Ultrasonic contrast medium comprising gas bubbles and solid lipophilic surfactant-containing microparticles and use thereof

Claim 1

An injectable contrast medium adapted for use as an ultrasonic diagnostic agent comprising a physiologically acceptable liquid vehicle containing suspended therein (a) microparticles comprising a mixture of (i) an amount effective to render the contrast medium suitable for use as a left heart imaging agent of at least one physiologically acceptable, essentially lipophilic surfactant selected from the group consisting of a lecithin, a lecithin fraction, a modification product of a lecithin fraction, a polyoxyethylene fatty acid ester, a polyoxyethylated sorbitan fatty acid ester, glycerol polyethylene glycol oxystearate, glycerol polyethylene glycol ricinoleate, an ethoxylated soy sterol, an ethoxylated castor oil, a hydrogenated derivative of an ethoxylated castor oil, cholesterol, a (C 8 -C 20 )-fatty acid, a physiologically acceptable salt of a (C 8 -C 20 ) fatty acid, a polyoxyethylene fatty acid, a sugar ester, a sucrose glyceride, an oxyloglyceride, a saturated (C 4 -C 20 )-fatty alcohol, an unsaturated (C 4 -C 20 ) fatty alcohol, a fatty acid, a fatty acid ester, a mono-, di-, or triglyceride, a sorbitan fatty acid, a physiologically acceptable salt of a sorbitan fatty acid, a polyoxyethylene fatty acid ester, ascorbyl palmitate, a xyloglyceride, a palm oil sucrose glyceride and a cottonseed oil sucrose glyceride, and (ii) at least one non-surfactant physiologically acceptable water soluble solid selected from the group consisting of an inorganic salt, an organic salt and a solid hydroxy compound; and (b) an amount of microbubbles effective to render the contrast medium ultrasonic image enhancing.

Claim 41

A method for altering the transmission characteristics of an aqueous liquid to an electromagnetic or elastic wave transmitted therethrough by dispersing in the liquid an amount effective to alter said transmission characteristics of a solid microbubble precursor particles which contains an amount of a gas effective to produce a suspension of microbubbles which alters the transmission characteristics of the liquid when the precursor is dispersed in the liquid and which, when dispersed in the liquid, forms an ultrasonically ectogenic entity including a gas phase which alters those transmission characteristics, which comprises employing a microbubble precursor containing a solid phase consisting essentially of an intimate mixture of 95-99.99% by weight of (a) at least one water soluble solid selected from the group consisting of an inorganic salt, an organic salt and a solid hydroxy compound, and (b) an amount from 5-0.01% by weight of a solid lipophilic group-containing compound effective to prevent the dissolution of the water soluble solid for at least about three seconds after the precursor is dispersed in the liquid, which lipophilic group-containing compound has an HLB (Hydrophilic-Lipophilic Balance) value, in the form that compound exists in the liquid, of no greater than about 20 and is selected from the group consisting of a lecithin, a lecithin fraction, a modification product of a lecithin fraction, a polyoxyethylene fatty acid ester, a polyoxyethylated sorbitan fatty acid ester, glycerol polyethylene glycol oxystearate, glycerol polyethylene glycol ricinoleate, an ethoxylated soy sterol, an ethoxylated castor oil, a hydrogenated derivative of an ethoxylated castor oil, cholesterol, a (C 8 -C 20 )-fatty acid, a physiologically acceptable salt of a (C 8 -C 20 ) fatty acid, a polyoxyethylene fatty acid, a sugar ester, a sucrose glyceride, an oxyloglyceride, a saturated (C 4 -C 20 )-fatty alcohol, an unsaturated (C 4 -C 20 ) fatty alcohol, a fatty acid, a fatty acid ester, a mono-, di-, or triglyceride, a sorbitan fatty acid, a physiologically acceptable salt of a sorbitan fatty acid, a polyoxyethylene fatty acid ester, ascorbyl palmitate, a xyloglyceride, a palm oil sucrose glyceride and a cottonseed oil sucrose glyceride, which microbubble precursor also comprises (c) an amount of a gas effective to produce a suspension of microbubbles when the solid phase is dispersed in the liquid.

Claim 42

A method for altering the transmission characteristics of an aqueous liquid to an electromagnetic or elastic wave transmitted therethrough by dispersing in the liquid an amount effective to alter said transmission characteristics of a solid microbubble precursor particles which contains an amount of a gas effective to produce a suspension of microbubbles which alters the transmission characteristics of the liquid when the precursor is dispersed in the liquid and which, when dispersed in the liquid, forms an ultrasonically ectogenic entity including a gas phase which alters those transmission characteristics, which comprises employing a microbubble precursor containing a solid phase consisting essentially of an intimate mixture of 95-99.99% by weight of (a) at least one water soluble solid selected from the group consisting of an inorganic salt, an organic salt and a solid hydroxy compound, and (b) an amount from 5-0.01% by weight of a solid lipophilic group-containing compound effective to prevent the dissolution of the water soluble solid for at least about three seconds after the precursor is dispersed in the liquid, which lipophilic group-containing compound has an HLB (Hydrophilic-Lipophilic Balance) value, in the form that compound exists in the liquid, of no greater than about 20 and is selected from the group consisting of a lecithin, a lecithin fraction, a modification product of a lecithin fraction, a polyoxyethylene fatty acid ester, a polyoxyethylated sorbitan fatty acid ester, glycerol polyethylene glycol oxystearate, glycerol polyethylene glycol ricinoleate, an ethoxylated soy sterol, an ethoxylated castor oil, a hydrogenated derivative of an ethoxylated castor oil, cholesterol, a (C 8 -C 20 )-fatty acid, a physiologically acceptable salt of a (C 8 -C 20 ) fatty acid, a polyoxyethylene fatty acid, a sugar ester, a sucrose glyceride, an oxyloglyceride, a saturated (C 4 -C 20 )-fatty alcohol, an unsaturated (C 4 -C 20 ) fatty alcohol, a fatty acid, a fatty acid ester, a mono-, di-, or triglyceride, a sorbitan fatty acid, a physiologically acceptable salt of a sorbitan fatty acid, a polyoxyethylene fatty acid ester, ascorbyl palmitate, a xyloglyceride, a palm oil sucrose glyceride and a cottonseed oil sucrose glyceride, which microbubble precursor also comprises (c) an amount of a gas effective to produce a suspension of microbubbles when the solid phase is dispersed in the liquid.