JP2022008060A - 新型コロナウイルス感染症(covid-19)の治療及び/又は予防剤 - Google Patents
新型コロナウイルス感染症(covid-19)の治療及び/又は予防剤 Download PDFInfo
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- JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 1
- KXFFQVUPQCREHA-UHFFFAOYSA-K sodium;2-hydroxypropane-1,2,3-tricarboxylate;iron(2+) Chemical compound [Na+].[Fe+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KXFFQVUPQCREHA-UHFFFAOYSA-K 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 description 1
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- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 235000012711 vitamin K3 Nutrition 0.000 description 1
- 239000011652 vitamin K3 Substances 0.000 description 1
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- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 239000011667 zinc carbonate Substances 0.000 description 1
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- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
Scientific Reports,2019,Vol.9,pp.no.8666,doi:https://doi.org/10.1038/s41598-019-44981-y Review in Medical Virology. 2021 Mar 16. doi: 10.1002/rmv.2231 「新型コロナウイルス感染症(変異株)への対応」厚生労働省(URL:https://www.mhlw.go.jp/content/10900000/000766545.pdf、アクセス日:2021年4月20日)
[項目1]
下記式(I)
で示される化合物又はその塩を含有する新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目2]
R1及びR2が水素原子であることを特徴とする、項目1に記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目3]
さらに、一種又は二種以上の金属含有化合物を含有することを特徴とする項目1又は2記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目4]
金属含有化合物が、鉄、マグネシウム、亜鉛、ニッケル、バナジウム、銅、クロム、モリブデン又はコバルトを含有する化合物であることを特徴とする項目3記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目5]
金属含有化合物が、鉄、マグネシウム又は亜鉛を含有する化合物であることを特徴とする項目3記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目6]
金属含有化合物が、鉄を含有する化合物であることを特徴とする項目3記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目7]
PPIX排出阻害剤と併用するための、項目1~6のいずれか1項記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目8]
PPIX排出阻害剤が、トランスポータ阻害剤またはエキソサイトーシス阻害剤である、項目7記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目9]
PPIX排出阻害剤が、ABCG2阻害剤またはダイナミン阻害剤である、項目7又は8記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目10]
PPIX排出阻害剤が、ABCG2阻害剤である、項目7~9のいずれか1項記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
[項目11]
下記式(I)
で示される化合物又はその塩を、薬学的許容される賦形剤と共に投与することを含む、新型コロナウイルス感染症(COVID-19)の治療及び/又は予防方法。
[項目12]
下記式(I)
で示される化合物又はその塩の、新型コロナウイルス感染症(COVID-19)の治療及び/又は予防における使用。
本明細書において、複数の数値の範囲が示された場合、それら複数の範囲の任意の下限値および上限値の組み合わせからなる範囲も同様に意味する。
本発明の対象である新型コロナウイルス(SARS-CoV-2)は、従来株のみでなく、変異株をも含む(非特許文献3、4等参照)。例えば、「N501Yの変異がある変異株」としては、英国で確認された変異株(VOC-202012/01)、南アフリカで確認された変異株(501Y.V2)、ブラジルで確認された変異株(501Y.V3)及びフィリピンで確認された変異株が挙げられ、また、「E484Kの変異がある変異株」としては、南アフリカで確認された変異株(501Y.V2)、ブラジルで確認された変異株(501Y.V3)及びフィリピンで確認された変異株が挙げられるが、これらに限定されない。
