WO1995001966A1 - Iodinated oligomeric compounds and diagnostic compositions containing the same - Google Patents
Iodinated oligomeric compounds and diagnostic compositions containing the same Download PDFInfo
- Publication number
- WO1995001966A1 WO1995001966A1 PCT/EP1994/002111 EP9402111W WO9501966A1 WO 1995001966 A1 WO1995001966 A1 WO 1995001966A1 EP 9402111 W EP9402111 W EP 9402111W WO 9501966 A1 WO9501966 A1 WO 9501966A1
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- WO
- WIPO (PCT)
- Prior art keywords
- hydroxy
- amino
- tris
- ethyl
- formula
- Prior art date
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- 0 Cc1cc(*)cc(O)c1 Chemical compound Cc1cc(*)cc(O)c1 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/50—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0438—Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0442—Polymeric X-ray contrast-enhancing agent comprising a halogenated group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and at least three atoms of bromine or iodine, bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D255/00—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00
- C07D255/02—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00 not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
Definitions
- This invention refers to contrast agents particularly useful for X-ray diagnostic examinations of vascular system of the human and animal body.
- X-ray imaging is a diagnostic technique widely used to rapidly detect a series of anomalies and/or pathological conditions of living tissues.
- Present X-ray contrast media preferably contain, as opacifying molecules, polyiodinated neutral aromatic compounds.
- Opacifying formulations able to selectively or preferentially direct to organs such as, for instance, liver, kidneys, gall-bladder or endowed with the characteristic of remaining for a sufficiently long time in the cardiocirculatory system before dispersing into the extra-vascular space or being excreted, for instance due to glomerular filtration, will be positively hailed by those investigating on the pathologies of the above mentioned districts.
- the amount of active principle administered could be reduced, and at the same time it could be obtained the desired image enhancement and a decrease of possible toxic effects.
- contrast agents for the cardiovascular system are particularly requested.
- the contrast agents currently used show a quite unsatisfactory pharmacokinetic behaviour. After intravenous administration, they rapidly distribute in a volume, called central distribution volume, corresponding to plasma and interstitial fluid in open-fenestrae endothelial organs such as liver or kidneys. At a slower rate they distribute into extravascular tissues and structures with continuous endothelia, that's to say the remaining tissues except for brain. Contrast media are excreted through renal filtration from plasmatic region.
- the administered dosis to a human being is diluted in a volume of about 14 litres (central department) in less than 1 minute and its concentration further decreases in the following minutes due to diffusion in the remaining extracellular spaces, previously discussed.
- the opacifying agent is uniformly distributed in a total body volume of about 25 litres and its concentration keeps decreasing due to kidney elimination.
- emulsions we can mention: a) radiopaque liposomes, b) iodinated ester of seed oils, i.e. of poppy-flower (EOE-13), c) perfluoro derivatives such as perfluorooctyl bromide (PFOB) (see H.W. Fischer, Invest. Radiol., 25, Suppl. 1, S2-S6, 1990). None of these contrastographic fluids was able to efficiently solve the technical problem previously disclosed.
- PFOB perfluorooctyl bromide
- X-ray opaque contrast agents encapsulating liposomes i.e. diatrizoate
- X-ray opaque contrast agents encapsulating liposomes generally show a low encapsulating capacity and/or poor stability to sterilization.
- Iodinated esters b) are metabolised and eliminated quite rapidly by the organism (more than 95% in about 5 min) and in addition they resulted quite toxic involving a high number of side reactions (about 4%).
- perfluoro derivatives need very high dosages to produce the desired contrast in vascular structures.
- Iodinated polymers i.e. polymeric chains, such as polyvynil or polysaccharide chains, binding to their framework, aromatic molecules preferably triiodinated, are still under investigation.
- This invention refers to a new family of polyiodinated compounds which has been particularly useful for the solution of the previously discussed problems.
- polyiodinated aromatic derivatives can be covalently bound to that molecules.
- said molecules can be obtained by binding to the central nucleus, through successive levels, non-iodinated aromatic precursors and then by performing a iodination on the obtained intermediate: this procedure has the advantage of using a total lower amount of toxic reagents in a terminal phase, in such way involving a better industrial exploitation and a more favourable environmental impact.
- Polyiodinated oligomers are produced endowed with high opacifying properties, good tolerability and well-defined molecular weight.
