JP5581500B2 - 虚血再灌流障害軽減用治療剤および治療装置 - Google Patents
虚血再灌流障害軽減用治療剤および治療装置 Download PDFInfo
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- JP5581500B2 JP5581500B2 JP2010053405A JP2010053405A JP5581500B2 JP 5581500 B2 JP5581500 B2 JP 5581500B2 JP 2010053405 A JP2010053405 A JP 2010053405A JP 2010053405 A JP2010053405 A JP 2010053405A JP 5581500 B2 JP5581500 B2 JP 5581500B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/0057—Pumps therefor
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/10—Preparation of respiratory gases or vapours
- A61M16/12—Preparation of respiratory gases or vapours by mixing different gases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/20—Valves specially adapted to medical respiratory devices
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Description
実験方法:
1.使用マウスと抗生剤の投与
実験にはC57BL/6J、10週齢雄性マウスを使用した。腸内に存在する細菌が発生させる水素の影響を取り除くため、抗生剤入りの飲み水と通常のエサを4日間自由摂取させ、実験開始18時間前から絶食させた。ただしこの期間も抗生剤入りの飲み水は自由摂取させた。抗生剤の効果を確認するため、実験開始前に呼気中の水素濃度を自作の呼気水素濃度測定回路を用いて測定し、水素濃度が測定感度限界以下であるマウスのみを実験に使用した。腸内細菌により発生する水素の影響を取り除かないと、結果のばらつきが大きく、吸入水素による効果を正しく判定することができない。
麻酔薬ペントバルビタールを腹膜内投与し、気管挿管後に人工呼吸器と接続し、呼吸管理を行った。左胸部を除毛・消毒した後、開胸を行ない、左冠状動脈前下行枝を絹糸で結紮することにより虚血状態を60分間維持した後、結紮した絹糸を解放して、再灌流を生じさせた。再灌流は血流の再開により確認した。再灌流の確認後、閉胸し、麻酔覚醒まで人工呼吸管理を行い、麻酔覚醒後は抜管して、室内気により管理を行った。
吸入時間は、再灌流開始(結紮解放)の5分前から再灌流開始の30分後までの35分間とした。対象とするガスを吸入させない群(酸素吸入による人工呼吸管理)を対照(コントロール)とし、水素吸入群、一酸化窒素吸入群、および本発明に従った水素/一酸化窒素併用吸入群に分けて、比較検討を行った。
再灌流開始から24時間経過後、再び上記のように麻酔、開胸および再結紮を行った。左室からEvans Blue染色液を注入し、虚血領域を同定した。冠動脈にEvans Blue染色液が行き渡ったことを確認してから、心臓を摘出した。摘出した心臓は1 mm幅にスライスして心臓切片を作成した。作成した心臓切片をTTC (2,3,5-トリフェニルテトラゾリウムクロリド) 染色液を用いて染色し、梗塞領域を同定し、実体顕微鏡を用いて撮影を行った。
回路構成は基本的には図1に示すものであった。水素は安全性を考えて、窒素中の水素濃度が4%の窒素希釈水素ガスボンベから供給した。一酸化窒素は、窒素中に800 ppmの一酸化窒素を含有するボンベから供給した。流量調整器および微量流量計を用いて、窒素中に酸素30%、水素2%、一酸化窒素80 ppmを含む混合ガスを、人工呼吸器を経てマウスの肺に吸入投与した。
実験結果:
実験結果を図3および図4に示す。
Claims (2)
- 酸素、水素、一酸化窒素を含有し、残部が不活性ガスからなる、虚血再灌流障害を軽減するための吸入用気体状薬剤組成物であって、
前記組成物中の酸素濃度が21〜98%、水素濃度が0.1〜4%、一酸化窒素濃度が40〜80ppmである、吸入用気体状薬剤組成物。 - 不活性ガス、酸素、水素、および一酸化窒素の各ガスの供給源と、各ガス供給源に接続された圧力調整器および流量計と、各ガスを供給源から供給するための供給経路とを備え、すべてのガス供給経路が投与前に合流して不活性ガス、酸素、水素および一酸化窒素から本質的になる混合ガスを形成するように配置されていることを特徴とする、患者に直接あるいは人工呼吸器を経て請求項1に記載の薬剤組成物を吸入投与することにより虚血再灌流障害を軽減するための治療装置。
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010053405A JP5581500B2 (ja) | 2010-03-10 | 2010-03-10 | 虚血再灌流障害軽減用治療剤および治療装置 |
PL11753240T PL2545926T3 (pl) | 2010-03-10 | 2011-03-02 | Środek terapeutyczny i urządzenie terapeutyczne do łagodzenia uszkodzeń niedokrwienno-reperfuzyjnych |
CN2011800195752A CN102883730A (zh) | 2010-03-10 | 2011-03-02 | 缺血再灌注损伤减轻用治疗剂及治疗装置 |
EP11753240.8A EP2545926B1 (en) | 2010-03-10 | 2011-03-02 | Therapeutic agent and therapeutic device for alleviating ischemia-reperfusion injury |
