JP6642892B2 - ジメチルアミノミケリオリドを含む肺線維化の治療薬 - Google Patents
ジメチルアミノミケリオリドを含む肺線維化の治療薬 Download PDFInfo
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- JP6642892B2 JP6642892B2 JP2018510880A JP2018510880A JP6642892B2 JP 6642892 B2 JP6642892 B2 JP 6642892B2 JP 2018510880 A JP2018510880 A JP 2018510880A JP 2018510880 A JP2018510880 A JP 2018510880A JP 6642892 B2 JP6642892 B2 JP 6642892B2
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Description
昆明マウス(雄性):中国人民解放軍軍事医学科学院の試験動物センターと、北京維通利華実験動物技術有限公司とにより提供された。
ACT001フマル酸塩:白色粉末、天津尚徳薬縁科技股▲ふん▼有限公司から購入、ロット番号20131112。
1.マウス肺線維化モデルの作成及び投与治療
1.1 マウス肺線維化モデルの作成
各群を12匹として、マウス36匹を正常群、対照群(肺線維化モデル群)及びACT001群(モデリング後にACT001を投与)にランダムに分けた。正常群のそれぞれに対して0.9%生理食塩水0.15mLを一括して強制胃内投与し、対照群及びACT001群のそれぞれに対してメチルビオロゲン水和物の水溶液0.15mLを一括して強制胃内投与した。
モデリングしてから三週後に、マウスに薬物を投与した。すなわち、正常群及び対照群に対して毎回0.9%生理食塩水0.1mLを強制胃内投与し、ACT001群に対して毎回ACT001水溶液0.1mLを強制胃内投与した。2日間置きに1回投与した。
モデリングしてから三週後と、投与してから二週後と、投与してから三週後とに、それぞれ正常群、対照群、ACT001群から4匹のマウスを選択して、頸椎脱臼により屠殺後、肺組織を取り、10%ホルマリンで2日間固定した後、肺組織表面における固定液を流水で洗浄し、病理組織脱水装置を用いて肺組織に対して脱水処理を行い、パラフィンで包埋し、包埋組織を切片して、H.E染色をして、スライドガラスを載せて、顕微鏡下で肺組織の変化を観察した。
1)モデル作成結果
図1に、正常マウスの肺組織切片図を示す。図2に、マウス肺線維化をモデリングしてから三週後のマウスの肺組織切片の効果図を示す。図2から明らかなように、モデリング群には明らかな肺線維化が発生した。具体的には、細胞外マトリックス成分が肺胞と間質内に蓄積し、線維組織が過剰に修復し、肺繊維が増殖し、肺間質が繊維化され、コラーゲンが蓄積して、肺胞構造が変化した。
ACT001を投与してから二週後にマウスを解剖して、ACT001の肺線維化への薬効を検出した。解剖後、マウスの肺組織を観察した。その結果を図3Aに示す。図3AはACT001を投与してから二週後のマウスの肺組織外部形態の立体顕微鏡下での効果図であり、図3Aから明らかなように、対照群と比べて、ACT001投与群は、肺組織がより一層赤くつやつやして、肺組織の血液供給が大幅に改善しており、肺組織の色は鮮やかな赤であり、肺組織の表面はより一層赤くつやつやしており、正常群のマウスの外観に相当する。これに対して、モデリングした非投与群のマウスは、肺組織表面の色が暗く、肺組織の表面は赤くつやつやしていなかった。以上から分かるように、ジメチルアミノミケリオリド(ACT001)投与群のマウスの肺組織では、血液供給が著しく改善された。ACT001の投与によって、肺の血液供給を改善して、生体の呼吸困難等の症状を緩和できることが分かった。
Claims (5)
- 生体の肺線維化レベルを反転して抑制し、肺細胞外マトリックスの過剰な蓄積を抑制し、肺の血液供給を改善するための薬物であることを特徴とする請求項1に記載の肺線維化の治療薬。
- 前記肺線維化の治療薬は、添加剤を含むことを特徴とする請求項1に記載の肺線維化の治療薬。
- 前記肺線維化の治療薬の剤型は、錠剤、カプセル剤、丸剤、座薬、エアロゾル、経口液剤、顆粒剤、散剤、注射剤、シロップ剤、薬酒、チンキ剤、ドロップ剤、フィルム剤又はそれらの組み合わせから選ばれることを特徴とする請求項1〜3のいずれか1項に記載の肺線維化の治療薬。
- 前記肺線維化の治療薬は、経口投与用、注射投与用、移植用、外用、噴霧投与用、吸入投与用又はそれらの組み合わせであることを特徴とする請求項4に記載の肺線維化の治療薬。
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AU2016390488B2 (en) | 2019-12-12 |
WO2017128163A1 (zh) | 2017-08-03 |
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