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    PROCESS
    4.
    发明公开
    PROCESS 审中-公开
    处理

    公开(公告)号：EP1915131A1

    公开(公告)日：2008-04-30

    申请号：EP06769601.3

    申请日：2006-08-09

    申请人： AstraZeneca AB

    发明人： LINDFORS, Lennart ,  SKANTZE, Urban

    IPC分类号： A61K9/10

    CPC分类号： A61K9/10 ,  A61K31/16 ,  A61K31/216 ,  A61K31/4422

    摘要： The present invention relates to a process for the preparation of a stable dispersion of particles, particularly sub-micron particles in an aqueous medium and to a stable dispersion of particles in a liquid medium. The process provided comprises the following steps: 1) combining a) an emulsion comprising a continuous aqueous phase; an inhibitor; a stabiliser; with b) the substantially water-insoluble substance; and 2) increasing the temperature to vicinity of the melting temperature of the substantially water-insoluble substance. The sub-micron dispersion provided exhibit reduced or substantially no particle growth during storage and reduced crystallisation rate of the substantially water insoluble active compound.

    摘要翻译： 本发明涉及一种制备稳定的颗粒分散体，特别是亚微米颗粒在含水介质中的稳定分散体和颗粒在液体介质中稳定分散体的方法。 所提供的方法包括以下步骤：1）合并a）包含连续水相的乳液; 一种抑制剂; 一个稳定器; 与b）基本上不溶于水的物质; 和2）将温度升高到基本上不溶于水的物质的熔化温度附近。 所提供的亚微米分散体在储存过程中表现出减少的或基本上没有颗粒生长并且降低了基本上不溶于水的活性化合物的结晶速率。

    STABLE DISPERSION OF SOLID PARTICLES COMPRISING A WATER-INSOLUBLE PYRAZINE COMPOUND
    8.
    发明公开
    STABLE DISPERSION OF SOLID PARTICLES COMPRISING A WATER-INSOLUBLE PYRAZINE COMPOUND 有权
    与水不溶性吡嗪连接稳定的固体颗粒分散

    公开(公告)号：EP1592451A1

    公开(公告)日：2005-11-09

    申请号：EP04707261.6

    申请日：2004-02-02

    申请人： AstraZeneca AB

    发明人： LINDFORS, Lennart

    IPC分类号： A61K47/14 ,  A61K9/51 ,  A61K9/14

    CPC分类号： A61K9/146 ,  A61K9/0019 ,  A61K9/5138 ,  A61K31/4965 ,  A61K31/497 ,  A61K47/14

    摘要： A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a pyrazine compound of formula (I), a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions obtainable by the process, solid particles obtainable by the process and use of such particles. The process provides a dispersion of solid particles in an aqueous medium, which particles exhibit reduced or substantially no particle growth mediated by Ostwald ripening. The process is particularly suitable for the preparation of small (sub-micron) aqueous dispersions of a substantially water-insoluble pharmacologically active substance.

    AQUEOUS DISPERSION COMPRISING STABLE NANOPARTICLES OF A WATER-INSOLUBLE PYRROLE CARBOXAMIDE AND AN EXCIPIENT LIKE MIDDLE CHAIN TRIGLYCERIDES
    9.
    发明公开
    AQUEOUS DISPERSION COMPRISING STABLE NANOPARTICLES OF A WATER-INSOLUBLE PYRROLE CARBOXAMIDE AND AN EXCIPIENT LIKE MIDDLE CHAIN TRIGLYCERIDES 审中-公开
    WITH中链甘油三酯作为辅助燃料A的水不溶性PYRROLCARBOXAMIDES的水性分散体稳定纳米粒子

    公开(公告)号：EP1592404A1

    公开(公告)日：2005-11-09

    申请号：EP04707263.2

    申请日：2004-02-02

    申请人： AstraZeneca AB

    发明人： LINDFORS, Lennart

    IPC分类号： A61K9/16 ,  A61K9/10 ,  C07D207/34

    CPC分类号： C07D207/416 ,  A61K9/145

    摘要： A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a pyrrole carboxamide compound of Formula I, a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions obtainable by the process, solid particles obtainable by the process and use of such particles. The process provides a dispersion of solid particles in an aqueous medium, which particles exhibit reduced or substantially no particle growth mediated by Ostwald ripening. The process is particlularly suitable for the preparation of small (sub-micron) aqueous dispersions of a substantially water-insoluble pharmacologically active substance.

    STABLE DISPERSION OF SOLID PARTICLES COMPRISING A WATER-INSOLUBLE PYRAZINE COMPOUND
    10.
    发明授权
    STABLE DISPERSION OF SOLID PARTICLES COMPRISING A WATER-INSOLUBLE PYRAZINE COMPOUND 有权
    与水不溶性吡嗪连接稳定的固体颗粒分散

    公开(公告)号：EP1592451B1

    公开(公告)日：2008-07-02

    申请号：EP04707261.6

    申请日：2004-02-02

    申请人： AstraZeneca AB

    发明人： LINDFORS, Lennart

    IPC分类号： A61K47/14 ,  A61K9/51 ,  A61K9/14

    CPC分类号： A61K9/146 ,  A61K9/0019 ,  A61K9/5138 ,  A61K31/4965 ,  A61K31/497 ,  A61K47/14

    摘要： A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a pyrazine compound of formula (I), a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions obtainable by the process, solid particles obtainable by the process and use of such particles. The process provides a dispersion of solid particles in an aqueous medium, which particles exhibit reduced or substantially no particle growth mediated by Ostwald ripening. The process is particularly suitable for the preparation of small (sub-micron) aqueous dispersions of a substantially water-insoluble pharmacologically active substance.