本発明の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤、並びに新型コロナウイルス(SARS-CoV-2)タンパク質発現抑制剤の有効成分として用いられる化合物は、式(I)で示される化合物又はその塩(以下、これらを総称して「ALA類」ということもある)として例示することができる。δ-アミノレブリン酸とも呼ばれる5-ALAは、式(I)のR1及びR2が共に水素原子の場合であり、アミノ酸の1種である。5-ALA誘導体としては、式(I)のR1が水素原子又はアシル基であり、式(I)のR2が水素原子、直鎖若しくは分岐状アルキル基、シクロアルキル基、アリール基又はアラルキル基である、5-ALA以外の化合物を挙げることができる。
ide and oxfendazole(anthelmintics); Ganciclovir (antiviral drug); Zidovudine、Lamivudine (NRTI);Leflunomide、A771726 (antirheumatic drugs); Diclofenac (analgesic and anti-inflammatory drug); Cimetidine (histamine H2-receptor antagonist); ME3277 (hydrophilic glycoprotein IIb/IIIa antagonist); Pitavastatin、Rosuvastatin (HMG-CoA reductase inhibitor); Dipyridamole (thromboxane synthase inhibitor); Glyburide (hypoglycemic agent); Nicardipine、nifedipine、nitrendipine (Ca2+ channel blocker); Olmesartan medoxomil (angiotensin II AT1-R antagonist); Befloxatone (selective monoamine oxidase inhibitor); Prazosin (alpha-1-adrenergic receptor antagonist); Riluzole (Na+ channels blocker); Amyloid-beta Zoledronic acid (osteotropic compound); Hesperetin conjugates、Kaempferol (flavonoid、WO2004/069233も参照); FTC (Fumitremorgin C)およびその誘導体 (Mol. Cancer Ther.,2002,1:417-425参照); エストロゲンや抗エストロゲン(Mol. Cancer Ther.,2003,2:105-112参照); novobiocin (Int.J.Cancer,2004,108:146-151参照); ジフェニルアクリロニトリル誘導体(WO2004/069243参照); 複素環
を有するアクリロニトリル誘導体(WO2006/106778、WO2009/072267参照)等を使用することができる。
本発明の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防方法またはこれらの方法に用いるための医薬において、ALA類、PPIX排出阻害剤、金属含有化合物または他の薬剤は、これらすべてを含む組成物としても、あるいは、それぞれを単独あるいはその一部のみを含有する組成物としても投与することできる。一態様において、ALA類と他の薬剤とを、それぞれ単独あるいはその一部のみを含有する組成物を用いる場合、これらを同時に投与してもよく、また、別々に投与してもよい。好ましくは、ALA類と他の薬剤との投与が相加的効果あるいは相乗的効果を奏することができるように組み合わせて投与することができる。ALA類と他の薬剤をそれぞれ単独あるいはその一部のみを含有する組成物を別々に投与する場合、それらの投与間隔は5分、10分、15分、20分、30分、45分、1時間、2時間、3時間、4時間、5時間、6時間、7時間、8時間、9時間、10時間、11時間、12時間等に設定できるが、これらに限定されない。
本発明の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤の剤型としては、上記投与経路に応じて適宜決定することができるが、注射剤、点滴剤、錠剤、カプセル剤、細粒剤、散剤、液剤、シロップ等に溶解した水剤、パップ剤、座薬剤等を挙げることができる。
本発明の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤の投与量・頻度・期間としては、新型コロナウイルス感染症(COVID-19)を治療又は予防しようとする動物の種類、年齢、体重、症状等により異なるが、例えばヒトに投与する場合、ALA類の投与量としては、5-ALA重量換算で、0.01-200mg/体重kg/日、好ましくは0.5-100mg/体重kg/日、より好ましくは1-50mg/体重kg/日、さらに好ましくは5-30mg/体重kg/日を挙げることができ、特に予防剤として用いる場合は、低用量を継続して摂取することが望ましい。例えば予防剤サプリメントとして投与する場合には、0.1-30mg/体重kg/日、好ましくは0.3~10mg/体重kg/日、より好ましくは1.0~5mg/体重kg/日などの投与量で投与することができる。投与頻度としては、一日一回~複数回の投与又は点滴等による連続的投与を例示することができる。治療剤または予防剤としての投与期間は、医師等当該技術分野の専門家が既知の方法により決定することができる。
