Microparticles useful as ultrasonic contrast agents

• US 20040086459A1
• Filed: 10/20/2003
• Published: 05/06/2004
• Est. Priority Date: 04/30/1997
• Status: Abandoned Application

• Current Assignee: Robert E. Short, Ronald K. Yamamoto, Thomas B. Ottoboni
• Original Assignee: Robert E. Short, Ronald K. Yamamoto, Thomas B. Ottoboni
• Inventors: Yamamoto, Ronald K., Ottoboni, Thomas B., Short, Robert E.
• Application Number:
  US10/690,045
• Publication Number:
  US 20040086459A1
• Time in Patent Office: Days
• US Class Current: 424/9.52
• 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 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 49/225 Microparticles, microcapsules gas-filled to be classified in A61K49/223

Abstract

Microparticles are provided comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microparticles contain a gas, liquid or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The microparticles are capable of passing through the capillary systems of a subject.

Claims

1. A composition comprising:

a plurality of microparticles, a majority of which have diameters in the range of about 1 to 10 micrometers, each of which comprises a shell enclosing a gas-filled hollow core, said shell comprising an outer layer of a cross-linked amphiphilic material and an inner layer of a biodegradable polymer; and

a sugar.

2. The composition of claim 1 in which the sugar is sucrose.

3. The composition of claim 1 which further comprises a surfactant.

4. The composition of claim 3 in which the surfactant is a poloxomer.

5. The composition of claim 1 which further comprises a water-soluble polymer.

6. The composition of claim 5 in which the water-soluble polymer is a medium molecular weight polyethylene glycol.

7. The composition of claim 1 in which the gas is nitrogen.

8. The composition of claim 1 in which the biodegradable polymer is selected from the group consisting of polycaprolactone, polylactice, polyglycolide,polylactide-polyglycolide copolymers, copolymers of lactides and lactones, delta-valerolactone, polyalkylcyanoacrylates, polyamides, polyhydroxybutyrates, polydioxanones, poly-beta-aminoketones, polyanhydrides, poly-(ortho)esters, polyglutamic acid, polyaspartic acid and esters of polyglutamic and polyaspartic acids.

9. The composition of claim 1 in which the cross-linked amphiphilic material is a cross-linked protein.

10. The composition of claim 9 in which the cross-linked protein is cross-linked human serum albumin.

11. The composition of claim 1 in which the cross-linked amphiphilic material is cross-linked with glutaraldehyde.

12. A composition comprising:

a plurality of microparticles, a majority of which have diameters in the range of about 1 to 10 micrometers, each of which comprises a shell enclosing a gas-filled hollow core, said shell comprising an inner layer of polylactide and an outer layer of glutaraldehyde cross-linked human serum albumin;

glycine; and

polyethylene glycol 3350.

13. The composition of claim 12 which is in the form of a dry cake and/or powder.

14. The composition of claim 12 which is in the form of an aqueous suspension.