JP2023528883A - 呼吸器系傷害改善用医薬組成物及び呼吸器系傷害改善用医薬組成物の製造のための用途 - Google Patents
呼吸器系傷害改善用医薬組成物及び呼吸器系傷害改善用医薬組成物の製造のための用途 Download PDFInfo
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Abstract
Description
本発明の一実施例において、この医薬組成物は、治療薬物を更に含む。この治療薬物は、例えば、抗菌薬、抗ウイルス薬(ウイルスの種類によって異なり、レボセビル(Remdesivir)、カルバムスタンメネート(Camostat mesylate)、ロピナビル(Lopinavir)、リトンビル(Ritonavir)、ファビラビル(Favipiravir)、アルビレン(Umifenovir)、アデノヌクレオチド類似体(adenosine nucleotide analogues)、プロテアーゼインヒビター(protease inhibitor)、RNAポリメラーゼ阻害剤(RNA polymerase inhibitor)、融合阻害剤(fusion inhibitor)、サイトカイン、エンテカビル、イミペネム、インターフェロンであってもよく、それらに限らない)、ベンゼン環薬、抗凝固薬(例えば、ヘパリン、ヴァルファリン(warfarin)、クロピドグレル、エチレンサリチル酸、ワルファン、リバロキサバン(Rivaroxaban)、アピキサバン(Apixaban)、Edoxaban、エノパリンナトリウムなど)、血栓溶性薬物(例えば、組織型プラスミノーゲン活性化因子(tissue-type plasogen activator:tPA)、プロトプラスト活性化因子(recombinant tissue activator:rt-PA)、トロンボモジュリン(thrombomodulin:TM)、血栓溶解酵素、フォンダパリヌクスなど)、α型遮断薬(例えば、α型交感神経遮断薬(α-adrenoceptor blockers)、Terazosin(Hytrinハイトリン)、Doxazosin(Doxabenドキサゾシン)、Tamsulosin(Harnalidgeタムスロシン)又はSilodosin(Uriefカプセルなど)、5α還元酵素阻害剤(5α-Reductase inhibitor、例えば、Finasteride (Proscarプロスカー)又はDutasteride (Avodartデュタステリドカプセル)など)、鼻腔うっ血除去薬(nasal decongestants)、鎮咳剤(Antitussive)、去痰剤(Expectorants)、痰溶解薬剤(Mucolytics)、気管又は気管支拡張剤(Bronchodilators、例えば、β二型交感神経刺激剤、抗コリン薬等)、抗生物質(例えば、アミノペニシリン(aminopenicillins)系抗生物質、カルボキシペニシリン(carboxypenicillins) 系抗生物質、スルホンアミド系及びトリメトキシフェニルピリミジン-スルファメトキサミド(Sulfonamides and trimethoprim-sulfamethoxazole)系抗生物質(例えば、TMP-SMXなど)、β-ラクタム(β-lactam)系抗生物質、ユニークなβ-ラクタム(unique β-lactam)系抗生物質(例えば、Monobactams又はcarbapenems)、非β-lactam系抗生物質(例えば、マクロライド(macrolide)又はテトラサイクリン(tetracycline))、セファランチン(Cephalosporins)系抗生物質、macrolide系抗生物質、フルオロキノロン系抗生物質(Fluoroquinolones:FQ)系抗生物質、バンコマイシン(vancomycin)、リファペンチン(Rifapentine)、クロラムフェニコール(chloramphenicol)、チゲサイクリン(tigecycline)等)、抗カビ薬(例えば、amphotericin B系抗カビ剤、imidazoles系抗カビ剤、Triazoles系抗カビ剤、Griseofulvin系抗カビ剤、Nucleoside