Abstract: Novel compounds of formula in which R1 and R2 are phospholipid fatty acid residues and A is an aliphatic and/or cycloaliphatic hydrocarbon chain optionally substituted by hydroxy and/or further carboxylic functions. The novel compounds are useful for making liposomes of enhanced stability and entrapping capacity.

Abstract: A power assisted method and injector device for controllably delivering to patients a dispersion medicament or diagnostically active agent, the homogeneity of which is preserved throughout delivery. Diagnostically active agents disclosed are gas microbubble suspensions useful in ultrasonic diagnostic imaging and liposomal formulations in which liposome vesicles are loaded with iodinated compounds.

Abstract: The invention relates to microcapsules to a microcapsule with a mean size from a fraction of micrometer to 1000 micrometers having a biodegradable membrane encapsulating a gas core. The membrane comprising one or more biodegradable water insoluble lipids or mixtures thereof and optionally mixtures of the lipids with up to 75% by weight of biodegradable polymers encapsulates the core which is filled with air or a gas. Microcapsules disclosed, may be non-coalescent, dry and instantly dispersible, when in suspension in a physiologically acceptable carrier are useful as delivery vehicles for therapeutically active agents and/or as contrast agents for echographic imaging of organs of human or animal body.

Abstract: The method of imaging the nonlinear components of ultrasound echo signals returned from scatterers comprises the steps of constructing a double-pulse excitation waveform, the two pulses composing this waveform having spectra with known relative frequency dependencies, differing in amplitude and phase so that the double-pulse waveform can be considered as a convolution of any single of said pulses with a known coding function, transmitting said double-pulse waveform within a single transmission of an ultrasound beam in the direction of said scatterers, deconvolving the received rf-waveform by a first appropriate decoding function to obtain a new rf-waveform, deconvolving said received rf-waveform by a second and different appropriate decoding function to obtain another rf-waveform, realigning in time both deconvolved rf-waveforms obtained from the same returned echo signal by a time delay as determined by the transmit-coding function, normalizing amplitudes and taking the sum of both rf-waveforms to effectivel

Abstract: The invention relates to microcapsules to a microcapsule with a mean size from a fraction of micrometer to 1000 micrometers having a biodegradable membrane encapsulating a gas core. The membrane comprising one or more biodegradable water insoluble lipids or mixtures thereof and optionally mixtures of the lipids with up to 75% by weight of biodegradable polymers encapsulates the core which is filled with air or a gas. Microcapsules disclosed, may be non-coalescent, dry and instantly dispersible, when in suspension in a physiologically acceptable carrier are useful as delivery vehicles for therapeutically active agents and/or as contrast agents for echographic imaging of organs of human or animal body.

Abstract: The invention concerns a method for administering bioactive substances to patients at selected sites in the body and remotely promoting delivery of said media to selected organs or tissues in the body. The method comprises providing an administrable formulation comprising, dispersed in an aqueous carrier liquid, liposomes filled with bioactive substances and gas-filled microspheres, injecting said formulation into the circulation of a patient so that it is directed to a site of interest, and applying ultrasound pulses to said site so as to make the gas-filled microbodies explode and the gas confined therein to expand in the carrier liquid, the energy of expansion of said confined gas causing the liposome vesicles to open and release the trapped substances at said site.

Abstract: The invention provides, as contrast signal generators in MR imaging of the digestive tract, paramagnetic metal chelates of novel acrylic compounds of formula C(R1R2)═CR3—CO—Z—Z (1) and/or C(R1R2)═CR3—CO—Z—Z—Z—CO—CR3═C(R1R2) (2) in monomer, oligomer, homopolymer and copolymer forms, in which the R1, R2 and R3 represent H or saturated or unsaturated C1-10 aliphatic radicals optionally substituted by one or more OH groups; Z is a covalent bond or a linker spacer and A is a moiety capable of fixing a paramagnetic metal by chelation. Compounds of type (1) useful in the present invention are, for instance the polyalkylene-aminopolycarboxylic acids such as NTA, EDTA, DTPA, DOTA and like structures, possibly involving additional substituents; an example is the compound BOPTA which is a DTPA derivative carrying a benzyloxypropyl group.