- the oligomer size can be increased through successive synthetic steps, thus spotting the corresponding ideal diagnostic application.
- some ionic species for instance iodinated aromatic nuclei with one or more free carboxylic or phenolic functions, these can be salified with a physiologically tolerable organic base preferably selected from primary, secondary or tertiary amines, or basic amino acids.
- Preferred organic bases can be for instance selected from ethanolamine, diethanolamine, morpholine, glucamine, N-methyl-glucamine, N,N-dimethyl-glucamine, lysine, arginine, ornithine.
- Salifying agents equally preferred are selected from physiologically tolerable inorganic bases, in particular those with alkali metal cations, such as lithium, potassium and sodium.
- oligomer central nucleus include a structure with chelating properties with regards to bi- or trivalent metal ions
- this property can be used to prepare chelates of oligomers with metal ions of atomic number included between 20 and 31, 39, between 42 and 44, 49 and between 57 and 83, preferably with paramagnetic metal ions such as Fe(2+), Cu(2+), Mn(2+), Fe(3+), Gd(3+), Dy(3+), Yb(3+), Eu(3+).
- 1 is an integer from 2 to 20
- n 1 to 100
- n is an integer from 0 to 2
- A is an organic core, which can be aliphatic, heterocyclic or aromatic and carries 2 to 20 groups B, as hereinbelow defined, or 2 to 20 organic residues ending with B,
- B is a single bond or a group selected from -CO-, - N(R)CO-, -CON(R)-, _N(Rl)-, -NHCO-O-, -NH-CO-NH-,
- R is H, or a straight or branched (C 1 -C 6 ) alkyl residue, or a straight or branched (C 1 -C 6 ) hydroxyalkyl residue with 1 to 5 -OH groups,
- R 1 is R or a -COR 2 group, wherein R 2 is a straight or branched (C 1 -C 6 ) alkyl residue, or a straight or branched (C 1 -C 6 ) hydroxyalkyl residue with 1 to 5
- A, B and 1 are as previously defined and
- L is a group of general formula (II)
- P and Q which are the same or different, are one of the groups -CON(R)R 3 , -N(R)-CO-R 4 , -O-X wherein
- R 3 is H, or a straight or branched (C 1 -C 6 ) alkyl residue, or a straight or branched (C 1 -C 6 ) hydroxyalkyl residue with 1-5 OH groups,
- R 4 is a cyclic or acyclic, straight or branched (C 1 - C 20 ) residue, interrupted or not by -O-, -N-, -P-, -S- or by imino, aryl, heteroaryl groups and/or with 1 to 6 hydroxy, alkoxy, amino, oxo, aryl, alkylaryl, heteroaryl groups,
- X is a negative charge, or H, or a -CH 2 -CO-Y group, where Y is one of the residues -O-R 5 or -N(R)R 3 , where R and R 3 are as previously defined and R 5 is a negative charge, or H, or a straight or branched (C 1 -C 6 ) alkyl residue, or straight or branched
- G is H, -CH 3 or -CH 2 -CH 3 ,
- A,B,l and m are as above defined, and
- L is a group of formula (II) as above defined, with the proviso that one of the two groups P and Q corresponds to an -E-F- residue wherein
- E is one the groups -N(R)-CO-, -CO-N(R)-, -O-, wherein R is as above defined, and
- F is a straight or branched (C 1 -C 20 ) residue, which is interrupted or not by -O-, -S-, -P-, -N(R 6 )- groups, being R 6 a residue R as above defined, or a -CO-R 7 group wherein R 7 is a straight or branched (C 1 -C 6 ) alkyl with 1-6 OH groups or which can carry from 1 to 6 substituents such as hydroxy, alkoxy, amino, oxo, aryl, heteroaryl groups, being F further characterized by a terminal group selected from -CO-, -O-, -N(R 6 )-, _ CO-N(R)-, -N(R)CO-, ureido, urethane, being R and
- M is a repetition unity, which can have different meanings for each unity, of general formula (III)
- P 1 and Q 1 are the same as P and Q as above defined, or one or both of them are an -E-F- residue as above defined, being each M group linked to the previous one through the terminal group of an F residue of the same, or through an ether bond in case said previous group contains hydroxy functions,
- A,B,M,l and m are as above defined, and
- L is a group of formula (II) in which both P and Q correspond to an -E-F- residue as above defined.
