Development of cranial nerve disorder ameliorating drug using hypoxia-selective nano DDS preparation for cardiopulmonary arrest

• Project/Area Number: 15K21178
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy; Emergency medicine
• Research Institution: The University of Tokushima
• Principal Investigator: ZAMAMI Yoshito 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (70550250)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心肺停止病態 / 心肺停止 / 脳神経障害

Outline of Final Research Achievements

In order to investigate whether hypoxia-selective nano DDS preparation shows neuroprotective effect under hypoxic conditions, an in vitro system using mouse hippocampal HT22 neurons was established. Exposure of HT22 neurons in a low oxygen incubator under 1% oxygen conditions for 6 hours resulted in a cell survival rate of 43%. In addition, thiopental as an anticonvulsant and nicorandil as a therapeutic agent for angina pectorally inhibited nerve cell death in hypoxic conditions in a concentration-dependent manner. From these results, it is considered that Two drugs which found neuroprotective effect in this study is useful for preparing hypoxia selective nano DDS formulations. In the future, we will investigate the efficacy by administering nano DDS formulated drug to cardiopulmonary arrest model rats and aim for development of post-resuscitation encephalopathy drugs.

Research Products

• [Journal Article] Meta-analysis of the efficacies of amiodarone and nifekalant in shock-resistant ventricular fibrillation and pulseless ventricular tachycardia (2017)
  • Author(s): Shiho Sato, Yoshito Zamami, Toru Imai, Satoshi Tanaka, Toshihiro Koyama, Takahiro Niimura, Masayuki Chuma, Tadashi Koga, Kenshi Takechi, Yasuko Kurata, Yutaka Kondo, Yuki Izawa-Ishizawa, Toshiaki Sendo, Hironori Nakura, Keisuke Ishizawa
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 12683
  • DOI: 10.1038/s41598-017-13073-0
  • NAID: 120006535023
  • URL: https://tokushima-u.repo.nii.ac.jp/records/2005543
  • Peer Reviewed / Open Access
• [Journal Article] Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest. (2017)
  • Author(s): 48)Niimura T, Zamami Y, Koyama T, Izawa-Ishizawa Y, Miyake M, Koga T, Harada K, Ohshima A, Imai T, Kondo Y, Imanishi M, Takechi K, Fukushima K, Horinouchi Y, Ikeda Y, Fujino H, Tsuchiya K, Tamaki T, Hinotsu S, Kano MR, Ishizawa K.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 17919-17919
  • DOI: 10.1038/s41598-017-17686-3
  • NAID: 120006535027
  • Peer Reviewed / Open Access
• [Journal Article] Drug Repositioning Research Utilizing a Large-scale Medical Claims Database to Improve Survival Rates after Cardiopulmonary Arrest (2017)
  • Author(s): Zamami Yoshito、Niimura Takahiro、Takechi Kenshi、Imanishi Masaki、Koyama Toshihiro、Ishizawa Keisuke
  • Journal Title: YAKUGAKU ZASSHI Volume: 137 Issue: 12 Pages: 1439-1442
  • DOI: 10.1248/yakushi.17-00139-3
  • NAID: 130006236513
  • ISSN: 0031-6903, 1347-5231
• [Journal Article] Pharmacological approach for drug repositioning against cardiorenal diseases (2017)
  • Author(s): Zamami Y, Imanishi M, Takechi K, Ishizawa K
  • Journal Title: The Journal of Medical Investigation Volume: 64 Issue: 3.4 Pages: 197-201
  • DOI: 10.2152/jmi.64.197
  • NAID: 130006105190
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] Calcitonin gene-related peptide pre-administration acts as a novel antidepressant in stressed mice (2017)
  • Author(s): Hashikawa-Hobara N, Ogawa T, Sakamoto Y, Matsuo Y, Ogawa M, Zamami Y, Hashikawa N
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 12559-12559
  • DOI: 10.1038/srep12559
  • Peer Reviewed / Open Access
• [Journal Article] Pharmaceutical Education Focused on Pharmacotherapy in Emergency Medical Care (2016)
  • Author(s): Zamami Y, Koyama T, Imai T, Takemoto A, Sagara H, Sendo T, Nakura H
  • Journal Title: YAKUGAKU ZASSHI Volume: 136 Issue: 7 Pages: 987-991
  • DOI: 10.1248/yakushi.15-00286-4
