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

• US 9,427,410 B2
• Filed: 10/11/2011
• Issued: 08/30/2016
• Est. Priority Date: 10/08/2010
• Status: Active Grant

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: Arizona Board of Regents (University of Arizona), The Board of Regents of the University of Colorado (University of Colorado System), University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Dayton, Paul A., Sheeran, Paul S., Matsunaga, Terry O., Borden, Mark A.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): LAMBERSKI, JENNIFER A
• Application Number:
  US13/876,165
• Publication Number:
  US 20130336891A1
• Time in Patent Office: 1,785 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 41/0028 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 Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/221 characterised by the targeting agent or modifying agent linked to the acoustically-active agent
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 49/226 Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
• CPC Class Codes: A61K 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50

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.

Claims

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.