analogues系抗カビ剤、Polyenes系抗カビ剤、triazole系抗カビ剤(例えば、voriconazole、itraconazole、posaconazoleなど)、echinocandin系抗カビ剤、voriconazole系抗カビ剤、Azole系抗カビ剤、isavuconazole、flucytosine、fluconazoleなど)、抗喘息薬(Antiasthmatic drugs)、抗炎症薬(例えば、抗ロイコトリエン製剤、ステロイド、非ステロイド抗炎症薬(NSAIDs)など)、抗酸化剤(抗炎症及び抗遊離基のためのもの、例えば、メラトニン、アントシアニンなど)、漢方薬エキス(例えば、マコット石の煮汁エキス(炙マオウ、ケイシ、柴胡、生姜、カッコウ、ブクリョウ、チョレイ、沢瀉、ハンゲ、サイシン、陳皮、ビャクジュツ、紫苔、カントウカ、ヤカン、オウゴン、生石膏、みかん、杏仁、山薬、炙カンゾウ)、イソフラボン系誘導体、フラボン系化合物、ドクダミベンジン、ケルセチン、ケルセチン-3-ラムノシド、ドクダミ(デカノイルアルデヒド)(decanoyl acetaldehyde)、ラウリルアルデヒド(lauric aldehyde)、l-ピネン(l-pinene)、リナロール(linlool)、カンフェン(camphene)、ミルセン(myrcene)、リモネン(limonene)、ボルネオールアセテート(bornyl acetate)、カリオフィレン(caryophellene)、アフォリン(afzelin)、ヒペリシン(hyperin)、ルチン(rutin)、ケルセチン(quercitrin)を含有する葉、イソケルセチン(isoquercitrin)を含有する花および果実、キンギンカ、トリテルペノイドサポニン、モチクリン、ニントウカン、キンガラニン、ホコウエイ、迷香酸、オレアノール酸、アルブチン、ルチン、夏枯草、擬タンポステロールパルミチン酸、クロロゲン酸、イソクロロゲン酸、コーヒー酸、アルカロイド、ベシン、ゴマシド、フェニルプロパノシド、シクロオレフィンエーテルテルペン、バンランコン注射液(4(Hキノジメドン、3カルボニルフェニル)-1(H)キノジメドン、安息香酸、シリンガ酸、アントラニル酸、サリチル酸)など)、抗体(例えば、タシマブ(Tocilizumab)、サルモシルトマブ(Sarilumab)、イカリズマブ(Eculizumab)、ケブザラ(Kevzara)、オクラ(Actemra))、ワクチン(本発明における吸着性薬物と結合可能なワクチン、例えば、mRNAワクチン、タンパク質ワクチン、アデノウイルスワクチン、弱毒化ワクチン、分子ワクチン、又はナノワクチン)であり、ひいては治癒者の血漿であるが、上記に限らず、そのうちの1種又はそれらの組み合わせであるが、それらに限らない。
8mgの本発明の炭素材料を秤り、50 ml 0.9%生理食塩水を加えて均一に混合した。炭素材料系は、活性炭素粉末であり、表面には何ら修飾がなく、比表面積は、1248.8 m2/gであり、平均粒径は、12.08ミクロン(μm)であり、粒径分布中央値(d50、Median)は、9.453ミクロン(μm)であり、細孔容積は、0.4285 ml/gである。
図1を参照すると、図1は、本発明の異なる濃度のリポ多糖(lipopolysaccharide:LPS)を用いた、COVID-19の異なる進行を模倣する概略図である。COVID-19患者の肺におけるARDSの予防のための化合物又は治療方法を試験するために、本発明は、リポ多糖を使用してARDSの病理モデルを誘導する。リポ多糖は、グラム陰性菌の細胞壁から精製された糖であり、これがエアロゾルによって齧歯類動物の肺に送達されると、Th1免疫応答を誘発し、気道への炎症細胞(主に好中球)の突入を引き起こし、そして肺のサイトカイン(cytoline)の実質的な増加を引き起こし、したがって、さまざまな度合いのARDSを引き起こす。本発明は、異なる濃度のリポ多糖を用いることで、COVID-19の異なる進行を模倣することができる。図1に示すように、疾患の時間が進行するにつれて、その横軸で示される時間は、初期感染(phase I)、肺傷害段階(phase II)、サイトカインストーム段階(phase III)及び回復期(phase IV)を含み、ここで肺傷害段階(phase II)の進行の半分で、肺の炎症反応が発見され、炎症反応はサイトカインストーム段階(phase III)でピークに達する。