  • NAID: 130005159456
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2016-07-01
  • Peer Reviewed
• [Journal Article] Evaluation of pharmaceutical lifesaving skills training oriented pharmaceutical intervention (2016)
  • Author(s): Yoshito Zamami, Toru Imai, Masaki Imanishi, Kenshi Takechi, Naoko Shiraishi, Toshihiro Koyama, Hidenori Sagara, Yasukazu Shiino, Toshiaki Sendo and Keisuke Ishizawa
  • Journal Title: Journal of Pharmaceutical Health Care and Sciences Volume: 2 Issue: 1 Pages: 21-21
  • DOI: 10.1186/s40780-016-0054-7
  • NAID: 120006937631
  • Peer Reviewed / Open Access
• [Journal Article] Vascular responses to compound 48/80 in rat mesenteric vascular beds (2016)
  • Author(s): Jin H, Li Z, Takatori S, Koyama T, Jin X, Zamami Y, Kawasaki H, Sun P
  • Journal Title: Can J Physiol Pharmacol Volume: 94 Issue: 6 Pages: 620-626
  • DOI: 10.1139/cjpp-2015-0442
  • Peer Reviewed
• [Journal Article] Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries (2016)
  • Author(s): Tangsucharit P, Takatori S, Zamami Y, Goda M, Pakdeechote P, Kawasaki H, Takayama F
  • Journal Title: J Pharmacol Sci Volume: 130 Issue: 1 Pages: 24-32
  • DOI: 10.1016/j.jphs.2015.12.005
  • NAID: 120006344936
  • Peer Reviewed
• [Presentation] 心肺蘇生後症候群治療薬の開発を目的としたドラッグリポジショニング研究 －大規模医療情報を活用した検討－ (2017)
  • Author(s): 新村 貴博, 座間味 義人, 石澤 有紀, 今西 正樹, 武智 研志, 福島圭穣, 堀ノ内 裕也, 池田 康将, 藤野 裕道, 土屋 浩一郎, 玉置 俊晃, 石澤 啓介
  • Organizer: 第255回 徳島医学会学術集会
• [Presentation] 大規模医療情報を活用して新規心肺蘇生後症候群治療薬の開発を志向したドラッグリポ ジショニング研究 (2017)
  • Author(s): 漆崎 汐里, 座間味 義人, 石澤 有紀, 新村 貴博, 武智 研志, 今西 正樹, 福島 圭穣, 堀之内 裕也, 池田 康将, 藤野 裕道, 土屋 浩一郎, 玉置 俊晃, 石澤 啓介
  • Organizer: 第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
• [Presentation] 大規模医療情報を活用して心肺停止患者の生存率向上を志向したドラッグリポジショニング研究 (2017)
  • Author(s): 座間味 義人, 小山 敏広, 石澤 有紀, 新村 貴博, 今西 正樹, 武智 研志, 堀ノ内 裕也, 桐野 靖, 中村 敏己, 寺岡 和彦, 池田 康将, 藤野 裕道, 土屋 浩一郎, 玉置 俊晃, 石津 啓介
  • Organizer: 第27回日本医療薬学会年会 シンポジウムS34-2
  • Invited
• [Presentation] 臨床薬理学集中講座修了後の研究活動～大規模医療情報を活用したドラッグリポジショニング研究を中心に～ (2017)
  • Author(s): 座間味 義人, 石澤 有紀, 新村 貴博, 武智 研志, 今西 正樹, 堀ノ内 裕也, 池田 康将, 藤野 裕道, 土屋 浩一郎, 玉置 俊晃, 石澤 啓介
  • Organizer: 第38回日本臨床薬理学会学術総会 シンポジウムS36-1
  • Invited
• [Presentation] Drug repositioning research aimed at improving the survival rate of patients with cardiopulmonary arrest using large-scale medical claims database (2017)
  • Author(s): Yoshito Zamami, Takahiro Niimura, Yuki Izawa-Ishizawa, Kenshi Takechi, Masaki Imanishi, Yashishi Krino, Toshimi Nakamura, Kazuhiko Teraoka, Keisuke Ishizawa
  • Organizer: ASHPMidyear2017Clinical Meeting＆Exhibition
  • Int'l Joint Research
• [Presentation] 症例データベースを活用して新規心肺蘇生薬の開発を目指したドラッグリポジショニング研究 (2016)
  • Author(s): 座間味 義人, 今西 正樹, 武智 研志, 小山 敏広, 大島 礼子, 樋之津 史郎, 狩野 光伸, 石澤 啓介
  • Organizer: 第2回日本医薬品安全性学会学術大会
  • Place of Presentation: 長良川国際会議場（岐阜県岐阜市）
  • Year and Date: 2016-07-23
• [Presentation] ドラッグリポジショニングを切り口とした新規心肺蘇生薬の探索研究-大規模医療情報を活用した検討- (2016)
  • Author(s): 座間味 義人, 今西 正樹, 武智 研志, 小山 敏広, 大島 礼子, 今井 徹, 樋之津 史郎, 狩野 光伸, 石澤 啓介
  • Organizer: 医療薬学フォーラム2016/第24回クリニカルファーマシーシンポジウム
  • Place of Presentation: 滋賀県立芸術劇場びわ湖ホール（滋賀県大津市）
  • Year and Date: 2016-06-25
• [Presentation] 外来診療棟を主としたMRSAの実態調査 (2016)
  • Author(s): 柴田 高洋, 今西 正樹, 座間味 義人, 中村 敏己, 寺岡 和彦, 石澤 啓介
  • Organizer: 医療薬学フォーラム2016/第24回クリニカルファーマシーシンポジウム
  • Place of Presentation: 滋賀県立芸術劇場びわ湖ホール（滋賀県大津市）
  • Year and Date: 2016-06-25
• [Presentation] 持参薬管理業務における周術期中止医薬品の管理ツール導入による効果 (2016)
  • Author(s): 石田 俊介, 坂本 久美子, 今西 正樹, 座間味 義人, 中村 敏己, 寺岡 和彦, 石澤 啓介
  • Organizer: 第19回日本医薬品情報学会総会・学術大会
  • Place of Presentation: 昭和薬科大学（東京都町田市）
  • Year and Date: 2016-06-04
• [Presentation] ケルセチン代謝産物Q3GAの血管内皮膚細胞に対する短期及び長期効果の検討 (2016)
  • Author(s): 石澤 有紀, 細岡 真由子, 斎藤 尚子, 堀ノ内 裕也, 今西 正樹, 座間味 義人, 池田 康将, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
  • Organizer: 第129回日薬理学会学会近畿部会
  • Place of Presentation: 広島県医師会館（広島県広島市）
• [Remarks] 研究業績
  • URL: http://pub2.db.tokushima-u.ac.jp/ERD/person/307098/work-ja.html