- this invention also include the salts of said compounds with physiologically acceptable organic bases selected from primary, secondary and tertiary amines or basic amino acids or inorganic bases whose cations are sodium, potassium, magnesium, calcium or their mixtures.
- this invention also include chelate complexes of said compounds with metal ions of elements having atomic number included between 20-31, 39, 42-44, 49 and 57-83.
- the organic core A can be derived from one of the following compounds:
- precursors, or derivatives of all iodinated contrast media known in the state of the art, ionic and non- ionic, monomers, dimers and trimers, can be used, of course modified with suitable reactive groups well known to the skilled chemist.
- a highly selective and opacifying contrastographic composition can be prepared and administered to patients, in which composition the active ingredient/s has/have well-defined structures and iodine content.
- the dosage of the opacifying material results to be completely reproducible.
- the compounds of formula (I) are extremely interesting because of their capability of remaining in plasma for a very long period. Their retention time values in plasma are quite similar, if not even higher, to those disclosed by Doucet et al., Invest. Radiol., 1991, for dextrane-based iodinated polymers.
- compound 22 (described in Example 20), i.e. 3,3',3"-[(hexahydro-1H-1,4,7-triazonin-1,4,7-triyl)tricarbonyl]tris[[[(5-hydroxy-2,4,6-triiodo-3,1-phenylene)carbonyl]amino]methyl]tris[5-(acetylamino)-N-[2-hydroxy-1-(hydroxymethyl)ethyl]]-2,4,6-triiodobenzamide], showed a retention time value in plasma, in rats, of 300 min, at a dosage of 100 ngl/kg.
- the temperature is gradually raised to 40oC and kept constant during 48 h.
- the solvent is evaporated under reduced pressure and the residue is treated with three 250 ml portions of CH 2 Cl 2 to give a solid which is dissolved in 350 ml of a H 2 O/MeOH - 4/1 solution.
- the solution is adjusted to pH 10.3 and kept at this value by addition of 71 ml of IN sodium hydroxide (0.071 mol) during 2 h at 45°C. Then the aqueous solution is neutralized at pH 7 with 37% HCl then evaporated to dryness.
- the crude residue is dissolved in 30 ml of H 2 O and percolated through Amberlite ® IR 120 and on Duolite ® A 30 B.
- the eluate is concentrated to obtain a residue which is chromatographed on silica gel. In this way, two main products are obtained, which are then purified by percolating them first through Amberlit IR 120, then through Duolite ® A 30 B.
- concentration of the eluate 3.2 g of compound (a) (0.0015 mol) and
- This product is obtained according to well-known methods by monosaponification of the corresponding di- methyl ester with sodium hydroxide.
- the chromatographic analysis is performed by transforming methyl 3-(chlorocarbonyl)-5-hydroxybenzoate into the corresponding methyl ester by reaction with a 3% MeOH solution, which is sprayed on the plate, after 30 min at R.T..
- a solution of 8 g of compound B) (0.0357 mol) in 35 ml of CHCl 3 and 15 ml of dimethylacetamide (DMA) is dropwise added to a solution of 1.54 g of octahydro-1H-1,4,7-triazonine (0.0112 mol) and 3.6 g of TEA (0.0357 mol) in 47 ml of CHCl 3 , under nitrogen atmosphere and at a temperature of 7-10°C. After 30 min at the same temperature and one night at 25°C, the solvent is evaporated under reduced pressure.
- DMA dimethylacetamide
- the product was prepared by reacting 3,3',3''-[(hexahydro-1H-1,4,7-triazonin-1,4,7-triyl)tri ⁇ carbonyl]tris[N-[2-hydroxy-1-(hydroxymethyl)ethyl]-5-hydroxy-2,4,6-triiodobenzamide] (prepared according to Example 2) with NaOH at pH 8. The solvent was evaporated and the residue was directly used in the successive step without any further purification.
- the mixture is heated to 50°C for 45 h and at 90oC for 47 h. After cooling the solvent is evaporated under reduced pressure.
- the crude residue is treated with five 100 ml portions of CH 2 Cl 2 giving a solid which is filtered and dissolved in 50 ml of H 2 O.
