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1. 发明授权

US06262183B1 Hydroxamic acid polymers formed from primary amide polymers 失效
标题翻译：由主要酰胺聚合物形成的羟肟酸聚合物
公开(公告)号：US06262183B1
公开(公告)日：2001-07-17
申请号：US08219160
申请日：1994-03-28
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： C08F2056
CPC分类号： C08F8/32 , C08F2800/10 , C08F8/42 , C08F220/56
摘要： Hydroxamic acid polymers which are comprised of hydroxamic groups and carboxylic acid groups wherein the carboxylic acid groups constitute less than about 3% of the functional groups. The polymers hereof are also especially useful in biomedical applications because, for example, the low concentration of carboxylic acid groups decreases the incidence of bioincompatibility. Additionally, the polymers exhibit anticoagulant activity, urease inhibition activity, metal chelating activity and ion exchange activity.
摘要翻译：由异羟肟基和羧酸基组成的羟肟酸聚合物，其中羧酸基构成少于官能团的约3％。这里的聚合物在生物医学应用中也特别有用，因为例如低浓度的羧酸组降低生物相容性的发生率。另外，聚合物显示抗凝血活性，脲酶抑制活性，金属螯合活性和离子交换活性。

2. 发明授权

US5128420A Method of making hydroxamic acid polymers from primary amide polymers 失效
标题翻译：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。

3. 发明授权

US5286763A Bioerodible polymers for drug delivery in bone 失效
标题翻译：用于骨中药物递送的生物可分解聚合物
公开(公告)号：US5286763A
公开(公告)日：1994-02-15
申请号：US908438
申请日：1992-06-30
申请人： Tobin N. Gerhart , Cato T. Laurencin , Abraham J. Domb , Robert S. Langer , Wilson C. Hayes
发明人： Tobin N. Gerhart , Cato T. Laurencin , Abraham J. Domb , Robert S. Langer , Wilson C. Hayes
IPC分类号： A61K9/00 , A61K9/20 , A61L17/10 , A61L24/00 , A61L27/18 , A61L27/22 , A61L27/54 , A61L27/58 , C08G67/04 , A61M31/00 , C08G63/02
CPC分类号： A61K9/0024 , A61K9/2027 , A61K9/2031 , A61K9/204 , A61L17/10 , A61L24/0015 , A61L27/18 , A61L27/227 , A61L27/54 , A61L27/58 , C08G67/04 , A61L2300/406 , A61L2300/414 , A61L2300/416 , A61L2300/604 , A61L2430/02
摘要： Bioerodible polymers which degrade completely into nontoxic residues over a clinically useful period of time, including polyanhydrides, polyorthoesters, polyglycolic acid, polylactic acid, and copolymers thereof, are used for the delivery of bioactive agents, including antibiotics, chemotherapeutic agents, inhibitors of angiogenesis, and simulators of bone growth, directly into bone.
摘要翻译：用于在临床有用的时间段内完全降解成无毒残留物的生物可降解聚合物，包括聚酐，聚原酸酯，聚乙醇酸，聚乳酸及其共聚物，用于递送生物活性剂，包括抗生素，化学治疗剂，血管发生抑制剂，和骨骼生长的模拟器，直接进入骨骼。

4. 发明授权

US4888176A Controlled drug delivery high molecular weight polyanhydrides 失效
标题翻译：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。

5. 发明授权

US4916204A Pure polyanhydride from dicarboxylic acid and coupling agent 失效
标题翻译：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。

6. 发明授权

US4933431A One step preparation of poly(amide-anhydride) 失效
标题翻译：聚（酰胺 - 酐）一步法制备
公开(公告)号：US4933431A
公开(公告)日：1990-06-12
申请号：US269448
申请日：1988-11-09
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： C08G67/04 , C08G69/08 , C08G69/10
CPC分类号： C08G69/08 , C08G67/04 , C08G69/10
摘要： A method for synthetizing 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 polymerizaiton 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实现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，双光气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，其中聚合物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。

7. 发明授权

US5718921A Microspheres comprising polymer and drug dispersed there within 失效
标题翻译：包含分散在其中的聚合物和药物的微球
公开(公告)号：US5718921A
公开(公告)日：1998-02-17
申请号：US691874
申请日：1996-08-02
申请人： Edith Mathiowitz , Claudy J.P. Mullon , Abraham J. Domb , Robert S. Langer
发明人： Edith Mathiowitz , Claudy J.P. Mullon , Abraham J. Domb , Robert S. Langer
IPC分类号： A61K9/50 , B01J13/02 , A61K9/52 , B01J13/12
CPC分类号： B01J13/02 , A61K9/5031 , Y10S514/866 , Y10S514/963 , Y10S514/965
摘要： A method for preparation of biodegradable polymeric drug delivery devices using relatively low temperatures and non-aqueous solutions which is particularly useful with polyanhydrides, thermolabile drugs, and in forming multi-layered devices. In a first embodiment, the polymer is dissolved in a volatile organic solvent, the drug is dispersed or dissolved in the polymer solution, the mixture is suspended in an organic oil, and the organic solvent is extracted into the oil, creating microspheres. The preferred polymers are polyanhydrides since they are biodegradable and have been proven to be useful in vivo. In a second embodiment, the polymer is dissolved in organic solvent with or without the drug, and the mixture is suspended in glycerol. The suspension is frozen and the organic solvent slowly evaporated. Using these embodiments, alone or in combination with other methods including the "hot melt" technique, multi-walled microspheres having each wall degrading at a different rate or containing different drugs can be manufactured.
摘要翻译：一种使用相对较低温度制备可生物降解的聚合物药物递送装置的方法以及非常适用于聚酐，不耐热药物和形成多层装置的非水溶液。在第一实施方案中，将聚合物溶解在挥发性有机溶剂中，将药物分散或溶解在聚合物溶液中，将混合物悬浮在有机油中，并将有机溶剂萃取到油中，形成微球体。优选的聚合物是聚酐，因为它们是可生物降解的并且已被证明在体内是有用的。在第二个实施方案中，将聚合物溶解在有或者没有药物的有机溶剂中，并将混合物悬浮在甘油中。将悬浮液冷冻并缓慢蒸发有机溶剂。使用这些实施方案，可单独使用或与包括“热熔融”技术在一起的其它方法结合使用，可以制造具有以不同速率降解或含有不同药物的各壁的多壁微球体。