本発明の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤は、新型コロナウイルス(SARS-CoV-2)の感染および/または新型コロナウイルス感染症(COVID-19)発症を原因として生じる様々な症状の治療および予防に適用することができる。そのような症状として、肺炎、発熱、咳、息切れ、呼吸困難、悪寒、悪寒を伴う震え、筋肉痛、頭痛、咽頭痛、味覚障害、または嗅覚障害を例示することができるが、これらに限定されない。
本発明の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤は、ヒト、サル、イヌ、ネコ、ミンク、牛、豚およびこれらの近縁動物、その他の哺乳類、鳥類等に投与することができる。
1.患者:53歳男性 1名
2.治療経過
2020年2月28日金曜日の夜から普段感じたことのない強い倦怠感と悪寒、鼻水、のどの痛み、胸の痛みを感じ、空咳があり、夜中に目が覚め、体温を測ったところ37.5℃であった。喉の渇きを癒やすためにオレンジジュースを飲用したが味を感じなかった。
耐えがたい倦怠感に眠ることもままならず、5-ALAリン酸塩50mgとSFC28.7mgを含有するサプリメント(カプセル)の摂取を2月29日土曜日に開始したところ、以下の経過が観察された。
2月29日土曜日
2:00 4カプセル摂取したところ悪寒が改善、体温は37.5℃
4:00 再び悪寒を感じたため2カプセル摂取、体温は37.2℃
5:00 咳、くしゃみは続く物ののどの痛みが軽減、体温は36.8℃
8:00 体温が37.9℃に上昇したため再び4カプセル摂取、体温は37.2に低下
10:00 体温37.5℃、2カプセル摂取、体温は37.1℃に低下
12:00 体温37.4℃、2カプセル摂取、体温は37.0℃に低下
15:00 体温37.2℃、2カプセル摂取、体温36.8℃に正常化、倦怠感が改善し始める。
19:00 体温36.9℃、夕食を採ることが出来、味覚が正常化、2カプセル摂取、就寝
3月1日日曜日
5:00 体温36.8℃ 4カプセル摂取、風邪症状軽快
10:00 体温36.9℃ 4カプセル摂取、症状なし
12:00 体温36.8℃ 4カプセル摂取、症状なし
16:00 体温36.8℃ 軽い筋肉痛を覚え、4カプセル摂取
17:30 筋肉痛軽快 体温36.9℃ 症状なし
その後4月17日に新型コロナウイルス(SARS-CoV-2)抗体検査試薬キット(倉敷紡績株式会社製品コードRF-NC002)を用いて男性患者の抗新型コロナウイルス抗体を調べたところ陽性であった。
以上の経過より、5-ALAの摂取によって、新型コロナウイルス感染症(COVID-19)の諸症状が短期間に著しく改善できることが明らかとなった。
(方法)
実験材料
アフリカミドリザル腎臓由来のVeroE6は北海道大学の高田博士より入手した。ヒト結腸癌由来のCaco-2細胞は大阪大学の飯田博士より入手した。
アフリカミドリザル腎臓由来のVeroE6細胞は、10% Fetal Bovine Serum (FBS)及び1% penicillin/streptomycin溶液を添加したDulbecco’s Modified Eagle Medium(DMEM)にて培養した。
Caco-2細胞も同様の方法で培養した。
5-アミノレブリン酸(5-ALA)塩酸塩は純水にて100 mM溶液に調製、クエン酸第一鉄ナトリウム(SFC)は純水と1N HClにて25 mM溶液に調製、fumitremorgin C(FTC)はDMSOにて5 mMに調製し、実験毎にそれらをDMEMにて希釈して使用した。免疫染色法では、goat serum、rabbit anti-SARS-CoV N antibody(NOVUS社)、Alexa Fluor 488 goat anti-rabbit(ThermoFisher Scientific社)、Hoechst 33342(ThermoFisher Scientific社)を使用した。
本実験で使用したSARS-CoV-2は、日本国内の感染者より分離された(A JPN/NGS/IA-1/2020,GISAID accession no. EPI-ISL-481251)。また、SARS-CoV-2の変異株として、国立感染症研究所より入手した英国株QK002(hCoV-19/Japan/QK002/2020、GISAID ID: EPI_ISL_768526)、英国株QHN001(hCoV-19/Japan/QHN001/2020、GISAID ID: EPI_ISL_804007)、英国株QHN002(hCoV-19/Japan/QHN002/2020、GISAID ID: EPI_ISL_804008)、ブラジル株TY7-501(hCoV-19/Japan/TY7-501/2021、GISAID ID: EPI_ISL_833366)、ブラジル株TY7-503(hCoV-19/Japan/TY7-503/2021、GISAID ID: EPI_ISL_877769)、南アフリカ株TY8-612(hCoV-19/Japan/ TY8-612/2021、GISAID ID: EPI_ISL_1123289)、の6株を用いた。ウイルスはVeroE6細胞を用いて継代し、3~4日間培養した後に培養上清を回収し、2000xgにて15分間遠心した後、上清を-80℃にて保存し、実験毎に解凍した後に使用した。本ウイルスを用いた感染実験は全て、長崎大学が有するBSL3実験室にて行った。
(a)VeroE6細胞を用いた試験
VeroE6細胞を96ウェルプレートに0.5x10^4 cells/wellの密度で播種し、細胞がプレート底に接着した後、各薬剤を培地に添加した。試験薬剤としては、5-ALA(1000uM)、5-ALA(1000uM)+FTC(10uM)、5-ALA(1000uM)+SFC(250uM)、5-ALA(1000uM)+SFC(250uM)+FTC(10uM)、FTC(10uM)を用いた。薬剤添加後、細胞を37℃にて48時間又は72時間培養した。その後、BSL3実験室にて、SARS-CoV-2を感染させた。感染開始から48時間後、感染細胞を4%パラホルムアルデヒド(PFA)にて一晩浸漬し、細胞の固定とウイルスの不活化を行った。更に細胞を0.2% TritonX-100にて透過処理した後、10% goat serumにてブロッキングを行い、rabbit anti-SARS-CoV N antibodyにて一次抗体処理し、Alexa Fluor 488 goat anti-rabbitにて二次抗体処理し、Hoechst 33342により細胞核の染色を行った。そして、Cytation 5細胞イメージングプレートリーダー(BioTek社)を用いて感染細胞の画像撮影を行った。それら画像の解析はCellProfiler画像解析ソフト(Broad Institute,MIT)を用いて行い、感染細胞数及び全細胞数を算出し、GraphPad Prism(MDF社)を用いてグラフの作成と統計処理を行った。
