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|Title:||Ultrasonic contrast agent with polymeric gas or air filled microballoons|
|Abstract:||Ultrasonic contrast compositions containing gas or air filled microballoons having a mean size in the range of 0.5 to 1000 microns bounded by a 50 to 500 nm thick biodegradable, interfacially deposited, synthetic polymer membrane which is deformable and resilient in an aqueous carrier liquid are described.|
|Inventor(s):||Bichon; Daniel (Montpellier, FR), Bussat; Philippe (Collonges S/Saleve, FR), Schneider; Michel (Troinex, CH)|
|Assignee:||Bracco International B.V. (NL)|
|Filing Date:||Aug 16, 1994|
|Claims:||1. An ultrasonic contrast agent comprising a suspension of air or gas microballoons in a physiologically acceptable aqueous carrier liquid in a concentration of 10.sup.5 to 10.sup.10 microballoons/ml, the microballoons having a mean size in the range of 0.5 to 1,000 microns, are bounded by a soft, elastic, 50-500 nm thick polymer membrane filled with air or a physiologically acceptable gas, the membrane being temporarily deformable under pressure variations and made from a biodegradable, synthetic, resilient, interfacially depositable polymer selected from the group consisting of polysaccharides, polylactides, polyglycolides, copolymers of polylactides and polyglycolides, copolymers of lactides and lactones, poly-(ortho)esters, polydioxanone, poly-.beta.-aminoketones, polyphosphazenes, polyanhydrides and polyalkyl-(cyano)acrylates. |
2. The ultrasonic contrast agent of claim 1, wherein the microballoons have size in the range of 0.5-10 .mu.m and the membrane is either impervious or permeable to bioactive liquids.
3. The ultrasonic contrast agent of claim 1, wherein the polymer membrane is porous and has porosity ranging from 50 to 2000 nanometers.
4. The ultrasonic contrast agent of claim 1, wherein the membrane polymer is polyglutanic or polyaspartic acid esters or amides and their copolymers with amino acids.
5. The ultrasonic contrast agent of claim 4, wherein the polyglutamic and aspartic acid esters or amides have side functions having formulae
wherein R is an alkyl or aryl substituent; R.sup.1 and R.sup.2 are H or lower alkyls, or R and R.sup.1 are connected together by a substituted or unsubstituted linking member to form a 5- or 6-membered ring; n is 1 or 2; p is 1, 2 or 3; m is an integer from 1 to 5 and X is a side chain of an amino acid residue.
6. The ultrasonic contrast agent of claim 1, wherein the polymer membrane also includes a plasticizer selected from isopropyl myristate and glyceryl monostearate.
7. The ultrasonic contrast agent of claim 1, wherein the polymer membrane also includes a surfactant.
8. The ultrasonic contrast agent of claim 1, wherein the polymer membrane also includes a phospholipid.
9. The ultrasonic contrast agent of claim 1, wherein the polymer membrane also includes a paraffin wax.
10. The ultrasonic contrast agent of claim 1, wherein microballoons are present in the suspension in a concentration of about 10.sub.6 to 10.sub.10 microballoons per ml.
11. The ultrasonic contrast agent of claim 10, wherein microballoons are present in the suspension in a concentration of about 10.sup.8 to 10.sup.10 microballoons per ml.
12. The ultrasonic contrast agent of claim 1, wherein the physiologically acceptable gas in the microballoons is selected from the group consisting of CO.sub.2, N.sub.2 O, methane, helium and a freon.
13. The ultrasonic contrast agent of claim 1, wherein the physiologically acceptable gas in the microballoons is a fluorine containing gas.
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