|Title:||Stable microbubbles suspensions injectable into living organisms|
|Abstract:||Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.|
|Inventor(s):||Schneider; Michel (Troinex, CH), Bichon; Daniel (Montpellier, FR), Bussat; Philippe (Collonqes S/Saleve, FR), Puginier; Jerome (Le Chable-Beaumont, FR), Hybl-Sutherland; Eva (Wiesbaden, DE)|
|Assignee:||Bracco International B.V. (NL)|
|Filing Date:||Jun 01, 1995|
|Claims:||1. An injectable composition comprising, as a suspension in an aqueous carrier phase, gas microbubbles of physiologically acceptable, fluorine-containing entrappable gas or a mixture of a fluorine-containing entrappable gas with CO.sub.2, N.sub.2 or NO.sub.2 stabilized by dissolved or dispersed surfactants at least one of which is a saturated film forming phospholipid in laminar or lamellar form. |
2. A suspension according to claim 1, wherein said flourine-containing gas is a freon.
3. A suspension according to claim 1, wherein the average bubble size is less than 50 .mu.m.
4. A suspension according to claim 3, wherein said bubble size is 0.5-50 .mu.m.
5. A suspension according to claim 1 in the form of an aqueous suspension.
6. A suspension according to claim 1, wherein the lamellar phospholipid is in the form of mono- or pluri-molecular membrane layers.
7. A suspension according to claim 6, wherein the lamellar phospholipid is a saturated phopholipid.
8. A suspension according to claim 7, wherein the phospholipid is selected from phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidyglycerol, phosphatidylinositol, cardiolipin and sphingomyelin.
9. A suspension according to claim 8, further containing substances selected from dicetylphosphate, cholesterol, ergosterol, phytosterol, sitosterol, lanosterol, tocopherol, propyl gallate, ascorbyl palmitate and butylated hydroxy-toluene.
10. A suspension according to claim 1, further containing dissolved viscosity enhancers or stabilizers selected from linear and cross-linked poly- and oligo-saccharides, sugars, hydrophilic polymers and iodinated compounds in a weight ratio to the surfactants comprised between about 1:5 to 100:1.
11. A suspension according to claim 1, further comprising up to 50% by weight of non-laminar surfactants selected from fatty acids, ester and ethers of fatty acids and alcohols with polyols.
12. A suspension according to claim 11, wherein the polyols are polyalkylene glycols, polyalkylenated sugars and other carbohydrates, and polyalkylenated glycerol.
13. A suspension according to claim 1 containing 10.sup.7 7-10.sup.8 microbubbles/ml.
14. A suspension according to claim 1 containing 10.sup.8 -10.sup.9 microbubbles/ml.
15. A suspension according to claim 1 containing 10.sup.10 -10.sup.11.
16. A suspension according to claim 1, wherein the microbubbles also contain .sup.133 Xe or .sup.81 Kr.