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    BIODEGRADABLE POLYPHOSPHORAMIDATES FOR CONTROLLED RELEASE OF BIOACTIVE SUBSTANCES
    2.
    发明申请
    BIODEGRADABLE POLYPHOSPHORAMIDATES FOR CONTROLLED RELEASE OF BIOACTIVE SUBSTANCES 审中-公开

    公开(公告)号：US20090004741A1

    公开(公告)日：2009-01-01

    申请号：US12137450

    申请日：2008-06-11

    申请人： Jun Wang ,  Hai-Quan Mao ,  Kam Weng Leong

    发明人： Jun Wang ,  Hai-Quan Mao ,  Kam Weng Leong

    IPC分类号： C12N15/87

    CPC分类号： C08L85/02 ,  A61K47/59 ,  C08G79/02

    摘要： The present invention is directed to a series of new polycationic biodegradable polyphosphoramidates. Process for making the polymers, compositions containing these polymers and bioactive ligands to enhance the cellular uptake ad intracellular trafficking, articles and methods for delivery of drugs and genes using these polymers are described. A gene delivery system based on these polymers is prepared by complex coacervation of nucleic acid (DNA or RNA) with polymers. Targeting ligands and molecules that could facilitate gene transfer can be conjugated to polymers to achieve selective and enhanced gene delivery. The current invention also provides a complex composition with buffering capacity.

    Biodegradable polyphosphates for controlled release of bioactive substances
    3.
    发明授权
    Biodegradable polyphosphates for controlled release of bioactive substances 失效
    可生物降解的聚磷酸盐，用于控释生物活性物质

    公开(公告)号：US07345138B2

    公开(公告)日：2008-03-18

    申请号：US10499898

    申请日：2002-05-14

    申请人： Jun Wang ,  Hai-Quan Mao ,  Kam Weng Leong

    发明人： Jun Wang ,  Hai-Quan Mao ,  Kam Weng Leong

    IPC分类号： C08G63/68 ,  C08G79/02

    CPC分类号： C08L85/02 ,  A61K9/1647 ,  A61K9/204 ,  A61K47/34 ,  A61K47/605 ,  A61K47/645 ,  A61K48/0041 ,  C08G79/04 ,  C12N15/87

    摘要： The present invention is directed to a biodegradable system for the controlled release of bioactive substances. This system comprises novel biodegradable and biocompatible polyphosphoesters that carry positive charges. Process for making these polyphosphoesters, compositions containing these polyphosphoesters and biologically active substances, articles and methods for delivery of drugs and genes using this system are described. A controlled gene delivery system based on these polyphosphoesters is prepared by complex coacervation of nucleic acid (DNA or RNA) with polymers. The release rates can be manipulated by adjusting the charge ratios of polyphosphoesters to nucleic acids. This gene delivery system yields a higher gene expression in muscle when injected intramuscularly.

    摘要翻译： 本发明涉及用于控制释放生物活性物质的可生物降解的系统。 该系统包含携带正电荷的新型生物可降解和生物相容性聚磷酸酯。 描述了制备这些聚磷酸酯的方法，含有这些聚磷酸酯和生物活性物质的组合物，使用该系统递送药物和基因的制品和方法。 通过核酸（DNA或RNA）与聚合物的复合凝聚来制备基于这些多聚磷酸酯的受控基因递送系统。 可以通过调节多聚磷酸酯与核酸的电荷比来操纵释放速率。 当肌内注射时，该基因递送系统在肌肉中产生较高的基因表达。

    Controlled delivery of therapeutic agents by insertable medical devices
    4.
    发明申请
    Controlled delivery of therapeutic agents by insertable medical devices 审中-公开

    公开(公告)号：US20050169969A1

    公开(公告)日：2005-08-04

    申请号：US11060383

    申请日：2005-02-17

    申请人： Weiping Li ,  Hai-Quan Mao ,  Kam Leong

    发明人： Weiping Li ,  Hai-Quan Mao ,  Kam Leong

    IPC分类号： A61L29/16 ,  A61L31/16 ,  A61K48/00 ,  A61K31/337 ,  A61K31/4745 ,  A61M31/00

    CPC分类号： A61L31/16 ,  A61L29/16 ,  A61L2300/258 ,  A61L2300/416 ,  A61L2300/602 ,  A61L2300/608 ,  A61L2300/802

    摘要： A medical device and method for transportation and release of a therapeutic agent into a mammalian body are disclosed. The medical device is coated with alternating layers of a negatively charged therapeutic agent and a cationic polyelectrolyte, following a controlled adsorption technique. The method is simple, with minimal perturbation to the therapeutic agent and uses clinically acceptable biopolymers such as human serum albumin. The amount of the therapeutic agent that can be delivered by this technique is optimized by the number of the layers of the therapeutic agent adsorbed on the surface of medical device. There is a washing step between alternate layers of the therapeutic agent and cationic polyelectrolyte carrier, so that the amount of the therapeutic agent on the insertable medical device represents the portion that is stably entrapped and adsorbed on to the medical device. The insertable medical device and method according to this invention are capable of reproducibly delivering therapeutic agent to a site in a mammalian body, and allow for a highly reproducible and controllable release kinetics of the therapeutic agent.

