Platinum bound to transferrin for use in the treatment of breast tumors

Abstract

A method of preparing an anti-breast tumor compound comprised of a toxic metal bound to the blood protein transferrin is disclosed which has superior therapeutic properties. When monomeric transferrin is bound to cis-Dichlorodiammineplatinum (II), a chemotherapeutic agent is produced which specifically attacks and kills rapidly multiplying breast tumor cells without damaging normal cells. In addition, the body's immune defenses against foreign substances are substantially not activated. In preferred embodiments, 1.8-2.2 atoms of platinum are bound to each molecule of transferrin. The platinum-transferrin is prepared by first protecting the sulfhydro groups on essentially iron free transferrin with an excess of cystine in solution. Cis-dichlorodiamine platinum (II) is then reacted with the iron-free transferrin in the presence of bicarbonate anion. The platinum transferrin is dialyzed to remove the weak organic acid and bicarbonate anion, and then passed through molecular sieves to separate the monomeric product which is thereafter concentrated to a therapeutically useful concentration.

I claim: 
     
       1. Monomeric platinum transferrin prepared by reacting cis-diamminedichloroplatinum II with essentially iron free human transferrin in the presence of cystine at 0°-5° C., then separating monomeric platinum transferrin from polymeric platinum transferrin. 
     
     
       2. Platinum transferrin of claim 1, wherein .[.platinum.]. .Iadd.transferrin .Iaddend.is reacted with cis-diamminedichloroplatinum II in the presence of bicarbonate anion. .Iadd. 
     
     
       3.  A method for preparing monomeric platinum transferrin comprising: reacting cis-diamminedichloroplatinum II with essentially iron-free human transferrin in the presence of cystine at 0°-5° C; and   separating monomeric platinum transferrin from polymeric platinum transferrin. .Iaddend. .Iadd.4. The method of claim 3, wherein the transferrin is reacted with cis-diamminedichloroplatinum II in the   
     
     
        presence of bicarbonate anion. .Iaddend. .Iadd.5.  A process for preparing a complex of serum transferrin and the cis isomer of diamminedichloroplatinum (II) comprising preparing an aqueous solution of serum transferrin and adding thereto a sufficient quantity of the cis isomer of diamminedichloroplatinum (II) to bring the final ratio of said cis isomer of diamminedichloroplatinum (II) to said serum transferrin to approximately a 2:1 molar ratio. .Iaddend.