JP2019531309A - チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 - Google Patents
チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 Download PDFInfo
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- JP2019531309A JP2019531309A JP2019518559A JP2019518559A JP2019531309A JP 2019531309 A JP2019531309 A JP 2019531309A JP 2019518559 A JP2019518559 A JP 2019518559A JP 2019518559 A JP2019518559 A JP 2019518559A JP 2019531309 A JP2019531309 A JP 2019531309A
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- lysophosphatidylcholine
- dmpc
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- dmpg
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Classifications
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- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
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Abstract
Description
基本構造:
カリウムチャネルは、遅延整流性カリウム電流Kirの迅速な構成成分を伝導し、それは、心臓活動電位の再分極に不可欠である。遺伝的欠陥又は有害な薬物の影響のいずれかに起因したhERG電流の低減は、活動電位延長、表面ECG上でのQT間隔の長期化、並びに「トルサード・ド・ポアンツ」不整脈及び突然死に対するリスクの増加を特徴とする遺伝性又は後天性QT延期症候群を招き得る。非抗不整脈化合物のこの望ましくない副作用が、薬物の市場からの取り下げを促してきた。hERGチャネル阻害のメカニズムに関する研究は、hERG電流阻止の状態、電圧及び使用依存度を決定する分子要因への有意な洞察を提供する。hERGにおける高親和性薬物結合部位及び薬物分子とのその相互作用の特性を変更させる変異は、生命に関わる不整脈に関して高いリスクで、電流増加及び遺伝性短期QT症候群を引き起こす(Thomas D1, 2006)。
ヒトether−a−go−go遺伝子関連心臓四量体カリウムチャネルは、変異されると、患者を、163個を上回る薬物に対して感受性にさせることができ、それは、イオン伝導を阻害して、活動電位をダウンレギュレートし得る(Credible Meds)。カリウムチャネルの影響の結果として、活動電位の延長が起きる。イオンチャネル活性薬物は、QTc間隔を直接増加させて、トルサード・ド・ポアンツ及び突然心臓死のリスクを増加させ得る(表1)。薬物に対する心筋細胞のカリウムチャネル感受性の増悪はまた、糖尿病を含む代謝性罹患状態と関連付けられ得る(Veglio M, 2002)か、又は特発性起源であり得る。
1−DMPC
2−DMPG
3−DMPC/DMPG 90:9
4−14:0 LysoPC
5−14:0 LysoPG
6−DMPC+ニロチニブ(0.1μM)
7−DMPG+ニロチニブ(0.1μM)
8−DMPC/DMPG 90:9+ニロチニブ(0.1μM)
9−14:0 LysoPC+ニロチニブ(0.1μM)
10−14:0 LysoPG+ニロチニブ(0.1μM)
ベースライン条件で行われる記録1
濃度1の存在下で行われる記録1
ベースライン条件で行われる記録1
正の対照の存在下で行われる記録1
n=上記全プロトコールを適用することができたパッチした応答細胞の数。
1.評判の悪い薬物曝露の時間枠
2.封の不安定性
3.パッチした細胞により発生するテール電流なし
4.正の対照の有意な効果なし
5.研究の持続期間にわたるキャパシタンス過渡振幅における10%を超える可変性
1- DMPC (水溶液中)
2- DMPG (水溶液中)
3- DMPC/DMPG90:9 (水溶液中)
