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    Microspheres for controlled release and processes to prepare these microspheres
    1.
    发明公开
    Microspheres for controlled release and processes to prepare these microspheres 失效
    Mikrosphärenzur gesteuerten Freisetzung und Verfahren zur Herstellung dieserMikrosphären

    公开(公告)号：EP0842657A1

    公开(公告)日：1998-05-20

    申请号：EP96203234.8

    申请日：1996-11-19

    申请人： OctoPlus B.V.

    发明人： The designation of the inventor has not yet been filed

    IPC分类号： A61K9/16

    CPC分类号： A61K9/1652 ,  A61K9/1664 ,  A61K9/1694 ,  Y10S977/906

    摘要： The present invention relates to a process for the preparation of a controlled release system, comprising forming of an aqueous two-phase system from at least two water soluble polymers, which polymers are incompatible in solution, at least one of these polymers being crosslinkable, the crosslinkable polymer phase being emulsified in the other polymer phase; adding at least one releasable compound which is soluble in the crosslinkable polymer phase in the aqueous solution, allowing the releasable compound to diffuse in the crosslinkable polymer phase; crosslinking the crosslinkable polymer to a degree that the pores in the crosslinked structure are substantially smaller than the particles size of the releasable compound; and separating the crosslinked structures enclosing the releasable compound from the other phase. Further, the invention relates to microspheres, at least 80 wt.% thereof having a particle size of between 1 nanometer and 50 µm, which microspheres are comprised of a degradable, crosslinked polymer encapsulating at least one releasable compound, the pore size of the crosslinked polymer being smaller than the particle size of the releasable compound.

    摘要翻译： 本发明涉及一种制备控制释放系统的方法，包括由至少两种水溶性聚合物形成水相两相体系，该聚合物在溶液中不相容，这些聚合物中的至少一种是可交联的， 可交联聚合物相在其他聚合物相中乳化; 在水溶液中加入可溶于可交联聚合物相的至少一种可释放化合物，使可释放化合物在可交联聚合物相中扩散; 将可交联聚合物交联到交联结构中的孔基本上小于可释放化合物的颗粒尺寸的程度; 并将包封可释放化合物的交联结构与另一相分离。 此外，本发明涉及至少80重量％的微球，其粒径在1纳米至50微米之间，该微球由包封至少一种可释放化合物的可降解的交联聚合物组成， 交联聚合物小于可释放化合物的粒度。

    POLY(ORGANO)PHOSPHAZENES FOR USE IN SYNTHETIC TRANSFECTION SYSTEMS
    2.
    发明公开
    POLY(ORGANO)PHOSPHAZENES FOR USE IN SYNTHETIC TRANSFECTION SYSTEMS 失效
    POLY（ORGANO）PHOSPHAZENE IN SYNTHETICHEN TRANSFEKTIONS-SYSTEMEN

    公开(公告)号：EP0787201A1

    公开(公告)日：1997-08-06

    申请号：EP96926662.0

    申请日：1996-08-16

    申请人： Introgene B.V. ,  OctoPlus B.V. ,  Universiteit Utrecht

    发明人： HENNINK, Wilhelmus, Everhardus ,  BOUT, Abraham

    IPC分类号： C12N15 ,  A61K47 ,  A61K48 ,  C12N5

    CPC分类号： C12N15/87 ,  A61K47/605 ,  A61K48/00

    摘要： The present invention relates to a synthetic transfection system comprising as a carrier a cationic, water soluble or water dispersible polyphosphazene. In addition, it relates to a method for introducing DNA fragments in target cells, comprising contacting these DNA fragments with a polyphosphazene which is at least partially substituted with cationic substituents and subsequently contacting the obtained transfection system wits target cells. Finally, the invention involves the use of a polyphosphazene which is at least partially substituted with cationic substituents as transfection vehicle.

    摘要翻译： PCT No.PCT / NL96 / 00324 Sec。 371日期：1997年6月30日 102（e）日期1996年6月30日PCT提交1996年8月16日PCT公布。 出版物WO97 / 07226 日本1997年2月27日本发明涉及一种合成转染系统，其包含阳离子，水分散性聚磷腈作为载体。 此外，本发明涉及在靶细胞中引入DNA片段的方法，包括使这些DNA片段与至少部分被阳离子取代基部分取代的聚磷腈接触，随后将获得的转染系统与靶细胞接触。 最后，本发明涉及使用至少部分被阳离子取代基取代的聚磷腈作为转染载体。

    Proces for the preparation of a controlled release system
    5.
    发明公开
    Proces for the preparation of a controlled release system 失效
    Verfahren zur Herstellung eines Systems mit gesteuerter Freisetzung

    公开(公告)号：EP1371364A1

    公开(公告)日：2003-12-17

    申请号：EP03077121.6

    申请日：1997-11-17

    申请人： OctoPlus B.V.

