公开(公告)号：EP0517740A4

公开(公告)日：1993-02-03

申请号：EP91904282

申请日：1991-02-05

Applicant: ADVANCED MAGNETICS INCORPORATED

Inventor： GROMAN, ERNEST, V. ,  JOSEPHSON, LEE

IPC: A61K33/26 ,  A61K47/26 ,  A61K49/00 ,  A61K49/18 ,  A61P7/06 ,  B01J13/00 ,  C08G18/18 ,  C08G18/20 ,  C08G18/24 ,  C08G18/26 ,  C08J9/14 ,  G01R33/28 ,  G11B5/708 ,  G01N31/00

CPC classification number: G01R33/5601 ,  A61K49/18 ,  A61K49/1809 ,  A61K49/1845 ,  A61K49/1863 ,  B82Y5/00 ,  C08G18/1808 ,  C08G18/1816 ,  C08G18/1825 ,  C08G18/2036 ,  C08G18/246 ,  C08G18/26 ,  C08G2101/00 ,  C08J9/144 ,  C08J2375/04 ,  Y10S514/814 ,  Y10T436/24

Abstract: This invention relates to compositions comprising a colloidal or particulate metal oxide which are stabilized by low molecular weight carbohydrates. The carbohydrates are characterized by the fact that (a) they are not retained on the surface of the metal oxide based on the equilibrium room temperature dialysis of about 2 ml of the metal oxide composition at 0.2 M metal concentration against deionized water; and (b) they impart sufficient stability to the metal oxide compositions such that the compositions can withstand heat stress without perceptible aggregation as determined by a prescribed test procedure.

公开(公告)号：EP0381742A4

公开(公告)日：1991-04-24

申请号：EP89909342

申请日：1989-08-03

Applicant: ADVANCED MAGNETICS INCORPORATED

Inventor： MENZ, EDWARD, T. ,  ROTHENBERG, JEFFREY, M. ,  GROMAN, ERNEST, V. ,  JOSEPHSON, LEE

IPC: A61B5/055 ,  A61K31/70 ,  A61K33/24 ,  A61K49/00 ,  A61K49/12 ,  A61K49/18 ,  A61K51/00 ,  A61K51/06 ,  C08G18/18 ,  C08G18/20 ,  C08G18/24 ,  C08G18/26 ,  C08J9/14 ,  G01R33/28 ,  A61B6/00 ,  G01N24/00

CPC classification number: G01R33/5601 ,  A61K49/085 ,  A61K49/12 ,  A61K49/18 ,  A61K49/1845 ,  A61K49/1848 ,  A61K49/1863 ,  A61K49/1866 ,  A61K49/1869 ,  A61K51/06 ,  A61K2123/00 ,  C08G18/1808 ,  C08G18/1816 ,  C08G18/1825 ,  C08G18/2036 ,  C08G18/246 ,  C08G18/26 ,  C08G2101/00 ,  C08J9/144 ,  C08J2375/04

Abstract: Magnetic resonance (MR) contrast agents are described whose in vivo biodistribution is based upon the ability of certain cells to recognize and internalize the MR contrast agents of the present invention, via receptor mediated endocytosis. The RME-type MR contrast agents are comprised of biodegradable superparamagnetic metal oxides associated with macromolecular species including serum proteins, hormones, asialoglycoproteins, galactose-terminal species, polysaccharides, arabinogalactan, or conjugates of these molecules with other polymeric substances such as a poly(organosilane) and dextran. An MR contrast agent prepared from biodegradable superparamagnetic iron oxide and asialofetuin, for example, arabinogalactan, is selectively localized in the hepatocytes of the liver with no significant accumulation in the spleen. The contrast agents provide an enhanced MR image and valuable information regarding the functional or metabolic state of the organ or tissue under examination.

公开(公告)号：EP0441797A4

公开(公告)日：1992-01-15

申请号：EP89910555

申请日：1989-08-16

Applicant: ADVANCED MAGNETICS INCORPORATED

Inventor： LEWIS, JEROME, M. ,  MENZ, EDWARD, T. ,  KENNY, FRANCIS, E. ,  GROMAN, ERNEST, V. ,  JOSEPHSON, LEE

IPC: A61K49/18 ,  C08G18/18 ,  C08G18/20 ,  C08G18/24 ,  C08G18/26 ,  C08J9/14 ,  G01R33/28 ,  A61B5/05

CPC classification number: G01R33/5601 ,  A61K49/18 ,  A61K49/1863 ,  A61K49/1887 ,  B82Y5/00 ,  C08G18/1808 ,  C08G18/1816 ,  C08G18/1825 ,  C08G18/2036 ,  C08G18/246 ,  C08G18/26 ,  C08G2101/00 ,  C08J9/144 ,  C08J2375/04 ,  Y10T436/24

Abstract: The preparation and isolation of biodegradable superparamagnetic MR imaging contrast agents for the vascular compartment is described. These aggregates are comprised of individual biodegradable superparamagnetic metal oxide crystals which aggregates have an overall means diameter less than about 4000 angstroms. The preferred vascular imaging contrast agent is comprised of aggregates of iron oxide crystals having an overall mean diameter less than about 500 angstroms. These contrast agents may be associated with a macromolecular species, which assist, among other things, in the preparation of these extremely small materials, and may be dispersed or dissolved in a physiologically acceptable medium. Preferred media also stabilize the materials against further aggregation even under harsh sterilization conditions. The autoclaved biodegradable superparamagnetic iron oxides of the invention are ideally suited for a pharmaceutical preparation and enjoy several advantages over prior intravascular imaging contrast including low osmolality, low effective dose requirements, high relaxivities, long blood lifetimes, rapid biodegradability, and versatility with respect to a wide range of applicable MR data acquisition parameters.