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51. 发明授权

US06689608B1 Porous biodegradable polymeric materials for cell transplantation 失效
标题翻译：用于细胞移植的多孔可生物降解聚合物材料
公开(公告)号：US06689608B1
公开(公告)日：2004-02-10
申请号：US09669760
申请日：2000-09-26
申请人： Antonios G. Mikos , Robert S. Langer , Joseph P. Vacanti , Linda G. Griffith , Georgios Sarakinos
发明人： Antonios G. Mikos , Robert S. Langer , Joseph P. Vacanti , Linda G. Griffith , Georgios Sarakinos
IPC分类号： C12N506
CPC分类号： C08J9/28 , A61F2/0077 , A61F2/18 , A61F2/186 , A61F2/28 , A61F2/30756 , A61F2/3094 , A61F2/30942 , A61F2/4241 , A61F2002/30011 , A61F2002/30062 , A61F2002/30156 , A61F2002/30299 , A61F2002/30304 , A61F2002/30929 , A61F2002/30971 , A61F2002/4251 , A61F2210/0004 , A61F2230/0023 , A61F2230/0063 , A61F2230/0093 , A61F2240/001 , A61F2240/002 , A61F2250/0023 , A61L27/18 , A61L27/38 , B01D67/003 , B01D2325/02 , C08J9/26 , C08L67/04
摘要： Polymeric materials are used,to make a pliable, non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, allows vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix following implantation, and the injection of cells uniformly throughout the implanted matrix without damage to the cells or patient. The introduced cells attach to the connective tissue within the matrix and are fed by the blood vessels. The preferred material for forming the matrix or support structure is a biocompatible synthetic polymer which degrades in a controlled manner by hydrolysis into harmless metabolites, for example, polyglycolic acid, polylactic acid, polyorthoester, polyanhydride, or copolymers thereof. The rate of tissue ingrowth increases as the porosity and/or the pore size of the implanted devices increases. The time required for the tissue to fill the device depends on the polymer crystallinity and is less for amorphous polymers versus semicrystalline polymers. The vascularity of the advancing tissue is consistent with time and independent of the biomaterial composition and morphology.
摘要翻译：使用聚合材料制成柔韧，无毒，可注射的多孔模板用于血管向内生长。通常在约100和300微米之间的孔径允许血管和结缔组织在植入后约10至90％的基质向内生长，并且在整个植入的基质中均匀注射细胞而不损伤细胞或患者。引入的细胞附着到基质内的结缔组织，并由血管进食。用于形成基质或支撑结构的优选材料是生物相容的合成聚合物，其通过水解以受控的方式降解成无害的代谢物，例如聚乙醇酸，聚乳酸，聚原酸酯，聚酐或其共聚物。随着植入装置的孔隙率和/或孔径增加，组织向内生长的速率增加。组织填充装置所需的时间取决于聚合物的结晶度，对于无定形聚合物与半结晶聚合物相比较少。前进组织的血管分布与时间一致，与生物材料组成和形态无关。

