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公开(公告)号：US20080268021A1
公开(公告)日：2008-10-30
申请号：US12215101
申请日：2008-06-24
IPC分类号： A61K9/70 , A61K31/403 , A61K31/4523
CPC分类号： A61K9/0051 , A61K9/7023
摘要： The present invention provides bioerodible, water-soluble pharmaceutical carriers for ocular (e.g., transconjunctival or transcorneal) delivery of pharmaceuticals for either systemic or local therapy.
摘要翻译： 本发明提供用于全身或局部治疗的药物的用于眼部（例如，结膜结肠或转角膜）递送的生物可腐蚀的水溶性药物载体。
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2.发明授权Methods of treatment of androgenic steroidal hormone dependent cancer with auger electron-emitting nucleoside analogs 失效用螺旋电子发射核苷类似物治疗雄激素类固醇激素依赖性癌症的方法公开(公告)号：US08470295B2
公开(公告)日：2013-06-25
申请号：US12599594
申请日：2008-05-09
CPC分类号： A61K31/00 , A61K38/1703 , A61K38/18 , A61K38/1866 , A61K38/195 , A61K38/20 , A61K38/22 , A61K45/06 , A61K48/00 , A61K51/0491 , A61K2300/00
摘要： A method is provided for treatment of disorders involving hyperproliferative cells, such as malignancies, advanced stage solid tumors like glioblastoma multiforme, and non-malignant hyperproliferative pathological conditions such as adult macular degeneration. A short range, unselective cell killing radiotherapeutic substance is administered, optionally in a spatially defined volume of tissue, optionally in combination with a mitogenic agent that stimulates or induces DNA biosynthesis. In this way, the percentage of hyperproliferative that are susceptible to killing by the radiotherapeutic agent is increased. Cancer stem cells can be induced to enter S phase with the mitogenic agent, then killed with the radiotherapeutic agent. Thus, not only does the combination effectively kill the transit amplifying cell population, the most rapidly replicating type of cell in a tumor, but it also effectively kills the tumor stem cells, which give rise to the transit amplifying cells, for a longer lasting anticancer effect.
摘要翻译： 提供了用于治疗涉及过度增殖细胞例如恶性肿瘤，晚期实体瘤如多形性成胶质细胞瘤的病症和非恶性过度增殖病理状况如成人黄斑变性的病症的方法。 任选地在空间上限定的组织体内施用短程，非选择性细胞杀伤放射治疗物质，任选与刺激或诱导DNA生物合成的促有丝分裂剂组合。 以这种方式，放射治疗剂易于杀死的过度增殖的百分比增加。 可以诱导癌干细胞与促有丝分裂剂进入S期，然后用放射治疗剂杀死。 因此，不仅组合有效地杀死了肿瘤中最快速复制型细胞的转运扩增细胞群，而且还有效地杀死了产生转运扩增细胞的肿瘤干细胞，以达到更持久的抗癌作用 影响。
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公开(公告)号：US20070231301A1
公开(公告)日：2007-10-04
申请号：US11692624
申请日：2007-03-28
申请人： Stephen L. Warren
发明人： Stephen L. Warren
CPC分类号： A61K38/21 , A61K38/212 , A61K39/04 , A61K2300/00
摘要： Novel methods and drug products for treating superficial bladder cancer (SBC) are disclosed, which involve parenteral administration of low doses of a type 1 interferon. The doses used are subtherapeutic for other solid tumors. Use of the novel methods and products in combination with other therapies for SBC is also described.
摘要翻译： 公开了用于治疗浅表性膀胱癌（SBC）的新方法和药物产品，其涉及低剂量的1型干扰素的肠胃外给药。 使用的剂量是其他实体瘤的次治疗剂。 还描述了与SBC的其它疗法组合使用新颖的方法和产品。
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公开(公告)号：US6007985A
公开(公告)日：1999-12-28
申请号：US348718
申请日：1994-12-02
申请人： Stephen L. Warren
发明人： Stephen L. Warren
CPC分类号： C12N9/1247 , C12N15/87 , A61K38/00
摘要： Antibodies to the large subunit of DNA-dependent RNA polymerase II (Pol II LS) and methods of use thereof, including use as research tools and for the diagnosis of proliferative diseases such as cancer and the screening of anti-cancer therapies, and a method for delivering molecules to predetermined sites in the nucleus of a cell using a molecule containing the C-terminal domain of the Pol II LS protein. The anti-Pol II LS antibodies are highly specific for phosphorylated Pol II LS and bind to the C-terminal domain of the Pol II LS molecule in a phosphorylation-dependent manner.
