Abstract: Infective aggregating forms of proteins such as PrP, amyloid, and tau are bound selectively in the presence of the normal form protein using a polyionic binding agent such as dextran sulphate or pentosan (anionic), or polyamine compounds such as pDADMAC (cationic) under selective binding conditions including the use of n-lauroylsarcosine at mildly alkaline pH, and may then be assayed.

Abstract: The invention provides improved methods and compositions for selectively binding and/or detecting an aggregating abnormal form of a protein in the presence of non-aggregating normal form of the protein.

Abstract: The invention relates to a dextran functionalized by at least one hydrophobic alpha-amino acid radical, said alpha-amino acid being grafted or bonded to the dextran by a bonding arm and a functional group. A hydrophobic amino acid radical is understood as being the product of coupling between the amine of the amino acid and an acid carried by the bonding arm, said dextran being amphiphilic at neutral pH. In an embodiment, the hydrophobic amino acid is selected from tryptophan derivatives, such as tryptophan, tryptophanol, tryptophanamide, 2-indole ethyl-amine and their alkaline cation salts. The present invention relates also to a pharmaceutical composition comprising one of the dextrans according to the invention.

Abstract: The present invention is related to a modified hydroxypolymer conjugates preferably a guanidine-dextran conjugate having a tumor cell killing activity. The modified hydroxypolymer conjugate is used as medicine, particularly for manufacturing a medicine or tumor killing composition for treating tumors. A method for producing said hydroxypolymer conjugate and a method for killing cancer cells and treating tumors is also disclosed. The invention is also related to a method for killing tumor cells and treating tumors by administering an effective amount of the modified hydroxypolymer conjugate.

Abstract: The present invention relates to improved methods for delivering bioadhesive, bioresorbable, anti-adhesion compositions. Antiadhesion compositions can be made of intermacromolecular complexes of carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, multivalent cations and/or polycations. The polymers are associated with each other, and are then used as fluids, gels or foams. By providing a product bag, the compositions can be delivered as gels or as sprays. By dissolving propellant gases in the compositions, the materials can be delivered as foams, which have decreased density, and therefore can adhere to surfaces that previously have been difficult to coat with antiadhesion gels. Delivery systems can also provide mechanisms for expelling more product, and for directing the flow of materials leaving the delivery system. Bioresorbable, bioadhesive, anti-adhesion, and/or hemostatic compositions are useful in surgery to prevent the formation and reformation of post-surgical adhesions.

Abstract: The invention concerns pharmaceutical compositions with wound healing or anti-complementary activity, and their uses, said compositions comprising, (1) at least a dextran derivative of general formula DMCaBbSuc, a, b, and c respectively representing the degrees of substitution in the groups MC, B and Su, wherein a?0.6, b=0 or ?0.1, and c=0 or ranges widely between 0.1 and 0.5 for a wound healing composition, and a?0.3, b?0.1 and c=0 or ranges widely between 0.1 and 0.4 for a composition with anti-complementary activity; (2) and at least a pharmaceutically acceptable carrier, said dextran derivative being present in a single unit dose or at a concentration adapted to the desired wound healing or anti-complementary activity.

Abstract: Pharmaceutical compositions containing C-21 modified epothilone derivatives, methods for their preparation and dosing regimen for administration of these epothilone compounds are provided. The compositions are stable and readily prepared for administration by dissolution in aqueous vehicles suitable for intravenous administration. A process for formulating C-21 modified epothilone derivatives for oral and parenteral administration is disclosed.

Abstract: The present invention provides a functionalized polymer which can be used extensively in the field of medical drugs as well as medical devices and which is obtainable in an organic synthetic manner from glycosaminoglycan controlling adhesion, migration and proliferation of cells via linkage to various cellular growth factors or cytokines or direct interactions with the cells. The functionalized polymer of the present invention is characterized in that it comprises a carbohydrate corresponding to at least a part of the basic structure of glycosaminoglycan introduced into a vinyl-type polymer chain.

