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    Pharmaceutical composition and process for its preparation
    2.
    发明授权
    Pharmaceutical composition and process for its preparation 失效
    药物组成及其制备方法

    公开(公告)号：US5211958A

    公开(公告)日：1993-05-18

    申请号：US877385

    申请日：1992-04-29

    申请人： Piet J. Akkerboom ,  Robert De Cocq ,  Maria Wegman

    发明人： Piet J. Akkerboom ,  Robert De Cocq ,  Maria Wegman

    IPC分类号： A61K9/20 ,  A61K31/65

    CPC分类号： A61K31/65 ,  A61K9/0095 ,  A61K9/2054

    摘要： A multi-purpose pharmaceutical tablet which can either be readily swallowed or dissolved in water to give a dispersion, comprising a tetracycline, microcrystalline cellulose or microfine cellulose, low substituted hydroxypropylcellulose and a thickening agent, preferably hydroxypropyl methylcellulose, and optionally other conventional adjuvants. The tablet may be easily swallowed as such, and when immersed in water, it affords a very fine dispersion within 30-60 seconds. The tablet may be prepared by direct compression, or by a wet granulation process in which a granulate is used which contains tetracycline and any substantial amount of a wet binding substance.

    摘要翻译： 可以容易地吞咽或溶解在水中以产生分散体的多用途药物片剂，其包含四环素，微晶纤维素或微细纤维素，低取代的羟丙基纤维素和增稠剂，优选羟丙基甲基纤维素，以及任选的其它常规佐剂。 片剂本身容易吞咽，浸渍于水中时，可在30-60秒内提供极细的分散体。 片剂可以通过直接压片或通过湿法制粒方法制备，其中使用含有四环素和任何显着量的湿结合物质的颗粒。

    Process for the preparation of hydroxyphosphinylureidobenzylpenicillins
    3.
    发明授权
    Process for the preparation of hydroxyphosphinylureidobenzylpenicillins 失效
    制备羟基氧化金刚烷基苄基青霉素的方法

    公开(公告)号：US4177189A

    公开(公告)日：1979-12-04

    申请号：US908221

    申请日：1978-05-22

    申请人： Piet J. Akkerboom ,  Geertruiida J. Lower ,  Willem J. Timp

    发明人： Piet J. Akkerboom ,  Geertruiida J. Lower ,  Willem J. Timp

    IPC分类号： C07D499/00 ,  C07D499/04 ,  C07D499/64 ,  C07D499/68 ,  C07F20060101 ,  C07F9/6561

    CPC分类号： C07F9/65611 ,  C07D499/00 ,  Y02P20/55

    摘要： An improved process for the preparation in high yields of a compound of the formula ##STR1## wherein R is an optionally substituted phenyl group, Y is selected from the group consisting of Me and a hydrocarbon, Me is a metal cation and E is selected from the group consisting of hydrogen and a metal cation comprising reacting a compound of the formula ##STR2## wherein Q is selected from the group consisting of hydrogen and a silyl protecting group, Rz is an optionally substituted phenyl with the proviso that any hydroxy group present on the phenyl are replaced by --OQz, wherein Qz is a silyl protecting group and Ez is a carboxyl protecting group, with a compound of the formula ##STR3## wherein Z is a halogen and X is selected from the group consisting of OY and Z at low temperatures under anhydrous conditions and carefully hydrolyzing the resulting product either with just enough water to remove protecting groups and hydrolyze the Z groups to hydroxy groups and, still under anhydrous conditions, reacting the compound obtained with an organic metal salt carrying a metal cation Me or, in the case wherein the organic solvent is water-insoluble, with an excess of water, followed by washing the mixture with water acidified to a pH of 0 to 3, extracting the organic phase with neutral water and forming a salt with a hydroxide or a salt carrying a salt-forming cation Me.

    摘要翻译： 一种用于以高产率制备式I化合物的改进方法，其中R是任选取代的苯基，Y选自Me和烃，Me是金属阳离子，E被选择 包括由氢和金属阳离子组成的组，其包括使式II化合物其中Q选自氢和甲硅烷基保护基，Rz是任选取代的苯基，条件是任何羟基 苯基中存在的苯基被-OQz取代，其中Qz是甲硅烷基保护基，Ez是羧基保护基，其中式III的化合物其中Z是卤素，X选自OY 和Z在低温条件下在低温条件下，用足够的水小心地水解所得产物以除去保护基团并将Z基团水解成羟基，并仍然在脱水 使所得化合物与携带金属阳离子Me的有机金属盐反应，或在有机溶剂不溶于水的情况下与过量的水反应，然后用酸化至pH为0的水洗涤混合物 至3，用中性水萃取有机相，并与携带成盐阳离子Me的氢氧化物或盐形成盐。