JP6830266B2 - Nash改善用組成物、nash改善用食品組成物、nash改善用飲料組成物、nashから肝硬変への移行予防用組成物及びnashから肝細胞癌への移行予防用組成物 - Google Patents
Nash改善用組成物、nash改善用食品組成物、nash改善用飲料組成物、nashから肝硬変への移行予防用組成物及びnashから肝細胞癌への移行予防用組成物 Download PDFInfo
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Description
<菌糸塊からの分離>
(1)培地の調製
下記表1に示す配合で、PSA培地及びPDA培地を調製し、試験管又は三角フラスコに分注した後、シリコセン(又は綿栓)を施しオートクレーブにより121℃20分高圧蒸気滅菌した。その後、試験管の場合は、滅菌後熱いうちに傾斜させてスラント(斜面)培地とし、三角フラスコの場合は、そのまま静置してプレート(平面)培地とした。
大きめのバシディオマイセテスX菌糸塊を手で割り、火炎滅菌したメスを冷却させてからバシディオマイセテスX断面より切片を切断し、火炎滅菌冷却後のピンセットで、(1)のPSA培地及びPDA培地スラントにバシディオマイセテスX切片を植菌した。なお操作は、無菌箱又はクリーンベンチ内の、無菌処理済み条件下で行った。
1cm角としたジャガイモ200gを、精製水を用いて煮沸後20分継続、冷却後、固液分離したジャガイモ浸出液、スクロース20g及びAgar1g(0.1%)に蒸留水を全量1Lとなるように加えて、Agar培地を調整した。なお、通常Agar培地は1.5〜2.0(培地1Lに対し、15g〜20g)のAgar添加するが、培養後の菌糸塊と、Agar培地の分離を容易にするため、また液体培地ではバシディオマイセテスXの切片が沈降しやすいため物理的強度を維持する目的で、0.1%添加することとした。この0.1%Agar培地を試験管に各5mLに分注し、シリコセンを施した後オートクレーブにより121℃20分間高圧蒸気滅菌した。その後、無菌処理済みの無菌箱内において、製造例1のスラントにおいて培養中のバシディオマイセテスX菌糸塊から切片を切除し、0.1%Agar培地に無菌操作により植菌した。24℃条件下でインキュベーターにおいて培養させたところ、24時間〜48時間後には発菌した。発菌後、24℃条件下で培養を継続すると、14日間でAgar培地上に菌糸が生育した。
<菌糸塊生産のためのおがくず培地による培養>
(1)種菌の培養
おがくず1L、脱脂ぬか15g、ふすま15g及びサンパール(菌糸活性剤・日本製紙製)5gに、水を加えて十分に攪拌し、培地を強く握って水がにじむ程度(湿式含水率70%程度)として、おがくず培地を調製した。この培地を三角フラスコに入れ、シリコセンを施した後、オートクレーブにより121℃40分高圧蒸気滅菌した。滅菌後24時間後に、製造例1のスラントにて培養中のバシディオマイセテスX菌糸を無菌箱内にて無菌操作によっておがくず培地に植菌した。なお、植菌は滅菌三角刀でスラントの一部を切除するようにし、菌糸にダメージを与えないよう行った。また、植菌の密度は、おがくず培地表面積の20%〜30%とした。24℃条件下で培養したところ3日後(遅くとも5日後)に発菌し、30日後には三角フラスコおがくず培地に菌糸が充満した。
(1)と同様にしたおがくず培地を調製し、この培地をポリプロピレン製ビンに入れ、フタをして、オートクレーブにより121℃40分高圧蒸気滅菌した。滅菌後24時間後、無菌処理済みの無菌箱内において無菌操作により、(1)で培養した種菌をポリプロピレン製ビンのおがくず培地に植菌した。なお、植菌の密度は、おがくず培地表面積がほぼ覆われる程度とした。24℃条件下で培養したところ、48時間後に発菌し、60日後にはポリプロピレン製ビン内のおがくず培地全体に菌糸が充満した。更に40日〜50日経過すると、ポリプロピレン製ビン内壁に菌糸が展開し、菌糸束を形成、更に培養を継続すると菌糸塊を形成した。
<バシディオマイセテスX乾燥粉末の製造>
菌糸の細胞壁に損傷を与え、細胞内容物が浸出することを容易にするため、製造例2で得られた生鮮バシディオマイセテスX菌糸塊を冷凍・凍結させ、凍結しているバシディオマイセテスX菌糸塊を常温解凍し、ミキサーを用いて破砕したものを乾燥して粉末に加工した(以下、「バシディオマイセテスX乾燥粉末」という)。
<バシディオマイセテスX抽出組成物乾燥粉末の製造>
