Microencapsulated fluorinated gases for use as imaging agents

• US 5,611,344 A
• Filed: 03/05/1996
• Issued: 03/18/1997
• Est. Priority Date: 03/05/1996
• Status: Expired due to Term

• Current Assignee: Acusphere Incorporated
• Original Assignee: Acusphere Incorporated
• Inventors: Straub, Julie A., Bernstein, Howard, Brush, Henry T., Wing, Richard E.
• Primary Examiner(s): MANUEL, GEORGE C
• Application Number:
  US08/611,248
• Time in Patent Office: 378 Days
• Field of Search: 128/660.07, 128/660.01, 128/662.02, 128/654, 424/4, 424/9, 424/673
• US Class Current: 600/458
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

Abstract

It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.

Claims

1. A method for enhancing ultrasonic imaging comprising enhancing the echogenicity of a synthetic polymeric microparticle comprising air by incorporating therein a fluorinated gas in place of the air in an amount effective to image the microparticle after administration to a patient.

2. The method of claim 1 wherein the gas is a perfluorocarbon.

3. The method of claim 2 wherein the gas is selected from the group consisting of CF₄, C₂ F₆, C₃ F₈, C₄ F₈, SF₆, C₂ F₄, and C₃ F₆.

4. The method of claim 3 wherein the gas is octafluoropropane.

5. The method of claim 1 wherein the microparticle is a microcapsule.

6. The method of claim 1 wherein the microparticle is a microsphere having voids therein.

7. The method of claim 1 wherein the microparticle is formed of a bioadhesive synthetic polymer.

8. The method of claim 1 wherein the microparticle is formed of a synthetic polymer selected from the group consisting of poly(hydroxy acids), polyanhydrides, polyorthoesters, polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terepthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polysiloxanes, poly(vinyl alcohols), poly(vinyl acetate), polystyrene, polyurethanes and co-polymers thereof, synthetic celluloses, polyacrylic acids, poly(butyric acid), poly(valeric acid), and poly(lactide-co-caprolactone), ethylene vinyl acetate, copolymers and blends thereof.

9. The composition of claim 8 wherein the microparticle is a microcapsule.

10. The composition of claim 8 wherein the microparticle is a microsphere having voids therein.

11. The composition of claim 8 wherein the microparticle is formed of a bioadhesive synthetic polymer.

12. The composition of claim 8 wherein the microparticle is formed of a synthetic polymer selected from the group consisting of poly(hydroxy acids) other than a polyethylene glycol and poly(lactic acid-co-glycolide) copolymer, polyanhydrides, polyorthoesters, polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terepthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polysiloxanes, poly(vinyl alcohols), poly(vinyl acetate), polystyrene, polyurethanes and co-polymers thereof, synthetic celluloses, polyacrylic acids, poly(butyric acid), poly(valeric acid), and poly(lactide-co-caprolactone), ethylene vinyl acetate, copolymers and blends thereof.

13. The composition of claim 8 wherein the gas is a perfluorocarbon.

14. The composition of claim 13 wherein the gas is selected from the group consisting of CF₄, C₂ F₆, C₃ F₈, C₄ F₈, SF₆, C₂ F₄, and C₃ F₆.

15. The composition of claim 14 wherein the perfluorocarbon is octafluoropropane.

16. A composition for administration to a patient for imaging with ultrasound comprising

a synthetic biocompatible polymeric microparticle having incorporated therein an effective amount of a fluorinated gas for enhanced imaging by ultrasound after administration to a patient as compared with the microparticle incorporating therein an equivalent volume of air, wherein the microparticle is not formed of a polyethylene glycol and poly(lactic acid-co-glycolide) copolymer and the gas is not a perfluorocarbon, and

a pharmaceutically acceptable carrier for administration of the microparticles to a patient.