公开(公告)号：US08821364B2

公开(公告)日：2014-09-02

申请号：US12552190

申请日：2009-09-01

Applicant: Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

Inventor： Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

IPC: A61N5/00 ,  A61N5/10

CPC classification number: A61N5/1001 ,  A61B90/39 ,  A61B2090/3966 ,  A61K9/0024 ,  A61K9/1647 ,  A61K45/06 ,  A61K51/0491 ,  A61K51/06 ,  A61K51/1251 ,  A61N2005/1024 ,  A61N2005/1087 ,  A61N2005/1089 ,  B29B7/945 ,  B29B2009/163 ,  B29C43/003 ,  B29C43/027 ,  B29K2067/046 ,  B29K2995/0037 ,  B29K2995/006

Abstract: A system, method and device for treating tumor cells utilizing a resorbable therapy seed made up of microspheres containing a beta- or alpha-particle-emitting radiation source and a resorbable polymer matrix. These seeds are implanted within the tumor and then rapidly dissolved so as to release the microspheres from the polymer matrix. These microspheres then spread within a preselected target area and provide radiation therapy in a predetermined amount and at a preselected rate according the specific needs and necessities of the users. The configuration of the microspheres, the types of radiation provided and the location and use of these microspheres provides desired localized treatment to target cells while preferentially avoiding or minimizing undesired damage to surrounding tissue. The present invention provides a method for making the seeds, as well as a method for utilizing the seeds as a part of the treatment method.

Abstract translation: 利用由含有β-或α-发射粒子的辐射源和可再吸收的聚合物基质的微球组成的可再吸收的治疗种子来治疗肿瘤细胞的系统，方法和装置。 将这些种子植入肿瘤内，然后快速溶解，从而将微球从聚合物基质中释放出来。 然后，这些微球体在预先选定的靶区域内扩散，并根据用户的具体需要和需要以预定量和预先选择的速率提供放射治疗。 微球的构型，所提供的辐射类型以及这些微球的位置和用途为靶细胞提供了期望的局部治疗，同时优先避免或最小化对周围组织的不期望的损伤。 本发明提供了一种种子的制造方法，以及作为处理方法的一部分使用种子的方法。

公开(公告)号：US20100056844A1

公开(公告)日：2010-03-04

申请号：US12552190

申请日：2009-09-01

Applicant: Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

Inventor： Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

IPC: A61M36/12

CPC classification number: A61N5/1001 ,  A61B90/39 ,  A61B2090/3966 ,  A61K9/0024 ,  A61K9/1647 ,  A61K45/06 ,  A61K51/0491 ,  A61K51/06 ,  A61K51/1251 ,  A61N2005/1024 ,  A61N2005/1087 ,  A61N2005/1089 ,  B29B7/945 ,  B29B2009/163 ,  B29C43/003 ,  B29C43/027 ,  B29K2067/046 ,  B29K2995/0037 ,  B29K2995/006

Abstract: A system, method and device for treating tumor cells utilizing a resorbable therapy seed made up of microspheres containing a beta- or alpha-particle-emitting radiation source and a resorbable polymer matrix. These seeds are implanted within the tumor and then rapidly dissolved so as to release the microspheres from the polymer matrix. These microspheres then spread within a preselected target area and provide radiation therapy in a predetermined amount and at a preselected rate according the specific needs and necessities of the users. The configuration of the microspheres, the types of radiation provided and the location and use of these microspheres provides desired localized treatment to target cells while preferentially avoiding or minimizing undesired damage to surrounding tissue. The present invention provides a method for making the seeds, as well as a method for utilizing the seeds as a part of the treatment method.