摘要翻译： DNA依赖性RNA聚合酶II（Pol II LS）的大亚基的抗体及其使用方法，包括用作研究工具和诊断增殖性疾病如癌症和抗癌疗法的筛选方法 用于使用含有Pol II LS蛋白的C-末端结构域的分子将分子递送至细胞核中的预定位点。 抗Pol II LS抗体对磷酸化的Pol II LS具有高度特异性，并以磷酸化依赖性方式结合Pol II LS分子的C末端结构域。
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公开(公告)号：US20090304576A1
公开(公告)日：2009-12-10
申请号：US12375349
申请日：2007-07-06
CPC分类号： A61K9/0024 , A61K9/0085 , A61K9/70 , A61K51/0491 , A61K51/1282 , A61N5/1007 , A61N2005/1024
摘要： A filament comprising a biocompatible material and a bioactive agent, adapted for implantation within the tissue of a patient wherein the bioactive agent is released over a period of time, is provided. An array of a plurality of the filaments implanted within the tissue of a patient, an array assembler, and a matrix comprising a plurality of filaments and a base adapted for implantation within the tissue of a patient, are further provided. A method for treatment of a malcondition in a patient comprises implantation of a filament, an array of filaments, or a matrix. The bioactive agent can be a chemotherapeutic agent or a radiotherapeutic agent. A radiotherapeutic agent is 123I- or 125I-IUDR, for example in treatment of an advanced stage localized brain tumor such as glioblastoma multiforme.
摘要翻译： 提供了包含生物相容性材料和生物活性剂的长丝，其适于植入患者组织内，其中生物活性剂在一段时间内释放。 还提供了植入患者组织内的多个细丝的阵列，阵列组装器，以及包括多个细丝的基质和适于植入患者组织内的基底。 用于治疗患者病情的方法包括将细丝植入，细丝阵列或基质。 生物活性剂可以是化学治疗剂或放射治疗剂。 放射治疗剂是123I-或125I-IUDR，例如在治疗晚期局部脑肿瘤如多形性成胶质细胞瘤中。
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公开(公告)号：US20090092650A1
公开(公告)日：2009-04-09
申请号：US11793296
申请日：2005-12-15
CPC分类号： A61K38/31 , A61K9/0021 , A61K9/19 , A61K47/34
摘要： The present invention relates to an octreotide sustained release delivery system for treatment of diseases relating to somatotropin and/or somatostatin. The sustained release delivery system of the invention includes a flowable composition containing an octreotide compound, and an implant containing the octreotide compound. The flowable composition may be injected into tissue whereupon it coagulates to become the solid or gel, monolithic implant. The flowable composition includes a biodegradable, thermoplastic polymer, an organic liquid and an octreotide compound.