    Biodegradable polyphosphoramidates for controlled release of bioactive substances
    5.
    发明申请
    Biodegradable polyphosphoramidates for controlled release of bioactive substances 失效
    用于生物活性物质控制释放的可生物降解的聚磷酸酰胺酯

    公开(公告)号：US20050119450A1

    公开(公告)日：2005-06-02

    申请号：US10500565

    申请日：2002-05-14

    申请人： Jun Wang ,  Hai-Quan Mao ,  Kam Leong

    发明人： Jun Wang ,  Hai-Quan Mao ,  Kam Leong

    IPC分类号： A61K47/48 ,  A61P1/08 ,  A61P1/10 ,  A61P1/12 ,  A61P9/10 ,  A61P11/02 ,  A61P11/06 ,  A61P21/06 ,  A61P35/00 ,  C08G79/02 ,  C08G79/04 ,  C08L85/02 ,  C12N15/11

    CPC分类号： C08G79/02 ,  A61K9/146 ,  A61K31/7088 ,  A61K47/34 ,  A61K47/605 ,  C08G79/04 ,  C08L85/02 ,  C08L2203/02 ,  C12N15/111 ,  C12N2320/32

    摘要： The present invention is directed to a series of new polycationic biodegradable polyphosphoramidates. Process for making the polymers, compositions containing these polymers and bioactive ligands to enhance the cellular uptake ad intracellular trafficking, articles and methods for delivery of drugs and genes using these polymers are described. A gene delivery system based on these polymers is prepared by complex coacervation of nucleic acid (DNA or RNA) with polymers. Targeting ligands and molecules that could facilitate gene transfer can be conjugated to polymers to achieve selective and enhanced gene delivery. The current invention also provides a complex composition with buffering capacity.

    摘要翻译： 本发明涉及一系列新的聚阳离子可生物降解的聚磷酸酰胺酯。 描述了制备聚合物的方法，含有这些聚合物的组合物和生物活性配体以增强细胞摄取和细胞内运输，用于递送药物和使用这些聚合物的基因的方法。 基于这些聚合物的基因递送系统通过核酸（DNA或RNA）与聚合物的复合凝聚来制备。 可以促进基因转移的靶向配体和分子可以与聚合物缀合以实现选择性和增强的基因递送。 本发明还提供具有缓冲能力的复合组合物。

    Method of immobilization of clusters of ligands on polymer surface and use in cell engineering
    6.
    发明申请
    Method of immobilization of clusters of ligands on polymer surface and use in cell engineering 审中-公开
    将配体簇固定在聚合物表面上并用于细胞工程中的方法

    公开(公告)号：US20050058685A1

    公开(公告)日：2005-03-17

    申请号：US10494830

    申请日：2003-09-06

    申请人： Hai-Quan Mao ,  Chao Yin ,  Ron-Xi Zhuo ,  Kam Leong

    发明人： Hai-Quan Mao ,  Chao Yin ,  Ron-Xi Zhuo ,  Kam Leong

    IPC分类号： C12N11/02 ,  A61F2/00 ,  A61L27/50 ,  C12N5/00 ,  C12N5/02 ,  C12N5/071 ,  C12N11/06

    CPC分类号： C12N11/06 ,  A61L27/50 ,  A61L2400/18 ,  C12N5/0068 ,  C12N5/067 ,  C12N2533/20 ,  C12N2533/30

    摘要： The present invention describes a method to immobilize high density of cell-specific ligands on polymeric surface for cell engineering applications. This method combines a surface-grafting polymerization procedure to yield high density of functional groups, and a chemical conjugation step to link cell-specific ligands to the surface functional groups. This surface functionalization scheme can be applied to polymeric materials in various forms, such as polymer membrane, film, fiber, hollow fiber, foam, etc. Tissue-engineering scaffolds can be functionalized with cell specific ligand in the same manner.

