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181. 发明授权

US06309635B1 Seeding parenchymal cells into compression resistant porous scaffold after vascularizing in vivo 失效
标题翻译：在体内血管化后将实质细胞接种到抗压多孔支架中
公开(公告)号：US06309635B1
公开(公告)日：2001-10-30
申请号：US08345217
申请日：1994-11-28
申请人： Donald E. Ingber , Robert S. Langer , Joseph P. Vacanti
发明人： Donald E. Ingber , Robert S. Langer , Joseph P. Vacanti
IPC分类号： A01N6300
CPC分类号： A61L27/3804 , A61F2/022 , A61F2/062 , A61L27/3839 , A61L2430/06 , C12N5/0068 , C12N5/0671 , C12N2501/18 , C12N2533/30 , C12N2533/40
摘要： A method is provided whereby cells having a desired function are seeded on and into biocompatible, biodegradable or non-degradable porous polymer scaffolding matrix, previously implanted in a patient and infiltrated with blood vessels and connective tissue, to produce a functional organ equivalent. The resulting organoid is a chimera formed of parenchymal elements of the donated tissue and vascular and matrix elements of the host. The matrix should be compression resistant and a non-toxic, porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, should allow vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix, and the injection of cells such as hepatocytes without damage to the cells or patient. The introduced cells attach to the connective tissue and are fed by the blood vessels. Immediately prior to matrix implantation portacaval shunts can be created to provide trophic stimulatory factors to the implanted matrix to enhance replication and function.
摘要翻译：提供了一种方法，其中具有期望功能的细胞接种在生物相容性，可生物降解或不可降解的多孔聚合物支架基质上，先前植入患者并渗入血管和结缔组织，以产生功能性器官当量。所得的有机体是由捐赠的组织的实质元素和宿主的血管和基质元素形成的嵌合体。基质应具有抗压缩性和无毒，多孔的模板用于血管向内生长。通常在约100和300微米之间的孔径应允许血管和结缔组织在基质的约10至90％内向内生长，并且注射细胞如肝细胞而不损伤细胞或患者。引入的细胞附着于结缔组织并由血管进食。在矩阵植入之前，可以产生口腔分流，以向植入的基质提供营养刺激因子以增强复制和功能。

182. 发明授权

US06306819B1 Method for regulating size of vascularized normal tissue 有权
标题翻译：调节血管化正常组织大小的方法
公开(公告)号：US06306819B1
公开(公告)日：2001-10-23
申请号：US09183556
申请日：1998-10-30
申请人： Maria Rupnick , Robert S. Langer , Judah Folkman
发明人： Maria Rupnick , Robert S. Langer , Judah Folkman
IPC分类号： A61K3800
CPC分类号： A61K38/484 , A61K31/00 , A61K31/336 , A61K31/454 , A61K38/39
摘要： Angiogenesis inhibitors are administered to patients in an amount effective to regulate normal, non-transformed vascularized tissue size and/or growth by regulating its vascular compartment. Examples of tissues that can be controlled include adipose tissue, intestinal polyps, muscle (including cardiac) tissue, and endometrial tissue. The response of these tissues to the angiogenesis inhibitors is dose-dependent, reversible, and common to a variety of different angiogenesis inhibitors (examples use TNP-470, angiostatin, and endostatin), based on studies in animal models of obesity, intestinal polyps, cardiac hypertrophy, and endometriosis. Initial studies conducted in an adipose tissue model (genetically obese mice and normal control mice) showed that the growth and mass of adipose tissue is under the control of microvascular endothelium. Expansion of adipose tissue was associated with endothelial cell proliferation. Inhibition of angiogenesis led to reduction in adipose tissue mass. Weight gain in animals receiving angiogenesis inhibitors was significantly restricted, in spite of increases in appetite sufficient to cause weight gain in paired-fed mice. Discontinuation of the inhibitor resulted in rapid expasion of the adipose tissue. The effect was dose-dependent, repeatedly reversible, and occurred in response to all of the inhibitors tested. Significant inhibition was also observed in both the intestinal polyp and cardiac hypertrophy animal models, using dosages of two-thirds or less than the dosages used to treat tumors. Preliminary results in an endometriosis model also show a clear trend towards decreased development of endometriosis in animals treated with angiogenesis inhibitors at a dosage of one-third the dosage used to treat tumors. No effect on normal tissue that was not proliferating, other than adipose tissue, was observed.
摘要翻译：血管生成抑制剂以有效调节正常，非转化的血管化组织尺寸和/或通过调节其血管隔室生长的量施用于患者。可以控制的组织的实例包括脂肪组织，肠息肉，肌肉（包括心脏）组织和子宫内膜组织。这些组织对血管生成抑制剂的反应是剂量依赖性的，可逆的，并且对多种不同的血管发生抑制剂是常见的（实例使用TNP-470，血管抑素和内皮抑制素），基于对肥胖，肠息肉动物模型的研究，心脏肥大和子宫内膜异位症。在脂肪组织模型（遗传肥胖小鼠和正常对照小鼠）中进行的初步研究表明，脂肪组织的生长和质量处于微血管内皮的控制之下。脂肪组织的扩张与内皮细胞增殖有关。抑制血管生成导致脂肪组织质量下降。接受血管生成抑制剂的动物的体重增加受到显着限制，尽管食欲增加足以引起配对饲喂小鼠的体重增加。抑制剂的停用导致脂肪组织的快速释放。该效应是剂量依赖性的，反复可逆的，并且响应所有测试的抑制剂而发生。在肠息肉和心脏肥大动物模型中也观察到显着的抑制作用，其使用剂量为用于治疗肿瘤的剂量的三分之二或更少。子宫内膜异位症模型的初步结果也显示出以血管生成抑制剂治疗的动物减少子宫内膜异位症发展的明显趋势，其剂量为用于治疗肿瘤的剂量的三分之一。观察到除了脂肪组织之外对正常组织没有增殖的影响。