52. 发明授权

US06537567B1 Tissue-engineered tubular construct having circumferentially oriented smooth muscle cells 失效
标题翻译：具有周向取向的平滑肌细胞的组织工程管状构建体
公开(公告)号：US06537567B1
公开(公告)日：2003-03-25
申请号：US09109427
申请日：1998-07-02
申请人： Laura E. Niklason , Jinming Gao , Robert S. Langer
发明人： Laura E. Niklason , Jinming Gao , Robert S. Langer
IPC分类号： A61F200
CPC分类号： A61L27/507 , C12M21/08 , C12M23/06 , C12M23/26 , C12M25/14 , C12M29/14 , C12M35/04 , C12N5/0068 , C12N5/0691 , C12N2500/20 , C12N2500/32 , C12N2503/04 , C12N2509/00 , C12N2533/40
摘要： Improved methods for the production of tissue-engineered constructs, including muscular tissue constructs such as vascular constructs, are disclosed. The methods include the use of improved substrates for cell growth, improved cell culture media for cell growth, and the use of distensible bodies to impart pulsatile stretching force to lumens of constructs during growth. Also disclosed are improved products and methods for making those products, including substrates and cell culture media, for tissue engineering and tissue culture generally. Improved muscular tissue constructs, including vascular constructs, are also disclosed, which may be used in medicine for the repair or replacement of damaged natural structures. In an embodiment, a muscular, tubular tissue-engineered construct is prepared having a wall of mammalian smooth muscle cells oriented circumferentially about a lumen of the construct at a cell density of at least 107 cells/cc.
摘要翻译：公开了用于生产组织工程构建体（包括肌肉组织构建体如血管构建体）的改进方法。所述方法包括使用用于细胞生长的改良底物，用于细胞生长的改进的细胞培养基，以及使用扩张体在生长过程中对构建体的内腔赋予脉动拉伸力。还公开了通常用于组织工程和组织培养的用于制造包括底物和细胞培养基的那些产物的改进的产品和方法。还公开了改进的肌肉组织构建体，包括血管构建体，其可用于医学中用于修复或替换受损的天然结构。在一个实施方案中，制备肌肉，管状组织工程改造的构建体，其具有以至少107个细胞/ cc的细胞密度围绕构建体的内腔定向的哺乳动物平滑肌细胞壁。

53. 发明授权

US06399102B1 Aerodynamically light particles for pulmonary drug delivery 有权
公开(公告)号：US06399102B1
公开(公告)日：2002-06-04
申请号：US09562988
申请日：2000-05-01
申请人： David A. Edwards , Giovanni Caponetti , Jeffrey S. Hrkach , Noah Lotan , Justin Hanes , Abdellaziz Ben-Jebria , Robert S. Langer
发明人： David A. Edwards , Giovanni Caponetti , Jeffrey S. Hrkach , Noah Lotan , Justin Hanes , Abdellaziz Ben-Jebria , Robert S. Langer
IPC分类号： A61K914
CPC分类号： A61K9/0075 , A61K9/1647 , A61K31/137
摘要： Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3 and a mass mean diameter between 5 &mgr;m and 30 &mgr;m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

54. 发明授权

US06326020B1 Local anesthetic formulations 失效
标题翻译：局部麻醉剂配方
公开(公告)号：US06326020B1
公开(公告)日：2001-12-04
申请号：US09079622
申请日：1998-05-15
申请人： Daniel S. Kohane , Charles B. Berde , Gary Strichartz , Robert S. Langer
发明人： Daniel S. Kohane , Charles B. Berde , Gary Strichartz , Robert S. Langer
IPC分类号： A61F200
摘要： Combinations of naturally occurring site 1 sodium channel blockers, such as tetrodotoxin (TTX), saxitoxin (STX), decarbamoyl saxitoxin, and neosaxitoxin (referred to jointly herein as “toxins”), with other agents, have been developed to give long duration block with improved features, including safety and specificity. In one embodiment, duration of block is greatly prolonged by combining a toxin with a local anesthetic, vasoconstrictor, glucocorticoid, and/or adrenergic drugs, both alpha agonists (epinephrine, phenylephrine), beta-blockers (propranalol), and mixed central-peripheral alpha-2 agonists (clonidine), or other agents. In another embodiment, the duration of nerve block from toxin can be greatly enhanced by the inclusion of amphiphilic or lipophilic solvents. In still another embodiment, the effectiveness of these compositions is enhanced by microencapsulation within polymeric carriers, preferably biodegradable synthetic polymeric carriers. Modality specific nerve block can be obtained using combinations of toxin with vanilloids.
摘要翻译：已经开发出天然存在的1位钠通道阻断剂如河豚毒素（TTX），沙毒素（STX），脱氨甲酰沙司苏辛和新西沙毒素（本文共同称为“毒素”）与其他药物的组合，以产生长期阻滞具有改进的特征，包括安全性和特异性。在一个实施方案中，通过将毒素与局部麻醉剂，血管收缩剂，糖皮质激素和/或肾上腺素能药物α激动剂（肾上腺素，去氧肾上腺素），β-阻滞剂（propranalol）和混合的中枢外周 α-2激动剂（可乐定）或其它药剂。在另一个实施方案中，通过包含两亲或亲脂性溶剂可以大大增强来自毒素的神经阻滞的持续时间。在另一个实施方案中，这些组合物的有效性通过聚合物载体（优选可生物降解的合成聚合物载体）内的微囊化来增强。可以使用毒素与香草素的组合获得形态特异性神经阻滞。