4- 14:0 LysoPC (水溶液中)
5- 14:0 LysoPG(水溶液中)
6- DMPC + ニロチニブ (0.1 μM) (水溶液中)
7- DMPG + ニロチニブ (0.1 μM) (水溶液中)
8- DMPC/DMPG90:9 + ニロチニブ (0.1 μM) (水溶液中)
9- 14:0 LysoPC + ニロチニブ (0.1 μM) (水溶液中)
10- 14:0 LysoPG + ニロチニブ (0.1 μM) (水溶液中)
11- ニロチニブ単独 (DMSO中)
米国特許公開第2010/0004549号明細書:System and Method of Serial Comparison for Detection of Long QT Syndrome (LQTS)。
米国特許公開第2008/0255464号明細書:System and Method for Diagnosing and Treating Long QT Syndrome。
米国特許公開第2007/0048284号明細書:Cardiac Arrhythmia Treatment Methods。
米国特許公開第2001/00120890号明細書:Ion Channel Modulating Activity I。
Claims (26)
- ヒト又は動物対象において活性剤又は薬物により引き起こされる心臓パターンにおける不規則性又は変化に起因する1又は2以上の心臓チャネル病又は状態を予防するための組成物であって、
前記活性剤又は薬物により引き起こされる心臓パターンにおける不規則性又は変化に起因する1又は2以上の心臓チャネル病又は状態を低減又は予防するのに有効な、経口投与用に適合されたある量のホスファチジルグリセロール、並びに1又は2以上の官能剤、チキソトロピー剤、又は官能剤及びチキソトロピー剤の両方
を含む組成物。 - ホスファチジルグリセロールが、リゾホスファチジルコリン、ラウロイル−リゾホスファチジルコリン、ミリストイル−リゾホスファチジルコリン、パルミトイル−リゾホスファチジルコリン、ステアロイル−リゾホスファチジルコリン、アラキドイル−リゾホスファチジルコリン、オレオイル−リゾホスファチジルコリン、リノレオイル−リゾホスファチジルコリン、リノレノイル−リゾホスファチジルコリン又はエルコイル−リゾホスファチジルコリンのうちの少なくとも1つを含む、請求項1に記載の組成物。
- 1又は2以上の官能剤が、1若しくは2以上の香味料、甘味料、冷却剤、色素、又はこれらの組合せ及び混合物を含む、請求項1に記載の組成物。
- 1又は2以上のチキソトロピー剤が、チキソトロピーマトリックスを形成し、多糖類、セルロース、カルボキシメチルセルロース、ガム、キサンタンガム、コラーゲン、ゼラチン、エーロゲル、ポリアクリルアミド、アルキド樹脂、又はシリカ−脂質の少なくとも1つから選択される、請求項1に記載の組成物。
- ホスファチジルグリセロールが空リポソームを形成し、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有する、請求項1に記載の組成物。
- ホスファチジルグリセロールが、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有するリポソームを形成する、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(DMPC)、12−ミステロイル−2−ヒドロキシ−sn−グリセロ−3−[ホスホ−rac−(グリセロール)](DMPG)、又はDMPC/DMPGである、請求項1に記載の組成物。
- ホスファチジルグリセロールが、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(DMPC)、12−ミステロイル−2−ヒドロキシ−sn−グリセロ−3−[ホスホ−rac−(グリセロール)](DMPG)、DMPC/DMPG、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホ−(1’−rac−グリセロール)(LysoPG)、又は1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(LysoPC)のうちの少なくとも1つを含む、請求項1に記載の組成物。
- ホスファチジルグリセロールが、短鎖脂肪酸は最大5個の炭素、中鎖は6〜12個の炭素、長鎖は13〜21個の炭素、超長鎖脂肪酸は22個を超える炭素であり、偶数及び奇数鎖の両方の脂肪酸を含むとさらに規定される、請求項1に記載の組成物。
