JP6998133B2 - リポ多糖を用いた脳機能改善剤、食品及び医薬品 - Google Patents
リポ多糖を用いた脳機能改善剤、食品及び医薬品 Download PDFInfo
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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
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Description
(1)アミロイドβタンパク質の脳内蓄積を抑制することによって脳機能を改善するための脳機能改善剤、食品又は医薬品であって、パントエア菌LPSからなるリポ多糖を有効成分とし経口投与、経皮投与又は口腔投与する、脳機能改善剤、食品又は医薬品。
(2)改善される脳機能が、加齢又は加齢に伴う脳疾患に起因して低下した認知機能であることを特徴とする請求項1の脳機能改善剤、食品又は医薬品。
(3)パントエア菌LPSを有効量含有する、請求項1に記載の脳機能改善剤、食品又は医薬品。
(4)アルツハイマー病を予防するための、請求項1に記載の脳機能改善剤、食品又は医薬品。
(5)パントエア菌LPSを1日投与単位あたり0.1~1mg/kg体重の割合で含有する請求項1に記載の脳機能改善剤、食品又は医薬品。
[実施例1]アルツハイマー病モデルマウスに対するパントエア菌LPSの経口投与試験方法
パントエア菌LPSは、杣らが開発したリポ多糖の発酵培養法(特許文献2)に従い、調製・精製されたもの(Lipopolysaccharide, Pantoea agglomerans〈LPS〉、自然免疫応用技研社)を使用した。実験には、アルツハイマー病モデルマウスとして12-14週齢の雄SAMP8マウス(Senescence accelerated mouse-prone 8/Ta Slc、日本SLC社)を使用し、1週間予備飼育後、体重により4群に分けた。35%脂肪を含む飼料(リサーチダイエット)を与え、0.3又は1mg/kg体重/dayのパントエア菌LPSを含む水を、自由飲水による経口投与で与えた。なお、コントロール群には、35%脂肪を含む飼料又は4%脂肪を含む飼料(リサーチダイエット)を与え、同様の方法で水を与えた。マウスの飼育は、温度湿度管理された動物施設にて、自由摂食、自由飲水、12時間光照射/12時間暗黒下の環境条件にて行った。17週間飼育後、以下に示す水迷路試験を1週間行い、学習機能を評価した。水迷路試験終了の翌日、心臓より採血をした。脳、肝臓、精巣上体周囲白色脂肪細胞を摘出した。本動物実験は香川大学動物実験委員会によって承認されている。
(1)NC群:4%脂肪を含む飼料(低脂肪飼料)及び水を自由摂取により与えた。
(2)PC群:35%脂肪を含む飼料(高脂肪飼料)及び水を自由摂取により与えた。
(3)パントエア菌LPS
0.3mg/kg体重/day群:高脂肪飼料及びパントエア菌LPS(0.3mg/kg体重/day)を含む水を自由摂取により与えた。
(4)パントエア菌LPS 1mg/kg体重/day群:高脂肪飼料及びパントエア菌LPS(1mg/kg体重/day)を含む水を自由摂取により与えた。
(1)装置
円筒形プール(直径100 cm、深さ40 cm)に水(23±1℃)を入れ、透明なプラットフォーム(直径10 cm)が水面下1cmに沈むように設置した。市販の黒色インクをプールの水に加え、水泳中のマウスがプラットフォームを視認できないようにした。プール水面の真上に市販のデジタルカメラを設置し、マウスの水泳を動画で記録した。水泳軌跡の解析は、画像解析ソフトAminalTrackerを用いて、「Neuroinformatics, 14, 479-481, 2016」記載の方法に従い行った。
試験前日に、マウスをプールに馴れさせるために、各々1回泳がせた。手順は、水面上1cmに固定したプラットフォームにマウスを20秒間静置したのち、30秒間自由に泳がせた。その後、実験者の手でマウスをプラットフォーム上に誘導し、20秒間静置した。また、プールに入れる際はマウスをプールの壁向きに入水させ、実験者は速やかにマウスから見えない位置に移動した。1~5日目はマウスにプラットフォームの位置を記憶させるトレーニングを実施した。トレーニングは1日に4回連続して行った。トレーニングの手順は、マウスを任意の位置からプールに入れ、60秒間泳がせ、水面下1cmに設置したプラットフォームを探索させた。プラットフォーム到達に要する時間を記録し、60秒で到達できない場合は60秒と記録した。また、時間内にプラットフォームに到達しないマウスは実験者の手でプラットフォームに誘導した。プラットフォームに到達後、20秒間静置し、マウスをプールから取り出した。6日目にプローブ試験を行った。プローブ試験は、プールからプラットフォームを取り除き、マウスを60秒間泳がせ、プールの各4分円領域内での滞在時間を測定した。なお、プローブ試験は各マウスにつき1回行った。
18週間の飼育後、体重は、NC群とPC群で有意な差が認められたが、パントエア菌LPS投与群との差は認められなかった。空腹時血糖値は、NC群と比較してPC群で明らかな増加、及びPC群と比較してパントエア菌LPS投与群で有意に低下した。同様に、HbA1cは、NC群と比較してPC群で明らかな増加、及びPC群と比較してパントエア菌LPS 1mg/kg体重/day群で有意に低下した。また、肝臓重量及び精巣上体周囲白色脂肪重量は、NC群と比較してPC群で明らかな増加、及びPC群と比較してパントエア菌LPS投与群での有意な低下が認められた(表1)。このことから、高脂肪飼料を摂取したマウスでは、2型糖尿病様の症状(血糖値やHbA1c値の上昇等)を発症しており、パントエア菌LPSの投与により、糖代謝機能が改善されることが分かる。
