	US 12,226,494 B2
	Pharmaceutical compositions comprising Gd-complexes and polyarylene additives
Silvio Aime, Turin (IT); Giuseppe Ferrauto, Turin (IT); Eliana Gianolio, Beinasco (IT); Luciano Lattuada, Cassina de' Pecchi (IT); and Alessandro Maiocchi, Monza (IT)
Assigned to BRACCO IMAGING S.P.A., Milan (IT)
Appl. No. 17/414,508
Filed by BRACCO IMAGING S.P.A., Milan (IT)
PCT Filed Dec. 17, 2019, PCT No. PCT/EP2019/085493 § 371(c)(1), (2) Date Jun. 16, 2021, PCT Pub. No. WO2020/127154, PCT Pub. Date Jun. 25, 2020.
Claims priority of application No. 18213354 (EP), filed on Dec. 18, 2018.
Prior Publication US 2022/0062444 A1, Mar. 3, 2022
Int. Cl. A61K 49/10 (2006.01); A61K 47/20 (2006.01)

CPC A61K 49/108 (2013.01) [A61K 47/20 (2013.01)]

10 Claims

1. A pharmaceutical composition comprising an adduct consisting of a macrocyclic gadolinium complex (Gd-complex), or a pharmaceutical salt thereof, and a water-soluble polyarylene additive, or a pharmaceutical salt thereof, wherein the Gd-complex is tetraazacyclododecane-based with 3 or 4 carboxylic acid substituents, or a tetrameric derivative thereof, wherein the water-soluble polyarylene additive, or a pharmaceutical salt thereof, comprises 4 carbocyclic fused aromatic rings that are substituted by 2, 3, or 4 hydrophilic substituent groups selected from the group consisting of —OH, —COOH, —SO₃H, —OSO₃H, and —NH₂, wherein the molar ratio of macrocyclic Gd-complex to polyarylene additive ranges from 1:1 to 1:10 (m/m) and wherein the macrocyclic Gd-complex has an association constant Ka for the polyarylene additive of at least 250 M⁻¹.