Project/Area Number |
11557193
|
Research Category |
Grant-in-Aid for Scientific Research (B).
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
医薬分子機能学
|
Research Institution | Osaka 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)
|
Keywords | PVP / 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.
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