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New chemically modified heparin production procedures
专利权人:
Dilafor AB
发明人:
ERIKSSON, Per-Olov,HOLMER, Erik Yngve
申请号:
ES14739914
公开号:
ES2646337T3
申请日:
2014.06.19
申请国别(地区):
ES
年份:
2017
代理人:
摘要:
A method of preparing a heparin derivative having an average molecular weight of about 4.6 to about 6.9 kDa and an anti-factor Xa activity of less than about 10 IU / mg, and wherein the heparin derivative has a disaccharide that is predominantly produced as shown in the following formula I ** Formula ** in which ** Formula ** and n is an integer from 2 to 20, corresponding to molecular weights between 1.2 and 12 kDa, and wherein the heparin derivative has signals in the region of 5.0 ppm to 6.5 ppm of a 1 H NMR spectrum with an intensity (proportion in%) less than or equal to about 4% relative to the signal at 5.42 ppm of the 1 H NMR spectrum of unfractionated heparin, which comprises the consecutive steps of: (i) oxidizing an acidic aqueous solution of unfractionated heparin by the addition of an oxidizing agent; (ii) depolymerize the oxidized heparin by subjecting the product of step (i) to an alkali to form an alkaline solution; (iii) maintaining said solution of step (ii) at an alkaline pH for a period of time required to provide depolymerized heparin with a molecular weight within the aforementioned range; and (iv) reducing the aldehyde end groups of said depolymerized heparin by adding a hydride reducing agent to the solution obtained in step (iii); wherein the period of time between the end of stage (i) and the beginning of stage (iv) is controlled in order to minimize the effect of residual oxidizing agents; and wherein said time period of stage (iii) is determined by analysis of said solution or by reference to a substantially identical stage (iii) carried out previously.Un procedimiento de preparación de un derivado de heparina que tiene un peso molecular promedio de aproximadamente 4,6 a aproximadamente 6,9 kDa y una actividad anti-factor Xa inferior a aproximadamente 10 UI/mg, y en el que el derivado de heparina tiene un disacárido que se produce predominantemente tal como se muestra en la fórmula I siguiente**Fórmula** en la que**Fórmula** y n es un núm
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中国工程科技知识中心
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