リポ多糖(lipopolysaccharide:LPS)を用いて、気管投与により7~9週間のSDラットを急性肺傷害動物モードに誘発した後、傷害前又は傷害後に上記処方の処置を施し、ラットの死亡又は瀕死現象及び炎症反応の発生が低減されるか否かを評価し、肺組織病理学的に本発明の医薬組成物が肺の傷害及び炎症反応を緩和するか否かを検討した。本実験の実験群の設計は表1に示すとおりである。
1.死亡率
処理後の死亡率は表2に示す通りであり、高濃度のLPSでは急性肺傷害を誘導するのに一定の死亡率を示したが(処理群A)、中等、低濃度のLPSでは急性肺損傷を誘導し(処理群Bと処理群C)、処理後には死亡率の低下に成功した。
A.肺タンパク質蓄積の改善の試験
滅菌後PBSで左肺葉を洗浄して気管支肺胞洗浄液(Bronchoalveolar lavage fluid:BALF)を回収し、酵素結合免疫吸着アッセイ(Enzyme-linked immunosorbent assay:ELISA )で総タンパク質量を測定した。実験結果は、図2を参照する。図2は、処理後の各気管支肺胞洗浄液群(BALF)の総タンパク質量のヒストグラムである。図2に示すように、処理群A(高用量)、処理群B(中等用量)及び処理群C(低用量)では、本発明の医薬組成物を用いることにより、BALF中の総タンパク質量を著しく低減でき、それぞれ52%、51%及び28%低減できることを見出し、本発明の医薬組成物が各段階の肺傷害に対して、肺タンパク質蓄積を改善する効能を有することが明らかになった。
滅菌後PBSで左肺葉を洗浄してBALFを採取し、ELISAによりIL-6及びIL-8等の炎症因子の濃度を定量した。図3と図4を参照すると、図3と図4はそれぞれ処理後の各群の気管支肺胞洗浄液群(BALF)のIL-6(図3)とIL-8(図4)のヒストグラムである。図3に示すように、処理群A(高用量)と処理群B(中等用量)では、本発明の医薬組成物を用いることにより、炎症因子IL-6の濃度を著しく低減することができる。図4に示すように、処理群A(高用量)では、IL-8の濃度を低減することができ、本発明の医薬組成物は、肺炎症反応を低減する効果を有することが明らかになった。
残りの肺葉(右頭蓋、右尾葉及び副葉を含む)を計量し、0.8~1.0mLの10%中性緩衝ホルマリン(neutral buffered formalin:NBF)で灌流し、次いで10倍体積の10% NBFで72~96時間、室温で保存する。定着後、肺葉を剪断し、ワックスで包埋し、ミクロトームで厚さ4~6ミクロンの切片に切断し、切片を均一にhematoxylin and eosin (H&E)染色した。
肺葉主要断面積(area of interest:AOI)の400X拡大写真を取って、中性多形核白血球浸潤(polymorphonuclear cell infiltration:PMNL infiltration )及び肺水腫(Intra alveolar edema)の等級判定を行った。各視野は≧95%の肺胞を含有しなければならず、肺浸潤及び肺水腫の観察および定量化は、10回のランダム評価によって行われ、表3は、スコアリングシステムを示す。
右正中肺葉を肺から切り出し、調整された体重で湿量基準まで秤量する。その後、試料を60℃のオーブンに24時間放置し、同じ較正用秤から乾燥重量を得た。図8を参照すると、図8は、それぞれ処理後の各群の肺水重量定量図である。図8に示すように、処理群A(高用量)、処理群B(中等用量)、及び処理群C(低用量)では、本発明の医薬組成物の使用により肺水重量を著しく低下できることを発見し、本発明の医薬組成物は肺組織の含水量を著しく低下させ、肺水腫改善効果を有することが明らかとなった。
