を低下させる作用(治療作用)であり得、好適には、内因的な血中トリプトファン濃度の上昇を抑制する作用であり、より好適には、精神的ストレスにより引き起こされる血中トリプトファン濃度の上昇を抑制する作用である。
血中トリプトファン濃度は、吸光法、蛍光法、クロマトグラフ法、電気泳動法などにより測定することができる。
したがって、血中のトリプトファン濃度の上昇を抑制できれば、ニコチン酸欠乏症の症状を改善することができると云える。
ここで、ニコチン酸欠乏症としては、皮膚炎、胃腸障害、精神症状が挙げられ、皮膚炎としては顔面、頸部、手足などの日光に当たる部分の発赤、水疱、痂皮形成や色素沈着が挙げられ、精神症状としては、疲労、不眠、食欲不振、無感情、認知症症状、不安、抑うつ状態、せん妄、幻覚等が挙げられ、本発明では、特にストレス状況下での不眠や食欲不振に対して有用である。不眠に対する作用としては、特に睡眠時間を増加させる作用、眠りの深さ(熟眠度)を高める作用、深い眠りの時間を増加させる作用が挙げられる。
製造例1(ラクトバチルス・カゼイを含む乳発酵物の製造)
ラクトバチルス・カゼイ(Lactobacillus casei)YIT 9029株を接種し、37℃で発酵させた脱脂粉乳溶液にシロップを混合し、香料を添加した後、均質化して容器に充填して発酵物を得た。この発酵物100mL中のラクトバチルス・カゼイの菌数は1011cfuであった。
また、プラセボとして、ラクトバチルス・カゼイを含まず、発酵物と同等の乳酸を添加して風味を調整した未発酵物を用いた。なお、その他の組成については、発酵物と同じである。
本実施例では、学術試験に伴うストレス応答に対する乳酸菌の飲用効果を二重盲検プラセボ対照並行群比較試験により評価した。
5年生に進学するための国家試験(学術試験)を控えた、喫煙習慣がなく、30歳未満の健康な医学部4年生51名を2群に分け、製造例1で調製した発酵乳(LcS群)またはプラセボ飲料(プラセボ群)を学術試験の8週間前(飲用開始前)から8週間、学術試験の前日まで毎日100mL摂取させた。飲用開始前、学術試験1日前(学術試験前)および学術試験2週後(学術試験後)に日本語版STAI(Spielberger,C.D著、日本語版 STAI(状態・特性不安検査)使用手引、1991年、三京房)にて状態不安を評価するとともに、血液(夕方に採取)および便を採取した。高速液体クロマトグラフィー法により、血漿トリプトファン、便中セロトニンを測定した。また、飲用期間中の体調不良の有無を調べた。最終的に、学術試験を受けなかった被験者4名を除外し、プラセボ群23名、LcS群24名を解析対象とした。
一方、血中トリプトファン濃度はプラセボ群では学術試験前に有意に増加したが、LcS群では有意な変化がみられなかった。すなわち、トリプトファン代謝異常がプラセボ群では認められたが、LcS群では認められず、LcSはトリプトファン代謝異常に対して予防作用を示すことが確認された。
なお、便中セロトニン濃度は、学術試験ストレスを最も強く感じている学術試験前では両群ともに低下し、群間で差はみられなかったことから、LcSによるトリプトファンの上昇抑制作用は、ストレスとの関係が知られているセロトニンとは無関係に発揮されたことが明らかになった。
学術試験ストレス下における学生の睡眠に対する乳酸菌の飲用効果を二重盲検プラセボ対照並行群比較試験により評価した。
学術試験を控えた、試験例1とは異なる、喫煙習慣がなく、30歳未満の健康な医学部4年生49名を対象に、試験例1と同様に二重盲検プラセボ対照並行群比較試験を行った。飲用開始前および学術試験の3〜5日前(学術試験前)にOSA睡眠調査票MA版(山本由華吏 他、脳と精神の医学、第10巻、第4号1999年、401-409)にて睡眠状態、及び小型1ch脳波計スリープスコープ(スリープウェル(株))にて睡眠中の脳波を各時点3日間計測した。脳波は原則2回目のデータを解析した。OSA睡眠調査票については3日間の平均スコアを算出した。最終的に、脱落者およびアンケートの信頼性に欠く被験者2名を除外し、プラセボ群23名、LcS群24名を解析対象とした。結果を表2及び3に示す。
学術試験ストレスを最も強く感じている学術試験前、脳波ノンレム睡眠(N3)の睡眠時間全体に対する割合は、プラセボ群で減少する傾向がみられた。しかし、LcS群はプラセボ群と比べて、わずかに増加する傾向がみられ、学術試験前において両群間で有意な差が認められた。すなわち、学術試験前において、LcSは学術試験ストレスにより減少する深い眠りの時間を増加させることが確認された。
Claims (4)
- ラクトバチルス・カゼイ(Lactobacillus casei)の菌体若しくはその処理物又はこれらを含有する発酵物を有効成分とする血中トリプトファン濃度上昇抑制剤(但し、睡眠改善又は気分改善のために使用する場合を除く)。
- ラクトバチルス・カゼイ(Lactobacillus casei)が、ラクトバチルス・カゼイ(Lactobacillus casei) YIT9029(FERM BP−1366)である請求項1記載の血中トリプトファン濃度上昇抑制剤。
- 1日摂取量が、ラクトバチルス・カゼイ(Lactobacillus casei)の生菌数として1011cfu以上である請求項1又は2記載の血中トリプトファン濃度上昇抑制剤。
- ラクトバチルス・カゼイ(Lactobacillus casei)の菌体若しくはその処理物又はこれらを含有する発酵物を有効成分とする血中トリプトファン濃度上昇抑制用食品(但し、睡眠改善又は気分改善のために使用する場合を除く)。
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