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1. 发明申请

WO2004006893A1 METHOD FOR PARTICLE PRECIPITATION USING NEAR-CRITICAL AND SUPERCRITICAL ANTISOLVENTS 审中-公开
标题翻译：使用临界和超临界反应的颗粒沉降的方法
公开(公告)号：WO2004006893A1
公开(公告)日：2004-01-22
申请号：PCT/NL2003/000516
申请日：2003-07-15
申请人： FEYECON DEVELOPMENT & IMPLEMENTATION B.V. , UNIVERSITEIT LEIDEN , PELLIKAAN, Hubert, Clemens , BORCHARD, Gerrit
发明人： PELLIKAAN, Hubert, Clemens , BORCHARD, Gerrit
IPC分类号： A61K9/16
CPC分类号： A61K9/5161 , A61K9/1652 , A61K9/1694 , A61K9/5192 , A61K48/0008 , A61K48/0041 , A61K2039/55555
摘要： The present invention is concerned with a continuous or semi-continuous process for the preparation of small particles through precipitation, which process employs (i) a fluid solution comprising a solvent and a solute to be precipitated and (ii) a non-gaseous antisolvent, said solvent being soluble in or miscible with the antisolvent and said solute being substantially insoluble in the antisolvent, said process comprising the successive steps of: a. combining the fluid solution and the antisolvent so as to achieve a condition of super saturation; b. allowing nucleation to commence and the nuclei formed to grow to particles with a volume weighted average diameter of between 5 nm and 50,000 nm, c. collecting the resulting particles and separating them from the antisolvent; wherein the solvent contains an organic solvent and less than 20 wt.% water and the solute comprises a charged carbohydrate polymer in combination with a second biopolymer component selected from the group consisting of polynucleotides, amino acid polymers and mixtures thereof; and wherein step a. and b. are carried out under a substantially constant pressure. Suitable examples of the charged carbohydrate polymer include chitosan polymers, heparin, hyaluronic acid polymers and derivatives thereof. The particles obtained from the above process may suitably be used for intracellular delivery of a polynucleotide and/or a polyamino acid in animals and humans.
摘要翻译：本发明涉及通过沉淀制备小颗粒的连续或半连续方法，该方法使用（i）包含溶剂和待沉淀的溶质的流体溶液，和（ii）非气态反溶剂，所述溶剂可溶于抗溶剂或与溶液混溶，所述溶质基本上不溶于抗溶剂，所述方法包括以下连续步骤：a。结合流体溶液和抗溶剂，以达到超饱和状态; 湾允许成核开始，并且形成的细胞核生长成体积加权平均直径在5nm和50,000nm之间的颗粒，c。收集所得颗粒并将其与抗溶剂分离; 其中所述溶剂含有有机溶剂和少于20重量％的水，并且所述溶质包含带电荷的碳水化合物聚合物与选自多核苷酸，氨基酸聚合物及其混合物的第二生物聚合物组分; 并且其中步骤a。和b。在基本恒定的压力下进行。带电碳水化合物聚合物的合适实例包括壳聚糖聚合物，肝素，透明质酸聚合物及其衍生物。从上述方法获得的颗粒可适合用于动物和人体中多核苷酸和/或多氨基酸的细胞内递送。

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