Abstract: The present invention relates to X-ray examinations and to the improvement of patient safety during such. More specifically the invention relates to X-ray diagnostic compositions having low concentrations of iodine and an optimized amount of electrolytes. The invention further relates to methods of X-ray examinations wherein a body is administered with an X-ray diagnostic composition comprising a low concentration of iodine and irradiated with a radiation dose.

Abstract: The present invention relates to a process for the preparation of iodinated X-ray contrast agents and in particular to key intermediates thereof. More particularly, the invention relates to a work-up process for preparation of a compound mixture comprising 1-formylamino-3,5-bis(2,3-bis(formyloxy)propan-1-ylcarbamoyl)-2,4,6-trioodobenzene, a key intermediate in the process for preparing Ioforminol. Further, the invention relates to a process for preparing Ioforminol, a contrast agent useful in X-ray imaging.

Abstract: The present invention relates to a process for the preparation of Ioforminol, a contrast agent useful in X-ray imaging. More particularly, the invention relates to preparation of Ioforminol from a compound mixture comprising 1-formylamino-3,5-bis(2,3-bis(formyloxy)propan-1-ylcarbamoyl)-2,4,6-trioodobenzene by a process comprising in situ hydrolysis and a bis-alkylation.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing two linked iodinated phenyl groups of the general formula R—N(CHO)—X—N(R3)—R wherein X denoted an optionally substituted alkylene group, R3 denotes a hydrogen atom or an acyl function and each R denotes a triiodinated phenyl residue further substituted by hydrophilic moieties. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

Abstract: An alternative acetylation process for the synthesis of 5-acetamido-N,N?-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound A”), an intermediate in the industrial preparation of non-ionic X-ray contrast agents, is described. The process can be performed on an industrial scale to produce Compound A with improved purity and improved yields compared to the established processes.

Abstract: Biodegradable computed tomography (CT) contrast agents comprising a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide are described herein. The contrast agents can be used to image a tissue region by administering an effective amount of the biodegradable CT contrast agent to a subject, allowing a sufficient amount of time for the biodegradable CT contrast agent to enter the tissue region, and performing x-ray computed tomography imaging of the tissue region of the subject.

Abstract: Disclosed herein is an iodine-containing radial-shaped macromolecule suitable for an active ingredient of the computed tomography (CT) contrast medium, a method to prepare the same, and a contrast medium composition including the same. With respect to the iodine-containing radial-shaped macromolecule according to the present invention, the duration of contrast enhancement has been significantly improved in comparison to that of the current small molecular contrast media compounds containing iodine.

Abstract: Radio-opaque biodegradable compositions are formed by modifying terminal groups of synthetic and natural biodegradable polymers such as polylactones with iodinated moieties. The biodegradable property of the compositions renders them suitable for use in medical field such as drug delivery, imaging. Compounds disclosed in this invention exist as neat liquid. Certain compositions disclosed in this invention form hydrophobic iodine rich domains when dissolved in water, such domains provide better contrasting properties as well as ability to dissolve hydrophobic bioactive drugs. Certain iodinated moieties disclosed in the invention are capable of cross linking natural proteins in situ in presence of suitable catalysts and co-catalysts.

Abstract: The present invention relates to compositions and methods for treating diseases and disorders including cancer and various other angiogenic-dependent diseases, vascular malfunctions, arteriovenous malformations (AVM), hemorrhagic processes and treatment of pain, in particular tumor-related pain by drug delivery and/or therapeutic embolization using microspheres. More particularly the invention relates to microspheres containing non-ionic contrast agents, to compositions comprising these microspheres, as well as methods for preparing and using such compositions for embolization therapy. The invention further relates to compositions and methods using detectable microspheres for targeted drug delivery, irrespective of whether embolization is also needed.

Abstract: The invention describes a process for the purification of iodinated aryl compounds where the purification is performed by continuous crystallization of a crude product in a solvent with addition of anti-solvent. The continuous crystallization process is performed in one or more crystallizers at a temperature up to the boiling point of the content of the crystallizer.

