公开(公告)号：US08425654B2

公开(公告)日：2013-04-23

申请号：US13212711

申请日：2011-08-18

申请人： Amanda M. Johnsen ,  Chuck Z. Soderquist ,  Bruce K. McNamara ,  Darrell R. Fisher

发明人： Amanda M. Johnsen ,  Chuck Z. Soderquist ,  Bruce K. McNamara ,  Darrell R. Fisher

IPC分类号： C22B4/04 ,  C22B59/00

CPC分类号： C01F17/0068 ,  B01J39/05 ,  B01J49/53 ,  C01F17/00 ,  G21G1/06 ,  G21G2001/0094

摘要： An alteration of the traditional zinc/zinc-amalgam reduction procedure which eliminates both the hazardous mercury and dangerous hydrogen gas generation. In order to avoid the presence of water and hydrated protons in the working solution, which can oxidize Eu2+ and cause hydrogen gas production, a process utilizing methanol as the process solvent is described. While methanol presents some flammability hazard in a radiological hot cell, it can be better managed and is less of a flammability hazard than hydrogen gas generation.

摘要翻译： 改变传统的锌/锌合金还原程序，消除了危险的汞和危险的氢气产生。 为了避免在工作溶液中存在水分和水合质子，其可以氧化Eu 2+并引起氢气产生，描述了使用甲醇作为加工溶剂的方法。 虽然甲醇在放射性热电池中存在一些可燃性危险，但可以更好地管理并且比氢气产生更易燃易燃危害。

公开(公告)号：US20080292545A1

公开(公告)日：2008-11-27

申请号：US12062745

申请日：2008-04-04

申请人： Yuehe Lin ,  Guodong Liu ,  Hong Wu ,  Jun Wang ,  Darrell R. Fisher

发明人： Yuehe Lin ,  Guodong Liu ,  Hong Wu ,  Jun Wang ,  Darrell R. Fisher

IPC分类号： A61K9/14 ,  A61K39/395 ,  A61K39/00 ,  A61K38/00 ,  A61K31/7088 ,  A61K51/08 ,  A61K49/04 ,  A61K49/14 ,  A61K49/00 ,  G01N33/53 ,  C12Q1/68

CPC分类号： A61K31/7088 ,  A61K9/5169 ,  A61K47/6929 ,  A61K48/00 ,  A61K51/1244 ,  B82Y5/00 ,  G01N33/5438 ,  G01N33/585

摘要： Apoferritin nanoparticles with functionalized surfaces have been prepared that include preselected agents within the cavity of the apoferritin molecule and preselected functionalized surface characteristics on the outer surface of the nanoparticle. Such materials provide for utilization and selective modification in a variety of applications including therapeutic and diagnostic uses. Examples of several of these applications are described herein. In addition a method for the creation of these materials by alternatively assembling, functionalizing, or functionalizing, disassembling and reassemblying the materials provides for creative customization of various types of materials applicable for varying types of applications which are also described herein.

摘要翻译： 已经制备了具有官能化表面的中铁素体纳米颗粒，其包括脱铁铁蛋白分子的腔内的预选药剂和纳米颗粒外表面上的预选的官能化表面特征。 这些材料提供了在各种应用中的利用和选择性修饰，包括治疗和诊断用途。 这里描述了几个这些应用的示例。 此外，通过交替地组装，功能化或功能化，拆卸和重新组装材料来创建这些材料的方法提供了适用于本文中描述的不同类型的应用的各种类型的材料的创造性定制。