183. 发明授权

US06241771B1 Resorbable interbody spinal fusion devices 失效
公开(公告)号：US06241771B1
公开(公告)日：2001-06-05
申请号：US09131716
申请日：1998-08-10
申请人： Joseph D. Gresser , Debra J. Trantolo , Robert S. Langer , Kai-Uwe Lewandrowski , Alexander M. Klibanov , Donald L. Wise
发明人： Joseph D. Gresser , Debra J. Trantolo , Robert S. Langer , Kai-Uwe Lewandrowski , Alexander M. Klibanov , Donald L. Wise
IPC分类号： A61F244
CPC分类号： A61F2/4455 , A61F2/30965 , A61F2/442 , A61F2002/2835 , A61F2002/30062 , A61F2002/30112 , A61F2002/30133 , A61F2002/30153 , A61F2002/30179 , A61F2002/30217 , A61F2002/30772 , A61F2002/30785 , A61F2002/30789 , A61F2002/30868 , A61F2002/30904 , A61F2002/30957 , A61F2210/0004 , A61F2230/0004 , A61F2230/0015 , A61F2230/0019 , A61F2230/0058 , A61F2230/0067 , Y10S623/926
摘要： A resorbable interbody fusion device for use in spinal fixation is disclosed. The device is composed of 25-100% bioresorbable or resorbable material. The interbody fusion device of the invention can be in any convenient form, such as a wedge, screw or cage. Preferably, the resorbable device of the invention is in the shape of a tapered wedge or cone, which further desirably incorporates structural features such as serrations or threads better to anchor the device in the adjoining vertebrae. The preferred device further comprises a plurality of peripheral voids and more desirably a central void space therein, which may desirably be filled with a grafting material for facilitating bony development and/or spinal fusion, such as an autologous grafting material. As the preferred material from which the resorbable interbody fusion device is manufactured is most likely to be a polymer that can produce acidic products upon hydrolytic degradation, the device preferably further includes a neutralization compound, or buffer, in sufficiently high concentration to decrease the rate of pH change as the device degrades, in order to prevent sterile abscess formation caused by the accumulation of unbuffered acidic products in the area of the implant.

184. 发明授权

US6095148A Neuronal stimulation using electrically conducting polymers 失效
标题翻译：使用导电聚合物进行神经元刺激
公开(公告)号：US6095148A
公开(公告)日：2000-08-01
申请号：US552761
申请日：1995-11-03
申请人： Venkatram R. Shastri , Christine E. Schmidt , Robert S. Langer , Joseph P. Vacanti
发明人： Venkatram R. Shastri , Christine E. Schmidt , Robert S. Langer , Joseph P. Vacanti
IPC分类号： A61L17/00 , A61L27/00 , A61L31/04 , A61L31/06 , A61L31/14 , C12N5/00 , C12N5/06 , C12N13/00 , A61B19/00
CPC分类号： C12N13/00 , A61L31/048 , A61L31/06 , A61L31/14 , C12M25/08 , C12M35/02 , C12M35/08 , C12N5/0068 , C12N2533/30 , C12N2533/40
摘要： Methods and support systems are provided for modifying the regeneration, differentiation, or function of cells. In one embodiment, electrically conducting biocompatible polymers may be used alone or in combination with a polymeric support for in vitro nerve cell regeneration, or in vivo to aid in healing nervous tissue defects. The conductive polymers may implanted adjacent to or seeded with nerve cells. Voltage or current is applied to the polymer in a range which induces the desired effect on the cells while not damaging the cells. The methods and systems can be used in a variety of applications to enhance in vivo or in vitro growth or regeneration of nervous tissue.
摘要翻译：提供了用于修饰细胞的再生，分化或功能的方法和支持系统。在一个实施方案中，导电生物相容性聚合物可以单独使用或与用于体外神经细胞再生的聚合物载体组合使用，或在体内用于帮助治愈神经组织缺陷。导电聚合物可以与神经细胞相邻或接种植入。电压或电流在一定范围内施加到聚合物上，该范围对细胞产生期望的影响，同时不破坏细胞。所述方法和系统可用于各种应用以增强神经组织的体内或体外生长或再生。