55. 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。

56. 发明授权

US06174952B1 Monolithic polymer composition having a water absorption material 有权
标题翻译：具有吸水材料的整体聚合物组合物
公开(公告)号：US06174952B1
公开(公告)日：2001-01-16
申请号：US09156720
申请日：1998-09-18
申请人： Ihab M. Hekal , Robert S. Langer , Alexander M. Klibanov , Edith Mathiowitz
发明人： Ihab M. Hekal , Robert S. Langer , Alexander M. Klibanov , Edith Mathiowitz
IPC分类号： C08J900
CPC分类号： C08L23/02 , B01J20/28014 , B01J20/28033 , B01J20/28042 , B29C45/16 , B65D81/264 , B65D81/266 , C08J9/26 , C08L23/0861 , C08L23/10 , C08L29/04 , C08L69/00 , C08L71/02 , C08L77/00 , C08L101/00 , F26B21/083 , Y10S521/905 , C08L2666/02 , C08L2666/14 , C08L2666/04 , C08L2666/22 , C08L29/00 , C08L71/00
摘要： The present invention includes processes and resulting structures for producing a modified polymer having interconnecting channels. The interconnecting channels act as controlled transmission passages through the polymer. A hydrophilic agent is blended into the polymer so that it is distributed within the polymer. In one embodiment, a water-absorbing material is blended into the polymer so that the water-absorbing material is distributed within the product. The product is solidified so that the hydrophilic agent forms passages in the product through which a desired composition is communicable to the water-absorbing material that is entrained within the product. The solidified product may be used to form a desired shaped article such as plug type inserts and liners for closed containers, or it may be formed into a film, sheet, bead or pellet.
摘要翻译：本发明包括用于生产具有互连通道的改性聚合物的方法和所得结构。互连通道充当通过聚合物的受控传输通道。将亲水剂混合到聚合物中，使其分散在聚合物内。在一个实施方案中，将吸水材料混合到聚合物中，使得吸水材料分布在产品内。产品被固化，使得亲水剂在产品中形成通道，通过该通道，期望的组合物可通过其吸入产品中的吸水材料连通。固化产品可以用于形成所需的成型制品，例如用于密封容器的塞子型插入件和衬垫，或者可以形成为膜，片，珠粒或丸粒。

57. 发明授权

US6060082A Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery 失效
公开(公告)号：US6060082A
公开(公告)日：2000-05-09
申请号：US844138
申请日：1997-04-18
申请人： Hongming Chen , Robert S. Langer
发明人： Hongming Chen , Robert S. Langer
IPC分类号： A61K9/127 , A61K38/28 , A61K39/00 , A61K39/05 , A61K48/00
CPC分类号： A61K39/05 , A61K38/28 , A61K39/00 , A61K48/00 , A61K9/1273 , A61K2039/541 , A61K2039/55555 , Y10S436/829 , Y10T428/2984
摘要： The present invention relates to targeted polymerized liposomes for oral and/or mucosal delivery of vaccines, allergens and therapeutics. In particular, the present invention relates to polymerized liposomes which have been modified on their surface to contain a molecule or ligand which targets the polymerized liposome to a specific site or cell type. More particularly, the invention relates to the use of polymerized liposomes modified to contain a carbohydrate or lectin on their surface.