摘要翻译： 本发明涉及用于治疗与生长激素和/或生长抑素有关的疾病的奥曲肽缓释递送系统。 本发明的持续释放递送系统包括含有奥曲肽化合物的可流动组合物和含有奥曲肽化合物的植入物。 可流动组合物可以注射到组织中，随后凝结成为固体或凝胶，整体式植入物。 可流动组合物包括可生物降解的热塑性聚合物，有机液体和奥曲肽化合物。
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7.发明授权Genetically engineered endothelial cells exhibiting enhanced migration and plasminogen activator activity 失效遗传工程化内皮细胞表现出增强的迁移和纤溶酶原激活物活性
公开(公告)号：US5336615A
公开(公告)日：1994-08-09
申请号：US820011
申请日：1992-01-06
CPC分类号： A61L27/507 , A61L31/005 , C07K14/82 , A61K38/00 , Y10S623/925
摘要： Genetically engineered endothelial cells which exhibit enhanced cell migration and enhanced urokinase-type plasminogen activator (u-PA) activity are provided. The cells are modified by incorporation of the coding sequence for the c-src gene so that the cells express elevated levels of the tyrosine kinase protein, pp60.sup.c-src. The C-src gene is a naturally occurring gene which appears to be present in all animal species and is highly conserved. Because of their enhanced migration rates, the modified cells can be used to efficiently seed denuded segments of vessels or natural or synthetic grafts prior to implantation. Because of their enhanced u-PA activity, the cells can reduce the probability of thrombus formation at sites of vessel damage, such as that produced during such surgical procedures as coronary angioplasty and vessel reconstruction with grafts, stents, or the like.
摘要翻译： 提供表现出增强的细胞迁移和增强的尿激酶型纤溶酶原激活物（u-PA）活性的遗传工程化内皮细胞。 通过掺入c-src基因的编码序列修饰细胞，使得细胞表达高水平的酪氨酸激酶蛋白质pp60c-src。 C-src基因是天然存在的基因，其似乎存在于所有动物物种中并且是高度保守的。 由于其增加的迁移速率，修饰的细胞可用于在植入之前有效地种植血管或天然或合成移植物的裸露段。 由于其增强的u-PA活性，细胞可以降低血管损伤部位处血栓形成的可能性，例如在诸如冠状动脉血管成形术和移植物，支架等的血管重建的外科手术过程中产生的血栓形成的可能性。
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公开(公告)号：US20110135569A1
公开(公告)日：2011-06-09
申请号：US12531825
申请日：2008-03-19
CPC分类号： A61K51/0491 , Y10T137/0402
摘要： Methods are provided for the local radiotherapy of cancers such as locally invasive, advanced stage solid tumors, and normal tissues penetrated by processes of cancerous tissue, through administration of Auger-electron emitting radionucleoside analogs using high-flow microinfusion techniques (“convection-enhanced delivery”). Direct infusion under pressure, at flow rates in excess of at least about 0.5 microliters/min of the radionucleosides provides for their mass transport through tissue to a much higher degree than could be achieved by passive, unpressurized diffusion. The unique properties of these radionucleoside analogs that provide for surprisingly effacacious delivery by high-flow microinfusion include rapid clearance from tissues following local injection without the benefit of sustained high-flow microinfusion, rapid and complete clearance via the blood stream, poor permeation of barriers such as the blood-brain barrier, and a highly potent, non-selective, but very short range killing effect on cells that are undergoing DNA replication that incorporate radionucleosides into their chromosomes.
摘要翻译： 通过使用高流量微灌注技术（“对流增强递送”）施用俄歇电子发射放射性核苷类似物，为局部放射治疗癌症的局部放疗提供了方法，例如局部侵袭性，晚期实体瘤和由癌组织进程穿透的正常组织 “）。 在压力下直接输注超过至少约0.5微升/分钟的放射性核苷的流速提供了它们通过组织传播的程度比通过被动的，未加压的扩散可以达到的程度高得多。 这些放射性核苷类似物的独特性质，通过高流量微灌注提供令人惊讶的高效递送，包括局部注射后从组织快速清除，而不受持续高流量微灌注的影响，通过血流快速和完全清除，障碍物渗透差 作为血脑屏障，以及对正在经历DNA复制的细胞的非常有效，非选择性但非常短程的杀伤作用，其将放射性核苷掺入染色体。
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公开(公告)号：US20100233081A1
公开(公告)日：2010-09-16
申请号：US12599594
申请日：2008-05-09
CPC分类号： A61K31/00 , A61K38/1703 , A61K38/18 , A61K38/1866 , A61K38/195 , A61K38/20 , A61K38/22 , A61K45/06 , A61K48/00 , A61K51/0491 , A61K2300/00
摘要： A method is provided for treatment of disorders involving hyperproliferative cells, such as malignancies, advanced stage solid tumors like glioblastoma multiforme, and non-malignant hyperproliferative pathological conditions such as adult macular degeneration. A short range, unselective cell killing radiotherapeutic substance is administered, optionally in a spatially defined volume of tissue, optionally in combination with a mitogenic agent that stimulates or induces DNA biosynthesis. In this way, the percentage of hyperproliferative that are susceptible to killing by the radiotherapeutic agent is increased. Cancer stem cells can be induced to enter S phase with the mitogenic agent, then killed with the radiotherapeutic agent. Thus, not only does the combination effectively kill the transit amplifying cell population, the most rapidly replicating type of cell in a tumor, but it also effectively kills the tumor stem cells, which give rise to the transit amplifying cells, for a longer lasting anticancer effect.
