US 12,303,516 B2
Methods and formulations for treatment of and/or protection against acute liver failure and other hepatotoxic conditions
Jacques Näsström, Bromma (SE); Sven Jacobsson, Stockholm (SE); Dennis Henriksen, Allerød (DK); and James Van Alstine, Stockholm (SE)
Assigned to Egetis Therapeutics AB, Stockholm (SE)
Filed by EGETIS THERAPEUTICS AB, Stockholm (SE)
Filed on Jan. 14, 2022, as Appl. No. 17/576,197.
Application 17/576,197 is a continuation of application No. 16/068,626, granted, now 11,260,060, previously published as PCT/IB2017/050115, filed on Jan. 10, 2017.
Claims priority of provisional application 62/361,605, filed on Jul. 13, 2016.
Claims priority of provisional application 62/277,232, filed on Jan. 11, 2016.
Prior Publication US 2022/0133739 A1, May 5, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61P 1/16 (2006.01); A61K 9/08 (2006.01); A61K 9/10 (2006.01); A61K 9/19 (2006.01); A61K 31/167 (2006.01); A61K 31/198 (2006.01); A61K 31/555 (2006.01); A61K 31/6615 (2006.01); A61P 13/12 (2006.01)
CPC A61K 31/555 (2013.01) [A61K 9/08 (2013.01); A61K 9/10 (2013.01); A61K 9/19 (2013.01); A61K 31/167 (2013.01); A61K 31/198 (2013.01); A61K 31/6615 (2013.01); A61P 1/16 (2018.01); A61P 13/12 (2018.01)] 21 Claims
 
1. A method of treating and/or protecting against acute liver failure induced by an acetaminophen overdose in an individual, comprising
(a) intravenously administering to the individual a solution comprising from about 100 to 500 mg/kg body weight of a first active agent comprising N-acetylcysteine (NAC), and
(b) intravenously administering to the individual a solution comprising from about 0.3 to 10 mg/kg body weight of a second active agent comprising a manganese complex selected from the group consisting of
(i) calmangafodipir, or a pharmaceutically acceptable salt thereof, and
(ii) a mixture of manganese N,N′-bis-(pyridoxal-5-phosphate)-ethylenediamine-N, N′-diacetic acid (MnDPDP), or a pharmaceutically acceptable salt thereof, and calcium N,N′-bis-(pyridoxal-5-phosphate)-ethylenediamine-N, N′-diacetic acid (CaDPDP), or pharmaceutically acceptable salt thereof, in an approximate calcium to manganese molar ratio of 4:1,
wherein the administration of the first active agent and the administration of the second active agent are each at a time 8 hours or more subsequent to the acetaminophen overdose.