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    • 6. 发明申请
    • NANOPARTICLES AND MICROPARTICLES OF NON-LINEAR HYDROPHILIC-HYDROPHOBIC MULTIBLOCK COPOLYMERS
    • 非线性疏水性疏水多元共聚物的纳米颗粒和微球
    • WO1995003356A1
    • 1995-02-02
    • PCT/US1994008287
    • 1994-07-22
    • MASSACHUSETTS INSTITUTE OF TECHNOLOGYDOMB, Abraham, J.GREF, RuxandraMINAMITAKE, YoshiharuPERACCHIA, Maria, TeresaLANGER, Robert, S.
    • MASSACHUSETTS INSTITUTE OF TECHNOLOGY
    • C08G81/00
    • A61K9/5146A61K9/5161A61K47/6921A61K47/6935A61K49/223A61K51/1241A61K51/1251A61K2123/00B82Y5/00C08G63/664C08G81/00
    • Particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified to achieve variable release rates or to target specific cells or organs. The particles have a core of a multiblock copolymer formed by covalently linking a multifunctional compound with one or more hydrophobic polymers and one or more hydrophilic polymers, and contain a biologically active material. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the particles. The typical size of the particles is between 180 nm and 10,000 nm, preferably between 180 nm and 240 nm, although microparticles can also be formed as described herein. The particles can include magnetic particles or radiopaque materials for diagnostic imaging, biologically active molecules to be delivered to a site, or compounds for targeting the particles. The particles have a prolonged half-life in the blood compared to particles not containing poly(alkylene glycol) moieties on the surface.
    • 提供的颗粒不被网状内皮系统的巨噬细胞迅速地从血液中清除,并且可被修饰以实现可变释放速率或靶向特定的细胞或器官。 颗粒具有通过共价连接多官能化合物与一种或多种疏水性聚合物和一种或多种亲水性聚合物形成的多嵌段共聚物的核心,并含有生物活性材料。 聚(亚烷基二醇)的末端羟基可用于共价附着到颗粒表面上的生物活性分子,包括靶向特定细胞或器官的抗体或影响颗粒的电荷,亲油性或亲水性的分子。 颗粒的表面也可以通过连接与形成颗粒核心的那些相同结构的可生物降解的聚合物来进行改性。 颗粒的典型尺寸在180nm和10,000nm之间,优选在180nm和240nm之间,尽管也可以如本文所述形成微粒。 颗粒可以包括用于诊断成像的磁性颗粒或不透射线的材料,要递送到位点的生物活性分子或用于靶向颗粒的化合物。 与不含表面上的聚(亚烷基二醇)部分的颗粒相比,颗粒在血液中具有延长的半衰期。