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Development of intelligent formulations for controlling drug release: a UGT1A1-based strategy

Research Project

Project/Area Number 17K15526
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionYokohama College of Pharmacy

Principal Investigator

Isobe Takashi  横浜薬科大学, 薬学部, 講師 (30440530)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsアルギン酸 / UGT1A1 / ビリルビン / 薬学
Outline of Final Research Achievements

It is difficult to predict the activity of metabolic enzymes in patients taking multiple concomitant drugs (e.g., elderly patients) owing to the drugs’ possible effects on induction and inhibition of metabolic those enzymes. Therefore, intelligent formulations are being developed that adjust drug release based on metabolic enzyme activity. In the present study, we aimed to develop an oral formulation that controls drug release by assessing uridine diphosphate glucuronosyltransferase 1A1 activity in the liver based on intestinal bilirubin concentration. We prepared alginate gel beads that released drugs at varying rates depending on the bilirubin concentration. Results showed that the drug release profile of alginate gel beads in the presence of bilirubin was affected by the molecular weight of alginic acid, calcium concentration at the time of preparation, and gelation time.

Academic Significance and Societal Importance of the Research Achievements

世界に先駆けて超高齢化社会に突入した日本において、高齢者への安全な薬物療法は国民のQOL(生活の質)の向上を考える上で重要です。服用薬が多く、薬による代謝酵素の変動を予測しづらい高齢者は副作用発生のリスクも高くなる傾向にあります。本研究で得られた成果は、患者ごとの代謝酵素の変動を把握し適切な量の薬物を放出するインテリジェント製剤の開発において有益な情報であり、この成果が高齢者など副作用発生リスクの高い患者への安全安心な薬の提供に役立つと考えております。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (5 results)

  • [Journal Article] Hydrolysis of di(2-ethylhexyl) phthalate in humans, monkeys, dogs, rats, and mice: An in vitro analysis using liver and intestinal microsomes2019

    • Author(s)
      Nobumitsu Hanioka, Takashi Isobe, Susumu Ohkawara, Sadayuki Ochi, Toshiko Tanaka-Kagawa, and Hideto Jinno
    • Journal Title

      Toxicol. in Vitro

      Volume: 54 Pages: 237-242

    • DOI

      10.1016/j.tiv.2018.10.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regioselective glucuronidation of daidzein in liver and intestinal microsomes of humans, monkeys, rats, and mice2018

    • Author(s)
      Hanioka N, Ohkawara S, Isobe T, Ochi S, Tanaka-Kagawa T, Jinno H
    • Journal Title

      Arch Toxicol

      Volume: 92 Issue: 9 Pages: 2809-2817

    • DOI

      10.1007/s00204-018-2265-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Naringenin glucuronidation in liver and intestine microsomes of humans, monkeys, rats, and mice2018

    • Author(s)
      Isobe T., Ohkawara S., Ochi S., Tanaka-Kagawa T., Jinno H., Hanioka N.
    • Journal Title

      Food and Chemical Toxicology

      Volume: 111 Pages: 417-422

    • DOI

      10.1016/j.fct.2017.11.057

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic glucuronidation of 4-tert-octylphenol in humans: inter-individual variability and responsible UDP-glucuronosyltransferase isoforms2017

    • Author(s)
      Isobe T., Ohkawara S., Tanaka-Kagawa T., Jinno H., Hanioka N.
    • Journal Title

      Archives of Toxicology

      Volume: 91 Issue: 11 Pages: 3543-3550

    • DOI

      10.1007/s00204-017-1982-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト肺ミクロゾームにおける吸入ステロイド薬の加水分解反応に対する2,2,4-トリメチル-1,3-ペンタンジオール ジイソブチラートの影響2020

    • Author(s)
      奥村 紗希,礒部 隆史,大河原 晋,香川(田中) 聡子,神野 透人,埴岡 伸光
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Hirsutella rhossiliensis糖脂質合成類縁体によるTHP-1細胞のLPS誘導性炎症メディエーター産生の抑制2020

    • Author(s)
      門松 隆夫,大河原 晋,礒部 隆史,香川(田中) 聡子,金谷 貴行,羽田 紀康,大塚 功,埴岡 伸光
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒトの肝臓、小腸および肺における2,2,4-トリメチル-1,3-ペンタンジオールジイソブチラートの加水分解反応:ミクロゾーム画分を用いるin vitro解析2019

    • Author(s)
      礒部 隆史,大河原 晋,香川(田中)聡子,神野 透人,埴岡伸光
    • Organizer
      フォーラム2019 衛生薬学・環境トキシコロジー
    • Related Report
      2019 Annual Research Report
  • [Presentation] ビリルビン濃度で薬物放出量が変化するアルギン酸ゲルビーズの調製条件に関する検討2019

    • Author(s)
      礒部 隆史、片岡 祐太、村上 雄大、加藤 輝隆、越智 定幸、埴岡 伸光
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 薬物放出量を決定するインテリジェント製剤へのアルギン酸ゲルビーズの利用2017

    • Author(s)
      加藤 嵐、礒部 隆史、大河原 晋、加藤 輝隆、越智 定幸、香川(田中) 聡子、神野 透人、埴岡 伸光
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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