Mallinckrodt Medical, Inc.

Mallinckrodt, Inc.

Other

Liebel-flarsheim Company LLC

David H White

Mills T Kneller

Youlin Lin

Steven R Woulfe

Rebecca A Wallace

Dennis L Nosco

Edward A Deutsch

William P Cacheris

Robert G Wolfangel

Karen F Deutsch

William H Ralston

Janet B Wilking

Thomas J Dunn

Linda Meeh

Dennis A Moore

Allan R Bailey

Michelle M Jones

David M Wong

William Z McCarthy

Narciso Ocampo Doran, Iii

Muthunadar P Periasamy

T Jeffrey Dunn

Mark E Bosworth

Richard G Johnson

Lynn A deLearie

Warren E Hall

Alexander N Petrov

Oliver Egan

Milorad M Rogic

Fiona Rooney

Raghavan Rajagopalan

Richard T Dean

Robert W Weber

Michael J Gentilcore

Muthanadar P Periasamy

Max D Adams

Wayne H Lin

Anna K Fukunaga

Hung V Nguyen

Robert E Vandas

Derick L Kaspar

A process for the preparation of iosimenol comprising reacting 5,5'-[(1,3-dioxo-1,3-propanediyl)diimino]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] (C-VI) with a 3-halo-1,2-propanediol in an aqueous solvent. A process for the preparation of C-VI comprising reacting 3,3&#x2032;-[(1,3-dioxo-1,3-propanediyl)diimino]bis[5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride] (C-V) with 3-amino-1,2-propanediol in the presence of an inorganic base and a suitable non-aqueous polar solvent. A process for the preparation of C-V comprising reacting 3-amino-5-(aminocarbonyl)-2,4,6-triiodobenzoyl chloride (C-IV) with malonyl dichloride in a solvent comprising a suitable ester solvent, a suitable nitrile solvent or mixtures thereof.

Process for the preparation of iosimenol

A process for separating soluble silica species such as monomeric silicic acid (or monosilicic acid) and low molecular weight soluble polymeric silica from impure water soluble compounds by membrane nanofiltration is provided. A process for separating soluble silica species and colloidal silica from impure water soluble compounds by reverse phase liquid chromatography is also provided.

Removal of silica from water soluble compounds by nanofiltration and reverse phase chromatography

Process for producing ioversol

Treated apatite particles are disclosed for enhancing medical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging ('MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, gastrointestinal tract, or tissue disease states is obtained. Depending on the diagnostic imaging technique, apatite particles are treated to be paramagnetic, radiopaque, or echogenic. The apatite particles may also be fluorinated to form stable fluoroapatite compositions useful for .sup.19 F imaging. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the above-described apatite particles and then performing the medical diagnostic procedure.

Treated apatite particles for medical diagnostic imaging

The present invention discloses a new process for producing ioversol (marketed as OPTIRAY.RTM.) comprising:

Treated apatite particles are disclosed for enhancing radical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging ('MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, gastrointestinal tract, or tissue disease states is obtained. Depending on the diagnostic imaging technique, apatite particles are treated to be paramagnetic, radiopaque, or echogenic. The apatite particles may also be fluorinated to form stable fluoroapatite compositions useful for .sup.19 F imaging. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the abovedescribed apatite particles and then performing the medical diagnostic procedure.

Treated apatite particles for ultrasound imaging

Treated calcium/oxyanion-containing particles are disclosed for enhancing medical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging ('MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, or tissue disease states is obtained. Depending on the diagnostic imaging technique, calcium/oxyanion-containing particles are treated to be paramagnetic, radiopaque, or echogenic. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the above-described particles and then performing the medical diagnostic procedure.

Treated calcium/oxyanion-containing particles for medical diagnostic

The present invention provides new and structurally diverse compositions comprising compounds of the general formula: ##STR1## wherein A is N or CR.sub.1, R.sub.1 is hydrogen, C.sub.1 -C.sub.8 alkyl, or C.sub.6 -C.sub.10 aryl, where the alkyl or aryl group may be optionally substituted with one or more hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl, C.sub.1 -C.sub.8 alkoxy, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 hydroxyaryl, C.sub.6 -C.sub.10 aryloxy, --CO.sub.2 R.sub.2, --CONR.sub.3 R.sub.4, or NR.sub.3 R.sub.4 ; R.sub.2 -R.sub.7 are as defined within; g, h, i, j, k and m may be the same or different and are an integer from one to about six; X is --CO.sub.2 H, --PO.sub.3 H.sub.2, --SO.sub.3 H or --CONHOH. Methods for imaging including MRI, X-ray and radiation diagnosis using compositions of the invention are also provided.

Functionalized tripodal ligands for x-ray & radioactive imaging

Processes for manufacturing diethylenetriaminepentaacetic acid ('DTPA') bis(amide) magnetic resonance imaging ('MRI') agents are disclosed. Specifically, processes for manufacturing [N,N'-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N'-tri acetato]gadolinium(III) are disclosed.

Process for manufacturing DTPA-bis amide magnetic resonance imaging

Treated apatite particles are disclosed for enhancing medical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging (37 MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, gastrointestinal tract, or tissue disease states is obtained. Depending on the diagnostic imaging technique, apatite particles are treated to be paramagnetic, radiopaque, or echogenic. The apatite particles may also be fluorinated to form stable fluoroapatite compositions useful for .sup.19 F imaging. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the abovedescribed apatite particles and then performing the medical diagnostic procedure.

Treated apatite particles for x-ray diagnostic imaging

The present invention provides new and structurally diverse compositions for diagnostic imaging comprising compounds of the general formula: ##STR1## wherein A is N or CR.sub.1, R.sub.1 is hydrogen, C.sub.1 -C.sub.8 alkyl, or C.sub.6 -C.sub.10 aryl, where the alkyl or aryl group may be optionally substituted with one or more hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl, C.sub.1 -C.sub.8 alkoxy, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 hydroxyaryl, C.sub.6 -C.sub.10 aryloxy, --CO.sub.2 R.sub.2, --CONR.sub.3 R.sub.4, or NR.sub.3 R.sub.4 ; D is O, --O(CH.sub.2).sub.2 O--, --O(CH.sub.2).sub.3 O--, or NR.sub.5 ; E is O, --O(CH.sub.2).sub.2 O--, --O(CH.sub.2).sub.3 O-- or NR.sub.6 ; F is O, --O(CH.sub.2).sub.2 O--, --O(CH.sub.2).sub.3 O-- or NR.sub.7 ; R.sub.2 -R.sub.7 are as defined within; g, h, i, j, k and m may be the same or different and are an integer from one to about six; X is --CO.sub.2 H, --PO.sub.3 H.sub.2, --SO.sub.3 H or --CONHOH.

Functionalized tripodal ligands for imaging applications

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

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Ballwin, MO, United States of America

David H White