Abstract: The present invention concerns injectable blood pool contrast agents for NMR and X-ray imaging purpose. These blood pool agents carry imaging contrast enhancers, e.g. paramagnetic or, respectively, radio-opaque compounds for imaging the circulation and/or circulation targeted organs. The blood pool agent compositions are formulated to protect the contrast agents from early removal by the reticulo-endothelial (RES) system of the liver and the spleen, so that they stay in the circulation long enough to provide good images of the blood vessels and blood perfused organs. X-ray and NMR imaging of the circulation and of targeted organs can strongly assist in diagnosing possible ailments in human and animal patients.

Abstract: The invention relates to injectable media for ultrasonic echography in the form of microbubbles or microballoons comprising at least two biocompatible substances A and B (gaseous at the body temperature) forming a mixture which when in suspension with usual surfactants, additives and stabilisers provides useful ultrasound contrast agents. At least one of the components (B) in the mixture is a gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml per ml of water at standard conditions. The presence of the first component (B) in the contrast medium may vary between 0.5 and 41 volume percent. The other component (A) of the ultrasound contrast media is a gas or a mixture of gases whose molecular weight is below 80 daltons. The second component is present in a proportion of between 59-99.5% by vol., and is preferably chosen from oxygen, air, nitrogen, carbon dioxide or mixtures thereof.

Abstract: The invention provides, as contrast signal generators in MR imaging of the digestive tract, paramagnetic metal chelates of novel acrylic compounds of formula C(R.sup.1 R.sup.2).dbd.CR.sup.3 --CO--Z--A (1) and/or C(R.sup.1 R.sup.2).dbd.CR.sup.3 --O--Z--A--Z--CO--CR.sup.3 .dbd.C(R.sup.1 R.sup.2) (2) in monomer, oligomer, homopolymer and copolymer forms, in which the R.sup.1, R.sup.2 and R.sup.3 represent H or saturated or unsaturated C.sub.1-10 aliphatic radicals optionally substituted by one or more OH groups; Z is a covalent bond or a linker spacer and A is a moiety capable of fixing a paramagnetic metal by chelation. Compounds of type (1) useful in the present invention are, for instance the polyalkylene-aminopolycaboxylic acids such as NTA, EDTA, DTPA, DOTA and like structures, possibly involving additional substituents; an example is the compound BOPTA which is a DTPA derivative carrying a benzyloxypropyl group.

Abstract: The invention relates to the application of hyperpolarized gases to magnetic resonance imaging (MRI) of living subjects. The invention also concerns administrable compositions, formulations, methods of making the compositions and formulations and contrast agents involving hyperpolarized gases, as well as their use in MRI.

Abstract: The invention relates to a dry deposit as a precursor to liposome vesicles, the precursor being a three dimensional expanded structure with bulk density between 0.01 and 0.001 g/cm.sup.3. The invention also concerns a method of making liposome vesicles with an enhanced entrapment capacity by dissolving one or more film forming lipids in at least one organic solvent to form a solution in a reaction vessel, evaporating the solvent to form an expanded three dimensional porous lipid structure, contacting the lipid deposit with an aqueous carrier phase, and producing liposome vesicles entrapping the carrier phase as well as an apparatus comprising an array of tubing or an inert packing which serves as a material support or a matrix surface for the deposition of lipids produced according to the method.

Abstract: Disclosed are suspensions of gas microbubbles immobilised within a frozen aqueous carrier liquid comprising usual additives and stabilisers, in which the carrier liquid is a physiologically acceptable, the immobilised gas microbubbles are microbubbles bound by an evanescent envelope or a tangible membrane. The suspensions, when in liquid form, are injectable and useful as a contrast agents in ultrasonic imaging of blood pool and tissue of living beings. The gas microbubbles are immobilised within the carrier by freezing a suspension of microbubbles with average sizes below 50 .mu.m, preferably below 10 .mu.m and more preferably between 2 .mu.m and 8 .mu.m, to a temperature between -1.degree. C. and -76.degree. C. and maintaining this temperature for prolonged periods of time. The microbubbles may be stabilised by a surfactant such as a lamellar phospholipid or may comprise a membrane made of synthetic or natural polymer or protein.

Abstract: Administrable factors or compositions to be directed to specific sites in the body of human and animal patients which comprise a medically and/or diagnostically effective moiety (I) and, coupled thereto by means of a linker (L), a substance (II) having specific affinity for specific sites in the organism.Linker "L" has a structure schematized by the formula:Y(W-Z-R).sub.m, m being 1, 2, or 4wherein the portion YW is an amphiphile, i.e. a segment comprised of a hydrophobic-lipophilic sequence "Y" and a hydrophilic-lipophobic sequence "W" connected covalently together, Z is a chemical bond or an intermediate connector sequence and R is a reactive function for effecting coupling with selected substances (II).

Abstract: The invention relates to a dry deposit as a precursor to liposome vesicles, the precursor being a three dimensional expanded structure with bulk density between 0.01 and 0.001 g/cm.sup.3. The invention also concerns a method of making liposome vesicles with an enhanced entrapment capacity by dissolving one or more film forming lipids in at least one organic solvent to form a solution in a reaction vessel, evaporating the solvent to form an expanded three dimensional porous lipid structure, contacting the lipid deposit with an aqueous carrier phase, and producing liposome vesicles entrapping the carrier phase as well as an apparatus comprising an array of tubing or an inert packing which serves as a material support or a matrix surface for the deposition of lipids produced according to the method.

Abstract: The invention relates to non-ionic triiodo aromatic compounds and compositions comprising triiodo aromatic polymers useful for X-ray imaging of gastro-intestinal tract. Disclosed compounds are acrylic acid esters of triiodobenzenes with a different degree of reticulation and their polymers/homopolymers. A method of making the polymers, method of making X-ray contrast agents using the polymers and use of the contrast agents is also disclosed.

Abstract: The invention relates to injectable media for ultrasonic echography in the form of microbubbles or microballoons comprising at least two biocompatible substances A and B (gaseous at the body temperature) forming a mixture which when in suspension with usual surfactants, additives and stabilisers provides useful ultrasound contrast agents. At least one of the components (B) in the mixture is a gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml per ml of water at standard conditions. The presence of the first component (B) in the contrast medium may vary between 0.5 and 41 volume percent. The other component (A) of the ultrasound contrast media is a gas or a mixture of gases whose molecular weight is below 80 daltons. The second component is present in a proportion of between 59-99.5% by vol., and is preferably chosen from oxygen, air, nitrogen, carbon dioxide or mixtures thereof.

Abstract: The invention concerns NMR imaging contrast compositions comprising magnetically responsive species coupled to physiologically acceptable amphipatic organic substrate materials in the form of mixed micelles suspended or dispersed in a physiologically acceptable aqueous liquid carrier. The compositions are particularly useful for diagnostic investigations of the blood-pool. The invention also concerns the preparation of the mixed micelles, as well as of injectable compositions containing the mixed micelles as contrast agents for MRI purpose.Once injected, the mixed micelles of the compositions behave as imaging contrast enhancers, e.g. they will improve the quality and resolution of the electronically processed images obtained during MRI examinations of the circulation and/or circulation targeted organs.

Abstract: Disclosed are suspensions of gas microbubbles immobilised within a frozen aqueous carrier liquid comprising usual additives and stabilisers, in which the carrier liquid is a physiologically acceptable, the immobilised gas microbubbles are microbubbles bound by an evanescent envelope or a tangible membrane. The suspensions, when in liquid form, are injectable and useful as a contrast agents in ultrasonic imaging of blood pool and tissue of living beings. The gas microbubbles are immobilised within the carrier by freezing a suspension of microbubbles with average sizes below 50 .mu.m, preferably below 10 .mu.m and more preferably between 2 .mu.m and 8 .mu.m, to a temperature between -1.degree. C. and -76.degree. C. and maintaining this temperature for prolonged periods of time. The microbubbles may be stabilised by a surfactant such as a lamellar phospholipid or may comprise a membrane made of synthetic or natural polymer or protein.

Abstract: Disclosed are suspensions of gas microbubbles immobilised within a frozen aqueous carrier liquid comprising usual additives and stabilisers, in which the carrier liquid is a physiologically acceptable, the immobilised gas microbubbles are microbubbles bound by an evanescent envelope or a tangible membrane. The suspensions, when in liquid form, are injectable and useful as a contrast agents in ultrasonic imaging of blood pool and tissue of living beings. The gas microbubbles are immobilised within the carrier by freezing a suspension of microbubbles with average sizes below 50 .mu.m, preferably below 10 .mu.m and more preferably between 2 .mu.m and 8 .mu.m, to a temperature between -1.degree. C. and -76.degree. C. and maintaining this temperature for prolonged periods of time. The microbubbles may be stabilised by a surfactant such as a lamellar phospholipid or may comprise a membrane made of synthetic or natural polymer or protein.