Methods for making ultrasound contrast agents

Patent metadata

Field	Value
Publication number	US-9789210-B1
Application number	US-201715461469-A
Country	US
Kind code	B1
Filing date	Mar 16, 2017
Priority date	Jul 6, 2016
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Provided herein are improved methods for preparing phospholipid formulations including phospholipid UCA formulations.

First claim

What is claimed is:

1. A method of ultrasound contrast imaging a subject comprising
(a) activating a phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres, wherein the phospholipid suspension comprises a phospholipid solution having DPPA, DPPC and MPEG5000-DPPE, in a mole % ratio of 10 to 82 to 8 (10:82:8), in propylene glycol, the MPEG5000-DPPE selected as having a calcium concentration of less than 115 parts per million (ppm), and the phospholipid solution having a calcium concentration of less than 0.7 ppm,
(b) administering the lipid-encapsulated gas microspheres to a subject, and
(c) obtaining an ultrasound image of the subject.

2. A method of ultrasound contrast imaging a subject comprising
(a) activating a phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres, wherein the phospholipid suspension comprises a phospholipid solution made under a methanol and toluene free condition and a methyl t-butyl ether free condition and having DPPA, DPPC and MPEG5000-DPPE, in a mole % ratio of 10 to 82 to 8 (10:82:8), in propylene glycol, the MPEG5000-DPPE having a calcium concentration of less than 115 parts per million (ppm), and the phospholipid solution having a calcium concentration of less than 0.7 ppm,
(b) administering the lipid-encapsulated gas microspheres to a subject, and
(c) obtaining an ultrasound image of the subject.

3. The method of claim 2 , wherein the calcium concentration is determined using atomic absorption spectroscopy.

4. The method of claim 1 , wherein the calcium concentration is determined using atomic absorption spectroscopy.

5. The method of claim 1 , wherein the calcium concentration is determined using inductively coupled plasma mass spectrometry (ICP-MS).

6. The method of claim 2 , wherein the calcium concentration is determined using inductively coupled plasma-mass spectrometry (ICP-MS).

7. The method of claim 1 , wherein the calcium concentration of DPPA is less than 780 ppm, the calcium concentration of DPPC is less than 90 ppm, and the calcium concentration of propylene glycol is less than 0.7 ppm.

8. The method of claim 2 , wherein the calcium concentration of DPPA is less than 780 ppm, the calcium concentration of DPPC is less than 90 ppm, and the calcium concentration of propylene glycol is less than 0.7 ppm.

9. The method of claim 2 , wherein MPEG5000-DPPE is selected as having a calcium concentration of less than 115 ppm.

Assignees

• Lantheus Medical Imaging Inc

Inventors

• Robinson Simon P
• Siegler Robert W
• Nguyen Nhung Tuyet
• Onthank David C
• Anklekar Tarakeshwar Vishwanath
• Van Kirk Charles Chester

Classifications

• A61K9/1277

  Preparation processes; Proliposomes · CPC title

• A61K49/223 Primary

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

• A61K49/227 Primary

  Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric · 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

• A61K49/226

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