US13/583,283 US9101556B2 (en) | 2010-03-10 | 2011-03-02 | Therapeutic agent and therapeutic device for alleviating ischemia-reperfusion injury |
PCT/JP2011/054747 WO2011111581A1 (ja) | 2010-03-10 | 2011-03-02 | 虚血再灌流障害軽減用治療剤および治療装置 |
ES11753240.8T ES2569178T3 (es) | 2010-03-10 | 2011-03-02 | Agente terapéutico y dispositivo terapéutico para aliviar el daño por isquemia-reperfusión |
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JP2010053405A JP5581500B2 (ja) | 2010-03-10 | 2010-03-10 | 虚血再灌流障害軽減用治療剤および治療装置 |
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JP2014102824A Division JP2014141536A (ja) | 2014-05-16 | 2014-05-16 | 虚血再灌流障害軽減用治療剤および治療装置 |
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JP2011184398A JP2011184398A (ja) | 2011-09-22 |
JP2011184398A5 JP2011184398A5 (ja) | 2012-10-18 |
JP5581500B2 true JP5581500B2 (ja) | 2014-09-03 |
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JP2010053405A Active JP5581500B2 (ja) | 2010-03-10 | 2010-03-10 | 虚血再灌流障害軽減用治療剤および治療装置 |
Country Status (7)
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US (1) | US9101556B2 (ja) |
EP (1) | EP2545926B1 (ja) |
JP (1) | JP5581500B2 (ja) |
CN (1) | CN102883730A (ja) |
ES (1) | ES2569178T3 (ja) |
PL (1) | PL2545926T3 (ja) |
WO (1) | WO2011111581A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI717348B (zh) | 2015-05-06 | 2021-02-01 | 美商中子療法股份有限公司 | 產生用於硼中子捕獲治療之中子的設備及方法 |
JP7103698B2 (ja) | 2020-12-11 | 2022-07-20 | 東莞理工学院 | 真空応力型試料環境デモ機 |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
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US10531655B2 (en) | 2011-12-02 | 2020-01-14 | The Regents Of The University Of California | Reperfusion protection solution and uses thereof |
US20150047634A1 (en) * | 2012-03-17 | 2015-02-19 | University Health Network | Device for delivering hydrogen to a subject |
WO2014024984A1 (ja) * | 2012-08-09 | 2014-02-13 | 大陽日酸株式会社 | 医療用の水素混合ガス供給装置 |
JP5228142B1 (ja) * | 2012-11-26 | 2013-07-03 | ミズ株式会社 | 生体用高濃度水素ガス供給装置 |
WO2015153287A1 (en) * | 2014-03-31 | 2015-10-08 | Zoll Medical Corporation | Blood filtering of inflammatory biomarkers to treat post-resuscitation syndrome |
TWI594772B (zh) * | 2014-04-18 | 2017-08-11 | 林信湧 | 一種用於治療高血壓之吸入式醫藥組成物及其備製方法 |
TWI586382B (zh) * | 2014-04-18 | 2017-06-11 | 林信湧 | 一種用於治療腎臟病之吸入式醫藥組成物及其備製方法 |
JP2014141536A (ja) * | 2014-05-16 | 2014-08-07 | Kitasato Institute | 虚血再灌流障害軽減用治療剤および治療装置 |
CN105012339A (zh) * | 2015-09-01 | 2015-11-04 | 王岱君 | 氢气在制备预防肢体缺血-再灌注损伤药物中的应用 |
BR112018006600B1 (pt) | 2015-10-01 | 2022-05-17 | Mallinckrodt Hospital Products IP Limited | Dispositivo e método para difusão de no de alta concentração com gás para terapia de inalação |
BR112018011803A2 (pt) * | 2015-12-11 | 2018-12-04 | Vero Biotech LLC | método e mecanismo para a administração de gases incluindo óxido nítrico |