185. 发明授权

US06046187A Formulations and methods for providing prolonged local anesthesia 失效
公开(公告)号：US06046187A
公开(公告)日：2000-04-04
申请号：US714783
申请日：1996-09-16
申请人： Charles B. Berde , Robert S. Langer , Joanne Curley , Jenny Castillo
发明人： Charles B. Berde , Robert S. Langer , Joanne Curley , Jenny Castillo
IPC分类号： A61K45/06 , A61K9/00 , A61K9/16 , A61K31/00 , A61K31/445 , A61K31/56 , A61K31/57 , A61K31/573 , A61P23/00 , A61P23/02
CPC分类号： A61K31/57 , A61K9/0024 , A61K9/1647 , Y10S514/818
摘要： The use of glucocorticosteroids in methods and formulations for prolonging and/or reactivating local anesthesia or local anesthesia previously induced by a local anesthetic agent, is disclosed.

186. 发明授权

US6041253A Effect of electric field and ultrasound for transdermal drug delivery 失效
标题翻译：电场和超声对透皮给药的影响
公开(公告)号：US6041253A
公开(公告)日：2000-03-21
申请号：US626021
申请日：1996-04-01
申请人： Joseph Kost , Uwe Pliquett , Samir S. Mitragotri , Robert S. Langer , James C. Weaver
发明人： Joseph Kost , Uwe Pliquett , Samir S. Mitragotri , Robert S. Langer , James C. Weaver
IPC分类号： A61K9/00 , A61K41/00 , A61M37/00 , A61N1/32 , A61N1/30
CPC分类号： A61N1/325 , A61B5/14514 , A61K41/0047 , A61K9/0009 , A61M37/0092 , A61N1/0412 , A61N1/327 , A61M2037/0007 , A61N1/042 , A61N1/0428
摘要： Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.
摘要翻译：可以通过施加电场（例如电穿孔或离子电渗疗法）来进一步增强超声波输送（递送或提取）期间分子的透皮转运。在优选实施例中，超声是低频超声，其引起角质层（SC）的脂质层的空化。该方法提供较高的药物透皮通量，允许快速控制透皮通量，并且能够在不存在电场的情况下以较低的超声强度进行药物递送或分析物提取。

187. 发明授权

US6025331A Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis 失效
标题翻译：包含肌钙蛋白亚基，其片段和类似物的药物组合物及其用于抑制血管生成的方法
公开(公告)号：US6025331A
公开(公告)日：2000-02-15
申请号：US961264
申请日：1997-10-30
申请人： Marsha A. Moses , Robert S. Langer , Dimitri G. Wiederschain , Inmin Wu , Arthur Sytkowski
发明人： Marsha A. Moses , Robert S. Langer , Dimitri G. Wiederschain , Inmin Wu , Arthur Sytkowski
IPC分类号： A61K38/00 , A61K31/00 , A61P9/00 , A61P35/00 , A61P43/00 , C07K14/435 , C07K14/47 , A61K38/16 , A61K38/17
CPC分类号： C07K14/4716 , A61K38/00
摘要： Pharmaceutical compositions containing therapeutically effective amounts of troponin C, I, or T, subunits, fragments, or analogs for the treatment of diseases or disorders involving abnormal angrogenesis.
摘要翻译：含有治疗有效量的肌钙蛋白C，I或T，亚单位，片段或类似物用于治疗涉及异常血管发生的疾病或病症的药物组合物。

