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    Controlled drug delivery high molecular weight polyanhydrides
    2.
    发明授权
    Controlled drug delivery high molecular weight polyanhydrides 失效
    受控药物递送高分子量聚酐

    公开(公告)号：US4888176A

    公开(公告)日：1989-12-19

    申请号：US61294

    申请日：1987-06-12

    申请人： Robert S. Langer ,  Abraham J. Domb ,  Cato T. Laurencin

    发明人： Robert S. Langer ,  Abraham J. Domb ,  Cato T. Laurencin

    IPC分类号： A61L17/10 ,  A61L27/18 ,  A61L27/58 ,  C08G67/04

    CPC分类号： C08G67/04 ,  A61L17/10 ,  A61L27/18 ,  A61L27/58

    摘要： A bioerodible controlled drug release device is produced as a homogeneous polymeric matrix from a high molecular weight polyanhydride and a suitable biologically active substance. The high molecular weight polyanhydride is defined by a molecular weight greater than 20,000 and an intrinsic viscosity greater than 0.3 dl/g. The controlled drug release device is preferrably formed by solvent casting with the biologically active substance and exhibits zero order release, improved correlation between the rate of release and polymer degradation, and an induction period between introduction to the eroding environment and the initial release of the biologically active substance. The controlled drug release devices are stable for extended periods of time, flexible and durable and not subject to fracture and disintegration.

    摘要翻译： 生物腐蚀控制药物释放装置由高分子量聚酐和合适的生物活性物质制成均匀的聚合物基质。 高分子量聚酐的分子量大于20,000，特性粘度大于0.3dl / g。 受控药物释放装置优选地通过与生物活性物质的溶剂流延形成并显示零级释放，改善释放速率和聚合物降解之间的相关性，以及引入到侵蚀环境和生物学上的初始释放之间的诱导期 活性物质。 受控药物释放装置长时间稳定，柔韧耐用，不会破裂和分解。

    Method of making hydroxamic acid polymers from primary amide polymers
    4.
    发明授权
    Method of making hydroxamic acid polymers from primary amide polymers 失效
    由一级酰胺聚合物制备异羟肟酸聚合物的方法

    公开(公告)号：US5128420A

    公开(公告)日：1992-07-07

    申请号：US283594

    申请日：1988-12-13

    申请人： Abraham J. Domb ,  Robert S. Langer ,  Ernest G. Cravalho ,  Gershon Golomb ,  Edith Mathiowitz ,  Cato T. Laurencin

    发明人： Abraham J. Domb ,  Robert S. Langer ,  Ernest G. Cravalho ,  Gershon Golomb ,  Edith Mathiowitz ,  Cato T. Laurencin

    IPC分类号： C08F8/32

    CPC分类号： C08F8/32 ,  C08F2800/10 ,  C08F2810/20

    摘要： A method for preparing hydroxamic acid polymers from primary amide polymers wherein polyvinyl monomers such as polyacrylamide are reacted with hydroxyl amine in aqueous solution at room temperature. The low reaction temperature is crucial to producing a high yield (70%) of polymer with hydroxamic acid groups and having a low carboxylic acid content (less than 15%, preferably less than 3%). The polymers display high metal affinity over a broad pH range.The polymers are particularly useful for biomedical applications due to the low carboxylic acid content and for the removal and purification of metals due to the high binding constants and rapid reaction rates.

    摘要翻译： 由聚酰胺聚合物制备异羟肟酸聚合物的方法，其中聚乙烯基单体例如聚丙烯酰胺在室温下与羟胺在水溶液中反应。 低反应温度对于用异羟肟酸基团产生高产率（70％）的聚合物和低羧酸含量（小于15％，优选小于3％）是至关重要的。 聚合物在宽pH范围内显示出高的金属亲和力。 由于高的结合常数和快速的反应速率，由于羧酸含量低以及金属的去除和纯化，聚合物特别适用于生物医学应用。

    Unsaturated polyanhydrides
    5.
    发明授权
    Unsaturated polyanhydrides 失效
    不饱和聚酐