Abstract: The present invention relates to folic acid-polysaccharide complexs and method of preparation thereof, more particularly relates to folic acid-Dextran complexs, method of preparation thereof, pharmaceutical compositions having said complex as active component and uses of said composition in therapy of tumors. The folic acid-polysaccharide complexs of the present invention have general formula of: (X)n—Y, wherein X is identical or different, and is selected from folic acid, derivatives of folic acid and other substances that can enter into cell via the pathway of folic acid receptor; Y is polysaccharide; n?1.

Abstract: Compounds that are modified polysaccharides having pendant aldehyde functionalities are disclosed. Each of the aldehyde functionalities is attached through a linker to a position corresponding to a hydrogen atom of a different hydroxyl group of unmodified polysaccharide. Also disclosed is a method for introducing an amine-reactive functionality into a dextran. The method comprises (a) reacting the dextran with an alkylating agent having a functionality that reacts with an hydroxyl group of the dextran thereby forming an alkylated dextran wherein the alkylating agent has an olefin group and (b) treating the alkylated dextran to convert the olefin group to an amine-reactive functionality. A polysaccharide can be conjugated to a biomolecule by carrying out the above method and reacting the amine-reactive functionality with an amine functionality on the biomolecule to produce polysaccharide conjugated to the biomolecule.

Abstract: The present invention relates to improved methods for making and using bioadhesive, bioresorbable, anti-adhesion compositions made of intermacromolecular complexes of carboxyl-containing polysaccharides, polyethers, polyacids, polyalkylene oxides, multivalent cations and/or polycations. The polymers are associated with each other, and are then either dried into membranes or sponges, or are used as fluids or microspheres. Bioresorbable, bioadhesive, anti-adhesion compositions are useful in surgery to prevent the formation and reformation of post-surgical adhesions. The compositions are designed to breakdown in-vivo, and thus be removed from the body. Membranes are inserted during surgery either dry or optionally after conditioning in aqueous solutions.

Abstract: A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C1-4)alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Abstract: Novel arylisothiocyanate compounds are described that are useful for activating alcohol-containing macromomolecules, for example polyethyleneglycols and cellulose, for covalent linkage to amino-groups of biomolecules, for example polypeptides such as antibodies, enzymes, and proteins.

Abstract: The present invention relates to the use of one or more non-digestible polysaccharides selected from the group consisting of dextrans having a molecular weight of 8 kD to 40,000 kD, hydrolysed (gluco)mannans having a molecular weight of 0.5 kD to 1,000 kD and hydrolysed (galacto) mannans having a molecular weigth of 0.5 kD to 1,000 kD for the preparation of a nutritional composition to reduce the uptake of high molecular weight substances, allergens and microorganisms through the intestinal wall, more particularly to reduce transport of high molecular weight substances, allergens and microorganisms through the tight junctions in the intestines, the rise in the viscosity of the nutritional composition caused by the polysaccharides being less than 20 mPa.s.

Abstract: The subject invention relates to a conjugate which may be used for the detection of an analyte in a test sample. In particular, the conjugate comprises a heterophilic carrier, at least 10 label groups, an analyte-specific binding pair member (e.g., an antibody or antigen with complexes with the antigen or antibody of interest, respectively) as well as a heterophilic linker which indirectly attaches the acridinium-containing compounds to the analyte-specific binding pair member.

Abstract: The invention is directed to an improvement in automated tissue staining system having evaporation inhibitor liquid covering the polynucleotide hybridization buffer-covered tissue on a slide, wherein the improvement comprises a polynucleotide hybridization buffer for in situ hybridization comprising a low molecular weight dextran sulfate having a molecular weight range from about 8,000 to about 16,000.

