US 12,449,418 B2
Gas-filled microvesicles with ligand
Philippe Bussat, Pers-Jussy (FR); Samir Cherkaoui, Feigeres (FR); and David Lazarus, Saint-Julien-en-Genevois (FR)
Assigned to Bracco Suisse SA, Cadempino (CH)
Appl. No. 17/415,974
Filed by Bracco Suisse SA, Cadempino (CH)
PCT Filed Dec. 19, 2019, PCT No. PCT/EP2019/086434
§ 371(c)(1), (2) Date Jun. 18, 2021,
PCT Pub. No. WO2020/127816, PCT Pub. Date Jun. 25, 2020.
Claims priority of application No. 18215695 (EP), filed on Dec. 21, 2018.
Prior Publication US 2021/0389320 A1, Dec. 16, 2021
Int. Cl. B01J 13/04 (2006.01); G01N 33/569 (2006.01)
CPC G01N 33/56972 (2013.01) [B01J 13/04 (2013.01)] 21 Claims
 
1. A suspension of gas-filled microvesicles comprising a physiologically acceptable gas with a stabilizing envelope, said envelope comprising:
a) a phospholipid
b) from 1% to 8% by moles of a first pegylated phospholipid containing a first polyethylene glycol (PEG)-chain with a first molecular weight (MW1) and comprising a reactive moiety, at least a portion of said first pegylated phospholipid being bound to a ligand through said reactive moiety; and
c) from 1% to 12% by moles of a second pegylated phospholipid containing a second PEG-chain with a second molecular weight (MW2) and not comprising a reactive moiety;
said suspension comprising less than 40% by moles of said ligand, either in free form or bound to said pegylated phospholipid, with respect to the molar amount of the pegylated phospholipid comprising said ligand in the envelope,
wherein an amount of the first and second pegylated phospholipid and a molecular weight of the first and second PEG-chain contained in said first and second pegylated phospholipid are correlated, as expressed by:
NPEG=MW1*mol %1+MW2*mol %2
Where:
MW1 and mol %1 respectively refer to molecular weight and to molar % of the PEG chain contained in the first pegylated phospholipid comprising the reactive moiety; and
MW2 and mol %2 respectively refer to molecular weight and molar % of the PEG chain contained in the second pegylated phospholipid not comprising the reactive moiety,
and wherein NPEG is higher than 90 up to 300.