本発明の一実施例において、この医薬組成物は、治療薬物を更に含む。この治療薬物は、例えば、抗菌薬、抗ウイルス薬(ウイルスの種類によって異なり、レボセビル(Remdesivir)、カルバムスタンメネート(Camostat mesylate)、ロピナビル(Lopinavir)、リトンビル(Ritonavir)、ファビラビル(Favipiravir)、アルビレン(Umifenovir)、アデノヌクレオチド類似体(adenosine nucleotide analogues)、プロテアーゼインヒビター(protease inhibitor)、RNAポリメラーゼ阻害剤(RNA polymerase inhibitor)、融合阻害剤(fusion inhibitor)、サイトカイン、エンテカビル、イミペネム、インターフェロンであってもよく、それらに限らない)、ベンゼン環薬、抗凝固薬(例えば、ヘパリン、ヴァルファリン(warfarin)、クロピドグレル、エチレンサリチル酸、ワルファン、リバロキサバン(Rivaroxaban)、アピキサバン(Apixaban)、Edoxaban、エノパリンナトリウムなど)、血栓溶性薬物(例えば、組織型プラスミノーゲン活性化因子(tissue-type plasogen activator:tPA)、プロトプラスト活性化因子(recombinant tissue activator:rt-PA)、トロンボモジュリン(thrombomodulin:TM)、血栓溶解酵素、フォンダパリヌクスなど)、α型遮断薬(例えば、α型交感神経遮断薬(α-adrenoceptor blockers)、Terazosin(Hytrinハイトリン)、Doxazosin(Doxabenドキサゾシン)、Tamsulosin(Harnalidgeタムスロシン)又はSilodosin(Uriefカプセルなど)、5α還元酵素阻害剤(5α-Reductase inhibitor、例えば、Finasteride (Proscarプロスカー)又はDutasteride (Avodartデュタステリドカプセル)など)、鼻腔うっ血除去薬(nasal decongestants)、鎮咳剤(Antitussive)、去痰剤(Expectorants)、痰溶解薬剤(Mucolytics)、気管又は気管支拡張剤(Bronchodilators、例えば、β二型交感神経刺激剤、抗コリン薬等)、抗生物質(例えば、アミノペニシリン(aminopenicillins)系抗生物質、カルボキシペニシリン(carboxypenicillins) 系抗生物質、スルホンアミド系及びトリメトキシフェニルピリミジン-スルファメトキサミド(Sulfonamides and trimethoprim-sulfamethoxazole)系抗生物質(例えば、TMP-SMXなど)、β-ラクタム(β-lactam)系抗生物質、ユニークなβ-ラクタム(unique β-lactam)系抗生物質(例えば、Monobactams又はcarbapenems)、非β-lactam系抗生物質(例えば、マクロライド(macrolide)又はテトラサイクリン(tetracycline))、セファランチン(Cephalosporins)系抗生物質、macrolide系抗生物質、フルオロキノロン系抗生物質(Fluoroquinolones:FQ)系抗生物質、バンコマイシン(vancomycin)、リファペンチン(Rifapentine)、クロラムフェニコール(chloramphenicol)、チゲサイクリン(tigecycline)等)、抗カビ薬(例えば、amphotericin B系抗カビ剤、imidazoles系抗カビ剤、Triazoles系抗カビ剤、Griseofulvin系抗カビ剤、Nucleoside analogues系抗カビ剤、Polyenes系抗カビ剤、triazole系抗カビ剤(例えば、voriconazole、itraconazole、posaconazoleなど)、echinocandin系抗カビ剤、voriconazole系抗カビ剤、Azole系抗カビ剤、isavuconazole、flucytosine、fluconazoleなど)、抗喘息薬(Antiasthmatic drugs)、抗炎症薬(例えば、抗ロイコトリエン製剤、ステロイド、非ステロイド抗炎症薬(NSAIDs)など)、抗酸化剤(抗炎症及び抗遊離基のためのもの、例えば、メラトニン、アントシアニンなど)、漢方薬エキス(例えば、マコット石の煮汁エキス(炙マオウ、ケイシ、柴胡、生姜、カッコウ、ブクリョウ、チョレイ、沢瀉、ハンゲ、サイシン、陳皮、ビャクジュツ、紫苔、カントウカ、ヤカン、オウゴン、生石膏、みかん、杏仁、山薬、炙カンゾウ)、イソフラボン系誘導体、フラボン系化合物、ドクダミベンジン、ケルセチン、ケルセチン-3-ラムノシド、ドクダミ(デカノイルアルデヒド)(decanoyl