公开(公告)号：US6117413A

公开(公告)日：2000-09-12

申请号：US968022

申请日：1997-11-12

申请人： Darrell R. Fisher ,  Chien M. Wai ,  Xiaoyuan Chen

发明人： Darrell R. Fisher ,  Chien M. Wai ,  Xiaoyuan Chen

IPC分类号： A61K51/10 ,  A61K51/12 ,  A61K51/00 ,  A61M36/14

CPC分类号： B82Y5/00 ,  A61K51/1093 ,  A61K51/1268

摘要： The invention pertains to compounds which specifically bind radionuclides, and to methods of making radionuclide complexing compounds. In one aspect, the invention includes a radionuclide delivery system comprising: a) a calix[n]arene-crown-[m]-ether compound, wherein n is an integer greater than 3, and wherein m is an integer greater than 3, the calix[n]arene-crown-[m]-ether compound comprising at least two ionizable groups; and b) an antibody attached to the calix[n]arene-crown-[m]-ether compound. In another aspect, the invention includes a method of making a radium complexing compound, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising n phenolic hydroxyl groups; b) providing a crown ether precursor, the crown ether precursor comprising a pair of tosylated ends; c) reacting the pair of tosylated ends with a pair of the phenolic hydroxyl groups to convert said pair of phenolic hydroxyl groups to ether linkages, the ether linkages connecting the crown ether precursor to the calix[n]arene to form a calix[n]arene-crown-[m]-ether compound, wherein m is an integer greater than 3; d) converting remaining phenolic hydroxyl groups to esters; e) converting the esters to acids, the acids being proximate a crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound; and f) providing a Ra.sup.2+ ion within the crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound.

摘要翻译： 本发明涉及特异性结合放射性核素的化合物，以及制造放射性核素络合化合物的方法。 一方面，本发明包括放射性核素递送系统，其包括：a）杯[n]芳烃 - 冠 - [m] - 醚化合物，其中n是大于3的整数，并且其中m是大于3的整数， 包含至少两个可离子化基团的杯[n]芳烃 - 冠 - [m] - 醚化合物; 和b）连接到杯[n]芳烃 - 冠 - [m] - 醚化合物的抗体。 另一方面，本发明包括制备镭络合化合物的方法，其包括：a）提供其中n为大于3的整数的杯[n]芳烃化合物，包含n个酚羟基的杯[n]芳烃化合物 ; b）提供冠醚前体，所述冠醚前体包含一对甲磺酰化的末端; c）使一对甲苯磺酰化的末端与一对酚羟基反应，以将所述一对酚羟基转化为醚键，将冠醚前体连接到杯[n]芳烃上形成杯[n] 芳烃 - 冠 - [m] - 醚化合物，其中m是大于3的整数; d）将剩余的酚羟基转化成酯; e）将酯转化为酸，酸接近杯[n]芳烃 - 冠 - [m] - 醚化合物的冠 - [m] - 醚部分; 和f）在杯[n]芳烃 - 冠 - [m] - 醚化合物的冠 - [m] - 醚部分内提供Ra2 +离子。

公开(公告)号：US08821364B2

公开(公告)日：2014-09-02

申请号：US12552190

申请日：2009-09-01

申请人： Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

发明人： Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

IPC分类号： A61N5/00 ,  A61N5/10

CPC分类号： 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

摘要： 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.

摘要翻译： 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

申请人： Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

发明人： Darrell R. Fisher ,  You Han Bae ,  Zhonggao Gao

IPC分类号： A61M36/12

CPC分类号： 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

摘要： 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.

摘要翻译： 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

申请人： Darrell R. Fisher ,  You Han Bae

发明人： Darrell R. Fisher ,  You Han Bae

IPC分类号： A61M36/12

CPC分类号： A61N5/1027 ,  A61N2005/1024 ,  A61N2005/1089

摘要： 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.

摘要翻译： 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：US06489617B1

公开(公告)日：2002-12-03

申请号：US09420313

申请日：1999-10-18

申请人： Darrell R. Fisher ,  David L. Alexander ,  Stanley Satz

发明人： Darrell R. Fisher ,  David L. Alexander ,  Stanley Satz

IPC分类号： G01T1164

CPC分类号： G21F5/02 ,  G21G4/06

摘要： Disclosed is a is an improved flood source, and method of making the same, which emits an evenly distributed flow of energy from a gamma emitting radionuclide dispersed throughout the volume of the flood source. The flood source is formed by filling a bottom pan with a mix of epoxy resin with cobalt-57, preferably at 10 to 20 millicuries and then adding a hardener. The pan is secured to a flat, level surface to prevent the pan from warping and to act as a heat sink for removal of heat from the pan during the curing of the resin-hardener mixture.

