JPWO2020009135A1 - インフルエンザの重症化を抑制するための抗インフルエンザウイルス剤 - Google Patents
インフルエンザの重症化を抑制するための抗インフルエンザウイルス剤 Download PDFInfo
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Abstract
Description
[1] ビフィドバクテリウム・ビフィダムを有効成分として含有する、抗インフルエンザウイルス剤。
[2] ビフィドバクテリウム・ビフィダムが、呼吸器におけるインフルエンザウイルス増殖抑制作用を有する、上記[1]に記載の抗インフルエンザウイルス剤。
[3] ビフィドバクテリウム・ビフィダムが、ビフィドバクテリウム・ビフィダム(Bifidobacterium bifidum)OLB6378株(受託番号NITE BP-31)である、上記[1]又は[2]に記載の抗インフルエンザウイルス剤。
[4] インフルエンザの重症化を抑制するための、上記[1]〜[3]のいずれかに記載の抗インフルエンザウイルス剤。
[5] ビフィドバクテリウム・ビフィダムが、ビフィドバクテリウム・ビフィダム菌体の培養物、加熱処理物、乾燥物、及び濃縮物、並びにそれらのうち2つ以上の組合せからなる群から選択される、上記[1]〜[4]のいずれかに記載の抗インフルエンザウイルス剤。
[6] 上記[1]〜[5]のいずれかに記載の抗インフルエンザウイルス剤を含む、インフルエンザの重症化を抑制するための食品。
[7] 上記[1]〜[5]のいずれかに記載の抗インフルエンザウイルス剤を含む、インフルエンザの重症化を抑制するための医薬。
本明細書は本願の優先権の基礎となる日本国特許出願番号2018-127101号の開示内容を包含する。
本発明は、ビフィドバクテリウム・ビフィダム、好ましくは、呼吸器におけるインフルエンザウイルス増殖抑制作用を有するビフィドバクテリウム・ビフィダムの、抗インフルエンザウイルス剤としての用途に関する。
ビフィドバクテリウム・ビフィダム(Bifidobacterium bifidum)OLB6378株(受託番号NITE BP-31)を、ホエイタンパク質分解培地(酵素分解したホエイタンパク質を主窒素源とする培地)中で、嫌気的に中和培養し、濃縮菌液を得た。濃縮菌液を80℃で10分以上インキュベートした後、凍結乾燥を行った。得られた凍結乾燥物は2.5×1011細胞/gを超える菌体濃度を示した。このようにして調製した、加熱処理OLB6378菌株の凍結乾燥物を、OLB6378濃縮粉末と称し、後述のとおり抗インフルエンザウイルス作用について試験した。
実施例1で調製したOLB6378濃縮粉末の抗インフルエンザウイルス作用を、インフルエンザウイルス感染後の「生存率」と「呼吸器での感染性ウイルス価(ウイルス増殖レベル)」の点から評価した。
BALB/cマウス(雌性、8週齢)(日本クレア)に、水(水投与群)又はOLB6378濃縮粉末の20%懸濁液(OLB6378/ビフィズス菌投与群)を0.2 ml/個体/日の用量で4週間にわたり連日経口投与した。経口投与開始後3週間の時点でマウスを麻酔薬ソムノペンチル(R)(有効成分ペントバルビタールナトリウム量で5 mg/kg体重)の腹腔内投与により麻酔し、マウス馴化インフルエンザウイルス株A/PR/8/34(H1N1)懸濁液20 μl(2×LD50 [半数致死量の2倍量相当]、0.1% BSA-PBS)を右側鼻腔に経鼻接種し、インフルエンザウイルスの下気道感染を引き起こした。また陽性対照として、水又はOLB6378濃縮粉末の20%懸濁液の投与に代えて、抗インフルエンザ薬である「オセルタミビル」(1 mg/kg体重/日)を上記と同様のインフルエンザウイルス接種の1時間前から6日後まで経口投与した。ウイルス接種開始から21日間マウスの生存率を記録した。生存検定はKaplan-Meier法のlog-rank検定により行った。
BALB/cマウス(雌性、8週齢)(日本クレア)に、水(水投与群)又はOLB6378濃縮粉末の20%懸濁液(OLB6378投与群;試験群)を0.2 ml/個体/日の用量で25日間(ウイルス接種21日前から3日後まで)連日経口投与した。経口投与開始後3週間の時点でマウスを麻酔薬ソムノペンチル(R)(有効成分ペントバルビタールナトリウム量で5 mg/kg体重)の腹腔内投与により麻酔し、マウス馴化インフルエンザウイルス株A/PR/8/34(H1N1)懸濁液20 μl(2×LD50 [半数致死量の2倍量相当]、0.1% BSA-PBS)を右側鼻腔に経鼻接種し、インフルエンザウイルスの感染を引き起こした。また陽性対照として、水又はOLB6378濃縮粉末の20%懸濁液の投与に代えて、抗インフルエンザ薬である「オセルタミビル」(1 mg/kg体重/日)を上記と同様のインフルエンザウイルス接種の1時間前から3日後まで経口投与した。ウイルス接種から4日後、マウスの気管支肺胞洗浄液(BALF)を調製した。気管支肺胞洗浄液の感染性ウイルス価をプラーク法により測定した。具体的には、MDCK細胞(イヌ腎臓尿細管上皮細胞由来の細胞株)を気管支肺胞洗浄液に暴露させた後、ウイルス感染による細胞変性により形成されたプラーク数をカウントし、気管支肺胞洗浄液1 mLあたりのプラーク形成数を感染性ウイルス価として評価した。統計学的処理は分散分析法(ANOVA)とDunnett検定により行った。