Claims (5)
- アミロイドβタンパク質の脳内蓄積を抑制することによって脳機能を改善するための脳機能改善剤、食品又は医薬品であって、パントエア菌LPSからなるリポ多糖を有効成分とし経口投与、経皮投与又は口腔投与する、脳機能改善剤、食品又は医薬品。
- 改善される脳機能が、加齢又は加齢に伴う脳疾患に起因して低下した認知機能であることを特徴とする請求項1に記載の脳機能改善剤、食品又は医薬品。
- パントエア菌LPSを有効量含有する、請求項1に記載の脳機能改善剤、食品又は医薬品。
- アルツハイマー病を予防するための、請求項1に記載の脳機能改善剤、食品又は医薬品。
- パントエア菌LPSを1日投与単位あたり0.1~1mg/kg体重の割合で含有する請求項1に記載の脳機能改善剤、食品又は医薬品。
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KR1020197038343A KR20200011490A (ko) | 2017-05-28 | 2017-12-04 | 리포 다당을 사용한 뇌기능 개선제, 식품 및 의약품 |
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IL270936A IL270936B2 (en) | 2017-05-28 | 2017-12-04 | A factor, food and drug that improve brain activity through lipopolysaccharide |
US16/617,540 US11278564B2 (en) | 2017-05-28 | 2017-12-04 | Brain function-improving agent, food, and medicine using lipopolysaccharide |
CN201780091325.7A CN110691599B (zh) | 2017-05-28 | 2017-12-04 | 使用脂多糖的脑功能改善剂、食品和药品 |
PCT/JP2017/043429 WO2018220886A1 (ja) | 2017-05-28 | 2017-12-04 | リポ多糖を用いた脳機能改善剤、食品及び医薬品 |
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Non-Patent Citations (3)
Title |
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INAGAWA, Hiroyuki et al.,Primed Activation of Macrophages by Oral Administration of Lipopolysaccharide Derived from Pantoea a,in vivo,2016年,Vol.30,pp.205-211,ISSN:0258-851X, 特に第210頁左欄第27行~第36行 |
KOBAYASHI, Y. et al.,Effect of Lipopolysaccharide Derived from Pantoea agglomerans on the Phagocytic Activity of Amyloid,Anticancer Res.,2016年,Vol.36(7),pp.3693-3698,ISSN:0250-7005, 特に「アブストラクト」、第3693頁右欄第1行~第7行、第19行、第3693頁右欄第 |
池田幸矢 ほか,マクロファージ細胞株RAW264.7におけるPantoea agglomerans由来LPSの貪食能活性化に関する検討,バイオ治療法研究会学術集会プログラム・抄録集,2016年,第20回,p.42,特に「背景・目的」欄 |
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EP3643314C0 (en) | 2023-08-30 |
IL270936B2 (en) | 2023-10-01 |
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IL270936B1 (en) | 2023-06-01 |
EP3643314A1 (en) | 2020-04-29 |
EP3643314B1 (en) | 2023-08-30 |
KR20220025912A (ko) | 2022-03-03 |
KR20200011490A (ko) | 2020-02-03 |
WO2018220886A1 (ja) | 2018-12-06 |
US20200179436A1 (en) | 2020-06-11 |
EP3643314A4 (en) | 2021-04-07 |
CN110691599A (zh) | 2020-01-14 |
JP2021169506A (ja) | 2021-10-28 |
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US11278564B2 (en) | 2022-03-22 |
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