Pledpharma Ab

Egetis Therapeutics Ab

Jacques Näsström

Sven Jacobsson

Michael Hall

Karl Reineke

Rolf Andersson

Jan-Olof G Karlsson

Tino Kurz

Christina McLaughlin

James Van Alstine

Dennis Bang Henriksen

Jan Olof Karlsson

Methods for treating and/or protecting against acute liver failure and other hepatotoxicities in an individual employ a combination of a first active agent comprising N-acetylcysteine and a second active agent comprising a manganese complex selected from the group consisting of (i) a calcium manganese mixed metal complex of N,N'-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N′-diacetic acid (DPDP) having a molar ratio of calcium to manganese in a range of from 1 to 10, or a pharmaceutically acceptable salt thereof, (ii) a mixture of manganese DPDP (MnDPDP), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing DPDP compound, or (iii) a mixture of manganese pyridoxyl ethylenediamine (MnPLED), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing pyridoxyl ethylenediamine (PLED) compound.

Methods and formulations for treatment of and/or protection against acute liver failure and other hepatotoxic conditions

Methods, formulations and kits for treating and/or protecting against acute liver failure and other hepatotoxicities in an individual employ a combination of a first active agent which replenishes, or decreases a loss of, functional glutathione in the individual, and a second active agent comprising a manganese complex selected from the group consisting of (i) a calcium manganese mixed metal complex of N,N'-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N&#x2032;-diacetic acid (DPDP) having a molar ratio of calcium to manganese in a range of from 1 to 10, or a pharmaceutically acceptable salt thereof, (ii) a mixture of manganese DPDP (MnDPDP), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing DPDP compound, or (iii) a mixture of manganese pyridoxyl ethylenediamine (MnPLED), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing pyridoxyl ethylenediamine (PLED) compound.

Methods for treatment of a pathological condition caused by oxidative stress in a patient comprise administering to the patient a mixed metal complex of a compound of Formula I, or a salt thereof, in an amount effective to reduce the oxidative stress. Pharmaceutical compositions are formed by suspending or dissolving a mixed metal complex of a compound of Formula I, or a salt thereof, in a liquid medium, optionally with one or more physiologically acceptable excipients. The mixed metals comprise calcium and manganese in a molar ratio of calcium to manganese in the range of 1-10: wherein X, R, R, R, and Rare as defined herein.

Calmangafodipir, a new chemical entity, and other mixed metal complexes, methods of preparation, compositions, and methods of treatment

Methods for treatment of a pathological condition caused by oxidative stress in a patient comprise administering to the patient a mixed metal complex of a compound of Formula I, or a salt thereof, in an amount effective to reduce the oxidative stress. The mixed metals comprise calcium and manganese in a molar ratio of calcium to manganese in the range of 1-10: wherein X, R, R, R, and Rare as defined herein.

A mixed metal complex of a compound of Formula I, or a salt thereof, wherein the mixed metals comprise a Group III-XII transition metal and a Group II metal: wherein X, R, R, R, and Rare as defined herein, is produced in a one step crystallization from a solution of the Group III-XII transition metal, the Group II metal, and a compound of Formula I. Methods for treatment of a pathological condition in a patient, for example, a pathological condition caused by the presence of oxygen-derived free radicals, comprise administering the mixed metal complex to the patient.

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Bromma, Sweden

Jacques Näsström