Abstract: An improved synthesis method for preparation of iodixanol, and a purification process through macroporous adsorption resin chromatographic column and recrystallization are provided. The synthesis method relates to dimerization of 5-acetamido-N,N?-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide (compound A) to prepare iodixanol, wherein excessive side reactions such as alkylation are effectively inhibited by controlling the pH of the reaction mixture with a boron-containing acidic substance or salts thereof such as boric acid. In this way, the conversion rate of compound A to iodixanol is 85-90%. The iodixanol crude product is purified by a macroporous adsorption resin chromatographic column, obtaining iodixanol product with recovery of 90-95% and purity of 96-98%. The iodixanol crude product is recrystallized in mixed solvent containing 2-methoxyethanol, obtaining iodixanol product with recovery of 90-95% and purity of greater than 99%.

Abstract: The present invention relates to compositions and methods for treating diseases and disorders including cancer and various other angiogenic-dependent diseases, vascular malfunctions, arteriovenous malformations (AVM), hemorrhagic processes and treatment of pain, in particular tumor-related pain by drug delivery and/or therapeutic embolization using microspheres. More particularly the invention relates to microspheres containing non-ionic contrast agents, to compositions comprising these microspheres, as well as methods for preparing and using such compositions for embolization therapy. The invention further relates to compositions and methods using detectable microspheres for targeted drug delivery, irrespective of whether embolization is also needed.

Abstract: The present invention generally relates to nonionic x-ray contrast media formulations, radiological compositions containing such agents and methods for x-ray visualization utilizing such compositions. The invention especially relates to injectable radiological compositions for x-ray visualization comprising a pharmaceutically acceptable vehicle and a mixture of a monomer, being a triiodo-substituted benzene nucleus, and a dimer, being two linked triiodo-substituted benzene nuclei, such that the mixture demonstrates favorable properties.

Abstract: 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?-[(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.

Abstract: Apparatus and methods are described herein for a container with a unit dose of a concentrated substance that can be diluted and orally consumed using the container. In some embodiments, an apparatus includes a container body that defines an opening in fluid communication with an interior of the container body. A cap is coupled to the container body and encloses the opening. A unit dose of a concentrated medicament or a concentrated contrast agent is disposed within the interior of the container body. The unit dose of concentrated medicament or contrast agent can be diluted to a select dilution strength with a volume of a liquid receivable through the opening and within the interior of the container body. In some embodiments, the apparatus can include a barrier member in which the container body and cap can be disposed to protect the medicament or contrast agent from light and/or moisture.

Abstract: Apparatus and methods are described herein for a container with a unit dose of a concentrated substance that can be diluted and orally consumed using the container. In some embodiments, an apparatus includes a container body that defines an opening in fluid communication with an interior of the container body. A cap is coupled to the container body and encloses the opening. A unit dose of a concentrated medicament or a concentrated contrast agent is disposed within the interior of the container body. The unit dose of concentrated medicament or contrast agent can be diluted to a select dilution strength with a volume of a liquid receivable through the opening and within the interior of the container body. In some embodiments, the apparatus can include a barrier member in which the container body and cap can be disposed to protect the medicament or contrast agent from light and/or moisture.

Abstract: The present invention teaches a micro-porous injectable, soft elastic, fully resorbable fibrin-based composition for use as a soft tissue lumen and void filler. The composition of the present application exhibits physical characteristics, such as mechanical properties, typically seen in elastomers and mechanical stability, which is superior to fibrin alone. A variety of properties of the composition of the present invention can be effectively fine-tuned and altered by adjusting type and content of the particles as well as of the plasticizer contained in the void filler composition.

Abstract: A process for the manufacture of iodixanol by performing a purification process of the crude product in a solvent comprising 1-methoxy-2-propanol. The crude product may be obtained in aqueous solution from dimerization of 5-acetamido-N,N?-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide (“Compound A”).

Abstract: 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?-[(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.

Abstract: The present invention relates to X-ray examinations and to the improvement of patient safety during such. More specifically the invention relates to X-ray diagnostic compositions having ultra-low concentrations of iodine. The invention further relates to methods of X-ray examinations wherein a body is administered with an X-ray diagnostic composition and irradiated with a reduced radiation dose.