Claims (7)
- ビフィドバクテリウム・ビフィダムを有効成分として含有する、抗インフルエンザウイルス剤。
- ビフィドバクテリウム・ビフィダムが、呼吸器におけるインフルエンザウイルス増殖抑制作用を有する、請求項1に記載の抗インフルエンザウイルス剤。
- ビフィドバクテリウム・ビフィダムが、ビフィドバクテリウム・ビフィダム(Bifidobacterium bifidum)OLB6378株(受託番号NITE BP-31)である、請求項1又は2に記載の抗インフルエンザウイルス剤。
- インフルエンザの重症化を抑制するための、請求項1〜3のいずれか1項に記載の抗インフルエンザウイルス剤。
- ビフィドバクテリウム・ビフィダムが、ビフィドバクテリウム・ビフィダム菌体の培養物、加熱処理物、乾燥物、及び濃縮物、並びにそれらのうち2つ以上の組合せからなる群から選択される、請求項1〜4のいずれか1項に記載の抗インフルエンザウイルス剤。
- 請求項1〜5のいずれか1項に記載の抗インフルエンザウイルス剤を含む、インフルエンザの重症化を抑制するための食品。
- 請求項1〜5のいずれか1項に記載の抗インフルエンザウイルス剤を含む、インフルエンザの重症化を抑制するための医薬。
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PCT/JP2019/026399 WO2020009135A1 (ja) | 2018-07-03 | 2019-07-03 | インフルエンザの重症化を抑制するための抗インフルエンザウイルス剤 |
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JP (1) | JPWO2020009135A1 (ja) |
CN (1) | CN112351693A (ja) |
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TWI805237B (zh) * | 2020-05-06 | 2023-06-11 | 葡萄王生技股份有限公司 | 乳酸菌用於製備抗病毒組合物的用途 |
TWI757735B (zh) * | 2020-05-06 | 2022-03-11 | 葡萄王生技股份有限公司 | 乳酸菌用於製備抗病毒組合物的用途 |
CN115886073A (zh) * | 2022-04-01 | 2023-04-04 | 北京三元食品股份有限公司 | 一种发酵乳 |
CN117018169A (zh) * | 2023-10-07 | 2023-11-10 | 广州菲勒生物科技有限公司 | 一种预防呼吸道病毒感染的营养组合物制剂 |
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WO2006087913A1 (ja) * | 2005-02-02 | 2006-08-24 | Meiji Dairies Corporation | 免疫賦活用組成物 |
JP2008520640A (ja) * | 2004-11-16 | 2008-06-19 | アニドラル エス.アール.エル. | プロバイオティクス細菌系組成物、ならびに、呼吸病態および/または呼吸器系感染の予防および/または治療、および腸機能改善へのその使用 |
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WO2008053444A2 (en) * | 2006-11-01 | 2008-05-08 | The Procter & Gamble Company | Treating a respiratory condition with bifidobacterium |
WO2017069163A1 (ja) * | 2015-10-19 | 2017-04-27 | 株式会社明治 | 乳児向けの感染防御剤 |
KR102570293B1 (ko) * | 2015-11-23 | 2023-08-25 | 내츄럴헬스케어 주식회사 | 발효 인삼 추출물을 포함하는 항 인플루엔자 바이러스 조성물 |
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JP2008520640A (ja) * | 2004-11-16 | 2008-06-19 | アニドラル エス.アール.エル. | プロバイオティクス細菌系組成物、ならびに、呼吸病態および/または呼吸器系感染の予防および/または治療、および腸機能改善へのその使用 |
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US20210268042A1 (en) | 2021-09-02 |
CN112351693A (zh) | 2021-02-09 |
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