    公开(公告)号：US5019379A

    公开(公告)日：1991-05-28

    申请号：US80090

    申请日：1987-07-31

    申请人： Abraham J. Domb ,  Robert S. Langer

    发明人： Abraham J. Domb ,  Robert S. Langer

    IPC分类号： A61K9/20 ,  A61L24/00 ,  A61L24/04 ,  C08G67/04

    CPC分类号： C08G67/04 ,  A61K9/2031 ,  A61L24/0042 ,  A61L24/046 ,  A61L2430/02

    摘要： A class of unsaturated polyanhydrides having double bonds available for secondary polymerization is disclosed. A crosslinked material having improved or different physical and mechanical properties can be prepared from these polyanhydrides, via secondary polymerization. The synthesis and characteristics of one unsaturated polyanhydride based on fumaric acid and its copolymers with aliphatic and aromatic diacids, prepared by either the melt-polycondensation method or by solution polymerization, is described in detail.These polymers are well suited for use in controlled release drug delivery devices. The polymers can also be used as a bioerodible bone cement where the polymer is first cast as a solution onto a bone fracture and then crosslinked by radiation or radical polymerization to yield a strong, adhesive material.

    摘要翻译： 公开了一类具有可用于二次聚合的双键的不饱和聚酐。 可以通过二次聚合从这些聚酐制备具有改善或不同物理和机械性能的交联材料。 详细描述了通过熔融缩聚法或通过溶液聚合制备的一种不饱和聚酐与富马酸及其与脂族和芳族二酸的共聚物的合成和特性。 这些聚合物非常适合用于控释药物递送装置。 聚合物也可以用作生物可蚀解的骨水泥，其中首先将聚合物作为溶液浇铸到骨折上，然后通过辐射或自由基聚合进行交联以产生强的粘合剂材料。

    Controlled local delivery of chemotherapeutic agents for treating solid tumors
    6.
    再颁专利
    Controlled local delivery of chemotherapeutic agents for treating solid tumors 有权
    用于治疗实体瘤的化疗药物的局部控制

    公开(公告)号：USRE37410E1

    公开(公告)日：2001-10-16

    申请号：US09363519

    申请日：1999-07-29

    申请人： Henny Brem ,  Robert S. Langer ,  Abraham J. Domb

    发明人： Henny Brem ,  Robert S. Langer ,  Abraham J. Domb

    IPC分类号： A61K914

    CPC分类号： A61K9/0085 ,  A61K9/2027 ,  A61K9/2031 ,  A61K9/204 ,  A61K31/337 ,  A61K31/4745 ,  A61K31/555

    摘要： A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended time period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed. The examples demonstrate the efficacy of paclitaxel and camptothecin delivered in polymeric implants prepared by compression molding of biodegradable and non-biodegradable polymers, respectively. The results are highly statistically significant.

    摘要翻译： 描述了用于将化学治疗剂局部递送至实体瘤的方法和装置，其中所述药物不穿过血脑屏障并且其特征在于体内生物利用度差和/或半衰期短。 这些装置包括在延长的时间段内释放药物的储存器，同时保持药剂的生物活性和生物利用度。 在最优选的实施方案中，该装置由可生物降解的聚合物基质组成，尽管储存器也可以由与植入的输注泵连接的不可生物降解的聚合物或储存器配制。 这些装置被植入到待治疗的肿瘤内或紧邻其中，或被手术切除的部位。 这些实施例证明分别通过压缩成型可生物降解和不可生物降解的聚合物制备的聚合物植入物中递送的紫杉醇和喜树碱的功效。 结果具有很高的统计学意义。

    Controlled local delivery of chemotherapeutic agents for treating solid tumors
    8.
    发明授权
    Controlled local delivery of chemotherapeutic agents for treating solid tumors 失效
    用于治疗实体瘤的化疗药物的局部控制

    公开(公告)号：US5846565A

    公开(公告)日：1998-12-08

    申请号：US750736

    申请日：1996-12-18

    申请人： Henry Brem ,  Robert S. Langer ,  Abraham J. Domb

    发明人： Henry Brem ,  Robert S. Langer ,  Abraham J. Domb

    IPC分类号： A61K9/00 ,  A61K9/20 ,  A61K9/22 ,  A61K31/282 ,  A61K31/337 ,  A61K31/47 ,  A61K31/4745 ,  A61K38/00 ,  A61K39/395 ,  A61K45/00 ,  A61K47/34 ,  A61K9/14

    CPC分类号： A61K9/0085 ,  A61K31/337 ,  A61K31/4745 ,  A61K31/555 ,  A61K9/2027 ,  A61K9/2031 ,  A61K9/204

    摘要： A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed.

