Preparation of a lipid blend and a phospholipid suspension containing the lipid blend

摘要

The present invention describes processes for the preparation of a lipid blend and a uniform filterable phospholipid suspension containing the lipid blend, such suspension being useful as an ultrasound contrast agent.

主权项

1. A process for preparing a lipid suspension for use with a perfluorocarbon gas as an ultrasound contrast agent, the method comprising:
(a) contacting phospholipids with a first non-aqueous solvent which causes the phospholipids to dissolve and form a lipid solution, wherein the contacting comprises the sequential addition of individual phospholipids to the first non-aqueous solvent wherein the phospholipids are 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, mono sodium salt (DPPA) and N-(methoxypolyethylene glycol 5000 carbamoyl)-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine, mono sodium salt (MPEG5000-DPPE), or combining said phospholipids with each other prior to their addition to the first non-aqueous solvent; (b) contacting the non-aqueous lipid solution of (a) with a second non-aqueous solvent which causes the phospholipids to precipitate out as a solid lipid blend; (c) collecting the solid lipid blend; (d) contacting the solid lipid blend with a third non-aqueous solvent which causes the lipid blend to dissolve to form a lipid blend solution; (e) contacting the lipid blend solution with an aqueous solution to yield the lipid suspension; and (f) filtering the lipid suspension through one or two sterilizing filters to form a filtered lipid suspension.