    发明人： Hennink, Wilhelmus, Everhardus ,  Franssen, Okke

    IPC分类号： A61K9/16

    CPC分类号： A61K47/36 ,  A61K9/1652

    摘要： The present invention relates to a process for the preparation of a system having good controlled release behaviour. It comprises two water-soluble polymers and a proteinaceous material.
    An aqueous two-phase system is formed, wherein the proteinaceous material is comprised in the dispersed phase. The dispersed phase is cross linked.

    摘要翻译： 本发明涉及制备具有良好控制释放行为的系统的方法。 它包含两种水溶性聚合物和蛋白质物质。 形成水相两相体系，其中蛋白质物质包含在分散相中。 分散相交联。

    Stabilisation of compositions comprising non-viral nucleic acid transfer compositions
    6.
    发明公开
    Stabilisation of compositions comprising non-viral nucleic acid transfer compositions 审中-公开
    on ten ten en en en ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten ten

    公开(公告)号：EP1022340A1

    公开(公告)日：2000-07-26

    申请号：EP99200176.8

    申请日：1999-01-21

    申请人： OctoPlus B.V.

    发明人： Hennink, Wilhelmus Everardus ,  Crommelin, Daniel Jan Anne

    IPC分类号： C12N15/87 ,  A61K48/00

    CPC分类号： C12N15/87 ,  A61K48/00

    摘要： The present invention relates to a method for preparing a storage-stable and/or transportable cell-delivery nucleic acid composition comprising preparing an aqueous solution comprising said nucleic acid and, optionally, at least one cationic polymer. Further, the invention relates to a method for preparing a storage-stable and/or transportable cell-delivery nucleic acid composition free of cryopreservative and/or lyopreservative comprising preparing an aqueous solution comprising said nucleic acid and, optionally, at least one cationic polymer. In a further aspect, the invention relates to a method for preparing a cell-delivery nucleic acid composition comprising preparing an aqueous solution comprising said nucleic acid and, optionally, at least one cationic polymer and, before use, storing said solution for at least 2 weeks at a temperature between 0 and approximately the denaturation temperature of said nucleic acid in said solution, preferably at a temperature between 0 and approximately 40 °C. In addition, the storable products of these methods, as well as the use of the stabilising compounds are part of the present invention.

    摘要翻译： 本发明涉及一种制备储存稳定和/或可运输的细胞递送核酸组合物的方法，包括制备包含所述核酸和任选的至少一种阳离子聚合物的水溶液。 此外，本发明涉及制备不含冷冻保存剂和/或冷冻保留剂的储存稳定和/或可运输细胞递送核酸组合物的方法，其包括制备包含所述核酸和任选的至少一种阳离子聚合物的水溶液。 另一方面，本发明涉及一种制备细胞递送核酸组合物的方法，包括制备包含所述核酸和任选的至少一种阳离子聚合物的水溶液，并且在使用前将所述溶液储存至少2 在0℃至大约所述溶液中的所述核酸的变性温度之间的温度下，优选在0℃和约40℃之间的温度下，优选在这些方法的可储存产物中，以及使用稳定化合物 是本发明的一部分。

    CATIONIC POLYACRYLATES AND POLY(ALKYL)ACRYLATES OR THE CORRESPONDING ACRYLAMIDES FOR USE IN SYNTHETIC TRANSFECTION SYSTEMS
    7.
    发明授权
    CATIONIC POLYACRYLATES AND POLY(ALKYL)ACRYLATES OR THE CORRESPONDING ACRYLAMIDES FOR USE IN SYNTHETIC TRANSFECTION SYSTEMS 失效
    阳离子聚丙烯酸酯和聚（烷基）丙烯酸酯或适合用于合成丙烯酰胺转染系统

    公开(公告)号：EP0859857B1

    公开(公告)日：2005-05-04

    申请号：EP96935575.9

    申请日：1996-10-25

    申请人： OctoPlus B.V.

    发明人： HENNINK, Wilhelmus, Everhardus ,  VAN DE WETERING, Petra

    IPC分类号： C12N15/87 ,  A61K47/48

    CPC分类号： C12N15/87 ,  A61K47/58

    摘要： The present invention relates to a synthetic transfection or blocking system comprising as a carrier a cationic, water soluble or water dispersible polyacrylate, a polyacrylamide, a poly(C1-6 alkyl)acrylate, or a poly(C1-6 alkyl)acrylamide. In addition, it relates to a method for introducing DNA fragments in target cells, comprising contacting these DNA fragments with a polyacrylate, polyacrylamide, a poly(C1-6 alkyl)acrylate or a poly(C1-6 alkyl)acrylamide, which is at least partially substituted with cationic substituents and subsequently contacting the obtained transfection system with target cells. Finally, the invention involves the use of a polyacrylate, a polyacrylamide, a poly(C1-6 alkyl)acrylate, or a poly(C1-6 alkyl)acrylamide, which is at least partially substituted with cationic substituents as a DNA carrier system.

    PROCESS FOR THE PREPARATION OF A CONTROLLED RELEASE SYSTEM
    9.
    发明公开
    PROCESS FOR THE PREPARATION OF A CONTROLLED RELEASE SYSTEM 失效
    制备控制释放系统的过程

    公开(公告)号：EP0941068A1

    公开(公告)日：1999-09-15

    申请号：EP97913531.0

    申请日：1997-11-17

    申请人： OctoPlus B.V.

    发明人： HENNINK, Wilhelmus, Everhardus ,  FRANSSEN, Okke

    IPC分类号： A61K9 ,  A61K47

    CPC分类号： A61K47/36 ,  A61K9/1652

    摘要： The present invention relates to a process for the preparation of a controlled release system, comprising forming of an aqueous two-phase system from at least two water soluble polymers, which polymers are incompatible in solution, at least one of these polymers being cross-linkable, the cross-linkable polymer phase being emulsified in the other polymer phase; adding at least one releasable compound which is soluble in the cross-linkable polymer phase in the aqueous solution, allowing the releasable compound to diffuse in the cross-linkable polymer phase; cross-linking the cross-linkable polymer before or after the releasable compound is added, preferably to a degree that the pores in the cross-linked structure are substantially smaller than the particles size of the releasable compound; and separating the cross-linked structures enclosing the releasable compound from the other phase. Further, the invention relates to microspheres, at least 80 wt.% thereof having a particle size of between 100 nanometer and 1000 νm, which microspheres are comprised of a degradable, cross-linked polymer encapsulating at least one releasable compound, the pore size of the cross-linked polymer being smaller than the particle size of the releasable compound.

    摘要翻译： 本发明涉及制备控制释放系统的方法，包括由至少两种水溶性聚合物形成水性两相体系，所述聚合物在溶液中不相容，这些聚合物中的至少一种可交联 ，可交联聚合物相在另一聚合物相中乳化; 在水溶液中加入至少一种可溶于可交联聚合物相的可释放化合物，使可释放化合物在可交联聚合物相中扩散; 在加入可释放化合物之前或之后使可交联聚合物交联，优选达到交联结构中的孔基本上小于可释放化合物的粒径的程度; 并将包封可释放化合物的交联结构与另一相分离。 此外，本发明涉及微球体，其至少80重量％具有100纳米至1000νm的粒径，该微球体包含包封至少一种可释放化合物的可降解交联聚合物，其孔尺寸为 交联聚合物小于可释放化合物的粒径。

    CATIONIC POLYACRYLATES AND POLY(ALKYL)ACRYLATES OR THE CORRESPONDING ACRYLAMIDES FOR USE IN SYNTHETIC TRANSFECTION OR BLOCKING SYSTEMS
    10.
    发明公开
    CATIONIC POLYACRYLATES AND POLY(ALKYL)ACRYLATES OR THE CORRESPONDING ACRYLAMIDES FOR USE IN SYNTHETIC TRANSFECTION OR BLOCKING SYSTEMS 失效
    阳离子聚丙烯酸酯和聚（烷基）丙烯酸酯或适合用于合成丙烯酰胺转染系统

    公开(公告)号：EP0859857A1

    公开(公告)日：1998-08-26

    申请号：EP96935575.0

    申请日：1996-10-25

    申请人： OctoPlus B.V.

    发明人： HENNINK, Wilhelmus, Everhardus ,  VAN DE WETERING, Petra

    IPC分类号： C12N15 ,  A61K47 ,  A61K48

    CPC分类号： C12N15/87 ,  A61K47/58

    摘要： The present invention relates to a synthetic transfection or blocking system comprising as a carrier a cationic, water soluble or water dispersible polyacrylate, a polyacrylamide, a poly(C1-6 alkyl)acrylate, or a poly(C1-6 alkyl)acrylamide. In addition, it relates to a method for introducing DNA fragments in target cells, comprising contacting these DNA fragments with a polyacrylate, polyacrylamide, a poly(C1-6 alkyl)acrylate or a poly(C1-6 alkyl)acrylamide, which is at least partially substituted with cationic substituents and subsequently contacting the obtained transfection system with target cells. Finally, the invention involves the use of a polyacrylate, a polyacrylamide, a poly(C1-6 alkyl)acrylate, or a poly(C1-6 alkyl)acrylamide, which is at least partially substituted with cationic substituents as a DNA carrier system.