公开(公告)号：WO1990001295A1

公开(公告)日：1990-02-22

申请号：PCT/US1989003352

申请日：1989-08-03

Applicant: ADVANCED MAGNETICS, INCORPORATED

Inventor： ADVANCED MAGNETICS, INCORPORATED ,  MENZ, Edward, T. ,  ROTHENBERG, Jeffrey, M. ,  GROMAN, Ernest, V. ,  JOSEPHSON, Lee

IPC: A61B06/00

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.

Abstract translation: 描述了磁共振（MR）造影剂，其体内生物分布基于某些细胞通过受体介导的胞吞作用来识别和内化本发明的MR造影剂的能力。 RME型MR造影剂由与大分子物质相关的可生物降解的超顺磁性金属氧化物组成，包括血清蛋白，激素，去唾液酸糖蛋白，半乳糖末端物质，多糖，阿拉伯半乳聚糖或这些分子与其他聚合物质的共轭物，如聚（有机硅烷 ）和葡聚糖。 由可生物降解的超顺磁性氧化铁和脱唾液酸蛋白（例如阿拉伯半乳聚糖）制备的MR造影剂选择性地定位在肝脏的肝细胞中，在脾脏中没有显着的积累。 造影剂提供增强的MR图像和关于被检查的器官或组织的功能或代谢状态的有价值的信息。

公开(公告)号：WO1990001899A1

公开(公告)日：1990-03-08

申请号：PCT/US1989003517

申请日：1989-08-16

Applicant: ADVANCED MAGNETICS, INCORPORATED

Inventor： ADVANCED MAGNETICS, INCORPORATED ,  LEWIS, Jerome, M. ,  MENZ, Edward, T. ,  KENNY, Francis, E. ,  GROMAN, Ernest, V. ,  JOSEPHSON, Lee

IPC: A61B05/05

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.

Abstract translation: 描述了用于血管隔室的可生物降解的超顺磁性MR成像造影剂的制备和分离。 这些聚集体由单个可生物降解的超顺磁金属氧化物晶体组成，其聚集体具有小于约4000埃的整体平均直径。 优选的血管成像造影剂由总平均直径小于约500埃的氧化铁晶体的聚集体组成。 这些造影剂可以与大分子物质相关联，其特别有助于制备这些极小物质，并且可以分散或溶解在生理上可接受的介质中。 优选的介质甚至在恶劣的灭菌条件下也稳定材料以防止进一步聚集。 本发明的高压灭菌的可生物降解的超顺磁性氧化铁理想地适用于药物制剂，并且比先前的血管内成像对比包括几个优点，包括低渗透压，低有效剂量要求，高松弛度，长血液寿命，快速生物降解性和相对于 广泛的适用MR数据采集参数。