Abstract: The invention concerns dextran derivatives, their applications as medicines with specific biological action, and their preparation method. Said derivatives correspond to the general formula DMCaBbSUcSd, in which: D represents a polysaccharide chain, preferably consisting of sequences of glucoside units, MC represents methylcarboxylate groups, B represents carboxymethylbenzylamide groups, Su represents sulphate groups, S represents sulphonate groups, a, b, c and d represent the degree of substitution (ds), respectively in groups, MC, B, Su and S; a being equal to 0 or ≧0.3, b being equal to 0 or ≧0.1, c being equal to 0 or ≧0.1 and d being equal to 0 or ≧0.

Abstract: High-concentration aqueous solutions of amphoteric surfactants, in particular betaines and amine oxides, are prepared by adding a water-soluble carbohydrate, preferably cyclodextrins or dextrans.

Abstract: The present invention relates to folic acid-polysaccharide complexs and method of preparation thereof, more particularly relates to folic acid-Dextran complexs, method of preparation thereof, pharmaceutical compositions having said complex as active component and uses of said composition in therapy of tumors. The folic acid-polysaccharide complexs of the present invention have general formula of: (X)n—Y, wherein X is identical or different, and is selected from folic acid, derivatives of folic acid and other substances that can enter into cell via the pathway of folic acid receptor; Y is polysaccharide; n≧1.

Abstract: Disclosed is a method for preparing a malto-oligosaccharide derived glycoside. Generally, the method comprises providing a malto-oligosaccharide and glycosylating the malto-oligosaccharide with an alcohol or a thiol under conditions suitable to form a malto-oligosaccharide derived glycoside. Also disclosed is a method for preparing a mixture of malto-oligosaccharide derived glycosides by providing a mixture of malto-oligosaccharides and glycosylating the malto-oligosaccharides with an alcohol or a thiol under substantially anhydrous conditions to form a mixture of malto-oligosaccharide derived glycosides.

Abstract: Compounds that are modified polysaccharides having pendant aldehyde functionalities are disclosed. Each of the aldehyde functionalities is attached through a linker to a position corresponding to a hydrogen atom of a different hydroxyl group of unmodified polysaccharide. Also disclosed is a method for introducing an amine-reactive functionality into a dextran. The method comprises (a) reacting the dextran with an alkylating agent having a functionality that reacts with an hydroxyl group of the dextran thereby forming an alkylated dextran wherein the alkylating agent has an olefin group and (b) treating the alkylated dextran to convert the olefin group to an amine-reactive functionality. A polysaccharide can be conjugated to a biomolecule by carrying out the above method and reacting the amine-reactive functionality with an amine functionality on the biomolecule to produce polysaccharide conjugated to the biomolecule.

Abstract: Compounds that are modified polysaccharides having pendant aldehyde functionalities are disclosed. Each of the aldehyde functionalities is attached through a linker to a position corresponding to a hydrogen atom of a different hydroxyl group of unmodified polysaccharide. Also disclosed is a method for introducing an amine-reactive functionality into a dextran. The method comprises (a) reacting the dextran with an alkylating agent having a functionality that reacts with an hydroxyl group of the dextran thereby forming an alkylated dextran wherein the alkylating agent has an olefin group and (b) treating the alkylated dextran to convert the olefin group to an amine-reactive functionality. A polysaccharide can be conjugated to a biomolecule by carrying out the above method and reacting the amine-reactive functionality with an amine functionality on the biomolecule to produce polysaccharide conjugated to the biomolecule.

Abstract: 1.

Abstract: A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C1-4)alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized-in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Abstract: An aqueous phase inhibitor for quenching free radical polymerization comprising a free radical quenching agent having a hydrophilic tail is disclosed, as well as a coating and related methods. In one embodiment, the free radical quenching agent can either be an N-hydroxylamine or an N-nitrosonamine, the hydrophilic tail can be a polyhydric alcohol tail and the inhibitor can be a concentrate in a liquid medium such as water, alcohol and mixture thereof.

Abstract: The use of a gel produced by polymerization of a dextran derivative which exhibits groups that contain an alkene structure, for separating nucleic acid by electrophoresis.

