Lipid encapsulated gas microsphere compositions and related methods
AssigneeLantheus Medical Imaging, Inc.
InventorsSimon P. Robinson, Nhung Tuyet Nguyen, Robert W. Siegler
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Abstract
The invention provides improved compositions relating to lipid-encapsulated gas microspheres and methods of their use.
Claims57
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising DPPA, DPPC and PEG5000-DPPE, and
- a perfluorocarbon gas, in a container,
- wherein the perfluorocarbon gas occupies about 60-85% of the container volume, and wherein when activated the composition comprises microspheres having an average diameter of about 1 micron to about 2 microns.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres having an average diameter ranging from about 1.0 micron to about 2.0 microns in a mixture of a lipid solution comprising DPPA, DPPC and PEG5000-DPPE and a perfluorocarbon gas in a container, wherein the perfluorocarbon gas occupies about 60-85% of the container volume.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising DPPA, DPPC and PEG5000-DPPE, and
- a perfluorocarbon gas, in a container,
- wherein the perfluorocarbon gas occupies about 60-85% of the container volume.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres in a mixture of a lipid solution comprising DPPA, DPPC and PEG5000-DPPE and a perfluorocarbon gas in a container, wherein the perfluorocarbon gas occupies about 60-85% of the container volume.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising DPPA, DPPC and PEG5000-DPPE, and
- a perfluorocarbon gas, in a container,
- wherein the perfluorocarbon gas occupies about 60-85% of the container volume, and wherein when activated the composition comprises about 0.5×109 to about 3.5×109 microspheres per mL.
A composition for use as an ultrasound contrast agent, comprising
- about 0.5×109 to about 3.5×109 lipid-encapsulated gas microspheres per mL in a mixture of a lipid solution comprising DPPA, DPPC and PEG5000-DPPE and a perfluorocarbon gas in a container, wherein the perfluorocarbon gas occupies about 60-85% of the container volume.
The composition of any of the foregoing claims, wherein the microspheres have an average diameter ranging from about 1.2 microns to about 1.8 microns.
The composition of any of the foregoing claims, wherein the microspheres have an average diameter of about 1.6 microns.
The composition of any of the foregoing claims, wherein at least 50% of the microspheres have a diameter of about 1.0 to about 2.0 microns.
The composition of any of the foregoing claims, wherein at least 70% of the microspheres have a diameter of about 1.0 to about 2.0 microns.
The composition of any one of the foregoing claims, wherein the lipid solution comprises DPPA, DPPC and PEG5000-DPPE in a mole % ratio of 10:82:8.
The composition of any one of the foregoing claims, wherein the PEG500-DPPE is MPEG5000-DPPE.
The composition of any one of the foregoing claims, wherein the perfluorocarbon gas is perfluoropropane.
The composition of any one of the foregoing claims, wherein the perfluorocarbon gas occupies about 65%, about 70%, about 75%, about 80% or about 85% of the volume of the container.
The composition of any one of the foregoing claims, wherein the lipid solution further comprises propylene glycol, glycerol, and saline.
The composition of any one of the foregoing claims, wherein the lipid solution further comprises propylene glycol, glycerol, buffer, and saline.
The composition of any one of the foregoing claims, wherein the lipid solution further comprises propylene glycol, glycerol, phosphate buffer, and saline.
The composition of any one of the foregoing claims, wherein the lipid solution further comprises saline, glycerol and propylene glycol in a weight ratio of 8:1:1.
The composition of any one of the foregoing claims, comprising about 1 ml lipid solution and about 2.75 ml of perfluorocarbon gas.