acetaldehyde)、ラウリルアルデヒド(lauric aldehyde)、l-ピネン(l-pinene)、リナロール(linlool)、カンフェン(camphene)、ミルセン(myrcene)、リモネン(limonene)、ボルネオールアセテート(bornyl acetate)、カリオフィレン(caryophellene)、アフォリン(afzelin)、ヒペリシン(hyperin)、ルチン(rutin)、ケルセチン(quercitrin)を含有する葉、イソケルセチン(isoquercitrin)を含有する花および果実、キンギンカ、トリテルペノイドサポニン、モチクリン、ニントウカン、キンガラニン、ホコウエイ、迷香酸、オレアノール酸、アルブチン、ルチン、夏枯草、擬タンポステロールパルミチン酸、クロロゲン酸、イソクロロゲン酸、コーヒー酸、アルカロイド、ベシン、ゴマシド、フェニルプロパノシド、シクロオレフィンエーテルテルペン、バンランコン注射液(4(Hキノジメドン、3カルボニルフェニル)-1(H)キノジメドン、安息香酸、シリンガ酸、アントラニル酸、サリチル酸)など)、抗体(例えば、タシマブ(Tocilizumab)、サルモシルトマブ(Sarilumab)、イカリズマブ(Eculizumab)、ケブザラ(Kevzara)、オクラ(Actemra))、ワクチン(本発明における吸着性薬物と結合可能なワクチン、例えば、mRNAワクチン、タンパク質ワクチン、アデノウイルスワクチン、弱毒化ワクチン、分子ワクチン、又はナノワクチン)であり、ひいては治癒者の血漿であるが、上記に限らず、そのうちの1種又はそれらの組み合わせであるが、それらに限らない。
8mgの本発明の炭素材料を秤り、50 ml 0.9%生理食塩水を加えて均一に混合した。炭素材料系は、活性炭素粉末であり、表面には何ら修飾がなく、比表面積は、1248.8 m2/gであり、平均粒径は、12.08ミクロン(μm)であり、粒径分布中央値(d50、Median)は、9.453ミクロン(μm)であり、細孔容積は、0.4285 ml/gである。
図1を参照すると、図1は、本発明の異なる濃度のリポ多糖(lipopolysaccharide:LPS)を用いた、COVID-19の異なる進行を模倣する概略図である。COVID-19患者の肺におけるARDSの予防のための化合物又は治療方法を試験するために、本発明は、リポ多糖を使用してARDSの病理モデルを誘導する。リポ多糖は、グラム陰性菌の細胞壁から精製された糖であり、これがエアロゾルによって齧歯類動物の肺に送達されると、Th1免疫応答を誘発し、気道への炎症細胞(主に好中球)の突入を引き起こし、そして肺のサイトカイン(cytoline)の実質的な増加を引き起こし、したがって、さまざまな度合いのARDSを引き起こす。本発明は、異なる濃度のリポ多糖を用いることで、COVID-19の異なる進行を模倣することができる。図1に示すように、疾患の時間が進行するにつれて、その横軸で示される時間は、初期感染(phase I)、肺傷害段階(phase II)、サイトカインストーム段階(phase III)及び回復期(phase IV)を含み、ここで肺傷害段階(phase II)の進行の半分で、肺の炎症反応が発見され、炎症反応はサイトカインストーム段階(phase III)でピークに達する。
リポ多糖(lipopolysaccharide:LPS)を用いて、気管投与により7~9週間のSDラットを急性肺傷害動物モードに誘発した後、上記処方の処置を傷害前に施すか又は傷害後に施し、ラットの死亡又は瀕死現象及び炎症反応の発生が低減されるか否かを評価し、肺組織病理学的に本発明の医薬組成物が肺の傷害及び炎症反応を緩和するか否かを検討した。本実験の実験群の設計は表1に示すとおりである。
1.死亡率
処理後の死亡率は表2に示す通りであり、高濃度のLPSでは急性肺傷害を誘導するのに一定の死亡率を示したが(処理群A)、中等、低濃度のLPSでは急性肺損傷を誘導し(処理群Bと処理群C)、処理後には死亡率の低下に成功した。