Abstract: The present invention relates to a novel process for preparing iopromide which is used as a contrast agent for X-ray, wherein 5-methoxyacetylamino-2,4,6-triiodoisophthalic acid (2,3-diacetoxypropyl)amide chloride of formula (19) and 5-methoxyacetylamino-2,4,6-triiodoisophthalic acid [(2,3-dihydroxy-N-methylpropyl)-(2,3-diacetoxypropyl)]diamide of formula (20) are introduced as intermediates, by which a bismer by-product generated during the preparation process can be removed even without an additional removal procedure and thus iopromide with high purity can be prepared in high yield.

Abstract: A process for the manufacture of iodixanol by performing a purification process of the crude product in a solvent comprising ethanol. The crude product may be obtained in aqueous solution from dimerisation of 5-acetamido-N,N?-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide (“Compound A”).

Abstract: The invention relates to a process for the preparation of a diagnostic X-ray composition. The composition comprises a non-ionic X-ray contrast agent in a pharmaceutically acceptable carrier. More particularly, the invention relates to a process for secondary production of X-ray compositions comprising X-ray contrast agents with a high dissolution temperature. When using the process of the invention, precipitation is avoided and degradation of the contrast agent is reduced. The process of the invention includes heat treatment of iodinated X-ray contrast agents at low pH.

Abstract: Compounds of formula (I) RA—CO—N(R2)—(CR12)n—N(R5)—RB and salts or optical active isomers thereof, wherein each R1 independently are the same or different and denotes a hydrogen atom, a hydroxyl group, a C1 to C4 straight of branched alkyl group or a C1 to C4 straight of branched oxyalkyl group; R2 denotes a hydrogen atom or a C1 to C4 straight of branched alkyl group; R5 independently are the same or different and denotes a acyl moiety; RA and RB independently are the same or different and denote a triiodinated phenyl group, preferably a 2,4,6-triiodinated phenyl group further substituted by two groups R3 in the 3 and 5 positions wherein each R3 are the same or different and denote a hydrogen atom or a non-ionic hydrophilic moiety, provided that at least one R3 group in the compound of formula (I) is a hydrophilic moiety; and n denotes a positive integer of 1 to 6.

Abstract: The present invention relates to compositions and methods for treating diseases and disorders including cancer and various other angiogenic-dependent diseases, vascular malfunctions, arteriovenous malformations (AVM), hemorrhagic processes and treatment of pain, in particular tumor-related pain by drug delivery and/or therapeutic embolization using microspheres. More particularly the invention relates to microspheres containing non-ionic contrast agents, to compositions comprising these microspheres, as well as methods for preparing and using such compositions for embolization therapy. The invention further relates to compositions and methods using detectable microspheres for targeted drug delivery, irrespective of whether embolization is also needed.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

Abstract: Compositions and methods for dual imaging and for dual chemotherapy and radiotherapy are disclosed. More particularly, the invention concerns compounds comprising the structure X1—Y—X2, wherein Y comprises two or more carbohydrate residues covalently attached to one another, X1 and X2 are diagnostic or therapeutic moieties covalently attached to Y, provided that when Y does not comprise a glucosamine residue, X1 and X2 are diagnostic moieties. The present invention also concerns methods of synthesis of these compounds, application of such compounds for dual imaging and treatment of hyperproliferative disease, and kits for preparing a radiolabeled therapeutic or diagnostic compound.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety containing amide functions allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety containing urea or urethane functions allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a hydrophilic aliphatic central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: Contrast media compositions comprising iodine containing contrast enhancing compounds of one or more monomeric non-ionic triiodinated aryl compounds and one or more dimeric non-ionic triiodinated aryl compounds. The bridge linking the two triiodinated aryl group of the dimeric compounds is substituted with a formyl function at least one nitrogen bridge atom.

Abstract: This invention relates to the manufacture of iodixanol (1,3-bis(acetamido)-N,N?-bis[3,5-bis (2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the purification of iodixanol by crystallization by using ultrasound.

Abstract: This invention relates to the manufacture of iodixanol(1,3-bis(acetamido)-N,N?-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the purification of iodixanol by crystallization by using wet milling.

