| 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, proteincompatible, buffered solution, a cosolvent selected from the group consisting of propylene glycol, ethanol, DMSO, and combinations thereof, and an additive comprising at least one C6-C18 carboxylic acid having a pH in the range from about 4.0 to 8.5 and at a temperature ranging from about 25 ~C to about 37 ~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 nonnucleophilic, protein-compatible, buffered solution and a cosolvent comprising t-butanol.
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