- the aqueous solution is percolated through Amberlite ® IR 120 and Duolite ® A 30 B. The eluate is concentrated to obtain a residue, which is crystallised from abs. EtOH.
- the precipitated TEA hydrochloride is filtered off and washed three times with 10 ml portions of AcOEt. Filtrates are collected, washed with 30 ml of H 2 O, 20 ml of 2N HCl and then with H 2 O to neutrality. The organic layer is evaporated to dryness to give a dense oil which is directly used in the successive step without any further purification. 25 g (0.047 mol) of compound A) are obtained.
- Example 3 (0.0049 mol) in 100 ml of DMA, 3.75 g of methyl bromoacetate (0.0240 mol) are added and the mixture is heated to 60°C during 2 h. After cooling, the solvent is evaporated under reduced pressure and an oily residue is obtained which solidifies by treatment with 100 ml of H 2 O. The precipitate is filtered and purified by silica gel chromatography to give 4.09 g
- the precipitate is filtered, which is constituted by triethylammonium chloride and sodium chloride.
- the filtrate is treated with 600 ml of AcOEt to give a solid which is filtered and dissolved in 100 ml of H 2 O.
- the solution is heated to 35°C, pH is adjusted to 12.5 by addition of 55 ml of 2N NaOH and pH is kept constant during 10 h by addition of further 55 ml of 2N NaOH.
- the filtrate is treated with 300 ml of AcOEt to give a solid which is filtered and dissolved in 75 ml of H 2 O.
- the solution is heated to 40°C, pH is adjusted to 10 and kept constant during 18 h by addition of 26.5 ml of 2N NaOH.
- the aqueous solution is percolated through Amberlite ® IR 120 and Duolite ® A 30 B. By concentration of the eluate, 2 g (0.00061 mol) of the title compound are obtained.
- a solution of 22.81 g of methyl 3-(chlorocarbonyl)-5-hydroxybenzoate (prepared according to Example 2) (0.104 mol) in 100 ml of CHCl 3 and 40 ml of DMA is dropwise added to a solution of 3.37 g of 2,2-bis(aminomethyl)-1,3-propanediamine (prepared according to Hodkin J.H., Heller J., J. Macromol. Sci. Chem. A3, 1969, 1067-1086) (0.0245 mol) and of 10.53 g of TEA (0.104 mol) in 80 ml of CHCl 3 , at a temperature of 0-5°C and under nitrogen atmosphere. The mixture is kept at 20°C during 16 h.
- the temperature is gradually increased up to 40°C and kept constant during 18 h.
- the solvent is evaporated under reduced pressure and the residue is diluted with CH 2 Cl 2 portions, to precipitate a solid, which is then filtered.
- the crude is dissolved in 200 ml of H 2 O:MeOH - 2:1.
- the solution pH is adjusted to 10.5 with 20 ml of sodium hydroxide 2N and then heated to 40oC during 4 h.
- the aqueous solution is concentrated under reduced pressure and percolated through Amberlite ® IR 120 Duolite ® A 30 B. By concentration of the eluate a residue of 22 g is obtained, then is purified on silica gel column to give 6.38 g (0.00219 mol) of the title compound.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP94920471A EP0707572A1 (en) | 1993-07-08 | 1994-06-29 | Iodinated oligomeric compounds and diagnostic compositions containing the same |
AU71251/94A AU7125194A (en) | 1993-07-08 | 1994-06-29 | Iodinated oligomeric compounds and diagnostic compositions containing the same |
JP7503801A JPH08512297A (en) | 1993-07-08 | 1994-06-29 | Iodinated oligomeric compound and diagnostic composition containing the same |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI93A001479 | 1993-07-08 | ||
