Imarx Pharmaceutical Corporation

The University of Arizona

University of Colorado

The University of North Carolina at Chapel Hill

Bristol-myers Squibb Medical Imaging, Inc.

Imar.sub.x Pharmaceutical Corp.

Other

Imarx Therapeutics, Inc.

Terry Onichi Matsunaga

Evan C Unger

David W Yellowhair

Thomas A Fritz

VaradaRajan Ramaswami

Guanli Wu

Mark A Borden

Paul Alexander Dayton

Paul Steven Sheeran

Marek Romanowski

Theodore P Trouard

Patricia A Schumann

Acoustically activatable particles having low vaporization energy are disclosed. A particle of material includes a first substance that includes at least one component that has a boiling point below 25&#xb0; C. at atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create the particle. The particle has a core consisting of a liquid and is an activatable phase change agent. The second substance includes a polymeric brush layer to prevent aggregation and coalescence.

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

Phase change nanodroplet conjugates and methods of making and using thereof are provided. The phase change nanodroplet conjugates include a nanodroplet having a gaseous precursor on the interior and an outer shell such as a lipid monolayer, a lipid bilayer, or a polymer layer. The phase change nanodroplet conjugates can have one or more nanoparticles attached to the outer layer, e.g. via a linker. The nanoparticles can include therapeutic, prophylactic, or diagnostic nanoparticles. The phase change nanodroplet conjugates can be used for the targeted delivery of a therapeutic, prophylactic, or diagnostic nanoparticle to a target region in a subject in need thereof. The methods can include applying an effective amount of ultrasound radiation to the target region to stimulate vaporization of the gaseous precursor followed by cavitation of the resultant bubble conjugate and release or dispersing of drug or drugs inside the liposomes. Methods of making phase change nanodroplet conjugates are also provided.

Phase change nanodroplet conjugates for targeted delivery

An acoustically activatable particle of material includes a first substance that includes a component that is a gas 25&#xb0; C. and atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create a droplet or emulsion that is stable at room temperature and atmospheric pressure. 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 to form a bubble. After formation of the bubble, the bubble is condensed into a liquid phase, which causes the bubble to transform into the droplet or emulsion having a core consisting of a liquid. The droplet or emulsion is an activatable phase change agent having a core consisting of a liquid at 25&#xb0; C. and atmospheric pressure. The first substance has a boiling point below 25&#xb0; C. at atmospheric pressure.

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.

Novel targeted compositions which may be used for diagnostic and therapeutic use. The compositions may comprise lipid, protein or polymer gas-filled vesicles which further comprise novel compounds of the general formula L-P-T, wherein L comprises a hydrophobic compound, P comprises a hydrophilic polymer, and T comprises a targeting ligand which targets tissues, cells or receptors, including myocardial cells, endothelial cells, epithelial cells, tumor cells and the glycoprotein GPIIbIIIa receptor. The compositions can be used in conjunction with diagnostic imaging, such as ultrasound, as well as therapeutic applications, such as therapeutic ultrasound.

Targeted compositions for diagnostic and therapeutic use

Targeted therapeutic delivery systems comprising gas- or gaseous precursor-filled lipid microspheres comprising a therapeutic are described. Methods for employing such microspheres in therapeutic delivery applications are also provided. Targeted therapeutic delivery systems comprising gas- or gaseous precursor-filled liposomes having a drug encapsulated therein are preferred. Methods of and apparatus for preparing such liposomes and methods for employing such liposomes in therapeutic delivery applications are also disclosed.

Therapeutic delivery systems

A container comprising an aqueous lipid suspension and a gaseous phase substantially separate from the aqueous stabilizing phase, useful in diagnostic imaging such as ultrasound and magnetic resonance imaging and in therapeutic applications, is disclosed.

Container with multi-phase composition for use in diagnostic and therapeutic applications

Methods of and apparatus for preparing temperature activated gaseous precursor-filled liposomes are described. Gaseous precursor-filled liposomes prepared by these methods are particularly useful, for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.

Method of preparing gas and gaseous precursor-filled microspheres

Therapeutic delivery systems comprising gaseous precursor-filled microspheres comprising a therapeutic are described. Methods for employing such microspheres in therapeutic delivery applications are also provided. Therapeutic delivery systems comprising gaseous precursor-filled liposomes having encapsulated therein a contrast agent or drug are preferred. Methods of and apparatus for preparing such liposomes and methods for employing such liposomes in therapeutic delivery applications are also disclosed.

Gas-filled lipid spheres for use in diagnostic and therapeutic

Targeted gas and gaseous precursor-filled liposomes

Lyophilized lipid compositions, as well as methods for their preparation, are embodied by the present invention. Gas-filled microspheres prepared using the lyophilized lipid composition are particularly useful, for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.

Method of preparing fluorinated gas microspheres

Methods for providing an image of an internal region of a patient. Embodiments of the methods involve administering to the patient a contrast agent which comprises a vesicle composition comprising, in an aqueous carrier, a gas or gaseous precursor and vesicles comprising lipids, proteins or polymers. The patient is scanned using diagnostic imaging, such as ultrasound, to obtain a visible image of the region. The contrast agent is administered to the patient at a rate to substantially eliminate diagnostic artifacts in the image. The methods are particularly useful for diagnosing the presence of any diseased tissue in the patient.

Methods for diagnostic imaging by regulating the administration rate of

Methods of and apparatus for preparing gas-filled liposomes are described. Gas-filled liposomes prepared by these methods are particularly useful, for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.

Growing community of inventors

Tucson, AZ, United States of America

Terry Onichi Matsunaga