Abstract: A method of modifying the binding properties on a surface of a solid phase on which there are nucleophilic groups, which is characterized in that the surface is treated with a solution of an activated polysaccharide; a method of immobilizing a chemical compound to a solid phase on which there are immobilized activated polysaccharides, whereby the chemical compound is contacted with the surface of the solid phase the binding properties of which are modified by the method according to the invention; an article which is characterized in that to the surface thereof an activated polysaccharide is fixated, such as activated dextran or activated agarose, and use of this article for use in solid phase reactions, in solid phase assay, solid phase peptide synthesis, solid phase nucleotide synthesis, solid phase enzyme processing, and joining of biological surfaces.

Abstract: The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery that anionic polymers effectively inhibit invasion of cells associated with detrimental healing processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion correlates with the anionic charge density of the polymer. Thus the present invention provides a large number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used.

Abstract: The invention relates to a process for the preparation of a fluorescent conjugate between a carrier molecule possessing at least one amino, hydroxyl, carboxyl and/or sulfhydryl group and a fluorophoric reagent possessing at least one functional group capable of reacting with said amino, hydroxyl, carboxyl and/or sulfhydryl group(s), which consists in bringing said carrier molecule and said fluorophoric reagent into contact with an aqueous solution of a water-soluble macrocycle.The invention further relates to the conjugates obtained by this process and to their use.

Abstract: New glucose-based surfactants and methods of their synthesis are described. The surfactants are synthesized through the preparation of an intermediate glucose 4,6-cyclic sulfate. The surfactants are economical to prepare and have excellent surface-active properties.

Abstract: Novel polysaccharide compounds are disclosed for decorating biomolecular surfaces to increase isotropic size and mask antigenicity. The oligosaccharides may be synthesized as repeating disaccharide units, or may be derived by acid hydrolysis of naturally occurring polysaccharides. Such natural sources include chondroitins obtained from shark cartilage, or hyaluronic acid. The polyanionic sulfate groups contained in the sugar moieties impart negative charges which repel the molecules from the negatively charged wall of capillaries, to lengthen retention times of decorated drug molecules, such as crosslinked hemoglobin, in the peripheral circulation.

Abstract: The invention relates to a process for the preparation of polysaccharide-N-arylcarbamates in suitable form as supports for chromatography, which process comprises adding to polysaccharide carbamates, which may be substituted in the aryl moiety, an N-aryl-1-lower-alkylcarbamate-containing solution of an organic solvent, with vigorous stirring, until the polysaccharide derivative is completely dissolved and then adding thereto an aqueous solution containing a high molecular weight surfactant and, with continued stirring, removing the organic solvent from the emulsion so obtained and isolating the solid particles and washing and drying them. The polysaccharide derivatives so obtained can be used as support materials for the chromatographic separation of enantiomers.

Abstract: Iodized polymers, comprising a skeleton consisting of a dextrane onto which are grafted groups of the formula (I). Application of the these compounds as contrast products.

Abstract: We have discovered that the stability of a dilute peroxidase-containing solution is greatly enhanced by the addition of a specific substrate for the peroxidase, in the absence of peroxide. We provide a peroxidase-containing reagent consisting of a buffered aqueous solution comprising a peroxidase or a peroxidase conjugate and a specific substrate for the peroxidase, in the absence of peroxide. The peroxidase may be a free peroxidase but for assay purposes is preferably a peroxidase bound to a specific binding component of an assay, to form a peroxidase conjugate. The peroxidase conjugate is preferably a conjugate between a peroxidase and an antigen or an antibody, most preferably an antibody. The peroxidase is preferably horseradish peroxidase.

Abstract: A method of preparing a tresyl-activated dextran is disclosed in which an aqueous solution of dissolved dextran is reacted with a tresylating agent in a hexamethylphosphoric triamide and/or N-methyl pyrrolidinone solvent, and the formed tresyl-activated dextran is recovered. A method of immobilizing a chemical compound to the surface of a solid phase having nucleophilic groups covalently bound or non-covalently bound is also disclosed, the method involving treating the surface with a solution of tresyl-activated dextran prepared as described above, and contacting the chemical compound with the treated surface. An article is also disclosed wherein tresy-activated dextran prepared as described above is fixed covalently to its surface.