A.肺タンパク質蓄積の改善の試験
滅菌後PBSで左肺葉を洗浄して気管支肺胞洗浄液(Bronchoalveolar lavage fluid:BALF)を回収し、酵素結合免疫吸着アッセイ(Enzyme-linked immunosorbent assay:ELISA )で総タンパク質量を測定した。実験結果は、図2を参照する。図2は、処理後の各気管支肺胞洗浄液群(BALF)の総タンパク質量のヒストグラムである。図2に示すように、処理群A(高用量)、処理群B(中等用量)及び処理群C(低用量)では、本発明の医薬組成物を用いることにより、BALF中の総タンパク質量を著しく低減でき、それぞれ52%、51%及び28%低減できることを見出し、本発明の医薬組成物が各段階の肺傷害に対して、肺タンパク質蓄積を改善する効能を有することが明らかになった。
滅菌後PBSで左肺葉を洗浄してBALFを採取し、ELISAによりIL-6及びIL-8等の炎症因子の濃度を定量した。図3と図4を参照すると、図3と図4はそれぞれ処理後の各群の気管支肺胞洗浄液群(BALF)のIL-6(図3)とIL-8(図4)のヒストグラムである。図3に示すように、処理群A(高用量)と処理群B(中等用量)では、本発明の医薬組成物を用いることにより、炎症因子IL-6の濃度を著しく低減することができる。図4に示すように、処理群A(高用量)では、IL-8の濃度を著しく低減することができ、本発明の医薬組成物は、肺炎症反応を低減する効果を有することが明らかになった。
残りの肺葉(右頭蓋、右尾葉及び副葉を含む)を計量し、0.8~1.0mLの10%中性緩衝ホルマリン(neutral buffered formalin:NBF)で灌流し、次いで10倍体積の10% NBFで72~96時間、室温で保存する。定着後、肺葉を剪断し、ワックスで包埋し、ミクロトームで厚さ4~6ミクロンの切片に切断し、切片を均一にhematoxylin and eosin (H&E)染色した。
肺葉主要断面積(area of interest:AOI)の400X拡大写真を取って、中性多形核白血球浸潤(polymorphonuclear cell infiltration:PMNL infiltration )及び肺水腫(Intra alveolar edema)の等級判定を行った。各視野は≧95%の肺胞を含有しなければならず、肺浸潤及び肺水腫の観察および定量化は、10回のランダム評価によって行われ、表3は、スコアリングシステムを示す。
右正中肺葉を肺から切り出し、調整された体重で湿量基準まで秤量する。その後、試料を60℃のオーブンに24時間放置し、同じ較正用秤から乾燥重量を得た。図8を参照すると、図8は、それぞれ処理後の各群の肺水重量定量図である。図8に示すように、処理群A(高用量)、処理群B(中等用量)、及び処理群C(低用量)では、本発明の医薬組成物の使用により肺水重量を著しく低下できることを発見し、本発明の医薬組成物は肺組織の含水量を著しく低下させ、肺水腫改善効果を有することが明らかとなった。
Claims (25)
- 呼吸器系傷害改善用医薬組成物であって、この医薬組成物は、吸着性薬物と、含水担体と、を含み、ここで、この吸着性薬物は、炭素材料と、分子篩と、正負帯電化合物と、を含むことを特徴とする呼吸器系傷害改善用医薬組成物。
- この吸着性薬物は、この含水担体を、懸濁液の濃度が0.001~1wt%となるように混合することを特徴とする
請求項1に記載の医薬組成物。 - この炭素材料は、活性炭、活性炭素繊維、炭素繊維、炭素球、活性炭素球、柱状活性炭、活性炭素粉、炭素粉、フラーレン(C60)、セルロース系炭素、竹炭、すす、カーボンエアロゲル、黒鉛、膨張黒鉛、カーボンナノチューブ、ナノカーボンボール、コークス球又はカーボンブラックのうちの1種又はそれらの組み合わせを含むことを特徴とする
請求項1に記載の医薬組成物。 - この炭素材料の比表面積(BET)は、300~3000m2/gであることを特徴とする
請求項1に記載の医薬組成物。 - この炭素材料の平均粒径は、0.1~500ミクロン(μm)であることを特徴とする