8. 发明授权

US5545409A Delivery system for controlled release of bioactive factors 失效
标题翻译：用于控制释放生物活性因子的递送系统
公开(公告)号：US5545409A
公开(公告)日：1996-08-13
申请号：US222880
申请日：1994-04-05
申请人： Cato T. Laurencin , Paul A. Lucas , Glenn T. Syftestad , Abraham Domb , Julianne Glowacki , Robert S. Langer
发明人： Cato T. Laurencin , Paul A. Lucas , Glenn T. Syftestad , Abraham Domb , Julianne Glowacki , Robert S. Langer
IPC分类号： A61K9/00 , A61K9/20 , A61L27/18 , A61L27/22 , A61L27/54 , A61L27/58 , C08G67/04 , A61F2/28 , A61K38/39 , C07K14/485 , C07K14/51
CPC分类号： A61K9/0024 , A61K9/2031 , A61K9/204 , A61L27/18 , A61L27/227 , A61L27/54 , A61L27/58 , C08G67/04 , A61L2300/252 , A61L2300/414 , A61L2300/604 , Y10S530/84
摘要： A composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive factors is described. The composition bioerodes in the biological environment of the subject at a controlled rate, thereby releasing the water soluble proteins at a rate which allows them to interact with local cell populations.
摘要翻译：描述了包含表面侵蚀聚合物基质和水溶性生物活性因子的水溶性蛋白质的控制释放组合物和方法。组合物以受控的速率在受试者的生物环境中生物反应，从而以允许其与局部细胞群体相互作用的速率释放水溶性蛋白质。

9. 发明授权

US5356630A Delivery system for controlled release of bioactive factors 失效
标题翻译：用于控制释放生物活性因子的递送系统
公开(公告)号：US5356630A
公开(公告)日：1994-10-18
申请号：US59516
申请日：1993-05-07
申请人： Cato T. Laurencin , Paul A. Lucas , Glenn T. Syftestad , Abraham Domb , Julianne Glowacki , Robert S. Langer
发明人： Cato T. Laurencin , Paul A. Lucas , Glenn T. Syftestad , Abraham Domb , Julianne Glowacki , Robert S. Langer
IPC分类号： A61K9/00 , A61K9/20 , A61L27/18 , A61L27/22 , A61L27/54 , A61L27/58 , C08G67/04 , A61F2/28 , A61K37/12 , C07K15/20 , C07K17/08
CPC分类号： A61K9/0024 , A61K9/2031 , A61K9/204 , A61L27/18 , A61L27/227 , A61L27/54 , A61L27/58 , C08G67/04 , A61L2300/252 , A61L2300/414 , A61L2300/604 , Y10S530/84
摘要： A composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive factors is described. The composition bioerodes in the biological environment of the subject at a controlled rate, thereby releasing the water soluble proteins at a rate which allows them to interact with local cell populations.
摘要翻译：描述了包含表面侵蚀聚合物基质和水溶性生物活性因子的水溶性蛋白质的控制释放组合物和方法。组合物以受控的速率在受试者的生物环境中生物反应，从而以允许其与局部细胞群体相互作用的速率释放水溶性蛋白质。

10. 发明授权

US5629009A Delivery system for controlled release of bioactive factors 失效
标题翻译：用于控制释放生物活性因子的递送系统
公开(公告)号：US5629009A
公开(公告)日：1997-05-13
申请号：US693466
申请日：1996-08-07
申请人： Cato T. Laurencin , Paul A. Lucas , Glenn T. Syftestad , Abraham Domb , Julie Glowacki , Robert S. Langer
发明人： Cato T. Laurencin , Paul A. Lucas , Glenn T. Syftestad , Abraham Domb , Julie Glowacki , Robert S. Langer
IPC分类号： A61K9/00 , A61K9/20 , A61L27/18 , A61L27/22 , A61L27/54 , A61L27/58 , C08G67/04 , A61F2/28 , A61K38/39 , C07K14/485 , C07K14/51
CPC分类号： A61K9/0024 , A61K9/2031 , A61K9/204 , A61L27/18 , A61L27/227 , A61L27/54 , A61L27/58 , C08G67/04 , A61L2300/252 , A61L2300/414 , A61L2300/604 , Y10S530/84
摘要： A composition and method for controlled release of water-soluble proteins comprising a surface-eroding polymer matrix and water-soluble bioactive factors is described. The composition bioerodes in the biological environment of the subject at a controlled rate, thereby releasing the water soluble proteins at a rate which allows them to interact with local cell populations.
摘要翻译：描述了包含表面侵蚀聚合物基质和水溶性生物活性因子的水溶性蛋白质的控制释放组合物和方法。组合物以受控的速率在受试者的生物环境中生物反应，从而以允许其与局部细胞群体相互作用的速率释放水溶性蛋白质。

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