Abstract translation: 利用由含有β-或α-发射粒子的辐射源和可再吸收的聚合物基质的微球组成的可再吸收的治疗种子来治疗肿瘤细胞的系统，方法和装置。 将这些种子植入肿瘤内，然后快速溶解，从而将微球从聚合物基质中释放出来。 然后，这些微球体在预先选定的靶区域内扩散，并根据用户的具体需要和需要以预定量和预先选择的速率提供放射治疗。 微球的构型，所提供的辐射类型以及这些微球的位置和用途为靶细胞提供了期望的局部治疗，同时优先避免或最小化对周围组织的不期望的损伤。 本发明提供了一种种子的制造方法，以及作为处理方法的一部分使用种子的方法。

公开(公告)号：US20100056843A1

公开(公告)日：2010-03-04

申请号：US12202954

申请日：2008-09-02

Applicant: Darrell R. Fisher ,  You Han Bae

Inventor： Darrell R. Fisher ,  You Han Bae

IPC: A61M36/12

CPC classification number: A61N5/1027 ,  A61N2005/1024 ,  A61N2005/1089

Abstract: A system, method and device for treating tumor cells utilizing a resorbable therapy seed made up of microspheres containing a beta-particle-emitting radiation source and a resorbable polymer matrix. These seeds are implanted within the tumor and then rapidly dissolved or broken so as to release the microspheres. These microspheres then spread within a preselected target area and provide radiation therapy in a predetermined amount and at a preselected rate according the specific needs and necessities of the users. The configuration of the microspheres, the types of radiation provided and the location and use of these microspheres provides desired localized treatment to target cells while preferentially avoiding undesired damage to surrounding tissue. The present invention provides a method for making the seeds, as well as a method for utilizing the seeds as a part of the treatment method.

Abstract translation: 利用由含有β-发射粒子的辐射源和可再吸收的聚合物基质的微球构成的可再吸收的治疗种子来治疗肿瘤细胞的系统，方法和装置。 将这些种子植入肿瘤内，然后快速溶解或破碎，以释放微球。 然后，这些微球体在预先选定的靶区域内扩散，并根据用户的具体需要和需要以预定量和预先选择的速率提供放射治疗。 微球的配置，所提供的辐射类型以及这些微球的位置和用途为靶细胞提供所需的局部治疗，同时优先避免对周围组织的不期望的损伤。 本发明提供了一种种子的制造方法，以及作为处理方法的一部分使用种子的方法。

公开(公告)号：US07659314B2

公开(公告)日：2010-02-09

申请号：US10846487

申请日：2004-05-14

Applicant: You Han Bae ,  Kun Na ,  Eun Seong Lee

Inventor： You Han Bae ,  Kun Na ,  Eun Seong Lee

IPC: A61K47/00 ,  A61K9/00 ,  A01K25/00

CPC classification number: A61K9/1075 ,  A61K9/0019 ,  A61K31/704 ,  C07D233/64 ,  C07D413/06 ,  C08F8/30

Abstract: Mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.

Abstract translation: 含有聚（L-组氨酸） - 聚（乙二醇）嵌段共聚物和聚（L-乳酸） - 聚（乙二醇）嵌段共聚物的混合胶束是在酸性微环境中释放药物的pH敏感药物载体，但是 不在血中 由于实体瘤的微环境是酸性的，所以这些混合胶束可用于治疗癌症，包括那些显示出多药耐药性的癌症。 靶向配体如叶酸也可以连接到混合的胶束上，以增强药物递送到细胞中。 公开了用这种药物治疗温血动物的方法。

公开(公告)号：US20090274753A1

公开(公告)日：2009-11-05

申请号：US12435283

申请日：2009-05-04

Applicant: You Han Bae ,  Kun Na ,  Eun Seung Lee

Inventor： You Han Bae ,  Kun Na ,  Eun Seung Lee

IPC: A61K9/12 ,  A61K31/704

CPC classification number: A61K9/1075 ,  A61K9/0019 ,  A61K31/704 ,  C07D233/64 ,  C07D413/06 ,  C08F8/30

Abstract: Mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.

