JP6289511B2 - 羊水塞栓の治療剤 - Google Patents
羊水塞栓の治療剤 Download PDFInfo
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- JP6289511B2 JP6289511B2 JP2015559504A JP2015559504A JP6289511B2 JP 6289511 B2 JP6289511 B2 JP 6289511B2 JP 2015559504 A JP2015559504 A JP 2015559504A JP 2015559504 A JP2015559504 A JP 2015559504A JP 6289511 B2 JP6289511 B2 JP 6289511B2
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- amniotic fluid
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- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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Description
(1)妊娠中または分娩後12時間以内に生じる;
(2)以下の症状または疾患のうち1つまたはそれ以上の集中的な医学的処置:
(a)心停止、
(b)分娩後2時間以内の原因不明の大量出血、
(c)播種性血管内凝固(DIC)、
(d)呼吸不全、
(3)観察された所見および症状が他の疾患では説明できない(非特許文献1を参照されたい)。
方法
分娩時の血清を、インフォームドコンセントのもと、対照群としての正常妊婦40人(年齢:31±5.1歳;在胎期間:273±11日;分娩時の出血量:590±367mL)、および潜在性AFEと診断された患者57人(年齢:34±4.5歳;在胎期間:267±19日;分娩時の出血量:4489±2900mL)から採取した。血清中C1インヒビター活性は、発色性合成基質を使用する方法により決定した。血清中C1インヒビター活性の基準値は70〜130%、検出限界は25%であり、25%未満の値は一律に25%であるものとして扱った。各群について得られた結果を、マンホイットニー検定により互いに比較した。
分娩時の血清中C1インヒビター活性は、対照群で53±21.0%、潜在性AFE群で35.5±13.5%であった。両群間には有意差(p<0.01)がある。潜在性AFE群の値は、対照群に比べ有意に低かった(図1)。さらに、個人のデータを比較すると、検出限界である25%未満のケース数が対照群で4(10%)、一方、潜在性AFE群で19(33.3%)であった。この両群間には有意差がある(図2)。
C1インヒビター活性が、分娩時の血清で減少していることが示される。C1インヒビター活性のこのような減少から、これがAFEにおいて分娩後のDIC型出血の誘導に関与している可能性が示唆される。というのは、C1インヒビターは、補体系だけでなくキニン産生系および凝固−線維素溶解系をも制御するからである。
頸管裂傷をきたし、縫合後も子宮出血の止まらなかった産褥婦1人(年齢34歳、在胎期間40週)が救急車で搬送され、潜在性AFEと診断された。この女性を、以下のように母体胎児集中治療室(MFICU)で処置した。
Claims (9)
- C1インヒビターを有効成分として含む、羊水塞栓の処置に使用するための治療剤。
- C1インヒビターは血漿由来の、または組換えC1インヒビターである、請求項1に記載の、使用するための治療剤。
- C1インヒビターは天然に生じるヒトタンパク質またはその変異型である、請求項1または2に記載の、使用するための治療剤。
- C1インヒビターはヒトC1インヒビターである、請求項1〜3のいずれか1項に記載の、使用するための治療剤。
- C1インヒビターはヒト血漿由来のC1インヒビターである、請求項1〜4のいずれか1項に記載の、使用するための治療剤。
- C1インヒビターは静脈内投与または皮下投与される、請求項1〜5のいずれか1項に記載の、使用するための治療剤。
- C1インヒビターは体重1kgあたり1〜1000ユニット、好ましくは体重1kgあたり5〜500ユニットの用量にて投与される、請求項1〜6のいずれか1項に記載の、使用するための治療剤。
- 前記インヒビターは(i)注射もしくは注入で単回用量にて、または(ii)各回を注射もしくは注入で複数回用量、好ましくは2回用量にて、または(iii)長期注入または長期適用で投与される、請求項1〜7のいずれか1項に記載の、使用するための治療剤。
- 前記インヒビターは、臨床的に潜在性の羊水塞栓の発症後、3時間以内、好ましくは1時間以内、より好ましくは30分以内、最も好ましくは直後に投与される、請求項1〜8のいずれか1項に記載の、使用するための治療剤。
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JP2013038170A JP2014162789A (ja) | 2013-02-28 | 2013-02-28 | 羊水塞栓症治療剤 |
JP2013038170 | 2013-02-28 | ||
EP13163205 | 2013-04-10 | ||
EP13163205.1 | 2013-04-10 | ||
PCT/EP2014/053902 WO2014131865A1 (en) | 2013-02-28 | 2014-02-28 | Therapeutic agent for amniotic fluid embolism |
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EP (1) | EP2961422B1 (ja) |
JP (1) | JP6289511B2 (ja) |
DK (1) | DK2961422T3 (ja) |
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DE4222534A1 (de) | 1992-07-09 | 1994-01-13 | Behringwerke Ag | Verwendung von Komplement-Inhibitoren zur Herstellung eines Arzneimittels zur Prophylaxe und Therapie von entzündlichen Darm- und Hauterkrankungen sowie Purpura |
DE4227762A1 (de) | 1992-08-24 | 1994-03-03 | Behringwerke Ag | Verwendung eines Kallikrein-Inhibitors zur Herstellung eines Arzneimittels zur Prophylaxe und Therapie bestimmter Krankheiten |
DK0716611T3 (da) * | 1993-09-01 | 2002-05-21 | Sanquin Bloedvoorziening | Fremgangsmåde til at reducere myocardielæsion under akut myocardieinfarkt |
AU6083899A (en) | 1999-09-16 | 2001-04-17 | Aventis Behring Gmbh | Combination of c1-inh and lung surfactant for the treatment of respiratory disorders |
EP2267026A1 (en) | 2000-04-12 | 2010-12-29 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US7087578B2 (en) * | 2000-05-24 | 2006-08-08 | Eli Lilly And Company | Formulations and methods for treating hypercoagulable states |
DE10112617A1 (de) * | 2001-03-14 | 2002-10-02 | Aventis Behring Gmbh | Verwendung eines C1-Esterase-Inhibitors zur Verhinderung oder Verzögerung der Abstoßung von Xenotransplantaten in Säugetieren |
ES2830499T3 (es) * | 2003-05-16 | 2021-06-03 | Pharming Intellectual Property B V | Inhibidor de C1 con una semivida corta para un tratamiento transitorio |
CA2632400C (en) | 2005-12-21 | 2016-06-07 | Pharming Intellectual Property Bv | Use of c1 inhibitor for the prevention of ischemia-reperfusion injury |
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US20160008425A1 (en) | 2016-01-14 |
JP2016513131A (ja) | 2016-05-12 |
US10441631B2 (en) | 2019-10-15 |
WO2014131865A1 (en) | 2014-09-04 |
EP2961422A1 (en) | 2016-01-06 |
DK2961422T3 (en) | 2017-01-16 |
EP2961422B1 (en) | 2016-09-28 |
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