JP5747205B2 - 抗インフルエンザ剤 - Google Patents
抗インフルエンザ剤 Download PDFInfo
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- JP5747205B2 JP5747205B2 JP2010053732A JP2010053732A JP5747205B2 JP 5747205 B2 JP5747205 B2 JP 5747205B2 JP 2010053732 A JP2010053732 A JP 2010053732A JP 2010053732 A JP2010053732 A JP 2010053732A JP 5747205 B2 JP5747205 B2 JP 5747205B2
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- extract
- influenza
- agaricus
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- ethanol
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Description
アガリクス ブラゼイ ムリルの乾燥子実体を約0.7cm角サイズに粗砕したもの300gをステンレス製耐圧釜に仕込み、イオン交換水3Lを添加し、常圧下、90℃で3時間抽出処理した後、減圧濾過して残渣を分離し第1抽出液を採取した。次いで、前記残渣にイオン交換水2.5Lを加えて同様に処理して第2抽出液を採取した。両抽出液を合わせて減圧濃縮及び凍結乾燥処理し、アガリクス茸抽出物(試料1)40.5gを得た。
製造例1において、常圧下を1.3気圧の加圧下に置き換えて同様に処理してアガリクス茸抽出物(試料2)88.0gを得た。
製造例2で得た試料2の一部50gにエタノール濃度が65%の含水エタノール400mLを加え、常圧下で一旦溶解後30℃にて1時間静置し、生じた沈殿物を遠心分離して前記含水エタノールに可溶の画分と不溶の画分に分別した。含水エタノール可溶画分は、減圧濃縮及び凍結乾燥して前記含水エタノールに可溶のアガリクス茸抽出物(試料3)17.4gを得た。又、含水エタノール不溶画分(沈殿物)は、加水後、減圧濃縮でアルコールを除去し凍結乾燥して前記含水エタノールに不溶のアガリクス茸抽出物(試料4)32.1gを得た。
アガリクス ブラゼイ ムリルの乾燥菌糸体300gをステンレス製耐圧釜に仕込み、イオン交換水3Lを添加し、常圧下、90℃で3時間抽出処理した後、精密濾過して残渣を分離し第1抽出液を採取した。次いで、前記残渣にイオン交換水2.5Lを加えて同様に処理して第2抽出液を採取した。両抽出液を合わせて減圧濃縮及び凍結乾燥し、アガリクス茸抽出物(試料5)143.2gを得た。
製造例4で得た試料5の一部50gにエタノール濃度が40%の含水エタノール400mLを加え、常圧下で一旦溶解後30℃にて1時間静置し、生じた沈殿物を遠心分離して採取した。この沈殿物に加水した後、減圧濃縮でアルコールを除去し更に乾燥処理して前記含水エタノールに不溶のアガリクス茸抽出物(試料6)30.6gを得た。
マッシュルームの生の子実体500gを約0.5mm角サイズに細断してステンレス製耐圧釜に仕込み、イオン交換水10Lを加え、常圧下、70℃で1時間抽出処理した後、減圧濾過して残渣を分離した抽出液を得た。次いで、この抽出液に最終エタノール濃度が50%になるようにエタノールを添加してゆるやかに攪拌し、常圧下、30℃にて5時間静置後、生じた沈殿物を遠心分離して採取した。更に、この沈殿物に加水、減圧濃縮及び凍結乾燥して、前記エタノール不溶分からなるアガリクス茸抽出物(試料7)40.5gを得た。
カシスの果実部の圧搾液1Lにエタノール濃度が70%の含水エタノール10Lを加え、常圧下、40〜50℃で30分間抽出処理し、残渣除去、濃縮及び乾燥処理してカシス抽出物(試料8)7.3gを得た。
クランベリーの果実部の乾燥物100gにエタノール濃度が70%の含水エタノール1Lを加え加え、50〜60℃で2時間抽出処理し、残渣除去、濃縮及び乾燥処理してクランベリー抽出物(試料9)21.6gを得た。
コケモモの果実及び葉の乾燥混合物100gにエタノール濃度が90%の含水エタノール1Lを加え加え、50〜60℃で2時間抽出処理し、残渣除去、濃縮及び乾燥処理してコケモモ抽出物(試料10)15.0gを得た。
アガリクス ブラゼイ ムリルの乾燥子実体を約0.7cm角サイズに粗砕したもの300gをステンレス製耐圧釜に仕込み、ヘキサン3Lを添加し、常温常圧下で1時間抽出処理後、減圧濾過して抽出液と残渣に分離した。抽出液を脱溶媒及び乾燥処理してヘキサン抽出物(比較試料1)を得た。この抽出物の成分は遊離脂肪酸、エルゴステロール等の遊離ステロール及びその配糖体、リン脂質、セラミド等の脂質類がほとんどを占め、遊離脂肪酸はリノール酸が主成分であった。
本試験において、インフルエンザウィルス株はインフルエンザウィルスA/NWS/33(H1N1)を用いた。又、細胞はMadin−Darby canine kidney(MDCK)細胞を、細胞の培養には2%fetal bovine serum(FBS)含有Eagle’s minimal essential medium(MEM)培地を用いた。