Abstract translation: 含有聚（L-组氨酸） - 聚（乙二醇）嵌段共聚物和聚（L-乳酸） - 聚（乙二醇）嵌段共聚物的混合胶束是在酸性微环境中释放药物的pH敏感药物载体，但是 不在血中 由于实体瘤的微环境是酸性的，所以这些混合胶束可用于治疗癌症，包括那些显示出多药耐药性的癌症。 靶向配体如叶酸也可以连接到混合的胶束上，以增强药物递送到细胞中。 公开了用这种药物治疗温血动物的方法。

公开(公告)号：US20090060955A1

公开(公告)日：2009-03-05

申请号：US11897979

申请日：2007-08-31

Applicant: You Han Bae ,  Eun Seong Lee ,  Dongin Kim ,  Yu Seok Youn ,  Kyung Taek Oh

Inventor： You Han Bae ,  Eun Seong Lee ,  Dongin Kim ,  Yu Seok Youn ,  Kyung Taek Oh

IPC: A61K9/00

CPC classification number: A61K9/1658 ,  A61K9/1641 ,  A61K9/167

Abstract: A drug delivery vehicle for targeted delivery of a drug mimics viral properties of size, capsid-like protein capsule, cell-specific entry, toxin release, destruction of infected cells, and migration to neighboring cells. This vehicle, termed a virogel, contains a hydrophobic polymeric core, a hydrophilic inner shell, a hydrophilic outer shell, and a ligand. An illustrative drug-loaded virogel includes poly(L-histidine-co-phenylalanine) as the core, doxorubicin loaded in the core, polyethylene glycol as the inner shell, bovine serum albumin as the outer shell, and folic acid as the ligand.

Abstract translation: 用于靶向递送药物的药物递送载体模拟大小的病毒性质，衣壳样蛋白质胶囊，细胞特异性进入，毒素释放，感染细胞的破坏以及迁移至相邻细胞。 这种载体，称为virogel，含有疏水聚合物芯，亲水内壳，亲水外壳和配体。 一种说明性的药物载体的virogel包括聚（L-组氨酸 - 共 - 苯基丙氨酸）为核心，负责核心的多柔比星，作为内壳的聚乙二醇，作为外壳的牛血清白蛋白，以及叶酸作为配体。

公开(公告)号：US20080213379A1

公开(公告)日：2008-09-04

申请号：US11998841

申请日：2007-11-30

Applicant: You Han Bae ,  Kun Na ,  Eun Seung Lee

Inventor： You Han Bae ,  Kun Na ,  Eun Seung Lee

IPC: A61K9/14

CPC classification number: A61K9/1075

Abstract: Drug delivery compositions for specific delivery of a drug to a tumor are described. These compositions include a core for sequestering the drug and a shell to which a ligand is attached for delivery of a drug to target cells. Since normal cells may also be targeted by the ligand, the compositions embed the ligand in the shell until the localized conditions surrounding the tumor cause the ligand to be displayed on the surface of the shell. One composition exhibits shrinkage of the shell at tumor pH, whereas another composition exhibits extension of the ligand at tumor pH. Still another composition causes the ligand to be exhibited at an elevated temperature.

Abstract translation: 描述了将药物特异性递送至肿瘤的药物递送组合物。 这些组合物包括用于螯合药物的核心和附着有配体的壳，以将药物递送至靶细胞。 由于正常细胞也可能被配体靶向，因此组合物将配体嵌入壳中，直到围绕肿瘤的局部条件导致配体显示在壳的表面上。 一种组合物在肿瘤pH下表现出壳的收缩，而另一种组合物在肿瘤pH下表现出配体的延伸。 另一种组合物使配体在升高的温度下显示出来。

