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Strategic formulization of nobiletin to improve its biopharmaceutical properties for COPD treatment

Research Project

Project/Area Number 16K18950
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionUniversity of Shizuoka

Principal Investigator

Sato Hideyuki  静岡県立大学, 薬学部, 講師 (70739242)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords難水溶性化合物 / Nobiletin / 溶解性改善 / 粉末吸入製剤 / 慢性閉塞性肺疾患 / 吸入粉末剤 / ポリフェノール / 炎症性肺疾患 / COPD / 肺疾患 / 抗炎症作用
Outline of Final Research Achievements

The aim of the present study is to develop novel inhalable formulation of Nobiletin (NOB) for the treatment of chronic obstructive pulmonary disease (COPD). NOB has been known as one of poorly water-soluble polyphenols isolated from citrus peel, which has anti-inflammatory effect, anti-oxidation, inhibition of fibrosis, and anti-apoptotic effect. These beneficial effects might contribute to treat COPD symptoms. Thus, to clarify the applicability of NOB to the treatment of COPD, various kinds of solubilization technologies were applied for developing NOB formulations. We successfully developed solubilized formulation to improve the biopharmaceutical properties of NOB, and a formulization technology to prepare inhalable formulation of poorly water-soluble materials.

Academic Significance and Societal Importance of the Research Achievements

慢性閉塞性肺疾患(COPD) の患者数は今後爆発的に増加し,WHO の試算によると2020 年までに世界第3 位の死亡原因になると予想されているにも関わらず,現在のCOPD の診断率は低く,適切な診断・治療が普遍的に実施されていない.また柑橘類由来ポリフェノールであるノビレチン (NOB) は COPD 治療に対するポテンシャルを有するものの,難水溶性をはじめとする物性の悪さのために COPD に対する応用研究がほとんどなされていない.本検討では,NOB を効果的に治療用するための製剤化研究とその剤形開発を戦略的に実行し,これら技術の有用性を明らかとすることに成功した.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (29 results)

All 2018 2017 2016 Other

All Int'l Joint Research (7 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Int'l Joint Research] シドニー大学(オーストラリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] プリンストン大学(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] プリンストン大学(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] シドニー大学(オーストラリア)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] プリンストン大学(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] シドニー大学(オーストラリア)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Respirable powder formulation of a shortened vasoactive intestinal peptide analog for treatment of airway inflammatory diseases2018

    • Author(s)
      Hiroki Suzuki, Takahiro Mizumoto, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
    • Journal Title

      Journal of Peptide Science

      Volume: 24:3 Issue: 3

    • DOI

      10.1002/psc.3069

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amourphous solid dispersion of cyclosporine A prepared with fine droplet drying process: Physicochemical and pharmacokinetic characterization2017

    • Author(s)
      Hiroki Suzuki, Tatsuru Moritani, Tadahiko Morinaga, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 519 Issue: 1-2 Pages: 213-219

    • DOI

      10.1016/j.ijpharm.2017.01.018

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] New nano-matrix oral formulation of nanoprecipitated cyclosporine A prepared with multi-inlet vortex mixer2017

    • Author(s)
      Hiroki Suzuki, Shun Hamao, Yoshiki Seto, Hideyuki Sato, Jennifer Wong, Robert K. Prud’homme, Hak-Kim Chan, Satomi Onoue
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 516 Issue: 1-2 Pages: 116-119

    • DOI

      10.1016/j.ijpharm.2016.11.031

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biopharmaceutical Evaluation of Novel Cyclosporine A Nano-matrix Particles for Inhalation2016

    • Author(s)
      Hideyuki Sato, Hiroki Suzuki, Keisuke Yakushiji, Jennifer Wong, Yoshiki Seto, Robert K. Prud’homme, Hak-Kim Chan, Satomi Onoue
    • Journal Title

      Pharmaceutical Research

      Volume: 33 Issue: 9 Pages: 2107-2116

    • DOI

      10.1007/s11095-016-1949-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Quercetin のナノ結晶固体分散体化による経口吸収性及び尿酸値低下作用向上: potassium oxonate 誘発性高尿酸血症ラットにおける尿酸値定量法の比較2018

    • Author(s)
      平野 樹、勝俣瑞木、後 英理、世戸孝樹、佐藤秀行、尾上誠良
    • Organizer
      第 138 回 日本薬学会 年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 体内動態制御および炎症性呼吸器疾患治療を指向した新規 celecoxib 吸入粉末剤2018

    • Author(s)
      當波 諒、鈴木寛貴、佐藤秀行、世戸孝樹、尾上誠良
    • Organizer
      第 138 回 日本薬学会 年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fine droplet drying 工法を用いた作用持続型カルシトニン粉末吸入剤の開発2018

    • Author(s)
      佐藤秀行、田畑藍子、三分一所靜香、森谷 樹、森永匡彦、水元隆博、世戸孝樹、尾上誠良
    • Organizer
      第 138 回 日本薬学会 年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fine droplet drying 工法による高機能性固体分散体製剤の開発 (5) -Quercetin の経口吸収性向上を指向した非晶質固体分散体-2018

    • Author(s)
      平野 樹、勝俣瑞木、森谷 樹、森永匡彦、世戸孝樹、佐藤秀行、尾上誠良
    • Organizer
      日本薬剤学会 第 33 回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cyclosporine A 含有 dry-emulsion の吸入粉末製剤による薬物動態制御2018

    • Author(s)
      佐藤秀行、小川久美子、湖城吉城、川端洋平、水元隆博、世戸孝樹、尾上誠良
    • Organizer
      第 34 回 日本 DDS 学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fine droplet drying 工法による高機能性固体分散体製剤開発 (6) -難水溶性機能性食品素材への応用検討-2018

    • Author(s)
      平野 樹、勝俣瑞木、森谷 樹、森永匡彦、世戸孝樹、佐藤秀行、尾上誠良
    • Organizer
      第 64 回 日本薬学会東海支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inhalable sustained-release particles of salmon calcitoninprepared with fine droplet drying process2018

    • Author(s)
      Hideyuki Sato, Aiko Tabata, Shizuka Sanbuissho, Tatsuru Moritani, Tadahiko Morinaga, Takahiro Mizumoto, Yoshiki Seto, Satomi Onoue
    • Organizer
      The 2nd Workshop for Japan-Korea Young Scientists on Pharmaceutics
    • Related Report
      2018 Annual Research Report
  • [Presentation] Salmon calcitonin-loaded sustained release particles prepared with fine droplet drying process for inhalation2018

    • Author(s)
      Hideyuki Sato, Aiko Tabata, Shizuka Sanbuissho, Tatsuru Moritani, Tadahiko Morinaga, Takahiro Mizumoto, Yoshiki Seto, Satomi Onoue
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] ナノ結晶固体分散体技術による nobiletin の経口吸収性及び腎保護作用向上2017

    • Author(s)
      平野 樹,仁平 拓也,世戸 孝樹,佐藤 秀行,尾上 誠良
    • Organizer
      第 32 年会 日本薬剤学会
    • Place of Presentation
      埼玉県大宮市
    • Year and Date
      2017-05-11
    • Related Report
      2016 Research-status Report
  • [Presentation] 非晶質固体分散体技術適応による nobiletin の尿酸値低下作用向上2017

    • Author(s)
      後 英里,仁平 拓也,佐藤 秀行,世戸 孝樹,尾上 誠良
    • Organizer
      第 32 年会 日本薬剤学会
    • Place of Presentation
      埼玉県大宮市
    • Year and Date
      2017-05-11
    • Related Report
      2016 Research-status Report
  • [Presentation] Flash nano-precipitation 法を用いた新規 Cyclosporine A 粉末吸入製剤開発2017

    • Author(s)
      佐藤秀行、鈴木寛貴、薬師寺恵介、Jennifer Wong、Hak-Kim Chan、Robert K. Prud’homme、世戸孝樹、尾上誠良
    • Organizer
      日本薬学会 第 137 年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Fine droplet drying 工法を用いた製剤化による cyclosporine A 経口吸収性向上2017

    • Author(s)
      鈴木寛貴、森谷 樹、森永匡彦、世戸孝樹、佐藤秀行、尾上誠良
    • Organizer
      日本薬剤学会 第 32 年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Nobiletin の生物薬剤学的特性向上を指向したナノ結晶固体分散体の開発2017

    • Author(s)
      平野 樹、仁平拓也、世戸孝樹、佐藤秀行、尾上誠良
    • Organizer
      第 42 回製剤・創剤セミナー
    • Related Report
      2017 Research-status Report
  • [Presentation] Sustained-Release Formulation of Salmon Calcitonin for Inhalation Prepared with Fine Droplet Drying (FDD) Process2017

    • Author(s)
      Hideyuki Sato
    • Organizer
      Inhalation Asia 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cyclosporine A-Loaded Nano-Matrix Particle Prepared with Multi-Inlet Vortex Mixer for Treatment of Airway Inflammatory Diseases2017

    • Author(s)
      Hiroki Suzuki
    • Organizer
      Inhalation Asia 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cyclosporine A-loaded nano-matrix particles prepared with multi-inlet vortex mixer for inhalation2017

    • Author(s)
      35.Hideyuki Sato, Hiroki Suzuki, Keisuke Yakushiji, Jennifer Wong, Yoshiki Seto, Robert K. Prud’homme, Hak-Kim Chan, Satomi Onoue
    • Organizer
      The 54th Japanese peptide symposium
    • Related Report
      2017 Research-status Report
  • [Presentation] PHARMACOKINETIC CONRTOL OF CYCLOSPORINE A EMPLOYING NOVEL NANO-MATRIX PARTICLES FOR INHALATION2016

    • Author(s)
      Hideyuki Sato, Hiroki Suzuki,Keisuke Yakushiji,Jennifer Wong,Yoshiki Seto,Robert K. Prud’homme,Hak-Kim Chan,Satomi Onoue
    • Organizer
      The 11th International ISSX Meeting
    • Place of Presentation
      韓国・釜山
    • Year and Date
      2016-06-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] 次世代吸入製剤とデバイスの開発2018

    • Author(s)
      佐藤 秀行,尾上 誠良
    • Total Pages
      252
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313535
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2022-02-21  

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