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

具有靶向功能的控释聚合物的新合成及其在DDS中的应用。

• 批准号: 11557193
• 负责人: KUBO Kazuyoshi
• 金额: $ 6.46万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557193/
• 关键词: 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

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.

合成了功能性聚乙烯吡咯烷酮（PVP）作为一种新型的高分子修饰剂，并对其作为药物传递系统（DDS）的效率和适用性进行了评价。以4，4 ′-偶氮二（4-氰基戊酸）为自由基引发剂，3-巯基丙酸为转移剂，通过自由基聚合（M（n）：6000，M（w）/M（n）：1.14）制备了主链一端带有羧基的PVP。白细胞介素-6（IL-6）通过赖氨酸氨基与聚乙烯吡咯烷酮（PVP）形成氨基键而偶联，PVP偶联IL-6（M-PVP-IL-6）的体内促血小板生成活性是天然IL-6的50倍以上。在M-PVP-IL-6处理的小鼠中未观察到副作用，如体重减轻。这些结果表明，PVP作为一种聚合物改性剂是一种有前途的DDS细胞因子和其他治疗药物的临床应用。

项目成果

Tsunoda S: "Molecular design of polyvinylpyrrolidone-conjugated interieukin-6 for enhancement of in vivo thrombopoieticactivity in mice."J Control Release.. 68. 335-341 (2000)

Tsunoda S：“聚乙烯吡咯烷酮缀合的 interieukin-6 的分子设计，用于增强小鼠体内血小板生成活性。”J Control Release.. 68. 335-341 (2000)

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)

Kamada H.等人：“缀合肿瘤坏死因子-α的分子设计；聚乙烯吡咯烷酮修饰的肿瘤坏死因子-α的合成和特征。”Biochem.Biophys.Res.Commun. 257. 448-453 (1999)

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)

Tsunoda S. 等人：“通过使用可逆氨基保护试剂的简单程序，选择性增强聚乙二醇化白细胞介素 6 的血小板生成活性”Br。

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)

Tsunoda S.等人：“用于增强小鼠体内血小板生成活性的聚乙烯吡咯烷酮缀合白细胞介素 6 的分子设计。”J Control Release.. 68. 335-341 (2000)

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)

Haruhiko Kamada：“缀合肿瘤坏死因子-α的分子设计；聚乙烯吡咯烷酮修饰的肿瘤坏死因子-α的合成和特性”Biochem.Biophys.Res.Commun.. 257. 448-453 (1999)