公开(公告)号：US6103865A

公开(公告)日：2000-08-15

申请号：US219141

申请日：1998-12-22

Applicant: You Han Bae ,  Sang Yeob Park

Inventor： You Han Bae ,  Sang Yeob Park

IPC: C08F265/10 ,  C08F8/00 ,  C08F20/60 ,  C08G75/30 ,  C08G75/00 ,  C08F28/00 ,  C08F228/00 ,  C08L33/14 ,  C08L41/00

CPC classification number: C08G75/30 ,  C08F20/60

Abstract: There are disclosed pH-sensitive polymers containing sulfonamide groups, which can be changed in physical properties, such as swellability and solubility, depending on pH and which can be applied for a drug-delivery system, bio-material, sensor, etc, and a preparation method therefor. The pH-sensitive polymers are prepared by introduction of sulfonamide groups, various in pKa, to hydrophilic groups of polymers either through coupling to the hydrophilic groups, such as acrylamide, N,N-dimethylacrylamide, acrylic acid, N-isopropylacrylamide, etc, of polymers or copolymerization with other polymerizable monomers. These pH-sensitive polymers may have a structure of linear polymer, grafted copolymer, hydrogel or interpenetrating network polymer.

Abstract translation: 公开了含有磺酰胺基团的pH敏感性聚合物，其可以根据pH改变物理性质，例如溶胀性和溶解性，并且可用于药物递送系统，生物材料，传感器等，以及 制备方法。 pH敏感聚合物通过将pKa中各种磺酰胺基团引入聚合物的亲水基团而制备，通过偶联到亲水基团，例如丙烯酰胺，N，N-二甲基丙烯酰胺，丙烯酸，N-异丙基丙烯酰胺等， 聚合物或与其它可聚合单体共聚。 这些pH敏感聚合物可以具有直链聚合物，接枝共聚物，水凝胶或互穿网络聚合物的结构。

公开(公告)号：US07951846B2

公开(公告)日：2011-05-31

申请号：US12435283

申请日：2009-05-04

Applicant: You Han Bae ,  Kun Na ,  Eun Seong Lee

Inventor： You Han Bae ,  Kun Na ,  Eun Seong Lee

IPC: A61K47/00 ,  A61K9/00 ,  A01K25/00

CPC classification number: A61K9/1075 ,  A61K9/0019 ,  A61K31/704 ,  C07D233/64 ,  C07D413/06 ,  C08F8/30

Abstract: Mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.

Abstract translation: 含有聚（L-组氨酸） - 聚（乙二醇）嵌段共聚物和聚（L-乳酸） - 聚（乙二醇）嵌段共聚物的混合胶束是在酸性微环境中释放药物的pH敏感药物载体，但是 不在血中 由于实体瘤的微环境是酸性的，所以这些混合胶束可用于治疗癌症，包括那些显示出多药耐药性的癌症。 靶向配体如叶酸也可以连接到混合的胶束上，以增强药物递送到细胞中。 公开了用这种药物治疗温血动物的方法。

公开(公告)号：US06562362B1

公开(公告)日：2003-05-13

申请号：US09706870

申请日：2000-11-07

Applicant: You Han Bae ,  Kun Na ,  Seong Il Kang ,  Jin Woo Yi ,  Moon Hee Han

Inventor： You Han Bae ,  Kun Na ,  Seong Il Kang ,  Jin Woo Yi ,  Moon Hee Han

IPC: A61F200

CPC classification number: A61L24/06 ,  A61L2430/36 ,  C08L33/24

Abstract: Disclosed are liquefied embolic materials capable of sol-gel phase transition in response to in vivo conditions, including temperature, ionic strength, and pH, and their uses. The liquefied embolic materials are made of copolymers based on temperature-sensitive isopropylacrylamide and ionic strength- and/or pH-sensitive monomers. In addition to finding excellent applications in the embolotherapy, the embolic materials can be used as extracellular matrixes for cell culture and for drug-delivery systems for cancer therapy.

Abstract translation: 公开了能够响应于体内条件（包括温度，离子强度和pH）及其用途而溶胶 - 凝胶相变的液化栓塞材料。 液化栓塞材料由基于温度敏感的异丙基丙烯酰胺和离子强度和/或pH敏感单体的共聚物制成。 除了在电疗法中找到优异的应用之外，栓塞材料可以用作细胞培养的细胞外基质和用于癌症治疗的药物递送系统。