CONJUGATE OF BIOLOGICALLY ACTIVE SUBSTANCES WITH $$$-FETOPROTEIN SHOWING THE SELECTIVE ACTION WITH RESPECT TO CANCER TUMORS, METHOD OF THEIR PREPARING (VARIANTS) AND PHARMACEUTICAL COMPOSITION BASED ON THEREOF

摘要

FIELD: medicine, oncology. SUBSTANCE: product: conjugates with $$$-fetoprotein showing the selective action with respect to cancer target-cells where the conjugated particles were bound by chemical bond and exhibiting resistance against proteases and other enzymes of biological fluids. Method of conjugate preparing involves interaction of protein or biologically active substance containing amino-group with succinylimidyl-trans-4-(N-maleiimidylmethyl)-cyclohexane-1-car-boxylate followed by cross-linking of the prepared derivative with biologically active substance or protein part of $$$-fetoprotein, respectively, by SH-groups. The latter can be incorporated additionally using 3-(2-pyridyldithio)-propionic acid succinimide ether. Variant: condensation of amino-groups of protein with aldehyde group of biologically active substance (parent or incorporated additionally after activation with periodate) followed by reduction of semiproduct with boron hydride. Pharmaceutical composition has effective amount of conjugate and carrier that can be useful for intravenous administration. Calichemycin is preferable active substance in conjugate. EFFECT: improved method of preparing, enhanced effectiveness of treatment.