摘要翻译： 公开了一种改进的洪水源及其制造方法，其从分散在洪水源的整个体积中的伽马射线放射性核素发射均匀分布的能量流。 通过用环氧树脂与钴-57的混合物填充底盘形成洪水源，优选10至20毫升，然后加入硬化剂。 盘固定在平坦的水平表面上，以防止盘变形，并在树脂 - 固化剂混合物固化过程中作为散热片从锅中除去热量。

公开(公告)号：US06869588B2

公开(公告)日：2005-03-22

申请号：US09853507

申请日：2001-05-09

申请人： Richard E. Weller ,  Michael A. Lind ,  Darrell R. Fisher ,  Anna Gutowska ,  Allison A. Campbell

发明人： Richard E. Weller ,  Michael A. Lind ,  Darrell R. Fisher ,  Anna Gutowska ,  Allison A. Campbell

IPC分类号： A61K9/10 ,  A61K47/34 ,  A61K51/00 ,  A61K51/06 ,  A61K51/12 ,  A61P35/00 ,  A61M36/14

CPC分类号： A61K51/06 ,  A61K51/1213

摘要： The present invention is a thermally reversible stimulus-sensitive gel or gelling copolymer radioisotope carrier that is a linear random copolymer of an [meth-]acrylamide derivative and a hydrophilic comonomer, wherein the linear random copolymer is in the form of a plurality of linear chains having a plurality of molecular weights greater than or equal to a minimum gelling molecular weight cutoff. Addition of a biodegradable backbone and/or a therapeutic agent imparts further utility. The method of the present invention for making a thermally reversible stimulus-sensitive gelling copolymer radionuclcide carrier has the steps of: (a) mixing a stimulus-sensitive reversible gelling copolymer with an aqueous solvent as a stimulus-sensitive reversible gelling solution; and (b) mixing a radioisotope with said stimulus-sensitive reversible gelling solution as said radioisotope carrier. The gel is enhanced by either combining it with a biodegradable backbone and/or a therapeutic agent in a gelling solution made by mixing the copolymer with an aqueous solvent.

摘要翻译： 本发明是一种热可逆刺激敏感凝胶或胶凝共聚物放射性同位素载体，其是[甲基]丙烯酰胺衍生物和亲水性共聚单体的线性无规共聚物，其中线性无规共聚物是多个直链的形式 具有大于或等于最小胶凝分子量截留值的多个分子量。 可生物降解骨架和/或治疗剂的添加赋予更多的效用。 制备热可逆刺激敏感胶凝共聚物放射性核素载体的本发明的方法具有以下步骤：（a）将刺激敏感的可逆胶凝共聚物与水性溶剂混合，作为刺激敏感的可逆胶凝溶液; 和（b）将放射性同位素与作为所述放射性同位素载体的所述刺激敏感性可逆胶凝溶液混合。 通过将共聚物与水性溶剂混合制成的胶凝溶液中的可生物降解骨架和/或治疗剂进行组合来增强凝胶。

公开(公告)号：US06296831B1

公开(公告)日：2001-10-02

申请号：US09058712

申请日：1998-04-10

申请人： Richard E. Weller ,  Michael A. Lind ,  Darrell R. Fisher ,  Anna Gutowska ,  Allison A. Campbell

发明人： Richard E. Weller ,  Michael A. Lind ,  Darrell R. Fisher ,  Anna Gutowska ,  Allison A. Campbell

IPC分类号： A61K5100

CPC分类号： A61K51/06 ,  A61K51/1213

摘要： The present invention is a thermally reversible stimulus-sensitive gel or gelling copolymer radioisotope carrier that is a linear random copolymer of an [meth]acrylamide derivative and a hydrophilic comonomer, wherein the linear random copolymer is in the form of a plurality of linear chains having a plurality of molecular weights greater than or equal to a minimum gelling molecular weight cutoff. Addition of a biodegradable backbone and/or a therapeutic agent imparts further utility. The method of the present invention for making a thermally reversible stimulus-sensitive gelling copolymer radionuclcide carrier has the steps of: (a) mixing a stimulus-sensitive reversible gelling copolymer with an aqueous solvent as a stimulus-sensitive reversible gelling solution; and (b) mixing a radioisotope with said stimulus-sensitive reversible gelling solution as said radioisotope carrier. The gel is enhanced by either combining it with a biodegradable backbone and/or a therapeutic agent in a gelling solution made by mixing the copolymer with an aqueous solvent.

