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The novel synthesis of controlled release polymer with targeting function and application to DDS.

Research Project

Project/Area Number 11557193
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field 医薬分子機能学
Research InstitutionOsaka University

Principal Investigator

KUBO Kazuyoshi  Graduate School of Pharmaceutical Sciences Associate Professor, 薬学研究科, 助教授 (00028846)

Co-Investigator(Kenkyū-buntansha) NAKAGAWA Shinsaku  Graduate School of Pharmaceutical Sciences Associate Professor, 薬学研究科, 助教授 (70207728)
MAYUMI Tadanori  Graduate School of Pharmaceutical Sciences Professor, 薬学研究科, 教授 (00098485)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsPVP / Drug-Carriers / Controlled release / Bioconjugation / 抗腫瘍作用 / DMMAn / 徐放 / ターゲティング / ハイブリッド化 / 徐放化 / Targeting
Research Abstract

Functional polyvinylpyrrolidone (PVP) was synthesized as a novel polymeric modifier for polymer-conjugated cytokines, and its efficiency and applicability as a drug delivery system (DDS) were evaluated. PVP with a carboxyl group at one end of the main chain was prepared by radical polymerization (M(n) : 6000, M(w)/M(n) : 1.14) with the aid of 4,4'-azobis (4-cyanovaleric acid) as a radical initiator and 3-mercaptopropionic acid as a transfer agent. Interleukin-6 (IL-6) was covalently conjugated via the formation of amino bonds between the lysine amino groups of IL-6 and PVP.PVP-conjugated IL-6, in which 60% of the fourteen lysine amino groups of IL-6 were estimated to be coupled with PVP (M-PVP-IL-6), showed more than 50-fold greater thrombopoietic potency in vivo than native IL-6. No side effects, such as body weight loss, were observed in the M-PVP-IL-6 treated mice. These results indicate that PVP as a polymeric modifier is a promising DDS for clinical application of cytokines and other therapeutic agents.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Tsunoda S.: "Selective enhancement of thrombopoieticactivity of PEGylat edint erleukin 6 by a simple procedureusing a reversible amino-protective reagent."Br.J.Haematol.. 112. 181-188 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamada H.: "Antitumor activity of tumor necrosis factor-alpha conjugated with polyvinylpyrrolidoneon solid tumors in mice"Cancer Res.. 60. 6416-6420 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsunoda S: "Molecular design of polyvinylpyrrolidone-conjugated interieukin-6 for enhancement of in vivo thrombopoieticactivity in mice."J Control Release.. 68. 335-341 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamada H.: "Molecular design of conjugated tumor necrosis factor-alpha : Synthesis and characteristics of polyvinyl pyrrolidone modified tumor necrosis facyor-alpha."Biochem.Biophys.Res.Commun.. 257. 448-453 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsunoda S.et al.: "Selective enhancement of thrombopoietic activity of PEGylated interleukin 6 by a simple procedure using a reversible amino-protective reagent."Br.J.Haematol.. 112. 181-188 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamada H.et al.: "Antitumor activity of tumor necrosis factor-alpha conjugated with polyvinylpyrrolidone on solid tumors in mice."Cancer Res.. 60. 6416-6420 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsunoda S.et al.: "Molecular design of polyvinylpyrrolidone-conjugated interleukin-6 for enhancement of in vivo thrombopoietic activity in mice."J Control Release.. 68. 335-341 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamada H.et al.: "Molecular design of conjugated tumor necrosis factor-alpha ; Synthesis and characteristics of polyvinyl pyrrolidone modified tumor necrosis facyor-alpha."Biochem.Biophys.Res.Commun.. 257. 448-453 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsunoda S.: "Selective enhancementofthrombopoieticactivity of PEGylat edint erleukin 6 by a simple procedureusing a reversible amino-protective reagent."Br.J.Haematol.. 112. 181-188 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kamada H.: "Antitumor activity of tumor necrosis factor-alpha conjugated with polyvinylpyrrolidone on solid tumors in mice"Cancer Res.. 60. 6416-6420 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsunoda S: "Molecular design of polyvinylpyrrolidone-conjugated in terleukin-6 for enhancement of in vivo thrombopoieticactivity in mice."J Control Release.. 68. 335-341 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Haruhiko Kamada: "Molecular design of conjugated tumor necrosis factor-alpha ; Synthesis and characteristics of polyvinyl pyrrolidone modified tumor necrosis factor-alpha"Biochem.Biophys.Res.Commun.. 257. 448-453 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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