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    • 2. 发明公开
    • PREPARATION METHOD FOR GLATIRAMER ACETATE
    • GLATIRAMER ACETATE的制备方法
    • EP3199544A2
    • 2017-08-02
    • EP15844092.5
    • 2015-11-26
    • Hybio Pharmaceutical Co., Ltd
    • YUAN, HuixingLI, GuotaoLIU, JianMA, YapingYUAN, Jiancheng
    • C07K14/00C07K1/02C07K1/06
    • C08G69/04C07K2/00C08G69/36
    • The present invention relates to a method for preparing glatiramer acetate, comprising the following steps: (1) dissolving L-alanine NCA, L-tyrosine NCA, L-glutamic acid-γ-benzyl ester NCA, and L-ε-trifluoroacetyl-lysine NCA in 1,4-dioxane as solvent, and stirring until a clarified solution is formed; (2) adding diethylamine for catalysis, stirring at 20-25°C, then slowly pouring the reaction solution into water, and collecting the produced white product; (3) adding the obtained product to a solution of hydrobromic acid in acetic acid, stirring at 23.0-25.0°C, pouring the reaction solution into purified water for quenching and stirring, subjecting the mixture to suction filtration to obtain a yellow solid, after repeating 3-5 times, subjecting the solid to blast drying to remove the moisture therein; and (4) dissolving the solid obtained in step (3) in a 1M piperidine aqueous solution at room temperature and stirring, subjecting the obtained solution to dialysis, adding glacial acetic acid to adjust the pH to 5.5-7.0, and lyophilizing.
    • (1)将L-丙氨酸NCA,L-酪氨酸NCA,L-谷氨酸-γ-苄基酯NCA和L-ε-三氟乙酰基赖氨酸溶解于乙醇中, NCA在1,4-二恶烷中作为溶剂,并搅拌直至形成澄清溶液; (2)加入二乙胺催化,在20-25℃下搅拌,然后将反应溶液缓慢倒入水中,收集生成的白色产物; (3)将得到的产物加入到氢溴酸的乙酸溶液中,在23.0-25.0℃下搅拌,将反应溶液倒入精制水中骤冷并搅拌,将混合物抽滤,得到黄色固体 重复3-5次,对固体进行鼓风干燥以除去其中的水分; (4)将步骤(3)中得到的固体在室温下溶解于1M哌啶水溶液中并搅拌,将得到的溶液进行透析,加入冰醋酸调节pH至5.5-7.0,冷冻干燥。
    • 7. 发明公开
    • METHOD FOR PREPARING ATOSIBAN ACETATE
    • VERFAHREN ZUR HERSTELLUNG VON ATOSIBAN-ACETAT
    • EP2537856A4
    • 2013-12-04
    • EP11850254
    • 2011-12-22
    • HYBIO PHARMACEUTICAL CO LTD
    • XIAO QINGLIU JIANLI HONGLINGMA YAPINGYUAN JIANCHENG
    • C07K7/06A61K38/08A61P15/06
    • C07K7/64C07K7/16
    • The present invention provides a method for preparing atosiban acetate. The method comprises the following steps of: synthesizing to obtain linear atosiban; dissolving the linear atosiban in an acetonitrile aqueous solution, adjusting the pH value with ammonia water, adding H 2 O 2 for oxidizing, filtering, purifying, and transferring salt to obtain the atosiban acetate. In the present invention, an appropriate route is provided, the linear atosiban is synthesized by adopting a solid phase method, and the atosiban is obtained by liquid phase oxidation. The method has the advantages of capabilities of solving the problem of insolubility of the linear atosiban, reducing the reaction size to the maximum extent and shortening reaction time, and being high in yield and easy to industrialize.
    • 本发明提供了一种制备醋酸托西班醋酸酯的方法。 该方法包括以下步骤:合成得到线性阿托西班; 将线性阿托西班溶解在乙腈水溶液中,用氨水调节pH值,加入H 2 O 2进行氧化,过滤,纯化和转移盐,得到醋酸阿托品。 在本发明中,提供了适当的路线,通过采用固相法合成线性阿托西班,通过液相氧化获得阿托西班。 该方法具有解决线性阿托西班不溶性问题的能力,最大限度地减少反应尺寸,缩短反应时间,产率高,易于工业化的优点。