48穴プレートにMDCK細胞を播き、2%FBS含有MEM培地で培養した後、同培地に溶解した試料とウィルス液(0.2PFU/Cell)を添加して室温で1時間放置した後、前記培養培地を除去し、さらに前記培地で3回洗浄して細胞に感染していないウィルスを除去した後、前記培地に溶解した試料を再度添加して37℃、5%CO2条件下で24時間培養した。培養終了後、−80℃の冷凍庫へ移し、細胞を死滅させた後、ウィルス量をプラークアッセイ法で測定した。片対数グラフ上で50%ウィルス増殖阻害濃度(IC50)を求めた。この結果を表1に示す。同表において、IC50の値が小さいものほど、インフルエンザウィルスの感染を阻害している効果が高いことを示す。
BALB/cマウス(雌、6週齢)に試料を2週間連続経口投与した後、A型インフルエンザウィルス(H1/N1株)を7.5(log)TCID50にて経鼻感染させた(一次感染)。該感染3日後、血液を採取してリンパ球の幼弱化試験を行った。更に、マウスを屠殺して脾臓を摘出し、該脾臓から調製したリンパ球のNK活性を測定した。
リンパ球幼若化試験は、回収した末梢血リンパ球を3H−Thymidine存在下でフィトヘマグルチニンPによる抗原刺激を行い96時間培養した後の3H−Thymidineの取込量を液体シンチレーションカウンターにて測定した。生理食塩水投与群を100として増減の割合を求めた。又、NK活性は、マウスの脾臓より調製したリンパ球を、51Crを標識したYac−1細胞を標的細胞として混合培養を行い、放出された51Cr量を液体シンチレーションカウンターにて測定し、次式によりNK活性を求めた。
%Lysis=100×((検体の51Cr遊離値(cpm)−自然51Cr遊離値(cpm))/(最大51Cr遊離値(cpm)−自然51Cr遊離値(cpm))
本試験の結果を表2にまとめた。
BALB/cマウス(雌、6週齢)に試料を2週間連続経口投与した後、A型インフルエンザウィルス(H1/N1株)を7.5(log)TCID50にて経鼻感染させた(一次感染)。インフルエンザウィルス感染後も引き続き試料の経口投与を試験期間中継続して行った。感染3週間後、9.5(log)TCID50にて再度前記インフルエンザウィルスを経鼻感染させた(二次感染)。二回目の感染後のマウスの生存数を観察した。試料は全て100mg/kgで経口投与した。本試験の結果を表3にまとめた。
製造例3に記載の方法で調製したアガリクス茸の子実体の熱水抽出物の含水エタノール沈殿画分(試料4):170部、ミツロウ:30部及びコーン油:50部を約50℃に加熱混合して均質にした後、カプセル充填機に供して、常法により1粒あたり内容量が300mgのゼラチン被覆ソフトカプセル製剤を試作した。また、前記試料4を製造例1の方法で調製したアガリクス茸の熱水抽出物(試料1)に置き換えることを除き同様に処理してソフトカプセル製剤を試作した。これらのカプセル製剤は経口摂取できる栄養補助食品又は医薬品として利用できる。
試作例1において、試料4:170部を試料4:100部及び製造例8の方法で調製したクランベリーの含水エタノール抽出物(試料9):70部の混合物に置きかえて同様に処理して栄養補助食品を試作した。
試作例1において、試料4:170部を製造例2の方法で調製したアガリクス茸の加圧熱水抽出物(試料2):130部及び製造例7の方法で調製したカシスの抽出物(試料8):40部の混合物に置きかえて同様に処理して栄養補助食品を試作した。
試料2:100部、製造例5の方法で調製したアガリクス茸の菌糸体抽出物のエタノール沈殿画分(試料6):30部、化工デンプン(松谷化学工業(株)製、商品名:「パインフロー」):70部、リン酸三カルシウム(米山化学工業(株)製):85部、及びセルロース35部を混合機に仕込み、10分間攪拌混合した。この混合物を直打式打錠機に供して直径7mm、高さ4mm、重量150mg/個の素錠を作成し、ついでコーティング機でシェラック被膜を形成させて錠剤形状の経口摂取用組成物を試作した。
市販のグレープジュース1000部に製造例6の方法で調製したアガリクス茸の子実体抽出物のエタノール不溶画分(試料7):10部及び試料9:3部を加えて十分に混合し均質なグレープ風味飲料を試作した。これは冷蔵庫で1週間保存しても外観及び風味に異状及び違和感は認められなかった。
Claims (4)
- アガリクス ブラゼイ ムリル(Agaricus blazei Murill)の子実体を80℃以上の熱水で30分〜5時間抽出処理して得た熱水抽出物を、さらにエタノール濃度が40%以上かつ70%以下のエタノール水溶液を用いて抽出処理して得られる、該エタノール水溶液に不溶の成分を有効成分として含有してなることを特徴とする抗インフルエンザ剤(但し、エキナセアとの併用は除く。)。
- スグリ属及びスノキ属からなる群から選択される1種又は2種の属に属する植物の乾燥粉末及び/又は抽出物を併用するものである請求項1に記載の抗インフルエンザ剤。
- スグリ属に属する植物がカシスであり、スノキ属に属する植物がクランベリー又はコケモモである請求項2に記載の抗インフルエンザ剤。
- 請求項1〜3のいずれか1項に記載の抗インフルエンザ剤を配合してなることを特徴とする医薬品、飼料又はペットフード。
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