Sterling Winthrop Inc.

Nycomed Imaging As

Amersham Health As

Sanofi

David L Ladd

Robert A Snow

John L Toner

Gregory L McIntire

Denton W Hoyer

Julia S Tan

Kenneth Robert Hollister

Dennis E Butterfield

Dennis K Fujii

Carl R Illig

Edward R Bacon

Torgrim Engell

Jasbir Singh

Thomas J Caulfield

Anne Kjersti Fahlvik

Paul Mark Henrichs

Anne Naevestad

George C Na

Natarajan Rajagopalan

Christopher Black

Vinay Chandrakant Desai

K Robert Hollister

Kenneth Edmund Kellar

Wolfgang H Gunther

Jennifer Wellons

Michel Gacek

Dennis Fujii

Marshall Beeber

Peng Guo

Xin Peng

Brian Weekley

Kenneth Edmund Keller

George Na

Dong Wei

Barbara Yuan

Jack Stevens

Manohar Tukaram Saindane

Barbara O Yuan

The invention provides an improved process for the synthesis of compounds carrying at least one phosphate group, especially polyalkylene glycol phosphate compounds, said process comprising the steps of: (a) reacting a compound containing at least one primary alcohol moiety with a diaryl- or diaralkyl-halophosphate whereby to form the corresponding diaryl- or diaralkyl-phosphate ester; (b) reductively cleaving the resulting product; and (c) if desired, repeating steps (a) and (b) with the product of step (b) whereby to produce a compound carrying two or more phosphate groups. Advantages of the process in accordance with the invention are that this avoids the production of by-products and results in products which are low in impurities. Also provided are novel diaryl- and diaralkyl-phosphate ester compounds, in particular polyethylene glycol diphenylphosphate ester and derivatives thereof.

Process for the preparation of polyether phosphates

The invention relates to MR contrast media containing composite nanoparticles, preferably comprising a superparamagnetic iron oxide core provided with a coating comprising an oxidatively cleaved starch coating optionally together with a functionalized polyalkyleneoxide which serves to prolong blood residence.

Constrast media

A composition suitable for use in diagnostic imaging or as a cell killing agent comprising a chelating residue linked via an amide linkage to a poly(alkylene oxide) moiety, said compisition having a molecular weight of at least 4,500; ##STR1## wherein: Z is a chelating residue;

Segmented chelating polymers as imaging and therapeutic agents

Disclosed are linear and cross-linked polymers suitable for use as a contrast agent for magnetic resonance imaging containing units comprising the residue of a poly(amine) moiety linked to a chelating agent and to one or more pendant (poly)alkylene oxides.

Low viscosity chelating polymers for diagnostic imaging

This invention provides therapeutic and diagnostic imaging compositions and methods featuring a polymer comprising units containing a poly(alkylene oxide) moiety linked to the residue of a chelating agent, said polymer having a cytotoxic agent associated therewith.

Therapeutic and diagnostic imaging compositions and methods

This invention provides compositions useful in MR imaging comprising a polymer comprising units comprising the residue of a chelating agent linked to a poly(alkylene oxide) moiety, the polymer having a paramagetic metal ion associated therewith.

MR imaging compositions and methods

The invention provides polymeric polychelants containing polymer repeat units of formula �L--Ch--L--B! (where Ch is a polydentate chelant moiety; L is an amide or ester linkage; B is a hydrophobic group providing a carbon chain of at least 4 carbon atoms between the L linkages it interconnects) or a salt or chelate thereof, with the proviso that where Ch is 2,5-biscarboxymethyl-2,5-diazahex-1,6-diyl, the polychelant is metallated with lanthanide or manganese ions or B provides a carbon chain of at least 10 carbon atoms between the L linkages it interconnects and their salts and chelates. The paramagnetic polychelates of the polychelants of the invention have remarkably high R.sub.1 relaxivities.

Polymeric contrast agents for medical imaging

A composition suitable for use in diagnostic imaging or as a cell killing agent comprising a chelating residue linked via an amide linkage to a poly(alkylene oxide) moiety, said composition having a molecular weight of at least 4,500; ##STR1## wherein: Z is a chelating residue;

Disclosed are pharmaceutical compositions containing low diol polyethylene glycol, covalently attached to superoxide and dismutase process of making the compositions. Also disclosed is a method of treatment of disease processes associated with the adverse effects on tissue of superoxide anions, such as ischemic events, reperfusion injury, trauma and inflammation.

Low diol polyalkylene oxide biologically active proteinaceous substances

In accordance with this invention, there is provided a polymer comprising units comprising the residue of a chelating agent linked to a poly(alkylene oxide) moiety, and a method for the preparation thereof. The polymer is particularly useful in therapeutic and diagnostic imaging compositions and as an antistatic agent.

Chelating polymers

The present invention provides compounds of the formula ##STR1## chelated with a paramagnetic metal ion wherein Z1 and Z2 each represent the atoms necessary to complete a monocyclic or polycyclic carbocyclic or heterocyclic ring system, said Z1 and Z2 independently optionally substituted with R.sup.6 and R.sup.7, respectively; R.sup.l, R.sup.2, R.sup.3 and R.sup.4 are independently carboxyalkyl (C.sub.1 -C.sub.2), --(CH.sub.2).sub.n --C(.dbd.O)--NH--R.sup.8, or --(CH.sub.2).sub.n --C(.dbd.O)--O--R.sup.8 R.sup.5 is carboxyalkyl (C.sub.1 -C.sub.2); R.sup.6 and R.sup.7 are independently hydrogen, benzyl, or benzyloxy, said benzyl or benzyloxy optionally substituted with one, two or three substituents selected from the group consisting of amino, isocyanato (--N.dbd.C.dbd.O), isothiocyanato (--N.dbd.C.dbd.S), --NH--C(.dbd.O)--X or --NH--C(.dbd.S)--X; R.sup.8 is alkyl (C.sub.1 -C.sub.20), --(CH.sub.2).sub.m --Ar, or polyhydroxyalkyl (C.sub.1 -C.sub.20); n is 1 or 2; m is 1 to 15; X is a targeting moiety; and Ar is phenyl optionally substituted with one, two or three substituents selected from the group consisting of amino, acylamino, hydroxy, alkyl (C1-C5) and halogen.

Cyclic triamine chelating agents

A new class of polyalkylene oxide vinyl sulfone reagents is described. Also described are a method by which these reagents can be prepared as well as a method for using them in hydrated media for the modification of proteins. The novel polymer-to-protein conjugates made by reacting these reagents with proteins have advantages over similar conjugates prepared with prior art reagents in that they are more stable against hydrolysis and retain the positive charge carrying capacity at amine sites at which the modifying reagents are attached.

Vinyl sulfone coupling of polyoxyalkylenes to proteins

This invention discloses a composition comprised of nanoparticles having a purified polymeric surfactant as a surface modifier adsorbed on the surface thereof and a cloud point modifier associated therewith, which cloud point modifier is present in an amount sufficient to increase the cloud point of the surface modifier. Preferred purified polymeric surfactants are purified polyalkyleneoxide substituted ethylenediamine surfactants. A preferred cloud point modifier is polyethylene glycol. This invention further discloses a method of making nanoparticles having a purified polymeric surfactant as a surface modifier adsorbed on the surface and a cloud point modifier associated therewith, comprised of contacting said nanoparticles with the cloud point modifier for a time and under conditions sufficient to increase the cloud point of the surface modifier.

Use of purified surface modifiers to prevent particle aggregation during

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Wayne, PA, United States of America

David L Ladd