US 11,925,695 B2
Methods for making ultrasound contrast agents
Simon P. Robinson, Stow, MA (US); Robert W. Siegler, Bedford, MA (US); Nhung Tuyet Nguyen, Westford, MA (US); David C. Onthank, Groton, MA (US); Tarakeshwar Vishwanath Anklekar, Billerica, MA (US); and Charles Chester Van Kirk, Beverly, MA (US)
Assigned to Lantheus Medical Imaging, Inc., North Billerica, MA (US)
Filed by Lantheus Medical Imaging, Inc., North Billerica, MA (US)
Filed on May 22, 2023, as Appl. No. 18/321,714.
Application 15/602,580 is a division of application No. 15/461,469, filed on Mar. 16, 2017, granted, now 9,789,210.
Application 18/321,714 is a continuation of application No. 17/325,173, filed on May 19, 2021, granted, now 11,857,646.
Application 17/325,173 is a continuation of application No. 16/315,643, granted, now 11,266,749, previously published as PCT/US2017/040755, filed on Jul. 5, 2017.
Application 16/315,643 is a continuation in part of application No. 15/602,580, filed on May 23, 2017, granted, now 9,913,919.
Application PCT/US2017/040755 is a continuation in part of application No. 15/461,469, filed on Mar. 16, 2017, granted, now 9,789,210.
Claims priority of provisional application 62/359,181, filed on Jul. 6, 2016.
Prior Publication US 2023/0293733 A1, Sep. 21, 2023
Int. Cl. A61K 49/22 (2006.01); A61B 8/08 (2006.01); C07F 9/09 (2006.01); C07F 9/10 (2006.01)
CPC A61K 49/223 (2013.01) [A61B 8/481 (2013.01); A61K 49/226 (2013.01); A61K 49/227 (2013.01); C07F 9/09 (2013.01); C07F 9/106 (2013.01)] 13 Claims
 
1. A method of ultrasound contrast imaging a subject using an ultrasound contrast agent having reduced batch-to-batch loss of total and individual phospholipid content comprising
a) controlling the calcium and/or magnesium concentration across multiple batches of a phospholipid solution to less than 0.7 ppm, wherein the phospholipid solution comprises one or more phospholipids in propylene glycol, combining one of the multiple batches of the phospholipid solution with an aqueous solution to form a phospholipid suspension, and filtering the phospholipid suspension through a 0.2 micron filter to form a filtered phospholipid suspension,
b) activating the filtered phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres,
c) administering the lipid-encapsulated microspheres to a subject, and
d) obtaining an ultrasound image of the subject.