摘要翻译： 提供了用于治疗涉及过度增殖细胞例如恶性肿瘤，晚期实体瘤如多形性成胶质细胞瘤的病症和非恶性过度增殖病理状况如成人黄斑变性的病症的方法。 任选地在空间上限定的组织体内施用短程，非选择性细胞杀伤放射治疗物质，任选与刺激或诱导DNA生物合成的促有丝分裂剂组合。 以这种方式，放射治疗剂易于杀死的过度增殖的百分比增加。 可以诱导癌干细胞与促有丝分裂剂进入S期，然后用放射治疗剂杀死。 因此，不仅组合有效地杀死了肿瘤中最快速复制型细胞的转运扩增细胞群，而且还有效地杀死了产生转运扩增细胞的肿瘤干细胞，以达到更持久的抗癌作用 影响。
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公开(公告)号：US6090784A
公开(公告)日：2000-07-18
申请号：US566190
申请日：1995-12-01
申请人： Stephen L. Warren
发明人： Stephen L. Warren
CPC分类号： C12N9/1247 , A61K47/48238 , C12N15/62 , A61K38/00 , C07K2319/09 , C07K2319/43 , C07K2319/90
摘要： A macromolecular delivery method that utilizes a series of peptides with unique and versatile nuclear targeting properties has been developed, where the peptides are derived from the COOH terminal domain (CTD) of the largest subunit of RNA polymerase II and include heptapeptide units similar or identical to the following consensus sequence: Tyrosine--Serine--Proline--Threonine--Serine--Proline--Serine (YSPTSPS).sub.x (SEQ ID NO. 1). When expressed in vivo, the CTD peptides are phosphorylated and they accumulate in discrete compartments within the nucleus. The CTD peptides concentrate indicator molecules in discrete subnuclear compartments where pre-mRNA molecules are synthesized and spliced. The length and composition of the CTD peptides can be manipulated to obtain different intranuclear partitioning properties. The CTD peptides are functional in the nuclei of S. cerevisiae, S. pombe, nematodes, insects, plants, and all vertebrates. Since the CTD peptides accumulate precisely in discrete sites inhabited by RNA polymerase II and the spliceosomes, they should be useful in genetic therapy technologies.
摘要翻译： 已经开发了利用具有独特且通用的核定向特性的一系列肽的大分子递送方法，其中肽衍生自RNA聚合酶II的最大亚基的COOH末端结构域（CTD），并且包括与肽聚合酶II相似或相同的七肽单元 以下共有序列：酪氨酸 - 丝氨酸 - 脯氨酸 - 苏氨酸 - 丝氨酸 - 脯氨酸 - 丝氨酸（YSPTSPS）x（SEQ ID NO.1）。 当在体内表达时，CTD肽被磷酸化并且它们积聚在细胞核内的离散区室中。 CTD肽将指示剂分子浓缩在离散的亚核隔室中，其中前mRNA分子被合成和剪接。 可以操纵CTD肽的长度和组成以获得不同的核内分配性质。 CTD肽在酿酒酵母，芽孢杆菌，线虫，昆虫，植物和所有脊椎动物的核中起作用。 由于CTD肽正好在RNA聚合酶II和剪接体所在的离散位点中积累，所以它们在遗传治疗技术中应该是有用的。
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