US4442843A
Expired / Lapsed
US
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Microbubble precursors and methods for their production and use
Assignee: Bayer Pharma AG
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Filing: 1981-11-17
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Granted: 1984-04-17
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Expires: 2001-11-17
Abstract
Abstract Microbubbles are formed in a liquid, e.g., blood 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.
Inventors
- 👤 Julia S. Rasor
- 👤 Ernest G. Tickner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 11:35
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61B; A61B8/00; A61B8/48; A61B8/481
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
142 words
In a method for altering the transmission characteristics of a liquid 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, the improvement 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.
Claim 2
Dependent Claim
142 words
In a method for altering the transmission characteristics of a liquid 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, the improvement 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.
Claim 3
Dependent Claim
11 words
A method according to claim 1, wherein the liquid is aqueous.
Claim 4
Dependent Claim
31 words
A method according to claim 2, wherein the liquid is the blood stream of a living being and the particulate solid is non-toxic and physiologically acceptable in the amount dissolved therein.
Claim 5
Dependent Claim
18 words
A method according to claim 3, wherein the solid particulate material is glucose, galactose, maltose or sodium chloride.
Claim 6
Dependent Claim
28 words
A method according to claim 2, wherein the solid is added as a suspension in a carrier liquid in which the particulate material is at least temporarily stable.
Claim 7
Dependent Claim
21 words
A method according to claim 5, wherein the carrier liquid is aqueous and comprises a compound which increases the viscosity thereof.
Claim 8
Dependent Claim
30 words
A method according to claim 1, wherein the solid particulate material is predominantly aggregates of at least about 10 microparticles whose average size is from about 1 to 50 micrometers.
Claim 9
Dependent Claim
66 words
A method according to claim 7, wherein the liquid is the blood stream of a living being and the particulate solid is non-toxic and physiologically acceptable in the amount dissolved therein and is added thereto as a suspension in carrier liquid in which the particulate material is at least temporarily stable and which is non-toxic and physiologically acceptable in the amount added to the blood stream.
Claim 10
Dependent Claim
23 words
A method according to claim 8, wherein the carrier liquid is aqueous and the solid precursor is glucose, galactose, maltose or sodium chloride.
Claim 11
Independent Claim
186 words
A method of enhancing ultrasonic images in the blood of a living test subject, comprising the steps of: (a) forming a fluid injectable suspension of: (i) a particulate solid which is non-toxic, physiologically acceptable material, soluble in blood and substantially free of microbubbles, whose particles 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 a carrier liquid which is non-toxic and physiologically acceptable and in which the particulate material is at least temporarily stable; (b) injecting a unit dosage amount of the fluid injectable suspension into the venous system of the test subject, thereby forming a cloud of microbubbles in the blood therein; and (c) obtaining an ultrasonic image of the blood opposite a location containing said microbubbles.
Claim 12
Independent Claim
186 words
A method of enhancing ultrasonic images in the blood of a living test subject, comprising the steps of: (a) forming a fluid injectable suspension of: (i) a particulate solid which is non-toxic, physiologically acceptable material, soluble in blood and substantially free of microbubbles, whose particles 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 a carrier liquid which is non-toxic and physiologically acceptable and in which the particulate material is at least temporarily stable; (b) injecting a unit dosage amount of the fluid injectable suspension into the venous system of the test subject, thereby forming a cloud of microbubbles in the blood therein; and (c) obtaining an ultrasonic image of the blood opposite a location containing said microbubbles.
Claim 13
Dependent Claim
18 words
A method according to claim 10, wherein the solid particulate material is glucose galactose, maltose or sodium chloride.
Claim 14
Dependent Claim
20 words
A method according to claim 10, wherein the carrier liquid is aqueous and has a viscosity substantially greater than water.
Claim 15
Dependent Claim
17 words
A method according to claim 12, wherein the particulate solid is glucose, galactose, maltose or sodium chloride.
Claim 16
Dependent Claim
37 words
A method according to claim 10, including as an added step determining both the velocity and position of said microbubbles from examination of said ultrasonic image and calculating blood flow rate from said velocity and position measurement.
Claim 17
Dependent Claim
29 words
A method according to claim 10, including as an added step calculating blood flow rate from the intensities of two images measured at said location using dye dilution techniques.
Claim 18
Independent Claim
145 words
A method of producing a sterile injectable composition of matter in unit dosage form and adapted for injection into the blood stream of a living being and generating microbubbles therein, comprising a particulate solid which is non-toxic, physiologically acceptable material, soluble in blood and substantially free of microbubbles, whose particles 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 composition of matter is dissolved supersaturated with respect to the gas in the area of the blood surrounding the microbubbles when they form therein, comprising forming the solid into aggregates of at least about 10 particles whose average size is from about 1 to 50 micrometers.
Claim 19
Independent Claim
145 words
A method of producing a sterile injectable composition of matter in unit dosage form and adapted for injection into the blood stream of a living being and generating microbubbles therein, comprising a particulate solid which is non-toxic, physiologically acceptable material, soluble in blood and substantially free of microbubbles, whose particles 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 composition of matter is dissolved supersaturated with respect to the gas in the area of the blood surrounding the microbubbles when they form therein, comprising forming the solid into aggregates of at least about 10 particles whose average size is from about 1 to 50 micrometers.
Claim 20
Dependent Claim
18 words
A method according to claim 16, wherein the solid particulate material is glucose, galactose, maltose or sodium chloride.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-04-17 | 1987-10-17 | 1988-04-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-17 | 1991-10-17 | 1992-04-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-17 | 1995-10-17 | 1996-04-17 | $7700.00 | Window Closed / Lapsed |