US 11,857,646 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 19, 2021, as Appl. No. 17/325,173.
Application 15/602,580 is a division of application No. 15/461,469, filed on Mar. 16, 2017.
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 15/602,580 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 2021/0338844 A1, Nov. 4, 2021
Prior Publication US 2022/0193274 A9, Jun. 23, 2022
This patent is subject to a terminal disclaimer.
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)] 21 Claims
 
1. A method for preparing a phospholipid suspension useful for preparing lipid-encapsulated gas microspheres comprising
forming a phospholipid solution that comprises (a) a DPPA, DPPC, and MPEG5000-DPPE phospholipid blend and propylene glycol, and (b) calcium and/or magnesium at a combined concentration of less than 0.7 ppm, wherein the phospholipid blend is formed in the presence of one or two but not all three of methanol, toluene and methyl t-butyl ether (MTBE), and
combining the phospholipid solution with an aqueous solution to form a phospholipid suspension.