METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS

摘要

Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.

主权项

1. A method of treatment of a tauopathy in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a high-purity diaminophenothiazinium compound of the following formula: wherein: each of R1 and R9 is independently —H, C1-4alkyl, C2-4alkenyl, or halogenated C1-4alkyl; each of R3NA and R3NB is independently C1-4alkyl, C2-4alkenyl, or halogenated C1-4alkyl; each of R7NA and R7NB is independently C1-4alkyl, C2-4alkenyl, or halogenated C1-4alkyl; and X is one or more anionic counter ions to achieve electrical neutrality; wherein high-purity is defined by:
at least 98% pure;less than 1% Azure B as impurity;less than 0.15% Azure A as impurity;less than 0.15% Azure C as impurity; andless than 0.05% Methylene Violet Bernthsen (MVB) as impurity.