Bioactive gas-encapsulated echogenic liposomes and methods for treating cardiovascular disease

Patent metadata

Field	Value
Publication number	US-10500227-B2
Application number	US-201514957705-A
Country	US
Kind code	B2
Filing date	Dec 3, 2015
Priority date	Dec 3, 2014
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

Echogenic liposomes (ELIP) formulated with an at least partially pegylated phospholipid bi-layer shell, encapsulated nitric oxide, and encapsulated perfluorocarbon of the formula CxFy in a ratio of about 1:1 by volume, wherein X is greater than or equal to 3, are disclosed, along with methods for treating a patients suffering from cardiovascular disease by administering the ELIP at a site remote from the target diseased section, monitoring presence of the ELIP at the target diseased section, and administering ultrasound upon detection of presence such that bioactive NO is released at the target diseased section.

First claim

What is claimed:

1. A microbubble comprising an at least partially pegylated phospholipid shell, encapsulated nitric oxide, and encapsulated perfluorocarbon of the formula C x F y , wherein X is 3 and Y is 8, wherein the ratio of NO to C x F y is about 1:1 or about 1:9 by volume.

2. The microbubble according to claim 1 , wherein the at least partially pegylated phospholipid shell comprises dipalmitoylphosphatidylcholine (DPPC), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-750] (DSPE-PEG750) in a molar ratio of 79:15:3:3.

3. A method of manufacturing the microbubble according to claim 1 , the method comprising:
providing an emulsion comprising phospholipids;
injecting a volume ratio of nitric oxide and C 3 F 8 into the emulsion;
agitating the emulsion; and
adjusting the temperature of the emulsion to room temperature, wherein freezing of the emulsion is avoided,
wherein at least some of the phospholipids are pegylated,
wherein the volume ratio of nitric oxide and the perfluorocarbon is about 1:1 or about 1:9.

4. The method according to claim 3 wherein the phospholipids consist of one or more of nonionic and anionic phospholipids.

5. A method comprising administering the composition of claim 1 to a patient.

6. The method of claim 5 , wherein the patient suffers from cardiovascular disease.

Assignees

• Univ Cincinnati

Inventors

• Holland Christy
• Raymond Jason
• Sutton Jonathan

Classifications

• A61K41/0028

  Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds · CPC title

• A61K33/00 Primary

  Medicinal preparations containing inorganic active ingredients · CPC title

• G01N33/5082

  Supracellular entities, e.g. tissue, organisms · CPC title

• A61K9/0009

  involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title