Gas-filled microvesicles with polymer-modified lipids
Image enhancing contrast agents for use in diagnostic and/or therapeutic methods, particularly in the form of gas-filled microvesicles, with enhanced stability. The gas-filled microvesicles are stabilized by a layer of amphiphilic material and comprise from 0.15% to 1.0% by moles of a lipid bearing a hydrophilic polymer. The lipid bearing a hydrophilic polymer is preferably a phospholipid linked to polyethyleneglycol.
1. Aqueous suspension of gas-filled microvesicles, wherein said microvesicles have a stabilizing envelope comprising a first phospholipid and from 0.15% by mole to 1% by mole of a polymer-modified lipid consisting of a lipid covalently bound to a hydrophilic polymer, wherein said lipid is a second phospholipid and said hydrophilic polymer is polyethyleneglycol.
2. A suspension according to claim 1 comprising at least 0.3% by mole of said lipid covalently bound to a hydrophilic polymer.
3. A suspension according to claim 1 comprising about 0.5% by mole of said lipid covalently bound to a hydrophilic polymer.
4. A suspension according to claim 1 , wherein said second phospholipid is a phosphatidylethanolamine.
5. A suspension according to claim 4 wherein said phosphatidylethanolamine is a fatty acid di-ester of phosphatidylethanolamine.
6. A suspension according to claim 1 wherein said polyethyleneglycol has a molecular weight of from about 500 to about 50,000 Daltons.
7. A suspension according to claim 1 wherein said polyethyleneglycol has a molecular weight of from about 1,000 to about 20,000 daltons.
8. Aqueous suspension of gas-filled microvesicles, wherein said microvesicles have a stabilizing envelope comprising a first phospholipid and from 0.15% by mole to 1% by mole of a polymer-modified lipid comprising a lipid covalently bound to a hydrophilic polymer, wherein said polymer-modified lipid contains no targeting ligand, and wherein said lipid is a second phospholipid and said hydrophilic polymer is polyethyleneglycol.
9. A suspension according to claim 8 comprising at least 0.3% by mole of said lipid covalently bound to a hydrophilic polymer.
10. A suspension according to claim 8 comprising about 0.5% by mole of said lipid covalently bound to a hydrophilic polymer.
11. A suspension according to claim 8 , wherein said second phospholipid is a phosphatidylethanolamine.
12. A suspension according to claim 11 wherein said phosphatidylethanolamine is a fatty acid di-ester of phosphatidylethanolamine.
13. A suspension according to claim 8 wherein said polyethyleneglycol has a molecular weight of from about 500 to about 50,000 Daltons.
14. A suspension according to claim 8 wherein said polyethyleneglycol has a molecular weight of from about 1,000 to about 20,000 daltons.