SOLUBLE COMPLEXES OF DRUG ANALOGS AND ALBUMIN

摘要

The present invention provides novel, non-covalently bound complexes of serum albumin and analogs of poorly soluble drugs, such as camptothecin. The novel complexes are significantly more water-soluble than the camptothecin analogs and are useful as prodrug forms of the camptothecin analogs for the treatment of mammalian cell proliferative diseases, such as cancer.

主权项

1. A non-covalently bound complex of a camptothecin analog and serum albumin in a molar ratio from about 1:1 to about 16:1, wherein:
the complex has a solubility in aqueous solution of at least 5 mg/ml, and the camptothecin analog comprises a compound of Formula I: wherein
R1 is OH or —OX, wherein X comprises a group that selectively binds serum albumin;R2-6 are each, independently, H, halo, OH, NO2 NH2, lower alkyl, O-lower alkyl, NH-lower alkyl, N(lower alkyl)2, lower alkyl-N(lower alkyl)2, lower alkyl-Si(lower alkyl)3,or
comprises a group that selectively binds serum albumin;
wherein R4 and R5 optionally, together form —OCH2CH2O—,R2 and R3 optionally, together formand
at least one of R1, R2, R3, R4, R5, and R6 comprises a group that selectively binds serum albumin.