New approaches to reducing adverse drug effects for answering clinical needs

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K14948
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: University of Yamanashi
• Principal Investigator: Uchida Atsushi 山梨大学, 医学部附属病院, 薬剤師 (40816865)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 光分解 / 活性酸素種 / ラジカルスカベンジャー

Outline of Final Research Achievements

This research project was aimed to develop a new pharmaceutical strategy to avoid photo-induced adverse effects of photolabile drugs, which has become an issue in clinical practice. Based on the occurrence of vascular pain induced by photodegradation of dacarbazine (DTIC), it was challenged to clarify the mechanism of photodegradation of DTIC and to design a new drug formulation based on the mechanism. In this study, reactive oxygen species were found to be partly involved in the photodegradation of DTIC, and addition of radical scavengers based on the photochemical properties of DtTIC was successfully used for photostabilization of DTIC. This finding might contribute to the provision of efficacious and safe medication for the clinical use of photolabile drugs.

Free Research Field

薬剤学

Academic Significance and Societal Importance of the Research Achievements

医薬品の光化学的特性に注目した研究は数多くなされているが，光化学的特性に基づいた光安定化手法は確立されていない．さらに，基礎的かつ科学的根拠に基づいた光安定化手法の臨床へのアプローチは未だにない．本研究成果は，医薬品の光化学的特性に基づいた新規光安定化手法を見出した．本手法は，臨床現場で生じている光照射での医薬品による副作用発現の科学的かつ本質的な回避をもたらし，より安心・安全な医療の提供に寄与すると期待できる．さらには，創薬段階で光安定性に課題を有する医薬品に，本検討で得られた方法論を適用することで，医薬品の開発の進展貢献可能な成果を得た．