IT93MI001479A IT1264690B1 (en) | 1993-07-08 | 1993-07-08 | IODURATED OLIGOMER COMPOSITES AND DIAGNOSTIC COMPOSITIONS CONTAINING THE SAME |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1995001966A1 true WO1995001966A1 (en) | 1995-01-19 |
Family
ID=11366554
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1994/002111 WO1995001966A1 (en) | 1993-07-08 | 1994-06-29 | Iodinated oligomeric compounds and diagnostic compositions containing the same |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0707572A1 (en) |
JP (1) | JPH08512297A (en) |
AU (1) | AU7125194A (en) |
IL (1) | IL110249A0 (en) |
IS (1) | IS4189A (en) |
IT (1) | IT1264690B1 (en) |
WO (1) | WO1995001966A1 (en) |
ZA (1) | ZA944923B (en) |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996009280A1 (en) * | 1994-09-22 | 1996-03-28 | Guerbet S.A. | Polyiodinated compounds, preparation and use thereof in x-ray radiology |
WO1996009281A1 (en) * | 1994-09-22 | 1996-03-28 | Guerbet S.A. | Iodinated derivatives, preparation and use thereof as contrast agents in x-ray radiology |
US5663413A (en) * | 1994-12-01 | 1997-09-02 | Dibra S.P.A. | Biphenyl iodinated derivatives and their diagnostic use |
DE19740403A1 (en) * | 1997-09-09 | 1999-03-11 | Schering Ag | New tri:iodo-phenyl compounds used in diagnosis and therapy |
EP1549322A2 (en) * | 2002-05-09 | 2005-07-06 | Biomira, Inc. | Lipid a and other carbohydrate ligand analogs |
EP1792894A2 (en) * | 2005-12-02 | 2007-06-06 | GE Healthcare AS | Contrast agents |
WO2007094680A1 (en) * | 2006-02-14 | 2007-08-23 | Ge Healhcare As | Contrast agents |
WO2007094677A1 (en) | 2006-02-14 | 2007-08-23 | Ge Healthcare As | Contrast agents |
WO2007094683A1 (en) | 2006-02-15 | 2007-08-23 | Ge Healthcare As | Contrast agents |
WO2007133090A1 (en) * | 2006-05-11 | 2007-11-22 | Ge Healthcare As | Contrast agents |
WO2007133088A1 (en) * | 2006-05-11 | 2007-11-22 | Ge Healthcare As | Contrast agents |
WO2008123779A1 (en) * | 2007-04-04 | 2008-10-16 | Ge Healthcare As | Trisubstituted triazamacrocycli c compounds and their use as contrast agents |
WO2009005364A1 (en) * | 2007-06-29 | 2009-01-08 | Ge Healthcare As | Contrast agents |
WO2009047319A1 (en) * | 2007-10-12 | 2009-04-16 | Ge Healthcare As | Contrast agents |
US7662859B2 (en) | 2007-02-16 | 2010-02-16 | Ge Healthcare As | Contrast agents |
US8329639B2 (en) | 2011-02-24 | 2012-12-11 | Oncothyreon Inc. | MUC1 based glycolipopeptide vaccine with adjuvant |
CN106928087A (en) * | 2017-03-13 | 2017-07-07 | 牡丹江医学院 | A kind of CT gastrointestinal tract contrast mediums and its application |
US10137209B2 (en) | 2015-06-04 | 2018-11-27 | Bayer Pharma Aktiengesellschaft | Gadolinium chelate compounds for use in magnetic resonance imaging |
WO2022129508A1 (en) * | 2020-12-18 | 2022-06-23 | Justesa Imagen S.A.U. | Organometallic compounds and their use as multimodal contrast media for diagnostic imaging |
US11814369B2 (en) | 2016-11-28 | 2023-11-14 | Bayer Pharma Aktiengesellschaft | High relaxivity gadolinium chelate compounds for use in magnetic resonance imaging |
US11944690B2 (en) | 2018-11-23 | 2024-04-02 | Bayer Aktiengesellschaft | Formulation of contrast media and process of preparation thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4062934A (en) * | 1975-06-04 | 1977-12-13 | Laboratoires Andre Guerbet | X-ray contrast media |
US4065554A (en) * | 1974-05-31 | 1977-12-27 | Laboratoires Andre Guerbet | X-ray contrast media |
US5019371A (en) * | 1990-11-21 | 1991-05-28 | Mallinckrodt Medical, Inc. | Novel x-ray contrast agents, compositions and methods |
WO1992004919A1 (en) * | 1990-09-13 | 1992-04-02 | Mallinckrodt Medical, Inc. | Novel magnetic resonance imaging agents |