    摘要翻译： 本发明描述了一种将高密度细胞特异性配体固定在聚合物表面上用于细胞工程应用的方法。 该方法结合了表面接枝聚合方法以产生高密度的官能团，以及将细胞特异性配体连接到表面官能团的化学共轭步骤。 该表面官能化方案可以应用于聚合物膜，膜，纤维，中空纤维，泡沫等各种形式的聚合物材料。组织工程支架可以以相同的方式用细胞特异性配体进行功能化。

    Biodegradable compositions comprising poly(cycloaliphatic phosphoester) compounds, articles, and methods for using the same
    8.
    发明授权
    Biodegradable compositions comprising poly(cycloaliphatic phosphoester) compounds, articles, and methods for using the same 失效
    包含聚（脂环族磷酸酯）化合物的生物可降解组合物，制品及其使用方法

    公开(公告)号：US06403675B1

    公开(公告)日：2002-06-11

    申请号：US09070204

    申请日：1998-04-30

    申请人： Wenbin Dang ,  Hai-quan Mao ,  Irina Kadiyala ,  Kam W. Leong ,  Zhong Zhao ,  James P. English

    发明人： Wenbin Dang ,  Hai-quan Mao ,  Irina Kadiyala ,  Kam W. Leong ,  Zhong Zhao ,  James P. English

    IPC分类号： A61K3180

    CPC分类号： C08G79/04 ,  A61K47/34 ,  A61L27/18 ,  A61L31/06 ,  Y10S623/924 ,  C08L85/02

    摘要： Biodegradable, flowable or flexible polymer compositions are described comprising a polymer having the recurring monomeric units shown in formula I: wherein: each of R and R′ is independently straight or branched alkylene, either unsubstituted or substituted with one or more non-interfering substituents; L is a divalent cycloaliphatic group; R″ is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is 5 to 1,000, wherein said biodegradable polymer is biocompatible before and upon biodegradation. In one embodiment, one or more of R, R′ or R″ is a biologically active substance. Amorphous compositions containing a biologically active substance, in addition to the polymer, and methods for controllably releasing biologically active substances using the compositions, are also described.

    摘要翻译： 描述了可生物降解的，可流动的或柔性的聚合物组合物，其包含具有式I所示的重复单体单元的聚合物：其中：R和R'各自独立地为未取代的或被一个或多个非干扰取代基取代的直链或支链亚烷基; L是二价脂环族基团; R“选自H，烷基，烷氧基，芳基，芳氧基，杂环或杂环氧基; andn为5至1,000，其中所述生物可降解聚合物在生物降解之前和之后是生物相容的。 在一个实施方案中，R，R'或R“中的一个或多个是生物活性物质。 还描述了除了聚合物之外含有生物活性物质的无定形组合物以及使用该组合物可控地释放生物活性物质的方法。

    Two-stage solution polymerization of high molecular weight poly(phosphoesters)
    10.
    发明授权
    Two-stage solution polymerization of high molecular weight poly(phosphoesters) 失效
    高分子量聚（磷酸酯）的两阶段溶液聚合

    公开(公告)号：US6008318A

    公开(公告)日：1999-12-28

    申请号：US98620

    申请日：1998-06-17

    申请人： Zhong Zhao ,  Hai-quan Mao ,  Kam W. Leong

    发明人： Zhong Zhao ,  Hai-quan Mao ,  Kam W. Leong

    IPC分类号： C08G79/04 ,  C08G79/02

    CPC分类号： C08G79/04

    摘要： A process for making a phosphoester polymer comprising the recurring monomeric units of formula I: ##STR1## wherein: X is --O-- or --NR"--, where R" is H or alkyl;L is a divalent organic moiety;R' is H, alkyl, alkoxy, aryl, aryloxy, heterocyclic, or heterocycloxy; andn is between about 25 to 2,000,is described. The process comprises the steps of:(a) polymerizing in the presence of a solvent p moles of a di-XH compound having formula II:H--X--L--X--H II wherein X and L are as defined above, with q moles, where p.apprxeq.q, of a phosphorodihalo compound to form a polymer of formula I, wherein n is about 12 to 1000, having a first molecular weight Mw.sub.1, wherein the solvent is present in an amount greater than about 5 ml of solvent per gram of compound of formula II;(b) removing at least about 25% of the solvent to form a more concentrated reaction mixture; and(c) further polymerizing the concentrated reaction mixture for an additional time sufficient to produce a polymer of formula I wherein n is between about 25 and 2,000, the polymer having a second molecular weight Mw.sub.2, which is significantly higher than Mw.sub.1.

    摘要翻译： 制备含有式I的重复单体单元的磷酸酯聚合物的方法：其中：X是-O-或-NR“ - ，其中R”是H或烷基; L是二价有机部分; R'是H，烷基，烷氧基，芳基，芳氧基，杂环或杂环氧基; 并且n在约25至2,000之间。 该方法包括以下步骤：（a）在溶剂的存在下聚合，其中p摩尔的q摩尔具有式II的二-XH化合物：其中X和L如上所定义，其中X和L如上所定义，其中p APPROX q， 的二卤代化合物以形成式I的聚合物，其中n为约12至1000，具有第一分子量Mw1，其中溶剂的存在量为每克式II化合物大于约5ml溶剂; （b）除去至少约25％的溶剂以形成更浓缩的反应混合物; 并且（c）将浓缩的反应混合物进一步聚合另外的时间足以产生其中n在约25和2,000之间的式I的聚合物，该聚合物具有明显高于Mw1的第二分子量Mw2。