Claims for Patent: 10,583,207

Summary for Patent: 10,583,207

Title:	Lipid-encapsulated gas microsphere compositions and related methods
Abstract:	The invention provides, inter alia, improved lipid formulations used to generate lipid-encapsulated gas microspheres, and methods of their use.
Inventor(s):	Robinson; Simon P. (Stow, MA), Siegler; Robert W. (Chelmsford, MA), Onthank; David C. (Groton, MA), Nguyen; Nhung Tuyet (Westford, MA)
Assignee:	Lantheus Medical Imaging, Inc. (North Billerica, MA)
Application Number:	15/203,725
Patent Claims:	1. A method of using lipid-encapsulated perfluoropropane gas microspheres for ultrasound contrast imaging comprising (1) forming lipid-encapsulated perfluoropropane gas microspheres by (a) forming a combined mixture by adding an aqueous diluent to a composition comprising a non-aqueous mixture in contact with a perfluoropropane gas, said non-aqueous mixture having less than 5% w/w (weight/weight) of water, and comprising DPPA, DPPC and MPEG-5000-DPPE in a ratio of about 10:82:8 (mole %), in propylene glycol and/or glycerol, and (b) activating the combined mixture to form lipid-encapsulated perfluoropropane gas microspheres, (2) administering the lipid-encapsulated perfluoropropane gas microspheres to a subject, and (3) obtaining an ultrasound image of the subject. 2. The method of claim 1, wherein the non-aqueous mixture has a lipid concentration of about 0.1 to about 10 mg per ml. 3. The method of claim 1, wherein the non-aqueous mixture consists essentially of DPPA, DPPC, MPEG5000-DPPE, propylene glycol, and glycerol. 4. The method of claim 3, wherein the weight ratio of DPPA, DPPC and MPEG5000-DPPE combined to propylene glycol to glycerol is in a range of about 1:100:100 to about 1:600:700. 5. The method of claim 1, wherein the lipid-encapsulated perfluoropropane gas microspheres have an average diameter ranging from about 1.0 microns to about 2.0 microns. 6. The method of claim 5, wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10.sup.8/mL after activation. 7. The method of claim 1, wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10.sup.8/mL after activation. 8. The method of claim 1, wherein activating the combined mixture comprises agitating the combined mixture for 20-45 seconds. 9. The method of claim 1, wherein the non-aqueous mixture consists essentially of DPPA, DPPC, MPEG5000-DPPE, and propylene glycol. 10. The method of claim 9, wherein the weight ratio of DPPA, DPPC and MPEG5000-DPPE, combined, to propylene glycol is in a range of about 1:100 to about 1:600. 11. A method of using lipid-encapsulated perfluoropropane gas microspheres for ultrasound contrast imaging comprising (1) forming lipid-encapsulated perfluoropropane gas microspheres by activating a composition comprising a non-aqueous mixture in contact with a perfluoropropane gas, said non-aqueous mixture having less than 5% w/w (weight/weight) water, and comprising DPPA, DPPC and MPEG5000-DPPE in a ratio of about 10:82:8 (mole %) in propylene glycol and/or glycerol, (2) administering the lipid-encapsulated perfluoropropane gas microspheres to a subject, and (3) obtaining an ultrasound image of the subject. 12. The method of claim 11, wherein the non-aqueous mixture has a lipid concentration of about 0.1 to about 10 mg per ml. 13. The method of claim 12, wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2). 14. The method of claim 11, wherein the non-aqueous mixture consists essentially of DPPA, DPPC, MPEG5000-DPPE, propylene glycol, and glycerol. 15. The method of claim 14, wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2). 16. The method of claim 11, wherein the lipid-encapsulated perfluoropropane gas microspheres have an average diameter ranging from about 1.0 microns to about 2.0 microns. 17. The method of claim 16, wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10.sup.8/mL after activation. 18. The method of claim 17, wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2). 19. The method of claim 16, wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2). 20. The method of claim 11, wherein the lipid-encapsulated perfluoropropane gas microspheres are present at a concentration of greater than 10.sup.8/mL after activation. 21. The method of claim 20, wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2). 22. The method of claim 11, wherein an aqueous diluent is added to the lipid-encapsulated perfluoropropane gas microspheres prior to step (2).