Preparation of a lipid blend and a phospholipid suspension containing the lipid blend
First Claim
1. A method comprising(a) formulating a lipid suspension with a perfluorocarbon gas to form an ultrasound contrast agent, and(b) using the ultrasound contrast agent in an imaging application in a subject, wherein the lipid suspension is made by(i) contacting phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, mono sodium salt (DPPA), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and N-(methoxypolyethylene glycol 5000 carbamoyl)-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine, mono sodium salt (MPEG5000-DPPE) with a first non-aqueous solvent to form a lipid solution, wherein contacting comprises(1) sequential addition of the individual phospholipids to the first non-aqueous solvent or(2) combining the individual phospholipids with each other prior to their addition to the first non-aqueous solvent;
- (ii) contacting the lipid solution of (i) with a second non-aqueous solvent which causes the phospholipids to precipitate out as a solid lipid blend;
(iii) collecting the solid lipid blend;
(iv) contacting the solid lipid blend with a third non-aqueous solvent which causes the lipid blend to dissolve to form a lipid blend solution; and
(v) contacting the lipid blend solution with an aqueous solution to yield the lipid suspension.
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Abstract
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.
407 Citations
28 Claims
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1. A method comprising
(a) formulating a lipid suspension with a perfluorocarbon gas to form an ultrasound contrast agent, and (b) using the ultrasound contrast agent in an imaging application in a subject, wherein the lipid suspension is made by (i) contacting phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, mono sodium salt (DPPA), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and N-(methoxypolyethylene glycol 5000 carbamoyl)-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine, mono sodium salt (MPEG5000-DPPE) with a first non-aqueous solvent to form a lipid solution, wherein contacting comprises (1) sequential addition of the individual phospholipids to the first non-aqueous solvent or (2) combining the individual phospholipids with each other prior to their addition to the first non-aqueous solvent; -
(ii) contacting the lipid solution of (i) with a second non-aqueous solvent which causes the phospholipids to precipitate out as a solid lipid blend; (iii) collecting the solid lipid blend; (iv) contacting the solid lipid blend with a third non-aqueous solvent which causes the lipid blend to dissolve to form a lipid blend solution; and (v) contacting the lipid blend solution with an aqueous solution to yield the lipid suspension. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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28. A method comprising:
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(a) contacting phospholipids with a first non-aqueous solvent which causes the phospholipids to dissolve and form a lipid solution, wherein the contacting comprises (i) sequential addition of the individual phospholipids to the first non-aqueous solvent, or (ii) combining the individual phospholipids with each other prior to their addition to the first non-aqueous solvent, and 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); (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 a lipid suspension; (f) formulating the lipid suspension with a perfluorocarbon gas to form an ultrasound contrast agent; and (g) using the ultrasound contrast agent in an imaging application in a subject.
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Specification