Abstract: This invention provides novel methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antiviral and antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. In particular embodiments, the antimicrobial drug is covalently linked to a microparticle via an organic linker molecule which is the target of a microorganism-specific protein having enzymatic activity.

Abstract: The invention relates generally to colloidal particle having a core material and a gelatin/aminodextran coating with pendent functional groups attached thereto. Biological substances or molecules, especially monoclonal antibodies, may be attached to said particles. The monoclonal antibody containing particles are useful in a variety of positive and negative biological assays.

Abstract: Compositions useful for regenerating cells and tissues comprise at least one functionalized dextran which has been substituted with carboxymethyl, benzylamide, or benzylamide sulfonate. These dextrans can be used alone or in combination with acid or basic fibroblast growth factors to enhance tissue or cell regeneration. Additionally, these dextrans enhance the stability of acid or basic fibroblast growth factors.

Abstract: A process for producing a saccharide carboxylic acid or a salt thereof characterized in that a microorganism belonging to the genus Pseudogluconobacter and capable of oxidizing a hydroxymethyl group and/or hemiacetal hydroxyl-associated carbon atom to a carboxyl group, or an artifact derived from the microorganism, is permitted to act on a hydroxymethyl and/or hemiacetal hydroxyl-containing saccharide or saccharide derivative to produce and accumulate the corresponding carboxylic acid and the carboxylic acid so accumulated is harvested and novel saccharide carboxylic acids produced by the above production method, and by the process, from a broad range of saccharides, saccharic acids having carboxyl groups derived from hydroxymethyl and/or hemiacetal OH groups can be produced with high selectivity and in good yield, the resultant saccharide acids are resistant to enzymatic degradation and have improved water solubility, among other characteristics.

Abstract: A process for producing a saccharide carboxylic acid or a salt thereof characterized in that a microorganism belonging to the genus Pseudogluconobacter and capable of oxidizing a hydroxymethyl group and/or hemiacetal hydroxyl-associated carbon atom to a carboxyl group, or an artifact derived from the microorganism, is permitted to act on a hydroxymethyl and/or hemiacetal hydroxyl-containing saccharide or saccharide derivative to produce and accumulate the corresponding carboxylic acid and the carboxylic acid so accumulated is harvested and novel saccharide carboxylic acids produced by the above production method, and by the process, from a broad range of saccharides, saccharic acids having carboxyl groups derived from hydroxymethyl and/or hemiacetal OH groups can be produced with high selectivity and in good yield, the resultant saccharide acids are resistant to enzymatic degradation and have improved water solubility, among other characteristics.

Abstract: This invention provides novel methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. In particular embodiments, the antimicrobial drug is covalently linked to a microparticle via an organic linker molecule which is the target of a microorganism-specific protein having enzymatic activity.

Abstract: This invention herein describes a method of facilitating the entry of drugs into cells at pharmokinetically useful levels and also a method of targeting drugs to specific organelles within the cell. This lipid/drug conjugate targeting invention embodies an advance over other drug targeting methods because through this method, intracellular drug concentrations may reach levels which are orders of magnitude higher than those achieved otherwise. Furthermore, it refines the drug delivery process by allowing therapeutic agents to be directed to certain intracellular structures. This technology is appropriate for use with antiproliferative drugs, in particular in combination with a multiplicity of other emolients and agents to make up topically-active substances such as salves, for rapid and efficient introduction of antiproliferative agents through the epidermis for treatment of skin diseases such as psoriasis.

Abstract: This invention provides novel methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. In particular embodiments, the antimicrobial drug is covalently linked to a microparticle via an organic linker molecule which is the target of a microorganism-specific protein having enzymatic activity.