-
1993
- 1993-07-08 IT IT93MI001479A patent/IT1264690B1/en active IP Right Grant
-
1994
- 1994-06-29 JP JP7503801A patent/JPH08512297A/en active Pending
- 1994-06-29 WO PCT/EP1994/002111 patent/WO1995001966A1/en not_active Application Discontinuation
- 1994-06-29 EP EP94920471A patent/EP0707572A1/en not_active Withdrawn
- 1994-06-29 AU AU71251/94A patent/AU7125194A/en not_active Abandoned
- 1994-07-07 IL IL11024994A patent/IL110249A0/en unknown
- 1994-07-07 ZA ZA944923A patent/ZA944923B/en unknown
- 1994-07-07 IS IS4189A patent/IS4189A/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4065554A (en) * | 1974-05-31 | 1977-12-27 | Laboratoires Andre Guerbet | X-ray contrast media |
US4062934A (en) * | 1975-06-04 | 1977-12-13 | Laboratoires Andre Guerbet | X-ray contrast media |
WO1992004919A1 (en) * | 1990-09-13 | 1992-04-02 | Mallinckrodt Medical, Inc. | Novel magnetic resonance imaging agents |
US5019371A (en) * | 1990-11-21 | 1991-05-28 | Mallinckrodt Medical, Inc. | Novel x-ray contrast agents, compositions and methods |
Non-Patent Citations (1)
Title |
---|
E. FELDER ET AL, IL FARMACO, vol. 32, no. 11, 1977, pages 835 - 844 * |
Cited By (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996009280A1 (en) * | 1994-09-22 | 1996-03-28 | Guerbet S.A. | Polyiodinated compounds, preparation and use thereof in x-ray radiology |
WO1996009281A1 (en) * | 1994-09-22 | 1996-03-28 | Guerbet S.A. | Iodinated derivatives, preparation and use thereof as contrast agents in x-ray radiology |
US5709846A (en) * | 1994-09-22 | 1998-01-20 | Guerbet S.A. | Iodinated derivatives, their preparation and their use as contrast agents in x-ray radiology |
US5851511A (en) * | 1994-09-22 | 1998-12-22 | Guerbet S.A. | Polyiodo compounds, their preparation and their use in X-ray radiology |
US5663413A (en) * | 1994-12-01 | 1997-09-02 | Dibra S.P.A. | Biphenyl iodinated derivatives and their diagnostic use |
DE19740403A1 (en) * | 1997-09-09 | 1999-03-11 | Schering Ag | New tri:iodo-phenyl compounds used in diagnosis and therapy |
DE19740403C2 (en) * | 1997-09-09 | 1999-11-11 | Schering Ag | New contrast media |
EP1549322A2 (en) * | 2002-05-09 | 2005-07-06 | Biomira, Inc. | Lipid a and other carbohydrate ligand analogs |
EP1549322A4 (en) * | 2002-05-09 | 2006-07-26 | Biomira Inc | Lipid a and other carbohydrate ligand analogs |
US8097593B1 (en) | 2002-05-09 | 2012-01-17 | Oncothyreon Inc. | Lipid A and other carbohydrate ligand analogs |
US7820627B2 (en) | 2002-05-09 | 2010-10-26 | Oncothyreon Inc. | Lipid A and other carbohydrate ligand analogs |
US7485753B2 (en) | 2005-12-02 | 2009-02-03 | Ge Healthcare As | Contrast agents |
EP1792894A3 (en) * | 2005-12-02 | 2007-08-15 | GE Healthcare AS | Contrast agents |
EP1792894A2 (en) * | 2005-12-02 | 2007-06-06 | GE Healthcare AS | Contrast agents |
US8071811B2 (en) | 2006-02-14 | 2011-12-06 | Ge Healthcare As | Contrast agents |
WO2007094677A1 (en) | 2006-02-14 | 2007-08-23 | Ge Healthcare As | Contrast agents |
WO2007094680A1 (en) * | 2006-02-14 | 2007-08-23 | Ge Healhcare As | Contrast agents |
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Also Published As
Publication number | Publication date |
---|---|
IT1264690B1 (en) | 1996-10-04 |
ITMI931479A0 (en) | 1993-07-08 |
AU7125194A (en) | 1995-02-06 |
IL110249A0 (en) | 1994-10-21 |
IS4189A (en) | 1995-01-09 |
JPH08512297A (en) | 1996-12-24 |
ZA944923B (en) | 1995-03-14 |
EP0707572A1 (en) | 1996-04-24 |
ITMI931479A1 (en) | 1995-01-08 |
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