|Title:|| Method of echographic imaging using polymeric gas or air filled microballoons|
|Abstract:||Ultrasonic echographic imaging body organs using 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 both deformable and resilient 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:||Mar 04, 1997|
|Claims:||1. A method of echographic imaging of organs or tissue of patients comprising: |
(a) administering by injection to human or animal patients an ultrasonic contrast agent comprising a suspension of air or gas microballoons in a physiologically acceptable aqueous carrier liquid, the microballoons having a mean size in the range of 0.5 to 1,000 microns and 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, and
(b) echographically imaging the patient.
2. The method of claim 1, wherein the air or gas filled microballoons suspended in a physiologically acceptable aqueous liquid carrier are administered orally, rectally or urethrally.
3. The method of claim 1, wherein the suspension is administered by injection into the blood stream of a living being.
4. The method of claim 1, in which the microballoons have a size in the 0.5-10 .mu.m range and the membrane is impervious or permeable to bioactive liquids.
5. The method of claim 4, in which the polymer membrane is porous and has porosity ranging from 50 nanometers to 2000 nanometers.
6. The method of claim 1, wherein the membrane polymer is polyglutamic or polyaspartic acid ester or amide.
7. The method of claim 6, wherein the polyglutamic and polyaspartic 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.
8. The method of claim 1, wherein the membrane polymer further contains isopropyl myrisate or glyceryl monostearate.
9. The microballoons of claim 1, wherein the membrane further comprises a paraffin wax.
10. The microballoons of claim 8, wherein the additives are polymers of molecular weight in the range of 1,000 to 15,000.
11. The microballoons of claim 10, wherein the polymers are selected from the group consisting of polylactides, polyglycolides, polyalkylene glycols and polyols.
12. The method of claim 1, wherein the membrane polymer is not biodegradable in the digestive tract is impervious to biological liquids and the contrast agent is administered orally rectally or urethrally.
13. The method of claim 12, wherein the membrane polymer is selected from the group consisting of polyolefins, polyacrylates, polyacrylonitrile, nonhydrolyzable polyesters, polyurethanes and polyureas.
14. The method of claim 1, wherein the microballoons are present in a concentration of about 10.sup.6 to 10.sup.10 microballoons/ml, said suspension being stable for at least thirty days.
15. The method of claim 14, wherein the gas in the microballoons is a fluorine containing gas.
16. The method of claim 15, wherein the fluorine containing gas is a freon.