Claims for Patent: 4,681,119

Summary for Patent: 4,681,119

Title:	Method of production and use of microbubble precursors
Abstract:	In the inventive method, microbubbles are formed in body liquid or carrier liquid, for example within the genitourinary or digestive systems in order to alter the transmission characteristics thereof to electromagnetic and sonic waves transmitted therethrough, by dissolving therein a solid particulate material, preferably as a suspension in a carrier liquid in which the particulate material is at least temporarily stable, the particles of which are substantially free of microbubbles and have a plurality of gas-filled voids communicating with the surface of the particles and providing nuclei for microbubble formation and the ratio of the mass of the particles to the volume of gas in the voids is sufficient to render the liquid in which the particulate material is dissolved supersaturated with respect to the gas in the voids in the area of the liquid surrounding the microbubbles when they are formed.
Inventor(s):	Rasor; Julia S. (Cupertino, CA), Tickner; Ernest G. (Gilroy, CA)
Assignee:	Schering Aktiengesellschaft (Berlin and Bergkamen, DE)
Application Number:	06/854,622
Patent Claims:	1. In a method for altering the transmission characteristics of a liquid-filled region of the body other than the cardiovascular system to an electromagnetic or elastic wave transmitted therethrough by dispersing in the liquid an amount of microbubbles effective to substantially alter such transmission characteristics of the liquid in the area thereof containing the microbubbles, wherein the microbubbles are formed by dissolving in the liquid a solid which is particulate, is substantially free of microbubbles, and consists predominantly of particles which have a plurality of gas-filled voids communicating with the surface of the particles and a plurality of nuclei for microbubble formation and the ratio of the mass of the particles to the volume of gas in the voids is sufficient to render the liquid in which the particulate material is dissolved supersaturated with respect to the gas in the voids in the area of the liquid surrounding the microbubbles, the improvement wherein the liquid is sterile water or sterile aqueous galactose solution and the solid is galactose. 2. The method according to claim 1, wherein the liquid is about 20% wt./vol. galactose solution. 3. The method according to claim 1, wherein the solid is .alpha.-D(+) galactose. 4. The method according to claim 1, wherein within 5-10 minutes prior to use the galactose is added to the water or galactose solution and the mixture shaken to yield a suspension of the microbubbles. 5. The method according to claim 4, wherein the solid is .alpha.-D(+) galactose wherein the liquid is about 20% wt./vol. galactose solution. 6. A method according to claim 1, wherein the liquid filled region is part of the digestive system. 7. A method according to claim 1, wherein the liquid filled region is part of the urinary system. 8. A method according to claim 1, wherein the liquid filled region is part of the reproductive system. 9. A method of enhancing ultrasonic images in a liquid filled region of the body other than the cardiovascular system of a living test subject, comprising the steps of: (a) forming a fluid injectable suspension of: (i) particulate galactose which is substantially free of microbubbles, whose paarticles are aggregates having gas filled voids therebetween of smaller particles having an average size in the range of from 1 to 250 micrometers, with the ratio of the mass of the smaller particles to the volume of gas in the voids therebetween effective to render blood in which the particulate solid is dissolved supersaturated with respect to the gas in the area of the blood surrounding the microbubbles when they form therein; in (ii) an amount of sterile water or a sterile galactose solution in which the solid galactose is at least temporarily stable; (b) injecting a unit dosage amount of the fluid injectable suspension into the liquid-filled region of the test subject, thereby forming a cloud of microbubbles in the liquid therein; and (c) obtaining an ultrasonic image of the liquid-filled region opposite a location containing said microbubbles. 10. The method according to claim 9, wherein the liquid is about 20% wt./vol. galactose solution. 11. The method according to claim 9, wherein the solid is .alpha.-D(+) galactose. 12. The method according to claim 9, wherein within 5-10 minutes prior to use the galactose is added to the water or galactose solution and the mixture shaken to yield a suspension of the microbubbles. 13. The method according to claim 12, wherein the solid is .alpha.-D(+) galactose wherein the liquid is about 20% wt./vol. galactose solution. 14. A method according to claim 13, wherein the liquid filled region is part of the digestive system. 15. A method according to claim 13, wherein the liquid filled region is part of the urinary system. 16. A method according to claim 13, wherein the liquid filled region is part of the reproductive system.

Details for Patent 4,681,119

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2004-07-21