Claims
- 1. A method of making encapsulated gas microspheres useful as an ultrasonic imaging agent comprising:
- a) providing an aqueous solution of a heat-denaturable protein at a temperature necessary to achieve incipient denaturation temperature during subsequent mechanical emulsification;
- b) combining the solution with a gas;
- c) emulsifying the protein solution and gas mixture by mechanically shearing the mixture to form a suspension of gas microbubbles having a mean diameter in the range of about 0.1 to about 10 microns; and
- d) encapsulating the gas microbubbles to form microspheres by mechanically cavitating the suspension to cause the protein to become denatured and thereby deposited at the gas-solution interface.
- 2. The method of claim 1 wherein said temperature is achieved by heating the solution.
- 3. The method of claim 1 wherein said temperature is achieved by including additives in the solution that alter the denaturation temperature of the protein.
- 4. The method of claim 1 wherein the protein is a naturally occurring protein.
- 5. The method of claim 4 wherein the protein is human serum albumin.
- 6. The method of claim 1 wherein the protein is a synthetic protein.
- 7. The method of claim 1 wherein the concentration of the protein in the solution is about 0.1 to 10% w/v.
- 8. The method of claim 1 wherein the concentration of the protein in the solution is about 1 to 5% w/v.
- 9. The method of claim 1 wherein the concentration of the protein in the solution is about 1% w/v.
- 10. The method of claim 1 wherein the gas is insoluble.
- 11. The method of claim 10 wherein the insoluble gas is sulfur hexafluoride, perfluoromethane, perfluoroethane, perfluoropropane, or perfluorobutane.
- 12. The method of claim 1 wherein the gas is air.
- 13. The method of claim 1 wherein the ratio of gas to protein solution is 5% to 200% v/v.
- 14. The method of claim 1 wherein the ratio of gas to protein solution is 20% to 100% v/v.
- 15. The method of claim 1 wherein steps (c) and (d) are effected by passing the mixture through a mill.
- 16. The method of claim 1 wherein the incipient denaturation temperature is about 1.degree. to 5.degree. C. below the denaturation temperature of the protein.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of application U.S. Ser. No. 08/187,656 filed Jan. 26, 1994 now abandoned which in turn is a continuation-in-part of U.S. Ser. No. 08/086,717 filed Jul. 2, 1993 now abandoned.
US Referenced Citations (6)
Foreign Referenced Citations (6)
Number |
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0324938 |
Jul 1989 |
EPX |
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Nov 1991 |
EPX |
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Nov 1992 |
EPX |
0554213 |
Aug 1993 |
EPX |
WO9205806 |
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Non-Patent Literature Citations (3)
Entry |
Ophir, J., et al., "Contrast agents in diagnostic ultrasound" Ultrasound in Medicine (1989) 15(4):319-333. |
Echols, J. B., "Filtration of polymer viscosified fluids" Adv. Filtr. Sep. Tech. (1990) 1:108-110. |
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Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
187656 |
Jan 1994 |
|
Parent |
86717 |
Jul 1993 |
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