Formulation of acoustically activatable particles having low vaporization energy and methods for using same

Patent metadata

Field	Value
Publication number	US-9427410-B2
Application number	US-201113876165-A
Country	US
Kind code	B2
Filing date	Oct 11, 2011
Priority date	Oct 8, 2010
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

Abstract

A method of producing particles of materials includes, with a first substance that includes at least one component that is a gas at room temperature and atmospheric pressure, extruding or emulsifying the first substance into or in the presence of a second substance to create a bubble in which the first substance is encapsulated by the second substance and wherein at least some of the first substance is in a gaseous phase, and causing the first substance to condense to a liquid phase, which causes the bubble to transform into a droplet or emulsion. The droplet or emulsion so created is an activatable phase change agent that is stable at room temperature and pressure.

First claim

What is claimed is:

1. A method or producing particles or materials for ultrasound activation, comprising:
extruding or emulsifying a first substance comprising at least one component that is a perfluorocarbon or perfluorochemical having a boiling point below 25° C. at atmospheric pressure into or in the presence of a second substance to create a bubble in which the first substance is encapsulated by the second substance and wherein at least some of the first substance exists in a gaseous phase at the time of encapsulation of the first substance within the second substance, and, after formation of the bubble, causing the first substance that is In the gaseous phase In the bubble to condense to a liquid phase, which causes the bubble to transform into a droplet or emulsion having a core consisting of a liquid; wherein the droplet or emulsion is an activatable phase change agent that remains a droplet having a core consisting or a liquid at 25° C. and atmospheric pressure, and wherein the first substance has a boiling point below 25° C. at atmospheric pressure.

2. The method of claim 1 wherein the first substance comprises at least one of decafluorobutane (DFB) or octafluoropropane (OFP).

3. The method of claim 1 wherein causing the first substance to condense to a liquid phase comprises coolind the first substance.

4. The method of claim 3 wherein causing the first substance to condense to a liquid phase comprises cooling the first substance to a temperature that is below the liquid-to-gas phase transition temperature of the component having the lowest liquid-to-gas phase transition temperature.

5. The method of claim 1 wherein causing the first substance to condense to a liquid phase comprises compressing the first substance.

6. The method of claim 5 wherein causing the first substance to condense to a liquid phase comprises compressing the first substance to a pressure that is above the gas-to-liquid phase transition pressure of the component having the highest gas-to-liquid phase transition pressure.

7. The method of claim 1 wherein the second substance comprises at least one of a lipid, a protein, a polymer, a gel, a surfactant, a peptide, or a sugar.

8. The method of claim 1 wherein the second substance comprises lung surfactants, arnphiphiles, proteins, or peptide components thereof in a sufficient quantity to fully encapsulate the liquid phase of the first substance.

9. The method of claim 8 wherein the amphiphiles comprise at least one of arriphiphilic polymers and copolymers, amphiphilic peptides, amphiphilic dendrimers, or amphiphilic nucleic acids.

10. The method of claim 1 wherein the diameter of the droplet or emulsion is less than one micron.

11. The method of claim 1 wherein the first substance comprises a mixture of a plurality of different components different from the second substance and each having a different activation energy, wherein an activation energy of the droplet or emulsion is adjustable based on the relative proportions of the plurality of different components.

12. The method of claim 11 wherein the first substance comprises a mixture of the perfluorocarbon or perfluorochemical component having a first activation energy and a second component having a second activation energy and wherein the activation energy of the droplet or emulsion is between the first and second activation energies.

Assignees

• Dayton Paul A
• Sheeran Paul S
• Matsunaga Terry O
• Borden Mark A
• Univ North Carolina Chapel Hill
• Univ Arizona
• Univ Colorado Regents

Inventors

• Dayton Paul A
• Sheeran Paul S
• Matsunaga Terry O
• Borden Mark A

Classifications

• A61K49/223

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

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K49/221

  characterised by the targeting agent or modifying agent linked to the acoustically-active agent · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K47/06

  Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite · CPC title