58. 发明授权

US6007845A Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers 失效
标题翻译：非线性亲水疏水多嵌段共聚物的纳米颗粒和微粒
公开(公告)号：US6007845A
公开(公告)日：1999-12-28
申请号：US582993
申请日：1996-03-25
申请人： Abraham J. Domb , Ruxandra Gref , Yoshiharu Minamitake , Maria Teresa Peracchia , Robert S. Langer
发明人： Abraham J. Domb , Ruxandra Gref , Yoshiharu Minamitake , Maria Teresa Peracchia , Robert S. Langer
IPC分类号： A61K9/51 , A61K9/50 , A61K9/14 , A61K9/16 , A61K9/48
CPC分类号： A61K9/5153 , Y10S514/963 , Y10T428/2985 , Y10T428/2989
摘要： Particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified to achieve variable release rates or to target specific cells or organs. The particles have a core of a multiblock copolymer formed by covalently linking a multifunctional compound with one or more hydrophobic polymers and one or more hydrophilic polymers, and contain a biologically active material. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the particles. The typical size of the particles is between 180 nm and 10,000 nm, preferably between 180 nm and 240 nm, although microparticles can also be formed as described herein. The particles can include magnetic particles or radiopaque materials for diagnostic imaging, biologically active molecules to be delivered to a site, or compounds for targeting the particles. The particles have a prolonged half-life in the blood compared to particles not containing poly(alkylene glycol) moieties on the surface.
摘要翻译： PCT No.PCT / US94 / 08287 Sec。 371日期1996年1月22日 102（e）日期1996年1月22日PCT提交1994年7月22日PCT公布。公开号WO95 / 03356 日期1995年2月2日提供了不被网状内皮系统的巨噬细胞迅速从血液中清除的颗粒，并且可以修饰以实现可变释放速率或靶向特定细胞或器官。颗粒具有通过共价连接多官能化合物与一种或多种疏水性聚合物和一种或多种亲水性聚合物形成的多嵌段共聚物的核心，并含有生物活性材料。聚（亚烷基二醇）的末端羟基可用于共价附着到颗粒表面上的生物活性分子，包括靶向特定细胞或器官的抗体或影响颗粒的电荷，亲油性或亲水性的分子。颗粒的表面也可以通过连接与形成颗粒核心的那些相同结构的可生物降解的聚合物来进行改性。颗粒的典型尺寸在180nm和10,000nm之间，优选在180nm和240nm之间，尽管也可以如本文所述形成微粒。颗粒可以包括用于诊断成像的磁性颗粒或不透射线的材料，要递送到位点的生物活性分子或用于靶向颗粒的化合物。与不含表面上的聚（亚烷基二醇）部分的颗粒相比，颗粒在血液中具有延长的半衰期。

