公开(公告)号：US5714586A

公开(公告)日：1998-02-03

申请号：US654505

申请日：1996-05-28

申请人： Martin P. Kunstmann ,  Irwin J. Hollander ,  Philip Hamann ,  Arthur Kunz

发明人： Martin P. Kunstmann ,  Irwin J. Hollander ,  Philip Hamann ,  Arthur Kunz

IPC分类号： A61K47/48 ,  C07K16/00 ,  A61K31/70 ,  A61K31/715 ,  C12P21/08

CPC分类号： A61K47/48369 ,  A61K47/48407 ,  A61K47/48684

摘要： A method is provided for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation. These conjugates are prepared by incubating a calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution, a cosolvent selected from the group consisting of propylene glycol, ethanol, DMSO, and combinations thereof, and an additive comprising at least one C.sub.6 -C.sub.18 carboxylic acid having a pH in the range from about 4.0 to 8.5 and at a temperature ranging from about 25.degree. C. to about 37.degree. C. for a period of time ranging from about 15 minutes to about 24 hours, and recovering monomeric calicheamicin derivative/carrier conjugates. Alternatively, the conjugates can be prepared by incubating the calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution and a cosolvent comprising t-butanol.

摘要翻译： 提供了用于制备具有更高的药物负荷/产率和降低的聚集的单体加利车霉衍生物/载体缀合物的方法。 这些缀合物通过将加利车霉素衍生物和蛋白质载体在包含非亲核性，蛋白质相容性缓冲溶液，选自丙二醇，乙醇，DMSO及其组合的共溶剂的溶液中孵育来制备，以及 添加剂，其包含至少一种pH为约4.0-8.5，温度为约25℃至约37℃的C 6 -C 18羧酸，时间为约15分钟至约 24小时，并回收单体加利车霉衍生物/载体缀合物。 或者，可以通过将加利车霉素衍生物和蛋白质载体温育在包含非亲核，蛋白质相容的缓冲溶液和包含叔丁醇的助溶剂的溶液中来制备缀合物。