各薬剤にて48時間の前処理を行った条件では、5-ALAとFTCを共添加することでSARS-CoV-2の感染を有意に抑制した。その他の薬剤添加条件では効果が認められなかった(図1)。各薬剤にて72時間の前処理を行った条件では、5-ALAとFTCの共添加、又は5-ALAとSFCとFTCの共添加により、SARS-CoV-2の感染が強く抑制された(図2)。
また、播種細胞数を1x10^4細胞/wellにすると、5-ALA単独の添加あるいは5-ALAとSFCの添加によりSARS-CoV-2の感染を有意に抑制した。
Caco-2細胞を用いた薬物評価試験では、SARS-CoV-2を感染させてから不活化までの時間を72時間に変更した点、および、感染させたウイルス量がVeroE6細胞では0.002MOIであったのに対して、Caco-2細胞では0.02MOIであった点を除いて同様に行った。
薬剤添加後72時間培養した後にSARS-CoV-2を感染させた場合、5-ALA単独又は5ALAとSFCの併用処理した細胞では、SARS-CoV-2の感染及び/又は増殖が強力に阻害された(図3)。Caco-2細胞では、薬剤添加後48時間培養した後にSARS-CoV-2を感染させた場合にも、同様のSARS-CoV-2感染及び/又は増殖阻害作用が得られた(図4)。
また、同様に変異株を感染させた場合でも、5-ALA単独又は5ALAとSFCの併用処理した細胞では、SARS-CoV-2への感染及び/又は増殖阻害効果が期待される。
本結果は、5-ALAがヒト細胞においてSARS-CoV-2感染及び/又は増殖阻害効果を示すことを裏付けるものである。
なお、Caco-2細胞は細胞外から供給される5-ALAの代謝を行うことが知られている(Biochem.Biophys.Rep.,2017.Vol/11,pp.105-111)。
SARS-CoV-2感染及び/又は増殖阻害効果における用量依存性を確認するために、各濃度の薬剤を試験した。
その結果、VeroE6細胞に対して5-ALA単独のIC50は570uMであり、5-ALAとSFCの併用適用のIC50は695uMであった。一方、SFCの単独適用はSARS-CoV-2感染及び/又は増殖阻害効果を示さなかった(図5)。
また、Caco-2細胞に対して5-ALA単独のIC50は39uMであり、5-ALAとSFCの併用適用のIC50は63uMであった。一方、SFCの単独適用はSARS-CoV-2感染及び/又は増殖阻害効果を示さなかった(図6)。
なお、試験したすべての濃度範囲(最大2000uM)で、5-ALAは有意な細胞毒性を示さなかった。
以上の結果は、5-ALAが様々な細胞型において、特異的かつ強力なSARS-CoV-2感染及び/又は増殖阻害効果を有することを示している。
Claims (10)
- R1及びR2が水素原子であることを特徴とする、請求項1に記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- さらに、一種又は二種以上の金属含有化合物を含有することを特徴とする請求項1又は2記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- 金属含有化合物が、鉄、マグネシウム、亜鉛、ニッケル、バナジウム、銅、クロム、モリブデン又はコバルトを含有する化合物であることを特徴とする請求項3記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- 金属含有化合物が、鉄、マグネシウム又は亜鉛を含有する化合物であることを特徴とする請求項3記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- 金属含有化合物が、鉄を含有する化合物であることを特徴とする請求項3記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- PPIX排出阻害剤と併用するための、請求項1~6のいずれか1項記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- PPIX排出阻害剤が、トランスポータ阻害剤またはエキソサイトーシス阻害剤である、請求項7記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- PPIX排出阻害剤が、ABCG2阻害剤またはダイナミン阻害剤である、請求項7又は8記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
- PPIX排出阻害剤が、ABCG2阻害剤である、請求項7~9のいずれか1項記載の新型コロナウイルス感染症(COVID-19)の治療及び/又は予防剤。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000510123A (ja) * | 1996-05-08 | 2000-08-08 | ニューヨーク・ブラッド・センター・インコーポレイテッド | ウイルス感染の治療方法 |
WO2014013664A1 (ja) * | 2012-07-19 | 2014-01-23 | Sbiファーマ株式会社 | インフルエンザウイルス感染症の予防・治療剤 |
WO2016163082A1 (ja) * | 2015-04-10 | 2016-10-13 | Sbiファーマ株式会社 | Ala類を含むウイルス感染症予防/治療剤 |
