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Enhanced Efficacy of Immunosuppressant by Modification at Molecular Level

Research Project

Project/Area Number 05671877
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 医薬分子機能学
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

TAKADA Kanji  Pharmaceutical University Department of Pharmaceutics, Professor, 薬学部, 教授 (30102106)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Yukako  Kyoto Pharmaceutical University, Department of pharmaceutics, Assistant, 薬学部, 助手 (30278444)
YASUI Hiroshi  Kyoto Pharmaceutical Univiersity, Department of pharmaceutics, Assistant, 薬学部, 助手 (20278443)
喜里山 暁子  京都薬科大学, 薬学部, 助手 (00234401)
上田 千晶  京都薬科大学, 薬学部, 副手 (20247787)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsCyclospor in A / Immunosuppressant / Molecular level Modification / Liposome / Lymphatic tissue / Bioadhesive / マイクロスフェア / リポソーム / リンパ系組織
Research Abstract

The representative immunosuppressants such as cyclosporin A (CyA) and tacrolimus (FK506) have unique pharmacological activities based on the suppression of the activating process of helper T cells by inhibiting the production of interleukin 2 (IL-2). However, the dose-dependent side effects like renal, hepatic and central nerve system are serious clinical problems. As both immunosuppressants are extremely hydrophobic water-insoluble drugs, the available dosage form is limited. Moreover, price of these drugs are very expensive. To solve these problems, there is a need to develop a new dosage form which elucidates immunosuppressive effect with minimum required amount of drug. We prepared several kinds of CyA liposome preparations to deliver CyA to its target organ that contain much lymphatic cells.
From CyA and egg yolk phosphatidylcholine, both liposomes and modified liposomes with bioadhesive polymer, Carbopol, were prepared. From the pharmacokinetic study using rats following iv infusion of test preparations, the distribution of CyA to the liver and the spleen that are rich in lymphatic cells were significantly increased as compared to the CyA solution. Using rat heart transplantation model system, the efficacy of these liposomes preparations were evaluated. Test preparations were injected to transplanted rats 10mg CyA/kg for 7 days and the survival time of the graft was determined.
As compared to the control value, 6.4(]SY.+-.])1.9 day, the mean survival days of liposome and modified liposomes were prolonged to 14.2(]SY.+-.])4.4 and 18.8(]SY.+-.])2.9 days, respectively. These results support the usefulness of targeting CyA to its site of action by physicochemical modification at molecular level.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] N. Katayama, T. Houjou and K. Takada: "Lymphatic transport of cyclospor in A from the abdominal cavity." International Jounal of Pharmaceutics. 110. 155-160 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. Sugioka, H. Odani, T. Ohta, H. Kishimoto, T. Yasumura and K. Takada: "Determination of a new immunosuppressant, mycophenol ate mofetil, and its active metabolite, mycophenolic acid, in rat and human body fluids by high-performance" Jounal of Chromatography. 654. 249-256 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. Katayama, R. Tanaka, Y. Ohno, C. Ueda, T. Houkou and K. Takada,: "Implantable slow release cyclosporin A(CyA)delivery system to thoracic lymph duct." International Journal of Pharmaceutics. 115. 87-93 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. Sugioka, S. H. Chen, K. Hayashida, H. Koyama, T. Ohta, H. Kishimoto, T. Yasumura and K. Takada: "Stability and pharmacokinetic studies of a new immunosuppressant, mycophenolate mofetil (RS-61433), in rats." Biopharmaceutics & Drug Disposition. 16. 591-601 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.Katayama, T.Houjou and K.Takada: "Lymphatic transport of cyclospor in A from the abdominal cavity." International Journal of Pharmaceutics. 110. 155-160 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.Sugioka, H.Odani, T.Ohta, H.Kishimoto, T.Yasumura and K.Takada: "Determination of a new immunosuppressant, mycophenolate mofetil, and its active metabolite, mycophenolic acid, in rat and human body fluids by high-performance liquid chromatography." Journal of Chromatography. 654. 249-256 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.Katayama, R.Tanaka, Y.Ohno, C.Ueda, T.Houjou and K.Takada: "Implantable slow release cyclospor in A (CyA) delivery system to thoracic lymph duct." International Journal of Pharmaceutics. 115. 87-93 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N.Sugioka, S.H.Chen, K.Hayashida, H.Koyama, T.Ohta, H.Kishimoto, T.Yasumura and K.Takada: "Stability and pharmacokinetic studies of a new immunosuppressant, mycophenolate mofetil (RS-61433), in rats." Biopharmaceutics & Drug Disposition. 16. 591-601 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] N. Katayama, R. Tanaka, Y. Ohno, C. Ueda, I. Houjou and K. Takada: "Implantable slow release cyclosporin A (CyA) delivery system to thoracic lymph duct." International Journal of Pharmaceutics. 115. 87-93 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] N.Katayama,T.Houjou and K.Takada: "Lymphatic transport of cyclosporin A from the abdominal cavity" Intern.J.Pharnaceut.110. 155-160 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Katayama,R.Tanaka,and K.Takada: "Implantable slow release cyclosporin A(CyA) delivery system to thoracic lymph duct" Intern.J.Pharnaceut.115. 87-93 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kanji Takada,Naohisa Katayama Akiko Kiriyama and Hisato Usuda: "Distribution characteristics ofimmunosuppressants FK506 and cyclosporin A in the blood compartment" Biopharmaceutics & Drug Disposition. 14. 659-672 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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