Abstract: The present invention teaches a micro-porous injectable, soft elastic, fully resorbable fibrin-based composition for use as a soft tissue lumen and void filler. The composition of the present application exhibits physical characteristics, such as mechanical properties, typically seen in elastomers and mechanical stability, which is superior to fibrin alone. A variety of properties of the composition of the present invention can be effectively fine-tuned and altered by adjusting type and content of the particles as well as of the plasticizer contained in the void filler composition.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds.

Abstract: This invention relates generally to the preparation of non-ionic X-ray contrast agents, iohexyl, ioversol, and iodixanol. It further relates to a method for improving the purity of 5-amino-N,N?-bis(2,3-dihydroxypropyl)-isophthalamide (or ABA), an intermediate in the industrial preparation of these non-ionic X-ray contrast agents. In particular, it relates to a method for significantly removing ABA monomethylester and ABA dimer from ABA by hydrolyzing ABA under a pH between about 12 to about 13 in an aqueous medium to convert ABA monomethylester to ABA monoacid, before the iodination reaction of ABA.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing two linked iodinated phenyl groups of the general formula R—N(CHO)—X—N(R3)—R wherein X denoted an optionally substituted alkylene group, R3 denotes a hydrogen atom or an acyl function and each R denotes a triiodinated phenyl residue further substituted by hydrophilic moieties. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

Abstract: Compounds of formula (I) RA—CO—N(R2)—(CR12)n—N(R5)—RB and salts or optical active isomers thereof, wherein each R1 independently are the same or different and denotes a hydrogen atom, a hydroxyl group, a C1 to C4 straight of branched alkyl group or a C1 to C4 straight of branched oxyalkyl group; R2 denotes a hydrogen atom or a C1 to C4 straight of branched alkyl group; R5 independently are the same or different and denotes a acyl moiety; RA and RB independently are the same or different and denote a triiodinated phenyl group, preferably a 2,4,6-triiodinated phenyl group further substituted by two groups R3 in the 3 and 5 positions wherein each R3 are the same or different and denote a hydrogen atom or a non-ionic hydrophilic moiety, provided that at least one R3 group in the compound of formula (I) is a hydrophilic moiety; and n denotes a positive integer of 1 to 6.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing two linked iodinated phenyl groups of the general formula wherein each R1 independently are the same or different and denotes a hydrogen atom or a C1 to C4 straight of branched alkyl group; each R2 independently are the same or different and denotes a hydrogen atom or a C1 to C4 straight of branched alkyl group; and each R3, R4 and R5 independently are the same or different and denote C1 to C6 straight of branched alkyl moieties substituted by 1 to 6 —OH groups. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing two linked iodinated phenyl groups of the general formula and salts or optical active isomers thereof, wherein each of R1, R2 and R3 independently are the same or different and denote a hydrogen atom or a C1 to C4 straight of branched alkyl group; each R4 independently are the same or different and denote C1 to C6 straight of branched alkyl moieties substituted by up to 6 —OH groups; and each R5 independently are the same or different and denote C1 to C6 straight or branched alkyl moieties substituted by up to 6 —OH groups. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging, and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing two linked iodinated phenyl groups of the general formula (I) and salts or optical active isomers thereof, wherein each of R1, R2 and R3 independently are the same or different and denote a hydrogen atom or a C1 to C4 straight of branched alkyl group; each R4 independently are the same or different and denote C1 to C6 straight of branched alkyl moieties substituted by up to 6 —OH groups; and each R5 independently are the same or different and denote C1 to C6 straight of branched alkyl moieties substituted by up to 6 —OH groups provided that at least one alkyl group is substituted with at least 2 hydroxy groups.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a tris(aminoalkyl)amine group allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: 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.

Abstract: A process for the production of iohexol comprises alkylating 5-Acetamido-N,N?-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide using 2(2-methoxy-ethoxy)-ethanol as solvent in the presence of a base, and optionally isolating crude iohexol from the reaction mixture. Preferably, the alkylating agent is 1-chloro-2,3 propanediol and the base is an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide.

Abstract: The present invention relates to iodine containing compounds containing a central optionally substituted cyclohexane central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety containing amide functions allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Abstract: The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a hydrophilic aliphatic central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.