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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：US07655254B2
公开(公告)日：2010-02-02
申请号：US11347601
申请日：2006-02-03
申请人： Paula Dennis , Michael A. Desjardin , Stan Lam , Kui Liu , James E. Matsuura , Latha Narayanan , Catherine M. Rohloff , Pauline C. Zamora
发明人： Paula Dennis , Michael A. Desjardin , Stan Lam , Kui Liu , James E. Matsuura , Latha Narayanan , Catherine M. Rohloff , Pauline C. Zamora
CPC分类号： A61K38/21 , A61F2250/0068 , A61K9/0004 , A61K9/0019 , A61K9/0024 , A61K9/10 , A61K9/1617 , A61K9/1623 , A61K9/1694 , A61K9/19
摘要： An implantable device includes a reservoir containing a suspension of an interferon in an amount sufficient to provide continuous delivery of the interferon at a therapeutically effective rate of 1 ng/day to 600 μg/day to maintain and achieve therapeutic blood or plasma levels of the interferon throughout a substantial period of the administration period.
摘要翻译： 可植入装置包括含有干扰素悬浮液的储存器，其量足以提供以1ng /天至600ug /天的治疗有效速率连续递送干扰素，以维持和实现干扰素的治疗血浆或血浆水平 在行政期间的相当长的一段时期。
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公开(公告)号：US08600479B2
公开(公告)日：2013-12-03
申请号：US12531808
申请日：2008-03-20
申请人： William D. Dalke , Kevin Lillehei , Thomas A. Jellison , Michael J. Gerber , James E. Matsuura , Stephen L Warren
发明人： William D. Dalke , Kevin Lillehei , Thomas A. Jellison , Michael J. Gerber , James E. Matsuura , Stephen L Warren
IPC分类号： A61B5/05
CPC分类号： A61K51/0491 , Y10T137/0402
摘要： A catheter system adapted for navigating, guiding and implanting a catheter or a plurality of catheters in a spatially-defined implantation within the tissue of a patient is provided. The system can include a tissue navigation system and a probe to inform the navigation system to guide emplacement of the catheters within a target tissue. The probe can provide images, such as fiberoptic visual images, or ultrasound images, or can provide radiolocation data, to guide the catheter emplacement. The catheters supply a pressurized liquid including a bioactive agent, such as can be used in the treatment of cancer, for example 123I- or 125I-IUDR. The system and methods provided can be used in the treatment of locally advanced tumors, such as cancers of the brain, head or neck, esophagus, prostate, ovary, liver, pancreas, bladder or rectum.
摘要翻译： 提供了一种导管系统，其适于在病人组织内的空间限定的植入物中导航，引导和植入导管或多个导管。 该系统可以包括组织导航系统和探针，以通知导航系统来引导导管在目标组织内的位置。 探针可以提供诸如光学视觉图像或超声图像的图像，或者可以提供无线电定位数据来引导导管放置。 导管提供包括生物活性剂的加压液体，例如可用于治疗癌症，例如123I-或125I-IUDR。 提供的系统和方法可用于局部晚期肿瘤的治疗，如脑，头颈部，食管，前列腺，卵巢，肝，胰腺，膀胱或直肠癌。
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公开(公告)号：US20100280494A1
公开(公告)日：2010-11-04
申请号：US12375583
申请日：2007-07-25
CPC分类号： A61M25/0662 , A61M25/0021 , A61M25/0032 , A61M25/0068 , A61M25/007 , A61M25/0074 , A61M25/008 , A61M25/0084 , A61M2025/0036 , A61M2025/0081 , A61M2025/0175
摘要： A catheter array system adapted for implanting a plurality of catheters within the tissue of a patient in a spatially defined array, comprising a plurality of catheters, a catheter guide template adapted to guide the implantation of catheters, and a liquid supply system including a pressurizer and a manifold, is provided. A method of treatment of a malcondition in a patient comprises implantation of a spatially definted array of catheters using the system is also provided. The bioactive agent can be a radiotherapeutic agent, a chemotherapeutic agent, a protein, an antibody, an oligonucleotide-based therapeutic agent such as siRNA, or a combination of agents. A preferred radiotherapeutic agent is 123I- or 125I-IUDR, for example in the treatment of locally advanced tumors, such as glioblastoma multiforme.
摘要翻译： 一种导管阵列系统，其适于在空间限定的阵列中将多个导管植入患者的组织内，包括多个导管，适于引导导管植入的导管引导模板，以及包括加压器和 提供了一个歧管。 还提供了一种治疗患者病情的方法，包括使用该系统植入空间有限的导管阵列。 生物活性剂可以是放射治疗剂，化学治疗剂，蛋白质，抗体，基于寡核苷酸的治疗剂如siRNA或药剂的组合。 优选的放射治疗剂是123I-或125I-IUDR，例如用于局部晚期肿瘤的治疗，例如多形性成胶质细胞瘤。
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公开(公告)号：US20100222668A1
公开(公告)日：2010-09-02
申请号：US12531808
申请日：2008-03-20
申请人： William D. Dalke , Kevin Lillehei , Thomas A. Jellison , Michael J. Gerber , James E. Matsuura , Stephen L. Warren
发明人： William D. Dalke , Kevin Lillehei , Thomas A. Jellison , Michael J. Gerber , James E. Matsuura , Stephen L. Warren
CPC分类号： A61K51/0491 , Y10T137/0402
摘要： A catheter system adapted for navigating, guiding and implanting a catheter or a plurality of catheters in a spatially-defined implantation within the tissue of a patient is provided. The system can include a tissue navigation system and a probe to inform the navigation system to guide emplacement of the catheters within a target tissue. The probe can provide images, such as fiberoptic visual images, or ultrasound images, or can provide radiolocation data, to guide the catheter emplacement. The catheters supply a pressurized liquid including a bioactive agent, such as can be used in the treatment of cancer, for example 123I- or 125I-IUDR. The system and methods provided can be used in the treatment of locally advanced tumors, such as cancers of the brain, head or neck, esophagus, prostate, ovary, liver, pancreas, bladder or rectum.
摘要翻译： 提供了一种导管系统，其适于在病人组织内的空间限定的植入物中导航，引导和植入导管或多个导管。 该系统可以包括组织导航系统和探针，以通知导航系统来引导导管在目标组织内的位置。 探针可以提供诸如光学视觉图像或超声图像的图像，或者可以提供无线电定位数据来引导导管放置。 导管提供包括生物活性剂的加压液体，例如可用于治疗癌症，例如123I-或125I-IUDR。 提供的系统和方法可用于局部晚期肿瘤的治疗，如脑，头颈部，食管，前列腺，卵巢，肝，胰腺，膀胱或直肠癌。
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7.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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