The composition of any one of the foregoing claims, wherein the lipid solution comprises about 0.75 to about 1.0 mg of lipids per ml of solution.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising about 0.1 mg to about 0.6 mg combined of DPPA, DPPC and PEG5000-DPPE per ml of solution, and
- a perfluorocarbon gas, in a container,
- wherein when activated the composition comprises microspheres having an average diameter of about 1 micron to about 2 microns.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres having an average diameter ranging from about 1.0 micron to about 2.0 microns in a mixture of a lipid solution and a perfluorocarbon gas in a container, wherein the lipid solution comprises about 0.1 to about 0.6 mg DPPA, DPPC and PEG5000-DPPE (combined) per ml of solution.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising about 0.1 mg to about 0.6 mg combined of DPPA, DPPC and PEG5000-DPPE per ml of solution, and
- a perfluorocarbon gas, in a container.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres in a mixture of a lipid solution and a perfluorocarbon gas in a container, wherein the lipid solution comprises about 0.1 to about 0.6 mg DPPA, DPPC and PEG5000-DPPE combined per ml of solution.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising about 0.1 mg to about 0.6 mg combined of DPPA, DPPC and PEG5000-DPPE per ml of solution, and
- a perfluorocarbon gas, in a container,
- wherein when activated the composition comprises about 0.1×109 to about 3.5×109 microspheres per mL.
A composition for use as an ultrasound contrast agent, comprising
- about 0.1×109 to about 3.5×109 lipid-encapsulated gas microspheres per mL in a mixture of a lipid solution and a perfluorocarbon gas in a container, wherein the lipid solution comprises about 0.1 to about 0.6 mg DPPA, DPPC and PEG5000-DPPE combined per ml of solution.
The composition of any one of the foregoing claims, wherein the container is a vial, a tube, or a syringe.
The composition of any one of the foregoing claims, wherein the container is a rubber-less container.
The composition of any one of the foregoing claims, wherein the container is a plastic container.
The composition of any one of the foregoing claims, wherein the container is a plastic syringe having a rubber-less plunger.
The composition of any one of the foregoing claims, wherein the container is a plastic syringe having a substantially flat-end plunger.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising DPPA, DPPC and PEG5000-DPPE, and
- a perfluorocarbon gas, in a container having an actual internal volume of less than 3 mL,
- wherein the perfluorocarbon gas occupies about 50-55% of the actual internal volume, and wherein when activated the composition comprises microspheres having an average diameter of about 1.0 micron to about 2.0 microns.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres having an average diameter ranging from about 1.0 micron to about 2.0 microns in a mixture of a lipid solution comprising DPPA, DPPC and PEG5000-DPPE and a perfluorocarbon gas in a container having an actual internal volume of less than 3 mL, wherein the perfluorocarbon gas occupies about 50-55% of the actual internal volume.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising DPPA, DPPC and PEG5000-DPPE, and
- a perfluorocarbon gas, in a rubber-less plastic container, optionally having an adjustable or fixed flat end,
- wherein the perfluorocarbon gas occupies about 50-55% of the container volume, and wherein when activated the composition comprises microspheres having an average diameter of about 1.0 micron to about 2.0 microns.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres having an average diameter ranging from about 1.0 micron to about 2.0 microns in a mixture of a lipid solution comprising DPPA, DPPC and PEG5000-DPPE and a perfluorocarbon gas in a rubber-less plastic container, optionally having an adjustable or fixed flat end, wherein the perfluorocarbon gas occupies about 50-55% of the container volume.
A composition used to form an ultrasound contrast agent, comprising
- a lipid solution comprising DPPA, DPPC and PEG5000-DPPE, and
- a perfluorocarbon gas, in a glass container having a v-shaped bottom,
- wherein the perfluorocarbon gas occupies about 50-55% of the container volume, and wherein when activated the composition comprises microspheres having an average diameter of about 1.0 micron to about 2.0 microns.
A composition for use as an ultrasound contrast agent, comprising
- lipid-encapsulated gas microspheres having an average diameter ranging from about 1.0 micron to about 2.0 microns in a mixture of a lipid solution comprising DPPA, DPPC and PEG5000-DPPE and a perfluorocarbon gas in a glass container having a v-shaped bottom, wherein the perfluorocarbon gas occupies about 50-55% of the container volume.
A method for producing an ultrasound contrast agent, comprising
- activating the composition of any one of the foregoing claims to form a population of lipid-encapsulated microspheres.
Dependencies are inferred from the claim text.