Carrier liquid solutions for the production of gas microbubbles, preparation thereof, and use thereof as contrast medium for ultrasonic diagnostics
First Claim
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1. A combination adapted when microbubbles are formed therein for use as contrast medium for ultrasonic diagnostics, consisting essentially of(a) an amount from about 0.01% to 10% by weight of at least one tenside, as a solution in an aqueous intravenously injectable physiologically acceptable aqueous carrier liquid, effective to impart a surface tension to the solution of less than 43 dyn/cm;
- (b) an amount from about 0.5% to 50% by weight of at least one viscosity-raising compound, as a solution in an aqueous intravenously injectable physiologically acceptable aqueous carrier liquid, effective to impart a viscosity to the solution of at least 20 mPa·
s;
wherein (a) and (b) are present in the combination as a single solution or as separate solutions which, when mixed, form the single solution; and
(c) a physiologically acceptable sterile gas for forming microbubbles in a mixture of (a) and (b).
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Abstract
The useful lifetime and the amount of microbubbles of a size less than 50 μm produced by mechanical agitation of an aqueous liquid employed as an ultrasonic contrast medium are increased by employing a liquid containing dissolved therein a tenside which reduces the surface tension of the liquid and a compound which raises the viscosity of the liquid.
434 Citations
26 Claims
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1. A combination adapted when microbubbles are formed therein for use as contrast medium for ultrasonic diagnostics, consisting essentially of
(a) an amount from about 0.01% to 10% by weight of at least one tenside, as a solution in an aqueous intravenously injectable physiologically acceptable aqueous carrier liquid, effective to impart a surface tension to the solution of less than 43 dyn/cm; -
(b) an amount from about 0.5% to 50% by weight of at least one viscosity-raising compound, as a solution in an aqueous intravenously injectable physiologically acceptable aqueous carrier liquid, effective to impart a viscosity to the solution of at least 20 mPa·
s;
wherein (a) and (b) are present in the combination as a single solution or as separate solutions which, when mixed, form the single solution; and(c) a physiologically acceptable sterile gas for forming microbubbles in a mixture of (a) and (b). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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18. In a method for altering the transmission characteristics of blood to an electromagnetic or elastic wave transmitted therethrough by the steps of forming an amount of microbubbles effective to substantially alter such transmission characteristics of blood in the area thereof containing the microbubbles in an intravenously injectable physiologically acceptable aqueous carrier liquid by mechanically agitating the carrier liquid in the presence of a physiologically acceptable gas, and dispersing the microbubble-containing carrier liquid in the blood, the improvement wherein the carrier liquid is substantially free of undissolved solids, has a surface tension of less than 43 dyn/cm and a viscosity of at least 20 mPa·
- s, and the physiologically acceptable gas is sterile.
- View Dependent Claims (19, 20, 21, 22, 23)
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24. A kit for preparing a liquid suspension of microbubbles suitable for use as a contrast medium for ultrasonic diagnostics, comprising
(a) a first sterile sealed container provided with a means for gaining access to the contents thereof with a hypodermic needle under sterile conditions and containing a solution in an intravenously injectable carrier liquid substantially free of undissolved solids, of an amount from 0.02% to 50% by weight of at least one tenside effective to lower the surface tension of the mixture produced when the solution in (a) is mixed with the solution in (b) to less than 43 dyn/cm; - and
(b) a second sterile sealed container provided with means for gaining access to the contents thereof with a hypodermic needle under sterile conditions and containing an amount of from about 1% to 50% by weight of a solution in an injectable aqueous liquid substantially free of undissolved solids of at least one viscosity-raising compound, effective to impart a viscosity to the mixture produced when the solution in (a) is mixed with the solution in (b) of at least 20 mPa·
s;
at least one of (a) and (b) also containing a sufficient amount of a sterile physiologically acceptable gas to produce microbubbles in the mixture of the solution in (a) and (b) when the mixture is mechanically agitated. - View Dependent Claims (25)
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26. A sealed vial containing a solution, in an intravenously injectable, physiologically acceptable aqueous carrier liquid substantially free of undissolved solids, of an amount from about 0.1% to 10% by weight of at least one tenside effective to substantially lower the surface tension of the carrier liquid and an amount of from about 0.5 to 50% by weight of at least one viscosity-raising compound effective to substantially raise the viscosity of the carrier liquid and a volume of a sterile physiologically acceptable gas sufficient to produce microbubbles in the solution when the solution and gas are mixed by mechanical agitation.
Specification
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Current AssigneeSchering Ag (Merck & Co., Inc.)
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Original AssigneeSchering Ag (Merck & Co., Inc.)
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InventorsHilmann, Juergen, Zimmermann, Ingfried, Muetzel, Wolfgang, Hoffmann, Rolf-Ruediger
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Primary Examiner(s)Howell, Kyle L.
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Assistant Examiner(s)Jaworski, Francis J.
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Application NumberUS06/434,034Time in Patent Office678 DaysField of Search128/653, 128/669-663, 424/2, 424/9US Class Current600/431CPC Class CodesA61K 49/223 Microbubbles, hollow micros...
