Targeted gas-filled microvesicles formulation

Patent metadata

Field	Value
Publication number	US-11071792-B2
Application number	US-202016867685-A
Country	US
Kind code	B2
Filing date	May 6, 2020
Priority date	Dec 18, 2014
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

Suspension of gas-filled microvesicles comprising a targeting ligand for binding to KDR or VEGF/KDR complex.
The suspension is obtained by reconstituting a freeze-dried residue with a carbohydrate-containing solution in the presence of a physiologically acceptable gas and is stabilized by the presence of histidine.

First claim

The invention claimed is:

1. A physiologically acceptable aqueous suspension of gas-filled microvesicles, said gas-filled microvesicles comprising a lipopeptide of formula II:

distearoyl-phosphatidyl-choline (DSPC), palmitic acid, and DPPE-PEG5000, and wherein
DSPC and palmitic acid are in a molar ratio of 95:5,
DPPE-PEG5000 is in a molar amount of 0.5% by molar ratio with respect to the lipopeptide, DSPC, and palmitic acid, and
the lipopeptide is in a molar amount of 0.5% by molar ratio with respect to the DSPC, palmitic acid, and DPPE-PEG5000.

2. The aqueous suspension according to claim 1 further comprising a carbohydrate.

3. The aqueous suspension according to claim 2 , wherein the carbohydrate is a glucose.

4. The aqueous suspension according to claim 2 further comprising histidine.

5. The aqueous suspension according to claim 4 , wherein concentration of the histidine in the aqueous suspension is from 1.5 mM to 20 mM.

6. The aqueous suspension according to claim 5 , wherein the concentration of the histidine in the aqueous suspension is from 2.5 mM to 10 mM.

7. The aqueous suspension according to claim 1 , wherein said gas-filled microvesicles comprise a fluorinated physiologically acceptable gas.

8. A pharmaceutical kit for preparing a reconstituted aqueous suspension of gas-filled microvesicles comprising:
(a) A first container comprising a physiologically acceptable gas in contact with a freeze-dried formulation comprising a lipopeptide of formula (II):

distearoyl-phosphatidyl-choline (DSPC), palmitic acid, and DPPE-PEG5000, wherein DSPC and palmitic acid are in a molar ratio of 95:5,
DPPE-PEG5000 is in a molar amount of 0.5% by molar ratio with respect to the lipopeptide, DSPC, and palmitic acid, and
the lipopeptide is in a molar amount of 0.5% by molar ratio with respect to the DSPC, palmitic acid, and DPPE-PEG5000; and

(b) a second container comprising a physiologically acceptable solution for reconstituting the freeze-dried formulation into a reconstituted aqueous suspension of gas-filled microvesicles.

9. The pharmaceutical kit according to claim 8 , wherein the physiologically acceptable solution comprises a carbohydrate.

10. The pharmaceutical kit according to claim 9 , wherein the carbohydrate is glucose.

11. The pharmaceutical kit according to claim 8 wherein the first container further comprises histidine.

12. The pharmaceutical kit according to claim 11 , wherein the histidine is in an amount capable of reconstitution to a concentration of from 1.5 mM to 20 mM in the reconstituted aqueous suspension of gas-filled microvesicles.

13. The pharmaceutical kit according to claim 12 , wherein the histidine is in an amount capable of reconstitution to a concentration of from 2.5 mM to 10 mM in the reconstituted aqueous suspension of gas-filled microvesicles.

14. A method for imaging a region of interest in a subject comprising administering an effective amount of the aqueous suspension of gas-filled microvesicles according to claim 1 to the subject, submitting said region of interest to ultrasound irradiation, and collecting respective echo signals from said region of interest.

Assignees

• Bracco Suisse Sa
• Braceo Suisse SA

Inventors

• Bussat Philippe
• Lassus Anne

Classifications

• A61B8/481 Primary

  involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream · CPC title

• A61K49/223 Primary

  Microbubbles, hollow microspheres, free gas bubbles, gas microspheres · CPC title

• A61K49/226

  Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels · CPC title