JP5981017B1 (ja) * | 2015-12-28 | 2016-08-31 | 学校法人慶應義塾 | 自己心拍再開後の予後を改善するための医薬組成物 |
US20170182088A1 (en) * | 2015-12-28 | 2017-06-29 | Geno Llc | Method and apparatus for administering nitric oxide with supplemental drugs |
US10828436B2 (en) * | 2016-04-05 | 2020-11-10 | Vanderbilt University | Administering the noble gas argon during cardiopulmonary resuscitation |
JP6712924B2 (ja) * | 2016-07-27 | 2020-06-24 | 学校法人慶應義塾 | 自己心拍再開後の予後を改善するための医薬組成物 |
JP6667817B1 (ja) | 2019-03-13 | 2020-03-18 | 住友精化株式会社 | ガス組成物及びその製造方法、並びにガス製品 |
JP2020176070A (ja) * | 2019-04-16 | 2020-10-29 | MiZ株式会社 | 脳卒中後の後遺症改善のための組成物 |
EP4056188A4 (en) * | 2019-11-08 | 2023-12-06 | School Juridical Person The Kitasato Institute | MEANS FOR PREVENTING OR TREATING ARRHYTHMIA AND DEVICE FOR PREVENTING OR TREATING ARRHYTHMIA |
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US5396882A (en) * | 1992-03-11 | 1995-03-14 | The General Hospital Corporation | Generation of nitric oxide from air for medical uses |
ATE209922T1 (de) | 1995-10-20 | 2001-12-15 | Air Liquide | Pharmazeutische zusammensetzung von stickstoffmonoxid |
US6656452B1 (en) * | 1997-10-21 | 2003-12-02 | The General Hospital Corporation | Use of inhaled NO as anti-inflammatory agent |
US6601580B1 (en) | 2000-06-28 | 2003-08-05 | The General Hospital Corporation | Enhancing therapeutic effectiveness of nitric oxide inhalation |
WO2005077005A2 (en) * | 2004-02-04 | 2005-08-25 | The General Hospital Corporation | Enhancing the effectiveness of an inhaled therapeutic gas |
US20090035383A1 (en) * | 2005-08-19 | 2009-02-05 | Shigeo Ohta | Scavenger of in vivo harmful reactive oxygen species and/or free radicals |
CN101347451A (zh) * | 2008-06-24 | 2009-01-21 | 中国人民解放军第二军医大学 | 一种具有治疗缺血再灌注损伤功能的含氢注射液 |
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2011
- 2011-03-02 WO PCT/JP2011/054747 patent/WO2011111581A1/ja active Application Filing
- 2011-03-02 ES ES11753240.8T patent/ES2569178T3/es active Active
- 2011-03-02 CN CN2011800195752A patent/CN102883730A/zh active Pending
- 2011-03-02 PL PL11753240T patent/PL2545926T3/pl unknown
- 2011-03-02 EP EP11753240.8A patent/EP2545926B1/en active Active
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI717348B (zh) | 2015-05-06 | 2021-02-01 | 美商中子療法股份有限公司 | 產生用於硼中子捕獲治療之中子的設備及方法 |
JP7103698B2 (ja) | 2020-12-11 | 2022-07-20 | 東莞理工学院 | 真空応力型試料環境デモ機 |
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US20130108715A1 (en) | 2013-05-02 |
EP2545926A4 (en) | 2013-08-14 |
CN102883730A (zh) | 2013-01-16 |
EP2545926A1 (en) | 2013-01-16 |
EP2545926B1 (en) | 2016-04-20 |
WO2011111581A1 (ja) | 2011-09-15 |
PL2545926T3 (pl) | 2016-07-29 |
US9101556B2 (en) | 2015-08-11 |
ES2569178T3 (es) | 2016-05-09 |
JP2011184398A (ja) | 2011-09-22 |
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