59. 发明授权

US5985320A Materials and methods for enhancing cellular internalization 失效
标题翻译：用于增强细胞内化的材料和方法
公开(公告)号：US5985320A
公开(公告)日：1999-11-16
申请号：US810275
申请日：1997-03-03
申请人： David A. Edwards , Daniel R. Deaver , Robert S. Langer
发明人： David A. Edwards , Daniel R. Deaver , Robert S. Langer
IPC分类号： A61K9/06 , A61K9/00 , A61K9/127 , A61K31/70 , A61K31/7088 , A61K38/00 , A61K38/22 , A61K38/43 , A61K38/55 , A61K39/395 , A61K47/10 , A61K47/26 , A61K47/32 , A61K47/36 , A61K47/38 , A61K48/00 , A61K49/00
CPC分类号： A61K9/0043 , A61K47/38 , A61K9/0034 , A61K47/10 , A61K47/26 , A61K47/36 , Y10S436/829
摘要： Compositions and methods for delivering agents across cell membranes are disclosed. The compositions include an agent to be delivered, a viscous material, such as a hydrogel, lipogel or viscous sol, and, optionally, a carrier that includes a ligand that binds to or interacts with cell surface receptors. The agent to be delivered binds to or otherwise interacts with cell surface receptors, is attached, either covalently or ionically to a molecule that binds to or interacts with a cell surface receptor, or is associated with the carrier. Agents to be delivered include bioactive compounds and diagnostic agents. The compositions have an apparent viscosity roughly equal to the viscosity of the cytosol in the cell to which the agent is to be delivered. The rate of cellular internalization is higher when the viscosity of the viscous material and that of the cytosol in the cell are approximately the same, relative to when they are not the same. The compositions enhance cellular entry of bioactive agents and diagnostic materials when administered vaginally, nasally, rectally ocularly, orally, or to the respiratory or pulmonary system.
摘要翻译：公开了用于递送细胞膜的药剂的组合物和方法。组合物包括待递送的试剂，粘性物质，例如水凝胶，脂凝胶或粘稠溶胶，以及任选的包含与细胞表面受体结合或与细胞表面受体相互作用的配体的载体。待递送的药剂与细胞表面受体结合或以其他方式相互作用，与结合细胞表面受体或与细胞表面受体相关的分子共价或离子地连接。待递送的试剂包括生物活性化合物和诊断剂。组合物的表观粘度大致等于试剂要递送的细胞中细胞溶胶的粘度。当粘性物质和细胞质中的细胞溶胶的粘度相差不大时，细胞内化速率较高。当阴道，鼻，直肠眼，口服或呼吸或肺部系统施用时，组合物增强生物活性剂和诊断材料的细胞进入。

60. 发明授权

US5912017A Multiwall polymeric microspheres 失效
标题翻译：多壁聚合物微球
公开(公告)号：US5912017A
公开(公告)日：1999-06-15
申请号：US906403
申请日：1992-07-01
申请人： Edith Mathiowitz , Robert S. Langer
发明人： Edith Mathiowitz , Robert S. Langer
IPC分类号： A61K9/16 , A61K9/50 , A61K9/52 , B01J13/12
CPC分类号： A61K9/1694 , A61K9/5089 , Y10S514/963 , Y10S514/965 , Y10T428/2987 , Y10T428/2989
摘要： A method for preparation of multi-layer polymeric microspheres formed from any degradable or non-degradable polymers which are not soluble in each other at a particular concentration, but which have a positive spreading coefficient in solution. The multi-layer microspheres produced by the method are distinguished by extremely uniform dimensioned layers of polymer and actual incorporation of the substance to be delivered into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in a volatile organic solvent, the substance to be incorporated is dispersed or dissolved in the polymer solution, the mixture is suspended in an aqueous solution and stirred, and the solvent is slowly evaporated, creating microspheres with an inner core formed by one polymer and an outer layer formed by the second polymer. In another embodiment, solvent is removed by spray drying. In still another embodiment, polymers are melted and combined with the substance to be incorporated, then cooled to form layered microspheres.
摘要翻译：一种由任何可溶解或不可降解的聚合物制备的多层聚合物微球的方法，它们在特定浓度下彼此不溶，但在溶液中具有正扩散系数。通过该方法制备的多层微球的特征在于聚合物尺寸非常均匀，并且实际掺入待递送到聚合物层中的物质。在该方法的优选实施方案中，将两种聚合物溶解在挥发性有机溶剂中，将待引入的物质分散或溶解在聚合物溶液中，将混合物悬浮在水溶液中并搅拌，并将溶剂缓慢蒸发，产生具有由一种聚合物形成的内芯和由第二聚合物形成的外层的微球。在另一个实施方案中，通过喷雾干燥除去溶剂。在另一个实施方案中，将聚合物熔化并与待掺入的物质组合，然后冷却形成层状微球。

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