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Preparation of high purity of Gadobutrol
专利权人:
BAYER INTELLECTUAL PROPERTY GMBH
发明人:
DR. PLATZEK JOHANNES,DR. TRENTMANN WILHELM
申请号:
ARP120101354
公开号:
AR086190A1
申请日:
2012.04.20
申请国别(地区):
AR
年份:
2013
代理人:
摘要:
2. The process of producing high purity dibutyltin compounds with purity (according to HPLC) of more than 99.7% or 99.8% or 99.9% and its application in the preparation of formula for parents. This process is carried out under controlled crystallization conditions. Latest development in the field of caffeine containing MRI agents (EP 0448191 B1, CA patent 1341176, EP 0643705 B1, EP 0986548 B1)EP 0596586 B1) includes the contrast agent for magnetic resonance tomography gadobutrol (Gadovist® 1.0) that has been approved for a relatively long time in Europe and more recently also in the US,with the name Gadovist®. Claim 1: Process for producing high purity gadobutrol (= the gadolinium complex of N- (1-hydroxymethyl-2,3-dihydroxypropyl) -1,4,7-triscarboxymethyl-1,4,7 , 10-tetraazacyclo-dodecane) characterized in that it comprises reacting ciclene (1,4,7,10-tetraazacyclododecane) with 4,4-dimethyl-3,5,8-trioxabicyclo [5.1.0] octane and lithium chloride in alcohol at high temperatures, rent with sodium monochloroacetate in alkaline medium, continuing the work in acidic conditions, remove salts and add gadolinium oxide, then adjust the pH with lithium hydroxide to a neutral to slightly basic value, concentrate the solution and add alcohol,After heating at low temperature, after cooling, separating and drying the crude oil, the crude oil is dissolved into water, purified by a series of ion exchange devices, then treated with activated carbon, then disinfected and filtered, then heated under reflux conditions, cooled and separated the product.Proceso para producir gadobutrol de alta pureza con una pureza (de acuerdo con HPLC) mayor de 99,7 ó 99,8 ó 99,9% y su uso para preparar una formulación farmacéutica para administración parenteral. El proceso se lleva a cabo usando condiciones de cristalización específicamente controladas. Los desarrollos más recientes en el campo de los agentes de contraste de resonancia magnética que contienen gadolinio (EP 0448191 B1, CA Patente 13411
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