Ultrasonic imaging system utilizing a long-persistence contrast agent

• US 20050244338A1
• Filed: 07/13/2005
• Published: 11/03/2005
• Est. Priority Date: 07/30/1993
• Status: Abandoned Application

• Current Assignee: Targeson, Inc.
• Original Assignee: Targeson, Inc.
• Inventors: Schutt, Ernest G.
• Application Number:
  US11/110,416
• Publication Number:
  US 20050244338A1
• Time in Patent Office: Days
• US Class Current: 424/9.520
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 49/227 Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric
• CPC Class Codes: G02B 6/0006 Coupling light into the fibre in general G02B6/4298

Abstract

An ultrasound contrast agent precursor composition comprising: a plurality of void containing polymeric structures; a fluorocarbon gas osmotic agent having a water solubility of not more than about 0.5 mM at 25° C. and one atmosphere; and a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form microbubbles upon addition of said microbubble precursor composition to an aqueous medium. An ultrasound contrast agent precursor composition comprising: lyophilized void containing structures; a perfluorocarbon gas osmotic agent, said gas osmotic agent dispersed in said voids; and a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form an ultrasound contrast agent upon addition of an aqueous liquid. An ultrasound contrast agent precursor composition comprising: spray dryed void containing structures; a perfluorocarbon gas osmotic agent, said gas osmotic agent dispersed in said voids; and a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form an ultrasound contrast agent upon addition of an aqueous liquid. An ultrasound contrast agent comprising a plurality of microbubbles comprising a phospholipid further comprising a perfluorocarbon gas osmotic agent.

Claims

1. An ultrasound contrast agent precursor composition comprising:

a plurality of void containing polymeric structures;

a fluorocarbon gas osmotic agent having a water solubility of not more than about 0.5 mM at 25°

C. and one atmosphere; and

a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form microbubbles upon addition of said microbubble precursor composition to an aqueous medium.

2. The composition of claim 1 wherein the gas osmotic agent is selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluoromethylcyclobutane, perfluoro-hexane, perfluorocyclohexane, perfluoromethylcyclopentane, per-fluorodimethylcyclobutane, perfluoroheptane, perfluorocyclo-heptane, perfluoromethylcyclohexane, perfluorodimethyl cyclo-pentane, perfluorotrimethyl cyclobutane and perfluoro triethylamine.

3. The composition of claim 1, wherein the composition further comprises a modifier gas.

4. The composition of claim 3, wherein the modifier gas is selected from the group consisting of nitrogen, oxygen, carbon dioxide, or mixtures thereof.

5. The composition of claim 3, wherein the mixture of the gas osmotic agent and modifier gas is effective to stabilize the microbubble preparation.

6. The composition of claim 3, wherein the modifier gas is air.

7. The composition of claim 1, wherein the polymeric structures comprise a synthetic polymer.

8. An ultrasound contrast agent comprising a plurality of microbubbles comprising a phospholipid further comprising a perfluorocarbon gas osmotic agent.

9. The ultrasound contrast agent of claim 8 wherein the gas osmotic agent is selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluoromethylcyclo-butane, perfluorohexane, perfluorocyclohexane, perfluoromethyl-cyclopentane, perfluorodimethylcyclobutane, perfluoroheptane, perfluorocycloheptane, perfluoromethylcyclohexane, perfluoro-dimethyl cyclopentane, perfluorotrimethyl cyclobutane and perfluoro triethylamine.

10. The ultrasound contrast agent of claim 8, wherein the ultrasound contrast agent further comprises a modifier gas.

11. The ultrasound contrast agent of claim 10, wherein the modifier gas is selected from the group consisting of nitrogen, oxygen, carbon dioxide, or mixtures thereof.

12. The ultrasound contrast agent of claim 10, wherein the mixture of the gas osmotic agent and modifier gas is effective to stabilize the microbubble preparation.

13. The ultrasound contrast agent of claim 10, wherein the modifier gas is air.

14. An ultrasound contrast agent precursor composition comprising:

lyophilized void containing structures;

a perfluorocarbon gas osmotic agent, said gas osmotic agent dispersed in said voids; and

a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form an ultrasound contrast agent upon addition of an aqueous liquid.

15. The ultrasound contrast agent precursor composition of claim 14 wherein the perfluorocarbon gas osmotic agent is selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluoromethylcyclo-butane, perfluorohexane, perfluorocyclohexane, perfluoromethyl-cyclopentane, perfluorodimethylcyclobutane, perfluoroheptane, perfluorocycloheptane, perfluoromethylcyclohexane, perfluoro-dimethyl cyclopentane, perfluorotrimethyl cyclobutane and perfluoro triethylamine.

16. The composition of claim 14, wherein the composition further comprises a modifier gas.

17. The composition of claim 16, wherein the modifier gas is selected from the group consisting of nitrogen, oxygen, carbon dioxide, or mixtures thereof.

18. The composition of claim 16, wherein the mixture of the gas osmotic agent and modifier gas is effective to stabilize the microbubble preparation.

19. The composition of claim 16, wherein the modifier gas is air.

20. An ultrasound contrast agent precursor composition comprising:

spray dried void containing structures;

a perfluorocarbon gas osmotic agent, said gas osmotic agent dispersed in said voids; and

a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form an ultrasound contrast agent upon addition of an aqueous liquid.

21. The ultrasound contrast agent precursor composition of claim 20 wherein the perfluorocarbon gas osmotic agent is selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluoromethylcyclo-butane, perfluorohexane, perfluorocyclohexane, perfluoromethyl-cyclopentane, perfluorodimethylcyclobutane, perfluoroheptane, perfluorocycloheptane, perfluoromethylcyclohexane, perfluoro-dimethyl cyclopentane, perfluorotrimethyl cyclobutane and perfluoro triethylamine.

22. The composition of claim 20, wherein the composition further comprises a modifier gas.

23. The composition of claim 22, wherein the modifier gas is selected from the group consisting of nitrogen, oxygen, carbon dioxide, or mixtures thereof.

24. The composition of claim 22, wherein the mixture of the gas osmotic agent and modifier gas is effective to stabilize the microbubble preparation.

25. The composition of claim 22, wherein the modifier gas is air.

26. An ultrasound contrast agent precursor composition comprising:

spray dried void containing structures;

a lyophilized cake of surfactant and bulking reagent;

a perfluorocarbon gas osmotic agent, said gas osmotic agent dispersed in said voids; and

a phospholipid associated with said structures, wherein said structures, said gas and said phospholipid are together adapted to form an ultrasound contrast agent upon addition of an aqueous liquid.

27. The ultrasound contrast agent precursor composition of claim 26 wherein the perfluorocarbon gas osmotic agent is selected from the group consisting of perfluoropropane, perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluoromethylcyclo-butane, perfluorohexane, perfluorocyclohexane, perfluoromethyl-cyclopentane, perfluorodimethylcyclobutane, perfluoroheptane, perfluorocycloheptane, perfluoromethylcyclohexane, perfluoro-dimethyl cyclopentane, perfluorotrimethyl cyclobutane and perfluoro triethylamine.

28. The composition of claim 26, wherein the composition further comprises a modifier gas.

29. The composition of claim 28, wherein the modifier gas is selected from the group consisting of nitrogen, oxygen, carbon dioxide, or mixtures thereof.

30. The composition of claim 28, wherein the mixture of the gas osmotic agent and modifier gas is effective to stabilize the microbubble preparation.

31. The composition of claim 28, wherein the modifier gas is air.