- ホスファチジルグリセロールが、飽和又は不飽和である3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、35、40、45、50、55又は56個以上の炭素を有する、請求項1に記載の組成物。
- 心臓パターンにおける不規則性若しくは変化に起因する心臓チャネル病若しくは状態が、心臓内の遅延整流性K+電流に関与するイオンチャネルの阻害、多形性心室性頻拍、QTc、LQT2、LQTSの延長、若しくはトルサード・ド・ポアンツである、又は、心臓、アレルギー若しくはがん関連疾患の治療に使用される活性剤若しくは薬物の投与により誘導されるIKrチャネル阻害の延長若しくはQT延長の治療若しくは予防に使用される、請求項1に記載の組成物。
- 薬物が、アルブテロール(サルブタモール)、アルフゾシン、アマンタジン、アミオダロン、アミスルプリド、アミトリプチリン、アモキサピン、アンフェタミン、アナグレリド、アポモルヒネ、アルフォルモテロール、アリピプラゾール、三酸化ヒ素、アステミゾール、アタザナビル、アトモキセチン、アジスロマイシン、ベダキリン、ベプリジル、ボルテゾミブ、ボスチニブ、抱水クロラール、クロロキン、クロルプロマジン、シプロフロキサシン、シサプリド、シタロプラム、クラリスロマイシン、クロミプラミン、クロザピン、コカイン、クリゾチニブ、ダブラフェニブ、ダサチニブ、デシプラミン、デクスメデトミジン、デクスメチルフェニデート、デキストロアンフェタミン(d−アンフェタミン)、ジヒドロアルテミシニン+ピペラキン、ジフェンヒドラミン、ジソピラミド、ドブタミン、ドフェチリド、ドラセトロン、ドンペリドン、ドーパミン、ドキセピン、ドロネダロン、ドロペリドール、エフェドリン、エピネフリン(アドレナリン)、エリブリン、エリスロマイシン、エスシタロプラム、ファモチジン、フェルバメート、フェンフルラミン、フィンゴリモド、フレカイニド、フルコナゾール、フルオキセチン、ホルモテロール、ホスカルネット、ホスフェニトイン、フロセミド(フルセミド)、ガランタミン、ガチフロキサシン、ゲミフロキサシン、ゲラニセトロン、ハロファントリン、ハロペリドール、ヒドロクロロチアジド、イブチリド、イロペリドン、イミプラミン(メリプラミン)、インダパミド、イソプロテレノール、イスラジピン、イトラコナゾール、イバブラジン、ケトコナゾール、ラパチニブ、レブアルブテロール(レブサルブタモール)、レボフロキサシン、レボメタジル、リスデキサンフェタミン、リチウム、メソリダジン、メタプロテレノール、メサドン、メタンフェタミン(Methamphetamine)(メタンフェタミン(methamfetamine))、メチルフェニデート、ミドドリン、ミフェプリストン、ミラベグロン、ミルタザピン、モエキシプリル/HCTZ、モキシフロキサシン、ネルフィナビル、ニカルジピン、ニロチニブ、ノルエピネフリン(ノルアドレナリン)、ノルフロキサシン、ノルトリプチリン、オフロキサシン、オランザピン、オンダンセトロン、オキシトシン、パリペリドン、パロキセチン、パシレオチド、パゾパニブ、ペンタミジン、パーフルトレン脂質ミクロスフェア、フェンテルミン、フェニレフリン、フェニルプロパノールアミン、ピモジド、ポサコナゾール、プロブコール、プロカインアミド、プロメタジン、プロトリプチリン、プソイドエフェドリン、クエチアピン、キニジン、硫酸キニーネ、ラノラジン、リルピビリン、リスペリドン、リトドリン、リトナビル、ロキシスロマイシン、サルメテロール、サキナビル、セルチンドール、セルトラリン、セボフルラン、シブトラミン、ソリフェナシン、ソラフェニブ、ソタロール、スパルフロキサシン、スルピリド、スニチニブ、タクロリムス、タモキシフェン、テラプレビル、テラバンシン、テリスロマイシン、テルブタリン、テルフェナジン、テトラベナジン、チオリダジン、チザニジン、トルテロジン、トレミフェン、トラゾドン、トリメトプリム−サルファ、トリミプラミン、バンデタニブ、バルデナフィル、ベムラフェニブ、ベンラファキシン、ボリコナゾール、ボリノスタット、又はジプラシドンから選択される、請求項1に記載の組成物。
- 心臓チャネル病、IKrチャネル阻害又はQT延長のうちの少なくとも1つを引き起こすヒトにおける活性剤又は薬物の投与から生じる1又は2以上の有害反応を引き起こす活性剤又は薬物で疾患を予防又は治療するための組成物であって、
基本構造:
