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    • 4. 发明授权
    • Biodegradable polymers chain-extended by phosphates, compositions, articles and methods for making and using the same
    • 通过磷酸盐,组合物,制品和制造和使用它们的方法延伸的可生物降解的聚合物
    • US06376644B1
    • 2002-04-23
    • US09654326
    • 2000-09-01
    • Hai-Quan MaoKam W. LeongZhong ZhaoJames P. English
    • Hai-Quan MaoKam W. LeongZhong ZhaoJames P. English
    • C08G7904
    • A61K9/0024A61K9/1647A61L17/12A61L26/0019A61L27/18C08G63/6922C08G63/912Y10S623/924C08L85/02
    • Biodegradable polymers are described comprising the recurring monomeric units shown in formula I or II: wherein X is —O— or —NR′—, where R′ is H or alkyl; L is a branched or straight chain aliphatic group having from 1-20 carbon atoms; M1 and M2 are each independently (1) a branched or straight chain aliphatic group having from 1-20 carbon atoms; or (2) a branched or straight chain, oxy-, carboxy- or amino-aliphatic group having from 1-20 carbon atoms; Y is —O—, —S— or —NR′—, where R′ is H or alkyl; R is H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; the molar ratio of x:y is about 1; the molar ratio n:(x or y) is between about 200:1 and 1:200; and the molar ratio q:r is between about 1:99 and 99:1; wherein said biodegradable polymer is biocompatible before and upon biodegradat. Processes for preparing the polymers, compositions containing the polymers and biologically active substances, articles useful for implantation or injection into the body fabricated from the compositions, and methods for controllably releasing biologically active substances using the polymers, are also described.
    • 描述包含式I或II所示的重复单体单元的生物可降解聚合物:其中X是-O-或-NR'-,其中R'是H或烷基; L是具有1-20个碳原子的支链或直链脂族基团; M1和M2各自独立地为(1)具有1-20个碳原子的支链或直链脂族基团; 或(2)具有1-20个碳原子的支链或直链,氧基,羧基或氨基 - 脂族基团; Y是-O - , - S-或-NR'-,其中R'是H或烷基; R是H,烷基,烷氧基,芳基,芳氧基,杂环或杂环氧基; x:y的摩尔比为约1; 摩尔比n:(x或y)在约200:1和1:200之间; 并且摩尔比q:r在约1:99和99:1之间; 其中所述可生物降解聚合物在生物降解之前和之后是生物相容的。 还描述了制备聚合物的方法,含有聚合物和生物活性物质的组合物,用于植入或注射到由组合物制造的身体中的制品,以及使用该聚合物可控地释放生物活性物质的方法。
    • 5. 发明授权
    • Controlled delivery of therapeutic agents by insertable medical devices
    • 通过可插入的医疗设备控制治疗剂的输送
    • US06899731B2
    • 2005-05-31
    • US09750779
    • 2001-01-02
    • Weiping LiHai-Quan MaoKam W. Leong
    • Weiping LiHai-Quan MaoKam W. Leong
    • A61L29/16A61L31/16A61F2/06A61K48/00
    • A61L31/16A61L29/16A61L2300/258A61L2300/416A61L2300/602A61L2300/608A61L2300/802
    • 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.
    • 公开了用于将哺乳动物体内的治疗剂输送和释放的医疗装置和方法。 在受控吸附技术之后,医疗装置涂覆有带负电的治疗剂和阳离子聚电解质的交替层。 该方法简单,对治疗剂的扰动最小,并且使用临床可接受的生物聚合物例如人血清白蛋白。 通过该技术可以递送的治疗剂的量通过吸收在医疗装置表面上的治疗剂的层数来优化。 在治疗剂和阳离子聚电解质载体的交替层之间存在洗涤步骤,使得可插入医疗装置上的治疗剂的量表示稳定地截留并吸附到医疗装置上的部分。 根据本发明的可插入医疗装置和方法能够将治疗剂可再现地递送到哺乳动物体内的部位,并且允许治疗剂的高度可重现和可控的释放动力学。
    • 10. 发明授权
    • Two-stage solution polymerization of high molecular weight
poly(phosphoesters)
    • 高分子量聚(磷酸酯)的两阶段溶液聚合
    • US6008318A
    • 1999-12-28
    • US98620
    • 1998-06-17
    • Zhong ZhaoHai-quan MaoKam W. Leong
    • Zhong ZhaoHai-quan MaoKam W. Leong
    • C08G79/04C08G79/02
    • C08G79/04
    • 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.
    • 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。