Abstract: A crosslinked, highly porous body derived from a water-soluble, hydrogel polymer, wherein the porous body is characterized in that it has an open-celled 3-dimensional lattice structure, a density of less than about 1.0 g/cm.sup.3 a surface area of equal to or greater than about 30 m.sup.2 /g, a compression strength of equal to or less than about 10% yield at 10 psi, and an average pore diameter of less than about 1000 Angstroms.When the hydrogel polymer used is guar gum, the resulting product is particularly useful for thermal insulation applications.

Abstract: Polysaccharides (e.g., dextran) of different molecular weights were substituted at the anomeric carbon with polyalkylene oxides of different molecular weights to give novel diblock copolymers. The copolymers inhibit bacterial aggregation. The copolymers are useful as antiplaque agents, as agents to prevent bacterial aggregation in an aqueous system or in a fermentation system.

Abstract: A radioactive diagnostic agent which comprises (1) the unit of a polyformyl compound having at least three formyl groups per molecule, (2) at least two units of an amino group-containing chelating compound bonded to the polyformyl compound with intervention of a methyleneimine linkage (--CH.dbd.N--) or a methyleneamine linkage (--CH.sub.2 NH--) formed by the condensation between the formyl group in the polyformyl compound and the amino group in the chelating compound, optionally followed by reduction, (3) at least one unit of an amino group-containing physiologically active substance bonded to the polyformyl compound with intervention of a methyleneimine linkage or a methyleneamine linkage formed by the condensation between the formyl group in the polyformyl compound and the amino group in the physiologically active substance, optionally followed by reduction, and (4) at least two radioactive metallic elements of which each is bonded to the chelating compound through a chelating bond.

Abstract: The present invention consists in a process for obtaining polymers with antiviral activity which is characterized in that beginning with oligo or polysaccharides with a specific structure, polymers with a specific number of carbonyl groups are obtained by oxidation; in that the carbonyl groups of the oxidized oligo/polysaccharides are made to react with amino groups of molecules carrying amino and sulfonated groups, such as aliphatic aminosulfonates, in water or in mixtures of water with water-miscible solvents, under specific temperature, time, and pH conditions, giving rise to polymers carrying sulfonated groups, which are purified by conventional processes; in that the sulfonated polymers thus obtained have antiviral activity and either lack or present very low toxicity and anticoagulant activity, and are thus suitable for the production of pharmaceutical preparations suitable for use in topical or systemic antiviral therapy in humans or in animals. It is applicable in the pharmaceutical industry.

Abstract: .sup.19 F labelled compounds are disclosed which are useful in methods of NMR imaging and spectroscopy. The compounds comprise a .sup.19 F-containing sensor moiety, and a transport polymer or substrate, and can optionally also comprise a spacer moiety to separate the sensor moiety and the transport polymer.

Abstract: To localize targets within the body (i.e., fixed intravascular antigens on emboli, neovascular endothelium, endothelium altered by regional inflammation) antibodies are linked via dextran spacer arms to rapidly cleared, Tc-99m labeled, microspheres. A micron-sized, albumin microsphere has been synthesized that is designed to enhance target surface interaction and to have a high antibody loading capacity. Stable, hydrophilic microspheres are produced from a pH dependent refolding of albumin followed by heat annealing. To couple dextran, the microspheres are derivatized with succinic anhydride and then linked via carbodiimide to succinic dihydrazide. After periodate oxidized dextran forms hydrazone linkages to the microspheres, additional dihydrazide coupled to the dextran spacer arm is used to link periodate oxidized IgG via its Fc domain carbohydrate. A milligram of the resulting 0.5-1.0 micron microspheres contains 50 to 350 ug of dextran and up to 10.sup.5 covalently bound IgG molecules per microsphere.

Abstract: There are provided paramagnetic compounds comprising a paramagnetic metal species chelated by a chelating moiety bound by an amide group to a linker group itself bound by an ester group to a macromolecule, wherein said linker group provides a carbon chain of at least 2 atoms between said amide group and said ester group. The novel compounds are particularly suitable as contrast agents, e.g. in magnetic resonance imaging.