製造例3で得られたバシディオマイセテスX乾燥粉末(乾燥重量4kg)を計りとり、水20Lを加えた後、適宜撹拌しながら4〜6時間静置培養した。その後、吸引濾過により固形物(以下、「バシディオマイセテスX抽出残渣」という)を除き、バシディオマイセテスX抽出組成物17.6kg(固形分:8.0%)を得た。最後に−40℃で予備凍結の後、凍結乾燥に供した(以下、バシディオマイセテスX抽出組成物乾燥粉末という)。
製造例4で得られたバシディオマイセテスX抽出組成物乾燥粉末を水に溶かし、1日の投与量が500mg/kg体重となるように調製したものを被験物とした。
生後間もないC57BL/6系雌性マウス各個体を、非アルコール性脂肪性肝炎(以下、「NASH」という)を発症させていない健常(正常)群(n=5)(以下、「Normal群」という)、軽度のNASHを発症させた無治療群(n=5)(以下、「HFD−8W群」という)、重度のNASHを発症させた無治療群(n=8)(以下、「NASH群」という)、及び重度のNASHを発症させ5%バシディオマイセテスX抽出組成物乾燥粉末を投与したNASH改善群(n=6)(以下、「NASH+Mushroom群」という)群の4群に分けた。
健常群のマウスを除いて、生後およそ1週目にマウスあたり200μgのストレプトゾトシン(streptozotocin:STZ)を皮下注射した。何れの群も通常飼料による生後4週間の予備飼育後、健常食又は高脂肪食(日本クレア社製、日本)を各群、次のように摂餌させた。
12週間又は16週間が経過した後に各試験群に対して一晩絶食をかけて空腹時採血を行い血液検査に供した。これらの結果を図1に示した。図1において、(a)〜(e)は各試験群の血液検査結果を示すグラフであり、(a)はALT濃度、(b)はAST濃度、(c)はAPL濃度、(d)はTC濃度、(e)はTG濃度をそれぞれ示す。
上記(1)の各試験後に犠死させた後に解剖して各試験群の体重(Body weight:BW)に対する肝重量(Liver weight:LW)及び脾臓重量(Spleen weight:Sp)と血糖値を測定し、その測定結果を図2に示した。図2において、(a)〜(c)は各試験群の各臓器量及び血糖値の測定結果を示すグラフであり、(a)は肝重量/体重、(b)は脾臓重量/体重、(c)は血糖値をそれぞれ示す。
上記(4)の解剖時に肝臓を採取し、ヘマトキシリン・エオシン染色(以下、「H&E染色」という)及びマッソントリクローム(Masson trichrome)染色(以下、「MT染色」という)を行って肝臓組織を観察し、その結果を図3に示した。
上記(2)の解剖時に採取し肝臓組織をポリトロンで処理し、BCA(bicinchoninicacid)法によりタンパク質の定量を行った。その後、2×sample bufferを加えてウエスタンブロッティングの試料とした。各試料中の総タンパクを10%SDS−polyaclylamidegel electrophoresis (SDS−PAGE)ゲルを用いて150V、50分で電気泳動し、10V、60分でニトロセルロース膜に転写した。転写後、この膜のバンドをPoncean Sで染色し確認した後、PBSで洗浄し、5%BSAを用いて1時間blockingを行った。
Claims (6)
- バシディオマイセテスX(Basidiomycetes−X)FERM BP−10011乾燥粉末又はその抽出組成物を有効成分とすることを特徴とするNASH改善用組成物。
- 粉末、顆粒、錠剤、カプセル、溶液状及びゲル状から選択される何れかの形態であることを特徴とする請求項1に記載のNASH改善用組成物。
- バシディオマイセテスX(Basidiomycetes−X)FERM BP−10011乾燥粉末又はその抽出組成物を有効成分とすることを特徴とするNASH改善用食品組成物。
- バシディオマイセテスX(Basidiomycetes−X)FERM BP−10011乾燥粉末又はその抽出組成物を有効成分とすることを特徴とするNASH改善用飲料組成物。
- バシディオマイセテスX(Basidiomycetes−X)FERM BP−10011乾燥粉末又はその抽出組成物を有効成分とし、NASHから肝硬変への移行を予防することを特徴とするNASHから肝硬変への移行予防用組成物。
- バシディオマイセテスX(Basidiomycetes−X)FERM BP−10011乾燥粉末又はその抽出組成物を有効成分とし、NASHから肝細胞癌への移行を予防することを特徴とするNASHから肝細胞癌への移行予防用組成物。
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |