Drug development for atopic dermatitis treatment : Rational prodrug design based on function of skin esterases

• Project/Area Number: 19590101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kumamoto University
• Principal Investigator: IMAI Teruko Kumamoto University, 薬学部, 教授 (70176478)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 経皮吸収 / プロドラッグ / 加水分解 / カルボキシルエステラーゼ / エステル交換反応 / 抗アレルギー薬 / 基質認識性 / 皮膚 / エステル交換 / 酵素

Research Abstract

皮膚内の加水分解活性を担う主な酵素としてカルボキシルエステラーゼを同定し、この酵素をターゲットとした皮膚滞留型のアトピー性皮膚炎治療薬をデザインした。すなわち、皮膚構造、酵素の存在部位および皮膚成分と薬物との親和性を考慮することにより、皮膚患部での活性薬物濃度を維持し、持続的に薬理活性を示すことができる薬物を設計し評価した。

Research Products

• [Journal Article] Permeability of 5-fluorouracil and its prodrugs in Caco-2 cell monolayers : evidence for shift from paracellular to transcellular transport by prodrug formation (2009)
  • Author(s): Masumi Imoto, Hidekazu Azuma, Ikuo Yamamoto, Masaki Otagiri, Teruko Imai
  • Journal Title: J Drug Deliv Sci Technol 19 Pages: 37-41
• [Journal Article] Permeability of 5-fluorouracil and its prodrugs in Caco-2 cell monolayers : Evidence for shift from paracellular to transcellular transport by prodrug formation (2009)
  • Author(s): Masumi Imoto
  • Journal Title: Journal of Drug Delivery Science and Technology 19(1) Pages: 37-41
  • Peer Reviewed
• [Journal Article] Carboxylesterase in the liver and small intestine of experimental animals and human (2007)
  • Author(s): Megumi Taketani, Mayumi Shii, Kayoko Ohura, Shinichi Ninomiya, Teruko Imai
  • Journal Title: Life Sci 81 Pages: 924-932
• [Journal Article] Intestinal first-pass metabolism via carboxylesterase in rat jejunum and ileum (2007)
  • Author(s): Kenji Masaki, Mitsuru Hashimoto, Teruko Imai
  • Journal Title: Drug Metab. Dispos. 35 Pages: 1089-1095
• [Journal Article] 吸収性改善を目的としたエステル誘導体の体内動態と加水分解 (2007)
  • Author(s): 今井輝子
  • Journal Title: 薬学雑誌 127 Pages: 611-619
  • NAID: 110006242865
  • Peer Reviewed
• [Journal Article] Intestinal first-pass metabolism via carboxylesterase in rat jejunum and ileum. (2007)
  • Author(s): Kenji Masaki
  • Journal Title: Drug Metabolism and Disposition 35(7) Pages: 1089-1095
  • Peer Reviewed
• [Journal Article] Involvement of Up-regulation of hepatic breast cancer resistance protein in decreased plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38) by coadministration of S-1 in rats (2007)
  • Author(s): Koji Yokoo
  • Journal Title: Drug Metabolism and Disposition 35(9) Pages: 1511-1517
  • Peer Reviewed
• [Journal Article] Carboxylesterase in the liver and small intestine of experimental animals and human. (2007)
  • Author(s): Megumi Taketani
  • Journal Title: Life Science 81(11) Pages: 924-932
  • Peer Reviewed
• [Presentation] Sf9を用いたHis tag修飾Hce2の発現とその酵素機能の評価 (2009)
  • Author(s): 續政哉, 今井輝子
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] 分泌型ヒトカルボキシルエステラーゼ2の発現とその触媒活性の評価 (2008)
  • Author(s): 續政哉, 今井輝子
  • Organizer: 日本薬物動態学会第23回年会
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-30
• [Presentation] Species Differences of Carboxylesterase Involved in Bioconversion of Ester-based Prodrug (2008)
  • Author(s): Teruko Imai
  • Organizer: France Japan 8th Drug Delivery Symposium
  • Place of Presentation: Cannes, France
  • Year and Date: 2008-10-08
• [Presentation] Species Differences of Carboxylesterase Involved in Bioconversion of Ester-based Prodrug (2008)
  • Author(s): 今井輝子
  • Organizer: 日仏DDS学会
  • Place of Presentation: フランス・カンヌ
  • Year and Date: 2008-10-08
• [Presentation] Prodrug design to improve the oral absorption of fexofenadine (2008)
  • Author(s): Kayoko Ohura, Teruko Imai
  • Organizer: Globalization of Pharmaceutics Education Network 2008
  • Place of Presentation: Leuven, Kingdom of Belgium
  • Year and Date: 2008-09-12
• [Presentation] 医薬品開発におけるエステラーゼの種差について (2008)
  • Author(s): 今井輝子
  • Organizer: 日本DDS学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-30
• [Presentation] 医薬品開発におけるエステラーゼの種差について (2008)
  • Author(s): 今井輝子
  • Organizer: 第24回日本DDS学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-29
• [Presentation] 粘膜代謝の修飾と経粘膜輸送 (2008)
  • Author(s): 今井輝子
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] 粘膜代謝の修飾と経粘膜輸送 (2008)
  • Author(s): 今井 輝子
  • Organizer: 日本薬学会第28年会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-03-27
• [Presentation] カルボキシエステラーゼの部位差・種差 (2008)
  • Author(s): 今井輝子
  • Organizer: 2007年度「医薬品の吸収性評価に関する検討会」
  • Place of Presentation: 滋賀
  • Year and Date: 2008-03-19
• [Presentation] 薬物動態を考慮した医薬品開発のために (2008)
  • Author(s): 今井輝子
  • Organizer: 第10回生命化学研究会
  • Place of Presentation: 熊本
  • Year and Date: 2008-01-11
• [Presentation] Rational prodrug design based on carboxylesterase activity (2007)
  • Author(s): Teruko Imai
  • Organizer: Thai Annual Research Meeting
  • Place of Presentation: Bangkok, The Kingdom of Thailand
  • Year and Date: 2007-12-12
• [Presentation] カルボキシルエステラーゼの基質認識性に基づくプロドラッグ設計 (2007)
  • Author(s): 今井輝子
  • Organizer: 第23回日本DDS学会
  • Place of Presentation: 熊本
  • Year and Date: 2007-06-14
• [Book] 分子薬物動態学 (2008)
  • Author(s): 今井輝子
  • Publisher: 南山堂