Gas-filled microvesicles
Lipid formulation particularly for preparing stable gas-filled microvesicles, comprising distearoyl-phosphatidylcholine (DSPC), dipalmitoylphosphatidylethanolamine-PEG5000 (DPPE-PEG5000) and palmitic acid in an advantageous relative molar ratio. The formulation is useful in particular for therapeutic application with ultrasounds.
1. A freeze-dried formulation, for preparing gas-filled microvesicles, comprising a mixture of the following lipid components: (a) distearoyl-phosphatidylcholine (DSPC), (b) dipalmitoylphosphatidyl-ethanolamine conjugated with polyethyleneglycol having a Mw of 5000 g/mol (DPPE-PEG5000) and (c) palmitic acid; said lipid components being in a respective molar amount a/b/c of 65 to 85/4 to 10/8 to 22,
wherein the formulation further comprises polyethylene glycol 4000 g/mol (PEG4000), and wherein the mixture of lipid components has a weight of from more than 0.3% to 0.5% with respect to the weight of PEG4000.
2. The freeze-dried formulation of claim 1 wherein said respective molar amount is of 70-80/5-8/12-21.
3. The freeze-dried formulation of claim 1 wherein said respective molar amount is of 72-76/6-9/15-20.
4. The freeze-dried formulation of claim 1 wherein said respective molar amount is of 74 (+/−1)/7.5 (+/−0.5)/18.5 (+/−1).
5. The freeze-dried formulation of claim 1 wherein said weight is from 0.35% to 0.45% by weight.
6. The freeze-dried formulation of claim 1 wherein said weight is from 0.38% to 0.40% by weight.
7. A sealed vial comprising from about 250 mg to about 350 mg of the freeze-dried formulation according to claim 1 .
8. A suspension of gas-filled microvesicles wherein said microvesicles comprise a mixture of lipid components DSPC, DPPE-PEG and palmitic acid in a respective molar amount of 65-85/4-10/8-22, wherein the suspension further comprises PEG4000, and wherein the mixture of lipid components has a weight of from more than 0.3% to 0.5% with respect to the weight of PEG4000.
9. The suspension of claim 8 wherein said respective molar amount is of 70-80/5-8/12-21.
10. The suspension of claim 8 wherein said respective molar amount is of 72-76/6-9/15-20.
11. The suspension of claim 8 wherein said respective molar amount is of 74 (+/−1)/7.5 (+/−0.5)/18.5 (+/−1).
12. The suspension of gas-filled microvesicles of claim 8 wherein said weight is from 0.35% to 0.45% by weight.
13. The suspension of gas-filled microvesicles of claim 8 wherein said weight is from 0.38% to 0.40% by weight.
14. A method of ultrasound therapeutic treatment comprising:
(i) administering to a patient a suspension of gas-filled microvesicles as defined in claim 8 and a therapeutic agent;
(ii) identifying a region of interest in said patient to be submitted to a therapeutic treatment, said region of interest comprising said suspension of gas-filled microvesicles; and
(iii) applying an ultrasound beam for therapeutically treating said region of interest;
whereby said ultrasound therapeutic treatment is enhanced by the presence of said suspension of gas-filled microvesicles in said region of interest.