WO2020218577A1 (ja) * | 2019-04-26 | 2020-10-29 | ネオファーマジャパン株式会社 | フラビウイルス感染症治療剤 |
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US7371773B2 (en) | 2003-02-04 | 2008-05-13 | Kabushiki Kaisha Yakult Honsha | Breast cancer resistance protein (BCRP) inhibitor |
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AU2014283588A1 (en) | 2013-06-18 | 2015-11-05 | Nestec S.A. | Filter unit for a capsule |
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US10987329B1 (en) | 2020-04-22 | 2021-04-27 | Nadimpally Satyavarahala Raju | Combination therapy for coronavirus infections including the novel corona virus (COVID-19) |
-
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000510123A (ja) * | 1996-05-08 | 2000-08-08 | ニューヨーク・ブラッド・センター・インコーポレイテッド | ウイルス感染の治療方法 |
WO2014013664A1 (ja) * | 2012-07-19 | 2014-01-23 | Sbiファーマ株式会社 | インフルエンザウイルス感染症の予防・治療剤 |
WO2016163082A1 (ja) * | 2015-04-10 | 2016-10-13 | Sbiファーマ株式会社 | Ala類を含むウイルス感染症予防/治療剤 |
WO2020218577A1 (ja) * | 2019-04-26 | 2020-10-29 | ネオファーマジャパン株式会社 | フラビウイルス感染症治療剤 |
Non-Patent Citations (12)
Title |
---|
"History of Changes for Study: NCT04542850", CLINICALTRIALS.GOV ARCHIVE [ONLINE], [RETRIEVED ON 2021.05.24], JPN6021020964, 6 September 2020 (2020-09-06), ISSN: 0004618423 * |
AM J PHYSIOL CELL PHYSIOL, vol. 308, JPN6021020939, 2015, pages 665 - 672, ISSN: 0004618425 * |
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 545, JPN6021020943, 29 January 2021 (2021-01-29), pages 203 - 207, ISSN: 0004618427 * |
BIOORGANIC CHEMISTRY, vol. Vol. 107, 104619, JPN6021040539, 5 January 2021 (2021-01-05), pages 1 - 11, ISSN: 0004618430 * |
BIORXIV (INTERNET ARCHIVE WAYBACK MACHINE) [ONLINE], [RETRIEVED ON 2021.05.17], JPN6021020955, 5 November 2020 (2020-11-05), ISSN: 0004618429 * |
EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 833, JPN7021001991, 2018, pages 25 - 33, ISSN: 0004618424 * |
FREE RADICAL BIOLOGY AND MEDICINE, vol. 161, JPN6021020958, 19 October 2020 (2020-10-19), pages 263 - 271, ISSN: 0004618420 * |
FRONTIERS IN VETERINARY SCIENCE, vol. Vol. 8, Article 647189, JPN6021020947, 10 February 2021 (2021-02-10), pages 1 - 6, ISSN: 0004618428 * |
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 16, JPN6021020942, 2015, pages 25865 - 25880, ISSN: 0004618426 * |
MEDICAL HYPOTHESES, vol. Vol. 144, 110242, JPN6021020960, 3 September 2020 (2020-09-03), pages 1 - 4, ISSN: 0004618421 * |
NATURE, vol. 579, JPN6021032661, 3 February 2020 (2020-02-03), pages 265 - 269, ISSN: 0004618419 * |
PLOS ONE, vol. Vol. 3, issue 12, e4023, JPN6021020962, 2008, pages 1 - 14, ISSN: 0004618422 * |
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