EP0633030A1
Expired / Lapsed
EP
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Protein encapsulated insoluble gas microspheres and their preparation and use as ultrasonic imaging agents
Assignee: Molecular Biosystems Inc
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Filing: 1994-07-04
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Granted: —
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Expires: 2014-07-04
Abstract
Abstract Encapsulated gas microspheres having improved pressure resistance and stability are made by: mixing an aqueous solution of a filmogenic protein such as human serum albumin with a water insoluble gas such as perfluoropropane and subjecting the mixture to ultrasonic or mechanical cavitation in the absence of oxygen in an apparatus that is closed to the atmosphere.
Inventors
- 👤 Karel J. Lambert
- 👤 Sheila Benay Podell
- 👤 Edward G. Jablonski
- 👤 Carl Hulle
- 👤 Kenneth Hamilton
- 👤 Rolf Lohrmann
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 11:08
CPC Classifications
A; A61; A61K; A61K49/00; B; B01; B01J; B01J13/00; B01J13/02; A61K49/22; A61K49/222; A61K49/223; B01J13/04
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
32 words
An ultrasonic imaging agent composition comprising an aqueous suspension of microspheres of a gas encapsulated by a heat-insolubilized filmogenic protein wherein the encapsulated gas is entirely a pharmacologically acceptable water insoluble gas.
Claim 2
Dependent Claim
20 words
An ultrasonic imaging agent composition comprising an aqueous suspension of microspheres of perfluoropropane gas encapsulated by a heat-insolubilized filmogenic protein.
Claim 3
Dependent Claim
48 words
An ultrasonic imaging agent composition comprising an aqueous suspension of microspheres of a gas encapsulated by a filmogenic protein which is heat insolubilized in the presence of the encapsulated gas and in the absence of oxygen, wherein the encapsulated gas is entirely a pharmacologically acceptable water insoluble gas.
Claim 4
Dependent Claim
30 words
The composition of any one of claims 1 to 3 wherein the solubility of gas in water at 25°C is less than 0.01 mL of gas per mL of water.
Claim 5
Dependent Claim
13 words
The composition of claim 1 or 3 wherein the insoluble gas is perfluoropropane.
Claim 6
Dependent Claim
17 words
The composition of any one of claims 1 to 5 wherein the protein is human serum albumin.
Claim 7
Independent Claim
56 words
A method of making encapsulated gas microspheres useful as an ultrasonic imaging agent comprising subjecting a mixture of an aqueous solution of a filmogenic protein and a pharmacologically acceptable insoluble gas to ultrasonic or mechanical cavitation, wherein the method is conducted in the absence of oxygen, and/or in an apparatus that is closed to the atmosphere.
Claim 8
Independent Claim
105 words
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.
Claim 9
Dependent Claim
19 words
The method of claim 8 wherein steps (c) and (d) are effected by passing the mixture through a mill.
Claim 10
Independent Claim
22 words
The method of any one of claims 7 to 9 wherein the protein is human serum albumin and the gas is perfluoropropane.
Claim 11
Dependent Claim
15 words
Encapsulated gas microspheres obtainable by the method of any one of claims 7 to 10.
Claim 12
Dependent Claim
18 words
A composition according to any one of claims 1 to 6 for use in a method of diagnosis.
Claim 13
Dependent Claim
70 words
A composition according to any one of claims 1 to 6 for use in a method to enhance the contrast of tissues and/or organs of a patient in an ultrasonic image thereof comprising: (a) injecting said composition into the patient, (b) applying ultrasonic energy to the tissue and/or organs, (c) detecting ultrasonic energy that is reflected from the tissues and/or organs, and (d) translating the reflected energy into an image.
References Cited (Backward Citations)
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