    摘要翻译： PCT No.PCT / US95 / 09805 Sec。 371日期：1996年12月18日 102（e）日期1996年12月18日PCT提交1995年8月2日PCT公布。 公开号WO96 / 03984 日期1996年2月15日描述了一种用于将化学治疗剂局部递送至实体瘤的方法和装置，其中所述药物不穿过血脑屏障，其特征在于生物利用度差和/或体内半衰期短。 这些装置由长期释放药物的储存器组成，同时保持药剂的生物活性和生物利用度。 在最优选的实施方案中，该装置由可生物降解的聚合物基质组成，尽管储存器也可以由与植入的输注泵连接的不可生物降解的聚合物或储存器配制。 这些装置被植入到待治疗的肿瘤内或紧邻其中，或被手术切除的部位。

    Pure polyanhydride from dicarboxylic acid and coupling agent
    10.
    发明授权
    Pure polyanhydride from dicarboxylic acid and coupling agent 失效
    来自二羧酸和偶联剂的纯聚酐

    公开(公告)号：US4916204A

    公开(公告)日：1990-04-10

    申请号：US80332

    申请日：1987-07-31

    申请人： Abraham J. Domb ,  Robert S. Langer ,  Eyal Ron ,  Steven Giannos ,  Rohit Kothari ,  Edith Mathiowitz

    发明人： Abraham J. Domb ,  Robert S. Langer ,  Eyal Ron ,  Steven Giannos ,  Rohit Kothari ,  Edith Mathiowitz

    IPC分类号： A61K31/335 ,  A61K31/365 ,  A61K31/39 ,  C08G67/04 ,  C08G69/08 ,  C08G69/10

    CPC分类号： A61K31/335 ,  A61K31/365 ,  A61K31/39 ,  C08G67/04 ,  C08G69/08 ,  C08G69/10 ,  Y10S514/863

    摘要： A method for synthesizing polyanhydrides in solution using coupling agents and a removable acid acceptor to effect a one-step polymerization of dicarboxylic acids. As used in the method, these coupling agents include phosgene, diphosgene, and acid chlorides. Insoluble acid acceptors include insoluble polyamines and crosslinked polyamines such as polyethyleneimine and polyvinylpyridine and inorganic bases such as K.sub.2 CO.sub.3, Na.sub.2 CO.sub.3, NaHCO.sub.3, and CaCO.sub.3. The only byproduct formed is a removable hydrochloric acid-acid acceptor.Examples are provided of the polymerization of highly pure polyanhydrides using phosgene, diphosgene or an acid chloride as the coupling agent, in combination with either an insoluble acid acceptor or a soluble acid acceptor in a solvent wherein the polymerization byproduct or polymer is insoluble.A particularly important application of these polyanhydrides is in the formation of drug delivery devices containing bioactive compounds. The method is also useful in the polymerization of dicarboxylic acids including heat liable dipeptides of glutamic or aspartic acid.

    摘要翻译： 使用偶联剂和可除去的酸受体在溶液中合成聚酐以进行二羧酸的一步聚合的方法。 如该方法所用，这些偶联剂包括光气，双光气和酰氯。 不溶性酸受体包括不溶性多胺和交联聚胺如聚乙烯亚胺和聚乙烯吡啶以及无机碱如K 2 CO 3，Na 2 CO 3，NaHCO 3和CaCO 3。 形成的唯一副产物是可除去的盐酸酸受体。 提供了使用光气，双极光或酰氯作为偶联剂的高纯度聚酐与在溶剂中的不溶性酸受体或可溶性酸受体组合的聚合反应，其中聚合副产物或聚合物是不溶的。 这些多酸酐的特别重要的应用是形成含有生物活性化合物的药物递送装置。 该方法也可用于二羧酸的聚合，包括谷氨酸或天冬氨酸的热应答二肽。