摘要翻译： 本发明是一种热可逆刺激敏感凝胶或胶凝共聚物放射性同位素载体，其是[甲基]丙烯酰胺衍生物和亲水共聚单体的线性无规共聚物，其中线性无规共聚物为多条直链形式，其具有 多个分子量大于或等于最小胶凝分子量截止值。 可生物降解骨架和/或治疗剂的添加赋予更多的效用。 制备热可逆刺激敏感胶凝共聚物放射性核素载体的本发明的方法具有以下步骤：（a）将刺激敏感的可逆胶凝共聚物与水性溶剂混合，作为刺激敏感的可逆胶凝溶液; 和（b）将放射性同位素与作为所述放射性同位素载体的所述刺激敏感性可逆胶凝溶液混合。 通过将共聚物与水性溶剂混合制成的胶凝溶液中的可生物降解骨架和/或治疗剂进行组合来增强凝胶。

公开(公告)号：US6075130A

公开(公告)日：2000-06-13

申请号：US191290

申请日：1998-11-10

申请人： Xiaoyuan Chen ,  Chien M. Wai ,  Darrell R. Fisher

发明人： Xiaoyuan Chen ,  Chien M. Wai ,  Darrell R. Fisher

IPC分类号： A61K47/48 ,  A61K51/12 ,  C07C259/06 ,  C07C311/29 ,  C22B3/26 ,  C22B3/32 ,  C22B59/00 ,  C22B60/00 ,  G21F9/12 ,  C07F5/02

CPC分类号： B82Y5/00 ,  A61K47/48707 ,  A61K51/1268 ,  C07C259/06 ,  C07C311/29 ,  C22B3/0006 ,  C22B3/0024 ,  C22B59/00 ,  C22B60/00 ,  G21F9/12 ,  C07C2103/92 ,  Y02P10/234

摘要： The invention pertains to compounds for binding lanthanide ions and actinide ions. The invention further pertains to compounds for binding radionuclides, and to methods of making radionuclide complexes. Also, the invention pertains to methods of extracting radionuclides. Additionally, the invention pertains to methods of delivering radionuclides to target locations. In one aspect, the invention includes a compound comprising: a) a calix[n]arene group, wherein n is an integer greater than 3, the calix[n]arene group comprising an upper rim and a lower rim; b) at least one ionizable group attached to the lower rim; and c) an ion selected from the group consisting of lanthanide and actinide elements bound to the ionizable group. In another aspect, the invention includes a method of extracting a radionuclide, comprising: a) providing a sample comprising a radionuclide; b) providing a calix[n]arene compound in contact with the sample, wherein n is an integer greater than 3; and c) extracting radionuclide from the sample into the calix[n]arene compound. In yet another aspect, the invention includes a method of delivering a radionuclide to a target location, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising at least one ionizable group; b) providing a radionuclide bound to the calix[n]arene compound; and c) providing an antibody attached to the calix[n]arene compound, the antibody being specific for a material found at the target location.

摘要翻译： 本发明涉及用于结合镧系离子和锕系离子的化合物。 本发明还涉及用于结合放射性核素的化合物以及制备放射性核素复合物的方法。 此外，本发明涉及提取放射性核素的方法。 此外，本发明涉及将放射性核素递送到目标位置的方法。 一方面，本发明包括一种化合物，其包含：a）杯[n]芳烃基，其中n是大于3的整数，所述杯[n]芳烃基包括上边缘和下边缘; b）连接到下边缘的至少一个可离子化基团; 和c）选自与可离子化基团结合的镧系元素和锕系元素的离子。 另一方面，本发明包括一种提取放射性核素的方法，包括：a）提供包含放射性核素的样品; b）提供与样品接触的杯[n]芳烃化合物，其中n是大于3的整数; 和c）将样品中的放射性核素提取到杯[n]芳烃化合物中。 在另一方面，本发明包括将放射性核素递送到目标位置的方法，包括：a）提供其中n为大于3的整数的杯[n]芳烃化合物，所述杯[n]芳烃化合物包含 至少一个可离子化基团; b）提供与杯[n]芳烃化合物结合的放射性核素; 和c）提供连接到杯[n]芳烃化合物的抗体，所述抗体对于在目标位置处发现的材料是特异性的。