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EP0052575A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Composition generating microbubbles

Assignee: Bayer Pharma AG
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Filing: 1981-11-17
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Granted: —
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Expires: 2001-11-17
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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 EP
Data Source google_patents
Last Synchronized 2026-10-23 05:47
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61B; A61B8/00; A61B8/06; A61B8/48; A61B8/481

Claims Analysis

Total Claims: 27
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
Dependent Claim 119 words
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.
Claim 12
Dependent Claim 119 words
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.
Claim 13
Dependent Claim 19 words
A composition of matter according to claim 10, wherein the particulate material is dextrose, galactose, maltose or sodium chloride..
Claim 14
Dependent Claim 31 words
A composition of matter according to claim 10, wherein the solid particulate material is aggregates of at least about 10 particles whose average size is from about 1 to 50 micrometers.
Claim 15
Dependent Claim 37 words
A composition of matter according to claim 10, as a fluid injectable suspension in an amount of a carrier liquid which is non-toxic and physiologically acceptable and in which the particulate material is at least temporarily stable.
Claim 16
Dependent Claim 22 words
A composition of matter according to claim 13, wherein the carrier liquid is aqueous and has a viscosity substantially greater than water.
Claim 17
Dependent Claim 19 words
A composition of matter according to claim 13, wherein the particulate material is glucose, galactose, maltose or sodium chloride.
Claim 18
Dependent Claim 103 words
A kit for providing a material for forming microbubbles in the bloodstream of a living being comprising (a) a first sealed container comprising means for gaining access to the contents thereof and containing a unit dosage amount of a particulate solid according to claim 10, and (b) a second sealed container comprising means for obtaining access to the contents thereof and containing a unit dosage amount of a carrier liquid which is non-toxic and physiologically acceptable and in which the particulate material is at least temporarily stable effective to form a fluid injectable suspension when mixed with the contents of the first container.
Claim 19
Dependent Claim 18 words
A kit according to claim 16, wherein the solid particulate material is glucose, galactose, maltose or sodium chloride.
Claim 20
Dependent Claim 65 words
A method of enhancing ultrasonic images in the blood of a living test subject, comprising the steps of: a) injecting a unit dosage amount of a composition of matter of claim 13 into the venous system of the test subject, thereby forming a cloud of microbubbles in the blood therein; and b) obtaining an ultrasonic image of the blood opposite a location containing said microbubbles.
Claim 21
Dependent Claim 18 words
A method according to claim 18, wherein the solid particulate material is glucose, galactose, maltose or sodium chloride.
Claim 22
Dependent Claim 21 words
A method according to claim 18, wherein the carrier liquid is aqueous and has a viscosity substantially greater than water. ,
Claim 23
Dependent Claim 17 words
A method according to claim 20, wherein the particulate solid is glucose, galactose, maltose or sodium chloride.
Claim 24
Dependent Claim 39 words
2 2. A method according to claim 18, 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 25
Dependent Claim 31 words
23 . A method according to claim 18, including as an added step calculating blood flow rate from the intensities of two images measured at said location using dye dilution techniques.
Claim 26
Dependent Claim 34 words
A method of producing a composition of matter according to claim 10, comprising forming the solid into aggregates of at least about 10 particles whose average size is from about 1 to 50 micrometers.
Claim 27
Dependent Claim 18 words
A method according to claim 24, wherein the solid particulate material is glucose, galactose, maltose or sodium chloride.

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