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    • 7. 发明公开
    • PROCESS FOR PREPARATION OF BEADS FOR IMAGING
    • 制备用于成像的小珠的过程
    • EP3216464A1
    • 2017-09-13
    • EP16159884.2
    • 2016-03-11
    • Stichting Katholieke Universiteit Nijmegen
    • Srinivas, MangalaKoshkina, OlgaFigdor, Carl Gustavde Vries, Ingrid Jolanda Monique
    • A61K49/00A61K49/18A61K49/22G01N29/04G01N29/24G01N24/08
    • A61K49/223A61K49/0002A61K49/1818G01N29/2418G01N2291/02475G01R33/281
    • The invention relates to a process for the preparation of beads comprising a biocompatible hydrophobic polymer, a perfluorocarbon and optionally a metal compound, comprising the steps of:
      a) adding the perfluorocarbon and optionally the metal compound to a solution of the biocompatible hydrophobic polymer in a polar solvent to provide a first liquid mixture,
      b) adding the first liquid mixture to an aqueous solution of a biocompatible surfactant under sonication to obtain a second liquid mixture,
      c) maintaining the sonication of the second liquid mixture while cooling,
      d) evaporating the polar solvent from the second liquid mixture to obtain a suspension of beads comprising the biocompatible hydrophobic polymer, the perfluorocarbon and optionally the metal compound,
      e) separating the beads from the suspension and preparing a water suspension of the beads and
      f) freeze-drying the water suspension to obtain the beads,
      wherein the addition of the first liquid mixture to the biocompatible surfactant in step b) is performed within a period of at most 10 seconds,
      wherein the sonication in step b) and the sonication in step c) are performed by a probe at an amplitude of at least 240 µm for 1-10 minutes and
      wherein the weight ratio of the biocompatible surfactant to the biocompatible hydrophobic polymer is at least 3:1.
    • 本发明涉及制备包含生物相容性疏水性聚合物,全氟化碳和任选的金属化合物的珠粒的方法,其包括以下步骤:a)将全氟化碳和任选的金属化合物加入生物相容性疏水性聚合物在 b)在超声处理下将第一液体混合物加入到生物相容表面活性剂的水溶液中以获得第二液体混合物,c)在冷却的同时维持第二液体混合物的超声处理,d)蒸发 从第二液体混合物中分离极性溶剂以获得包含生物相容性疏水性聚合物,全氟化碳和任选的金属化合物的珠粒的悬浮液,e)从珠粒中分离珠粒并制备珠粒的水悬浮液,以及f) 水悬浮液以获得珠子,其中将第一液体混合物添加至生物相容性物质 步骤b)中的表面活性剂在至多10秒的时间内进行,其中步骤b)中的超声处理和步骤c)中的超声处理通过探针在至少240μm的幅度下进行1-10分钟,并且其中 生物相容性表面活性剂与生物相容性疏水性聚合物的重量比至少为3:1。