請求項1に記載の医薬組成物。 - この炭素材料の細孔容積は、0.1~3.0ml/gであることを特徴とする
請求項1に記載の医薬組成物。 - この炭素材料の細孔直径は、1~500ナノメートル(nm)の間にあることを特徴とする
請求項1に記載の医薬組成物。 - この医薬組成物は、噴霧剤、吸入剤又は液体懸濁剤であることを特徴とする
請求項1に記載の医薬組成物。 - この医薬組成物は、助剤、賦形剤又は推進剤を更に含むことを特徴とする
請求項1に記載の医薬組成物。 - 抗菌薬、抗ウイルス薬、ベンゼン環薬、抗凝固薬、血栓溶性薬物、α型遮断薬、5α還元酵素阻害剤、鼻腔うっ血除去薬(nasal decongestants)、鎮咳剤(Antitussive)、去痰剤(Expectorants)、痰溶解薬剤(Mucolytics)、気管又は気管支拡張剤(Bronchodilators)、抗生物質、抗カビ薬、抗喘息薬(Antiasthmatic drugs)、抗炎症薬、抗酸化剤、漢方薬エキス、抗体又はワクチンを更に含むことを特徴とする
請求項1に記載の医薬組成物。 - この炭素材料上に酸素官能基、水酸官能基、水酸基、カルボン酸、アルデヒド基、炭酸を更に含むことを特徴とする
請求項1に記載の医薬組成物。 - 金属イオン、磁気物質、カチオン化合物、アニオン化合物又はハロゲンイオンのうちの1種又はそれらの組み合わせを更に含むことを特徴とする
請求項1に記載の医薬組成物。 - 呼吸器系傷害改善用医薬組成物の製造のための用途であって、この医薬組成物は、吸着性薬物と、含水担体と、を含み、ここで、この吸着性薬物は、炭素材料と、分子篩と、正負帯電化合物と、を含むことを特徴とする呼吸器系傷害改善用医薬組成物の製造のための用途。
- この吸着性薬物は、この含水担体を、懸濁液の濃度が0.001~1wt%となるように混合することを特徴とする
請求項13に記載の用途。 - この炭素材料は、活性炭、活性炭素繊維、炭素繊維、炭素球、活性炭素球、柱状活性炭、活性炭素粉、炭素粉、フラーレン(C60)、セルロース系炭素、竹炭、すす、カーボンエアロゲル、黒鉛、膨張黒鉛、カーボンナノチューブ、ナノカーボンボール、コークス球又はカーボンブラックのうちの1種又はそれらの組み合わせを含むことを特徴とする
請求項13に記載の用途。 - この炭素材料の比表面積(BET)は、300~3000m2/gであることを特徴とする
請求項13に記載の用途。 - この炭素材料の平均粒径は、0.1~500ミクロン(μm)であることを特徴とする
請求項13に記載の用途。 - この炭素材料の細孔容積は、0.1~3.0ml/gであることを特徴とする
請求項13に記載の用途。 - この炭素材料の細孔直径は、1~500ナノメートル(nm)の間にあることを特徴とする
請求項13に記載の用途。 - この医薬組成物は、噴霧剤、吸入剤又は液体懸濁剤であることを特徴とする
請求項13に記載の用途。 - この医薬組成物は、助剤、賦形剤又は推進剤を更に含むことを特徴とする
請求項13に記載の用途。 - 抗菌薬、抗ウイルス薬、ベンゼン環薬、抗凝固薬、血栓溶性薬物、α型遮断薬、5α還元酵素阻害剤、鼻腔うっ血除去薬(nasal decongestants)、鎮咳剤(Antitussive)、去痰剤(Expectorants)、痰溶解薬剤(Mucolytics)、気管又は気管支拡張剤(Bronchodilators)、抗生物質、抗カビ薬、抗喘息薬(Antiasthmatic drugs)、抗炎症薬、抗酸化剤、漢方薬エキス、抗体又はワクチンを更に含むことを特徴とする
請求項13に記載の用途。 - この炭素材料上に酸素官能基、水酸官能基、水酸基、カルボン酸、アルデヒド基、炭酸を更に含むことを特徴とする
請求項13に記載の用途。 - 金属イオン、磁気物質、カチオン化合物、アニオン化合物又はハロゲンイオンのうちの1種又はそれらの組み合わせを更に含むことを特徴とする
請求項13に記載の用途。 - この医薬組成物の投与タイミングは、(1)無酸素装置支援(room air)での血中酸素飽和度≦94%であること、(2)放射線学的証拠が肺浸潤を示すことであることを特徴とする
請求項13に記載の用途。
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