Nycomed Imaging As

Nycomed Salutar, Inc.

Ge Healthcare As

Amersham Health As

Harald Dugstad

Jo Klaveness

Arne Berg

Torsten Almen

Roald Skurtveit

Pal Rongved

Pangl Rongved

Klaus D Krautwurst

Per Strande

Sook-Hui Kim

Klaes Golman

Lars-Goran Wistrand

Sven Goran Andersson

P&aring;l Rongved

Unni Nordby Wiggen

Tomas Klingstedt

Rune Fossheim

Scott M Rocklage

Alan D Watson

Michael Droege

Hakan Wikstrom

Jere D Fellman

Per Antonius Foss

Torsten Alm En

Brent Segal

Ib Luenbach

Oyvind Antonsen

Morten Eriksen

Ib Leunbach

Martha Garrity

Sigmund Frigstad

Lars Stubberud

Pål Rongved

Hanno Priebe

Shaun P Crofts

Audun Tornes

Joan F Carvalho

Jan Solberg

Trygve Gulbrandsen

Richard J Himmelsbach

Julian Cockbain

Terje Thomassen

Jorunn Undheim Braenden

Balin Balinov

Hangkan Wikstrom

Michel Gacek

David Johnson

Jorunn Br&aelig;nden

Jonny Østensen

Jorunn Brænden

C Allen Chang

O Slashedyvind Antonsen

Joseph Arukwe

Jan Alfheim

Inger Reidun Fjeldskaar Aukrust

Ultrasound contrast agents comprising microbubbles of biocompatible gas, e.g. a sulphur halide or a perfluorocarbon, stabilized by opsonisable amphiphilic material, e.g. a membrane-forming lipid such as a phospholipid, especially a negatively charged phospholipid such as a phosphatidylserine, may exhibit prolonged contrast-generating residence time in the liver following intravenous administration.

Contrast agents

This invention relates generally to non-ionic X-ray contrast agents. It further relates to the synthesis of iodixanol. In particular, it relates to alternative dimerisation reagents in the conversion of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide ('Compound A') to iodixanol.

Alternative dimerisation reagents for synthesis of iodixanol

The invention provides a method of contrast agent drug candidate selection which involves: (i) obtaining a combinatorial library comprising an admixture of potential contrast agent drug candidates each incorporating a reporter moiety which is detectable in the animate human or non-human animal body (e.g. mammalian, avian or reptilian body), said library comprising a plurality of said reporter moieties which are interdistinguishably detectable in said body; (ii) administering said library to an animate human or non-human animal body; (iii) identifying in vivo one or more of said reporter moieties which has a desired distribution and/or elimination pattern in said body and thereby identifying a member of said library which has said pattern site or a sub-set of said library which contains a member of said library which has said pattern.

Selection of contrast agent drug from a combinatorial library

The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula C,R,wherein three non-adjacent R groups are iodine and the remaining R groups are non-ionic, hydrophilic moieties, said compound being water soluble at 20&deg; C. to a concentration of at least 350 mgl/ml and which in aqueous solution at 20&deg; C. at a concentration of 350 mgl/ml has a viscosity no greater than 13.8 mPas.

Iodinated x-ray contrast media

Microparticulate contrast agents comprising gas or a gas precursor encapsulated by a non-polymeric and non-polymerisable wall-forming material are readily characterisable materials exhibiting surprising structural integrity and stability.

Dry microparticles for use as a contrast agent

Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful as efficacious contrast agents. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.

Microbubbles surrounded by a monolayer of negatively charged phospholipids as contrast agents

Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful both as efficacious contrast agents per se and as intermediates in the preparation of contrast agents wherein the phospholipids are crosslinked or polymerised. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.

Method of making lyophilized microbubble compositions useful as contrast agents

Ultrasound contrast agents having microbubbles of gas or a gas precursor encapsulated by non-proteinaceous crosslinked or polymerised amphiphilic moieties, e.g. in the form of micelles, exhibit good stability in vivo upon administration and may if desired incorporate biodegradable linkages so as to possess particular desired levels of biodegradability.

Microbubble-containing contrast agents having a non-proteinaceous

The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula I ##STR1## (wherein n is 0 or 1, and where n is 1 each C.sub.6 R.sub.5 moeity may be the same or different; each group R is a hydrogen atom, an iodine atom or a hydrophilic moiety M or M.sub.1, two or three non-adjacent R groups in each C.sub.6 R.sub.5 moiety being iodine and at least one, and preferably two or three, R groups in each C.sub.6 R.sub.5 moiety being M or M.sub.1 moieties; X denotes a bond or a group providing a 1 to 7 atom chain linking two C.sub.6 R.sub.5 moieties or, where n is 0, X denotes a group R; each M independently is a non-ionic hydrophilic moiety; and each M.sub.1 independently represents a C.sub.1-4 alkyl group substituted by at least one hydroxyl group and optionally linked to the phenyl ring via a carbonyl, sulphone or sulphoxide group, at least one R group being an M.sub.1 moiety; with the proviso that where n is zero either at least one M.sub.1 group other than a hydroxymethyl or 1,2-dihydroxyethyl group is present or then if one hydroxymethyl or 1,2-dihydroxyethyl M.sub.1 group is present at least one nitrogen-attached or hydroxylated-C.sub.3-4 alkyl moiety-containing M group is also present) and isomers thereof.

Contrast media

Novel extended polymer surfactants comprising a methoxy-terminated polyethylene glycol hydrophilic block acylated with a hydrophobic moiety comprising a chain of at least two fatty acid units, e.g. an acyloxyacyl group such as 16-hexadecanoyloxyhexadecanoyl, are useful in the preparation of polymer-based gas-containing contrast agents by emulsion techniques.

The present invention provides a polyethylene glycol (PEG) ester surfactant comprising at least one polyethylene glycol moiety and at least one fatty acyl moiety characterized in that said moieties are linked by a linkage incorporating a biodegradable methylene diester unit of formula (I)

Surfactants

Polychelants as contrast enhancing agents

An x-ray contrast medium containing a multinuclear complex of the formula (M.sub.6 (.mu..sub.3 B).sub.8 A.sub.v).sub.x L.sub.w, wherein M is Mo, W, Re Tc, V, Nb, Ta, Ru, or Fe; .mu..sub.3 B represent a tridentate bridging atom; A is a non-bridging atom; L is a ligand coordinately bonded to at least one M atom; x is a positive integer; and v and w are independently zero or positive integers.

Multinuclear complexes for X-ray imaging

Polymeric surfactant-encapsulated microbubbles and their use in

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Oslo, Norway

Harald Dugstad