(式中、R1又はR2は、任意の偶数又は奇数鎖の脂肪酸であり得、R3は、H、アシル、アルキル、アリール、アミノ酸、アルケン、アルキンであり得る)を有し、前記薬物により引き起こされる心臓チャネル病、IKrチャネル阻害又はQT延長のうちの少なくとも1つを低減又は予防するのに有効な、経口投与用に適合されたある量のリゾホスファチジルグリセロール;
IKrチャネル阻害又はQT延長のうちの少なくとも1つを引き起こす1又は2以上の活性剤又は薬物;並びに
1又は2以上の官能剤、チキソトロピー剤、又は官能剤及びチキソトロピー剤の両方
を含む組成物。 - 1又は2以上の官能剤が、1若しくは2以上の香味料、甘味料、冷却剤、色素、又はこれらの組合せ及び混合物を含む、請求項12に記載の組成物。
- 1又は2以上のチキソトロピー剤が、チキソトロピーマトリックスを形成し、多糖類、セルロース、カルボキシメチルセルロース、ガム、キサンタンガム、コラーゲン、ゼラチン、エーロゲル、ポリアクリルアミド、アルキド樹脂、又はシリカ−脂質の少なくとも1つから選択される、請求項12に記載の組成物。
- ホスファチジルグリセロールが空リポソームを形成し、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有する、請求項12に記載の組成物。
- ホスファチジルグリセロールが、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有するリポソームを形成する、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(DMPC)、12−ミステロイル−2−ヒドロキシ−sn−グリセロ−3−[ホスホ−rac−(グリセロール)](DMPG)、又はDMPC/DMPGである、請求項12に記載の組成物。
- 心臓パターンにおける不規則性若しくは変化に起因する心臓チャネル病若しくは状態が、心臓内の遅延整流性K+電流に関与するイオンチャネルの阻害、多形性心室性頻拍、QTc、LQT2、LQTSの延長、若しくはトルサード・ド・ポアンツである、又は、組成物が、心臓、アレルギー、若しくはがん関連疾患の治療に使用される1若しくは2以上の薬物の投与により誘導されるIKrチャネル阻害の延長若しくはQT延長の治療若しくは予防に使用される、請求項12に記載の組成物。
- リポソームが、脂質又はリン脂質壁を含み、前記脂質又は前記リン脂質が、ホスファチジルコリン(レシチン)、リゾレシチン、リゾホスファチジルエタノール−アミン、ホスファチジルセリン、ホスファチジルイノシトール、スフィンゴミエリン、ホスファチジルエタノールアミン(セファリン)、カルジオリピン、ホスファチジン酸、セレブロシド、リン酸ジセチル、ホスファチジルコリン、及びジパルミトイル−ホスファチジルグリセロール、ステアリルアミン、ドデシルアミン、ヘキサデシル−アミン、パルミチン酸アセチル、リシノール酸グリセロール、ステアリン酸ヘキサデシル、ミリスチン酸イソプロピル、両性アクリルポリマー、脂肪酸、脂肪酸アミド、コレステロール、コレステロールエステル、ジアシルグリセロール、及びコハク酸ジアシルグリセロールからなる群から選択される、請求項12に記載の組成物。
- 薬物が、アルブテロール(サルブタモール)、アルフゾシン、アマンタジン、アミオダロン、アミスルプリド、アミトリプチリン、アモキサピン、アンフェタミン、アナグレリド、アポモルヒネ、アルフォルモテロール、アリピプラゾール、三酸化ヒ素、アステミゾール、アタザナビル、アトモキセチン、アジスロマイシン、ベダキリン、ベプリジル、ボルテゾミブ、ボスチニブ、抱水クロラール、クロロキン、クロルプロマジン、シプロフロキサシン、シサプリド、シタロプラム、クラリスロマイシン、クロミプラミン、クロザピン、コカイン、クリゾチニブ、ダブラフェニブ、ダサチニブ、デシプラミン、デクスメデトミジン、デクスメチルフェニデート、デキストロアンフェタミン(d−アンフェタミン)、ジヒドロアルテミシニン+ピペラキン、ジフェンヒドラミン、ジソピラミド、ドブタミン、ドフェチリド、ドラセトロン、ドンペリドン、ドーパミン、ドキセピン、ドロネダロン、ドロペリドール、エフェドリン、エピネフリン(アドレナリン)、エリブリン、エリスロマイシン、エスシタロプラム、ファモチジン、フェルバメート、フェンフルラミン、フィンゴリモド、フレカイニド、フルコナゾール、フルオキセチン、ホルモテロール、ホスカルネット、ホスフェニトイン、フロセミド(フルセミド)、ガランタミン、ガチフロキサシン、ゲミフロキサシン、ゲラニセトロン、ハロファントリン、ハロペリドール、ヒドロクロロチアジド、イブチリド、イロペリドン、イミプラミン(メリプラミン)、インダパミド、イソプロテレノール、イスラジピン、イトラコナゾール、イバブラジン、ケトコナゾール、ラパチニブ、レブアルブテロール(レブサルブタモール)、レボフロキサシン、レボメタジル、リスデキサンフェタミン、リチウム、メソリダジン、メタプロテレノール、メサドン、メタンフェタミン(Methamphetamine)(メタンフェタミン(methamfetamine))、メチルフェニデート、ミドドリン、ミフェプリストン、ミラベグロン、ミルタザピン、モエキシプリル/HCTZ、モキシフロキサシン、ネルフィナビル、ニカルジピン、ニロチニブ、ノルエピネフリン(ノルアドレナリン)、ノルフロキサシン、ノルトリプチリン、オフロキサシン、オランザピン、オンダンセトロン、オキシトシン、パリペリドン、パロキセチン、パシレオチド、パゾパニブ、ペンタミジン、パーフルトレン脂質ミクロスフェア、フェンテルミン、フェニレフリン、フェニルプロパノールアミン、ピモジド、ポサコナゾール、プロブコール、プロカインアミド、プロメタジン、プロトリプチリン、プソイドエフェドリン、クエチアピン、キニジン、硫酸キニーネ、ラノラジン、リルピビリン、リスペリドン、リトドリン、リトナビル、ロキシスロマイシン、サルメテロール、サキナビル、セルチンドール、セルトラリン、セボフルラン、シブトラミン、ソリフェナシン、ソラフェニブ、ソタロール、スパルフロキサシン、スルピリド、スニチニブ、タクロリムス、タモキシフェン、テラプレビル、テラバンシン、テリスロマイシン、テルブタリン、テルフェナジン、テトラベナジン、チオリダジン、チザニジン、トルテロジン、トレミフェン、トラゾドン、トリメトプリム−サルファ、トリミプラミン、バンデタニブ、バルデナフィル、ベムラフェニブ、ベンラファキシン、ボリコナゾール、ボリノスタット、又はジプラシドンから選択される、請求項12に記載の組成物。
- 活性剤又は薬物により引き起こされる、ヒト又は動物対象における1又は2以上の心臓チャネル病、心臓パターンにおける不規則性若しくは変化、IKrチャネル阻害又はQT延長を予防又は治療する方法であって、前記活性剤又は薬物がヒト又は動物対象における疾患を治療するのに使用され、
前記ヒト又は動物対象へ、前記活性剤又は薬物により引き起こされる1又は2以上の心臓チャネル病、心臓パターンにおける不規則性若しくは変化、IKrチャネル阻害、又はQT延長を低減又は予防するのに有効な、経口投与用に適合されたある量のリゾホスファチジルグリセロール;
前記疾患を治療するのに十分な有効量の前記活性剤又は薬物であって、経口供給されるリゾホスファチジルグリセロールが、前記少なくとも1つの心臓チャネル病、心臓パターンにおける不規則性若しくは変化、IKrチャネル阻害又はQT延長を低減又は排除する、活性剤又は薬物;並びに
1又は2以上の官能剤、チキソトロピー剤、又は官能剤及びチキソトロピー剤の両方
を投与するステップを含む、前記方法。 - ホスファチジルグリセロールが、リゾホスファチジルコリン、ラウロイル−リゾホスファチジルコリン、ミリストイル−リゾホスファチジルコリン、パルミトイル−リゾホスファチジルコリン、ステアロイル−リゾホスファチジルコリン、アラキドイル−リゾホスファチジルコリン、オレオイル−リゾホスファチジルコリン、リノレオイル−リゾホスファチジルコリン、リノレノイル−リゾホスファチジルコリン又はエルコイル−リゾホスファチジルコリンのうちの少なくとも1つを含む、請求項20に記載の方法。
- 1又は2以上の官能剤が、1若しくは2以上の香味料、甘味料、冷却剤、色素、又はこれらの組合せ及び混合物を含む、請求項20に記載の方法。
- 1又は2以上のチキソトロピー剤が、チキソトロピーマトリックスを形成し、多糖類、セルロース、カルボキシメチルセルロース、ガム、キサンタンガム、コラーゲン、ゼラチン、エーロゲル、ポリアクリルアミド、アルキド樹脂、又はシリカ−脂質の少なくとも1つから選択される、請求項20に記載の方法。
- ホスファチジルグリセロールが空リポソームを形成し、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有する、請求項20に記載の方法。
- 心臓パターンにおける不規則性又は変化に起因する心臓チャネル病又は状態が、心臓内の遅延整流性K+電流に関与するイオンチャネルの阻害、多形性心室性頻拍、QTc、LQT2、LQTSの延長、又はトルサード・ド・ポアンツである、請求項20に記載の方法。
