Microbubble tether for diagnostic and therapeutic applications

Patent metadata

Field	Value
Publication number	US-2018344880-A1
Application number	US-201816102368-A
Country	US
Kind code	A1
Filing date	Aug 13, 2018
Priority date	Nov 21, 2014
Publication date	Dec 6, 2018
Grant date	—

Abstract

The present disclosure relates to a composition of albumin microbubbles to which are bound one or more moieties that exhibit a binding preference for the albumin microbubbles relative to free, native HSA. Production of the albumin microbubble composition and use of the albumin microbubble composition in ultrasound mediated delivery of therapeutic or diagnostic agents is also discussed.

First claim

1 . A composition, comprising:
an albumin microbubble comprising an albumin shell; a therapeutic or diagnostic agent; and a cyanine 5 derivative linking the albumin microbubble and the therapeutic or diagnostic agent.

2 . The composition of claim 1 , wherein the albumin shell comprises partially denatured, partially cross-linked human serum albumin.

3 . The composition of claim 1 , wherein the therapeutic or diagnostic agent comprises a small molecule drug or a nucleic acid structure.

4 . The composition of claim 1 , wherein the cyanine 5 derivative comprises polyethyleneglycol units.

5 . The composition of claim 1 , wherein the albumin microbubble has a diameter between about 1 μm to about 10 μm.

6 . An ultrasound-based treatment method, comprising:
introducing an albumin microbubble composition into a patient, wherein the albumin microbubble composition comprises: an albumin shell, a molecule of interest, and a moiety binding the molecule of interest to the albumin shell, wherein the moiety preferentially binds to the albumin shell relative to free, native human serum albumin; and directing ultrasonic energy at an anatomic region of interest to cause cavitation of the albumin microbubbles at the anatomic region of interest.

7 . The ultrasound-based treatment method of claim 6 , further comprising:
visualizing the presence of albumin microbubbles at the anatomic region of interest based on fluorescence of the moiety.

8 . The ultrasound-based treatment method of claim 6 , wherein the molecule of interest comprises a small molecule drug or a nucleic acid structure.

9 . The ultrasound-based treatment method of claim 6 , wherein the moiety comprises a cyanine 5 derivative.

10 . The ultrasound-based treatment method of claim 6 , wherein the moiety preferentially binds to the albumin shell relative to free, native human serum albumin at a ratio greater than 2.

11 . The ultrasound-based treatment method of claim 6 , wherein the moiety preferentially binds to the albumin shell relative to free, native human serum albumin at a ratio greater than 4.0.

Assignees

• Gen Electric

Inventors

• Butts Matthew David
• Castle Jason William
• Torres Andrew Soliz
• Roberts Jeannette Christine
• Kandapallil Binil Itty Ipe

Classifications

• A61K9/0009 Primary

  involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis · CPC title

• A61K9/5052

  Proteins, e.g. albumin · CPC title

• A61K49/223 Primary

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