Development of new antimalarial trandermal agent

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07086
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Okayama University
• Principal Investigator: Kim Hye-Sook 岡山大学, 医歯薬学総合研究科, 准教授 (70314664)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: マラリア / 過酸化物 / 外用剤 / 経皮吸収 / 新薬候補

Outline of Final Research Achievements

I found the usefulness for slow-released transdermal agent of new antimalarial endoperoxides (N-89 and N-251) found as our new antimalarial drug research. As a suitable base of ointment of end-peroxide's, polyethylene glycol (PEG) 400 and PEG4000 in a ratio of 8: 1 was selected and pharmacokinetic analysis and antimalarial efficacy evaluation was performed using a ointment preparation containing N-89 under same conditions. As a result, an excellent antimalarial effect and a complete cure effect were obtained by applying an ointment preparation containing 60 mg / kg of N-89 twice a day for 3 days at 4 Cm2 of transdermal area. All mice completely cured until infection rate of 1.5% in malaria group, but in mice with an infection rate of more than 1.5% will be propose to be used in combination with an clinically used antimalarial drugs which long half-life.

Free Research Field

感染症制御、医薬品開発

Academic Significance and Societal Importance of the Research Achievements

マラリアによる死亡の９割は5歳未満の乳幼児である現状から、経口投与による治療は難しく、注射器等を用いる治療は現地の状況を鑑みて、推奨出来ない。我々は経口投与で優れた抗マラリア薬効と完治効果を示す新規抗マラリア薬候補として見出した有機合成化合物・ N-89, N-251が非侵襲性で乳幼児へのマラリア治療に適用可能であることを見出した。即ち、N-89とN-251の薬効を長期間持続しながら副作用が発現した時に対処しやすい剤形である経皮吸収型製剤が in vivo 実験でマラリアを完治することを明らかにした。この結果は単剤で安価でかつ簡便に重症マラリアで死亡するアフリカの乳幼児の救命に貢献できる。