- 薬物が、アルブテロール(サルブタモール)、アルフゾシン、アマンタジン、アミオダロン、アミスルプリド、アミトリプチリン、アモキサピン、アンフェタミン、アナグレリド、アポモルヒネ、アルフォルモテロール、アリピプラゾール、三酸化ヒ素、アステミゾール、アタザナビル、アトモキセチン、アジスロマイシン、ベダキリン、ベプリジル、ボルテゾミブ、ボスチニブ、抱水クロラール、クロロキン、クロルプロマジン、シプロフロキサシン、シサプリド、シタロプラム、クラリスロマイシン、クロミプラミン、クロザピン、コカイン、クリゾチニブ、ダブラフェニブ、ダサチニブ、デシプラミン、デクスメデトミジン、デクスメチルフェニデート、デキストロアンフェタミン(d−アンフェタミン)、ジヒドロアルテミシニン+ピペラキン、ジフェンヒドラミン、ジソピラミド、ドブタミン、ドフェチリド、ドラセトロン、ドンペリドン、ドーパミン、ドキセピン、ドロネダロン、ドロペリドール、エフェドリン、エピネフリン(アドレナリン)、エリブリン、エリスロマイシン、エスシタロプラム、ファモチジン、フェルバメート、フェンフルラミン、フィンゴリモド、フレカイニド、フルコナゾール、フルオキセチン、ホルモテロール、ホスカルネット、ホスフェニトイン、フロセミド(フルセミド)、ガランタミン、ガチフロキサシン、ゲミフロキサシン、ゲラニセトロン、ハロファントリン、ハロペリドール、ヒドロクロロチアジド、イブチリド、イロペリドン、イミプラミン(メリプラミン)、インダパミド、イソプロテレノール、イスラジピン、イトラコナゾール、イバブラジン、ケトコナゾール、ラパチニブ、レブアルブテロール(レブサルブタモール)、レボフロキサシン、レボメタジル、リスデキサンフェタミン、リチウム、メソリダジン、メタプロテレノール、メサドン、メタンフェタミン(Methamphetamine)(メタンフェタミン(methamfetamine))、メチルフェニデート、ミドドリン、ミフェプリストン、ミラベグロン、ミルタザピン、モエキシプリル/HCTZ、モキシフロキサシン、ネルフィナビル、ニカルジピン、ニロチニブ、ノルエピネフリン(ノルアドレナリン)、ノルフロキサシン、ノルトリプチリン、オフロキサシン、オランザピン、オンダンセトロン、オキシトシン、パリペリドン、パロキセチン、パシレオチド、パゾパニブ、ペンタミジン、パーフルトレン脂質ミクロスフェア、フェンテルミン、フェニレフリン、フェニルプロパノールアミン、ピモジド、ポサコナゾール、プロブコール、プロカインアミド、プロメタジン、プロトリプチリン、プソイドエフェドリン、クエチアピン、キニジン、硫酸キニーネ、ラノラジン、リルピビリン、リスペリドン、リトドリン、リトナビル、ロキシスロマイシン、サルメテロール、サキナビル、セルチンドール、セルトラリン、セボフルラン、シブトラミン、ソリフェナシン、ソラフェニブ、ソタロール、スパルフロキサシン、スルピリド、スニチニブ、タクロリムス、タモキシフェン、テラプレビル、テラバンシン、テリスロマイシン、テルブタリン、テルフェナジン、テトラベナジン、チオリダジン、チザニジン、トルテロジン、トレミフェン、トラゾドン、トリメトプリム−サルファ、トリミプラミン、バンデタニブ、バルデナフィル、ベムラフェニブ、ベンラファキシン、ボリコナゾール、ボリノスタット、又はジプラシドンから選択される、請求項20に記載の方法。
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US15/297,901 | 2016-10-19 | ||
PCT/US2017/057446 WO2018075801A1 (en) | 2016-10-19 | 2017-10-19 | Protective effect of dmpc, dmpg, dmpc/dmpg, egpg, lysopg and lysopc against drugs that cause channelopathies |
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CA3039596C (en) | 2022-04-12 |
CN109843331A (zh) | 2019-06-04 |
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KR20190042775A (ko) | 2019-04-24 |
CN111481508A (zh) | 2020-08-04 |
AU2017345473A1 (en) | 2019-04-18 |
MX2019004222A (es) | 2019-06-10 |
WO2018075801A1 (en) | 2018-04-26 |
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