|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, hydrophillc 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 (Collonges 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. A method of imaging organs in a living body, said method comprising |
administering to said body a composition consisting of a suspension of air or gas microbubbles in a physiologically acceptable aqueous carrier phase the suspension comprising one or more dissolved or dispersed surfactants, at least one of which is a film forming surfactant present in the composition at least partially in lamellar or laminar form; and
subjecting said body to ultrasonic echography.
2. A method according to claim 1, wherein said suspension is administered by injection.
3. A method according to claim 2, wherein 0.1 to 2 ml of the suspension containing 10.sup.7 -10.sup.11 microbubbles/ml, is injected into a peripheral vein thereby providing opacification of the left heart under echographic measurements, the microbubbles being in the size range from 0.5-10 .mu.m.
4. A method according to claim 1, wherein the film forming surfactant is a phospholipid selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, cardiolipin and sphingomyelin.
5. A method according to claim 1, wherein the composition further comprises substances selected from the group consisting of dicetyl-phosphate, cholesterol, ergosterol, phytosterol, sitosterol, lanosterol, tocopterol, propyl gallate, ascorbyl palmitate and butylated hydroxytoluene.
6. A method according to claim 4, wherein the suspension further comprises viscosity enhancers or hydrosoluble stabilizers selected from the group consisting of linear and cross-linked poly- and oligo-sacchrides, sugars and hydrophilic polymers.
7. A method according to claim 6, wherein the hydrosoluble stabilizers are present in a weight ratio to the surfactants between about 1:5 and 100:1.
8. A method according 1, wherein the surfactants comprise up to 50% by weight of non-laminar surfactants selected from the group consisting of fatty acids, esters and ethers of fatty acids, alcohols with polyols and polyalkylenated glycerol.
9. A method according to claim 8, wherein the surfactants comprise polyalkylene glycols and poly alkylenated sugars.
10. A method according to claim 1, wherein the composition comprises freeze dried liposomes.
11. A method of transporting in the bloodstream or body cavities of a host bubbles of a foreign gas active therapeutically or diagnostically, said method comprising the step of administering to said host a suspension of a formulation as defined in claim 1.
12. A method according to claim 1, wherein said composition is administered by injection.