188. 发明授权

US5985309A Preparation of particles for inhalation 失效
标题翻译：吸入颗粒的制备
公开(公告)号：US5985309A
公开(公告)日：1999-11-16
申请号：US971791
申请日：1997-11-17
申请人： David A. Edwards , Robert S. Langer , Rita Vanbever , Jeffrey Mintzes , Jue Wang , Donghao Chen
发明人： David A. Edwards , Robert S. Langer , Rita Vanbever , Jeffrey Mintzes , Jue Wang , Donghao Chen
IPC分类号： A61K9/16 , A61K31/135 , A61K31/137 , A61K38/28 , A61K38/38 , A61K13/00
CPC分类号： A61K9/1647 , A61K31/135 , A61K31/137 , A61K38/28 , A61K38/38
摘要： Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm.sup.3 and a mass mean diameter between 5 .mu.m and 30 .mu.m, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration.
摘要翻译：提供了将具有正或负电荷的治疗剂的表面活性剂和/或亲水或疏水配合物和用于药物递送至肺系统的带电分子的相反电荷的颗粒，以及用于其合成和给药的方法。在优选的实施方案中，颗粒由可生物降解的材料制成，并且具有小于0.4g / cm 3的振实密度和5μm至30μm之间的质量平均直径，其一起产生颗粒的空气动力学直径在约一和三微米。颗粒可以由可生物降解的材料如可生物降解的聚合物形成。例如，颗粒可以由聚（乳酸）或聚（乙醇酸）或其共聚物形成。或者，颗粒可以仅由治疗剂或诊断剂和表面活性剂形成。表面活性剂可以结合在颗粒表面上，例如通过在颗粒形成之后涂覆颗粒，或者通过在形成颗粒之前将表面活性剂并入形成颗粒的材料中。示例性表面活性剂包括磷酸甘油酯，例如二棕榈酰磷脂酰胆碱（DPPC）。这些颗粒可以有效地雾化，用于给呼吸道施用以允许全身或局部递送各种各样的治疗剂。正电荷或带负电荷的治疗剂与相反电荷分子的复合物的形成可以允许在给药后将药剂释放到血流中的释放速率。

189. 发明授权

US5922340A High load formulations and methods for providing prolonged local anesthesia 失效
标题翻译：高负荷配方及方法，可延长局部麻醉
公开(公告)号：US5922340A
公开(公告)日：1999-07-13
申请号：US714782
申请日：1996-09-16
申请人： Charles B. Berde , Robert S. Langer , Joanne Curley , Jenny Castillo
发明人： Charles B. Berde , Robert S. Langer , Joanne Curley , Jenny Castillo
IPC分类号： A61K9/00 , A61K9/16 , A61K9/20 , A61K31/165 , A61K31/167 , A61K31/245 , A61K31/445 , A61K31/47 , A61K45/06 , A61K9/50 , A61K9/52 , A61L15/64
CPC分类号： A61K45/06 , A61K31/165 , A61K31/167 , A61K31/245 , A61K31/445 , A61K31/47 , A61K9/1641 , A61K9/1647 , A61K9/2031 , A61K9/0024 , Y10S514/817
摘要： A formulation for inducing sustained local anesthesia in a patient comprising a substrate comprising a high load of local anesthetic by weight and an effective amount of a biocompatible, controlled release material to obtain a reversible nerve blockade or anesthesia effect when implanted or injected in a patient, and a non-toxic glucocorticosteroid agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the glucocorticosteroid agent.
摘要翻译：一种用于在患者中诱导持续局部麻醉的制剂，其包含基于重量的高负荷局部麻醉剂和有效量的生物相容性控制释放材料的基质，以在植入或注射到患者体内时获得可逆神经阻断或麻醉作用，和无毒性糖皮质激素剂，其有效地延长局部麻醉的持续时间比不含糖皮质激素药物的时间长。

190. 发明授权

US5843741A Method for altering the differentiation of anchorage dependent cells on an electrically conducting polymer 失效
标题翻译：改变导电聚合物上锚定依赖细胞分化的方法
公开(公告)号：US5843741A
公开(公告)日：1998-12-01
申请号：US283402
申请日：1994-08-01
申请人： Joyce Y. Wong , Donald E. Ingber , Robert S. Langer
发明人： Joyce Y. Wong , Donald E. Ingber , Robert S. Langer
IPC分类号： C12N5/00 , C12N13/00
CPC分类号： C12N5/0068 , C12N13/00 , C12N2533/30
摘要： Described is a method and cell culture system for altering the proliferation, differentiation, or function of anchorage dependent cells which includes associating the cells with a surface formed of an electrically conducting polymer and applying an effective amount of a voltage to change the oxidation state of the polymer without damaging the cells.
摘要翻译：描述了一种用于改变锚定依赖性细胞的增殖，分化或功能的方法和细胞培养系统，其包括将细胞与由导电聚合物形成的表面缔合并施加有效量的电压以改变所述细胞的氧化态聚合物，而不破坏细胞。

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