Mallinckrodt Medical, Inc.

Mallinckrodt, Inc.

Youlin Lin

David H White

Mills T Kneller

Rebecca A Wallace

David M Wong

Thomas J Dunn

William Z McCarthy

Steven R Woulfe

William P Cacheris

Donald R VanDeripe

Mark E Bosworth

Richard G Johnson

Muthanadar P Periasamy

Warren E Hall

James R Wheatley

Richard T Dean

Robert W Weber

T Jeffrey Dunn

Kenneth R Smith

Lynn A deLearie

Narciso Ocampo Doran, Iii

Hybrid agents for enhancing in vivo diagnostic imaging of body organs and tissues, and methods of preparing and using the same.

Iodo-phenylated chelates for magnetic resonance imaging

Methods and compositions are disclosed for enhancing .sup.19 F magnetic resonance imaging which utilize trifluoromethyl derivatives of iodinated X-ray contrast media. Typical magnetic resonance contrast media within the scope of the present invention include bis(trifluoromethyl)benzene derivatives, tris(trifluoromethyl)benzene derivatives, tetrakis(trifluoromethyl)benzene derivatives, and other related trifluoromethylated benzene derivatives.

Trifluoromethyl analogs of X-ray contrast media for magnetic resonance

The use of a minimal excess of acetoxyacetylchloride as a reagent in the synthesis of N,N'-bis(2,3-dihydroxypropyl)-5-N-(2-hydroxy-ethyl)glycolamido-2,4,6-triio doisophthalamide.

Synthesis of ioversol using a minimal excess of acetoxyacetylchloride

X-ray contrast agents, compositions and methods

Iodo-phenylated chelates for x-ray contrast

Methods and compositions are disclosed for enhancing .sup.19 F magnetic resonance imaging which utilize trifluorometyl derivatives of iodinated X-ray contrast media. Typical magnetic resonance contrast media within the scope of the present invention include bis(trifluoromethyl)benzene derivatives, tris(trifluoromethyl)benzene derivatives, tetrakis(trifluoromethyl)benzene derivatives, and other related trifluoromethylated benzene derivatives.

Methods and compositions are disclosed for enhancing magnetic resonance imaging which utilize hydrophilic free radical compounds as magnetic resonance contrast media. Typical magnetic resonance contrast media within the scope of the present invention include stable hydrophilic free radicals having a hydrophilic moiety, such as polyhydroxyalkyl groups and heterocyclic amino-alcohols such as dihydroxypyrrolidine, dihydroxypiperidine, and trihydroxypiperidine, and a stable free radical moiety, such as a nitroxide, phenoxy, or phenoxazinyl free radical moiety.

Hydrophilic free radicals for magnetic resonance imaging

The use of azeotropic distillation to dry 5-amino-N,N'bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide, an intermediate in the production of N,N'-bis(2,3-dihydroxypropyl)-5-N-(2-hydroxyethyl)glycolamido-2,4,6-triiod oisophthalamide.

Use of azeotropic distillation in process to dry 5-amino-N,N'bis

The use of reverse osmosis as an alternative or substitute method for the purification of a crude diagnostic agent. X-ray contrast agent, magnetic resonance imaging agent, or radiopharmaceuticals are purified by passing through a cross-linked reverse osmosis membrane.

Purification of X-ray contrast agent, magnetic resonance imaging agent,

An improved process for the reversed phase chromatographic decolorization, separation, and purification of water-soluble, nonionic contrast media compounds from solutions containing nonionic compound impurities involves the steps of (a) packing a chromatographic column with a chromatographic packing material; (b) passing through the column a solution containing a water-soluble, nonionic contrast media compound and nonionic compounds as impurities at a loading ratio between approximately 10 to 1 and 1.5 to 1 wt. packing material/total wt. nonionic compounds; and (c) eluting the column to produce an eluate containing substantially pure, water-soluble, nonionic contrast media compound or MRI agent. The process can be economically practiced on a factory scale and efficiently removes non-polar impurities difficult to remove by conventional methods.

Reversed phase chromatographic process

Triiodinated isophthalamide derivatives, useful as X-ray contrast agents, having at least one amide group derived from the amino-alcohol, 3-(N-2-hydroxyethyl)amino-1,2-propanediol, which provides high water solubility and low mammalian toxicity, and methods of preparing them. Methods of preparing 3-(N-2-hydroxyethyl)amino-1,2-propanediol are provided.

Process for preparing nonionic X-ray contrast agents

The use of chloroacetylchloride as an alternative or substitute reagent for acetoxychloride in the synthesis of N,N'- bis (2,3-dihydroxypropyl)-5-N-(2-hydroxyethyl)glycolamido-2,4,6-triiodoisophth alamide.

Synthesis of ioversol using chloroacetyl chloride

The use of reverse osmosis as an alternative or substitute method for the purification of a crude diagnostic agent. In the purification process a crude Ioversol solution is contacted with a cross-linked membrane under pressure, forcing the low molecular weight impurities within the crude Ioversol solution through the membrane pores and retaining Ioversol molecules.

Purification of crude Ioversol using reverse osmosis

Nonionic X-ray contrast agents, compositions and methods

The compound N-(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl)-glycolamido]-N'-methyl-2,4,6 -triiodoisophthalamide and similar such compounds may be used as x-ray contrast agents which are water-soluble, safe and in an aqueous solution are non-viscous. Methods of preparing N-(2,3-dihydroxypropyl)-5-[N-(2-hdyroxyethyl)glycolamido]-N'-methyl-2,4,6- triiodoisophthalamide are provided.

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Chesterfield, MO, United States of America

Youlin Lin