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1. 发明申请

WO0166155A3 ACTINIUM-225 COMPLEXES AND CONJUGATES FOR RADIOIMMUNOTHERAPY 审中-公开
标题翻译： ACTINIUM-225配合物和缀合物用于放射性免疫治疗
公开(公告)号：WO0166155A3
公开(公告)日：2002-06-06
申请号：PCT/US0105927
申请日：2001-02-23
申请人： MA DANGSHE , MCDEVITT MICHAEL R , SCHEINBERG DAVID A , SIMON JAIME , KIEFER GARRY E , FRANK R KEITH , GULYAS GYONGYI
发明人： MA DANGSHE , MCDEVITT MICHAEL R , SCHEINBERG DAVID A , SIMON JAIME , KIEFER GARRY E , FRANK R KEITH , GULYAS GYONGYI
IPC分类号： A61K51/04 , A61K51/10
CPC分类号： A61K51/1093 , A61K51/0482 , A61K51/0497 , A61K51/1027
摘要： Actinium-225 ( Ac) complexes with functionalized chelants of the formula (I) wherein: each Q is independently hydrogen or (CHR )pCO2R; Q is hydrogen or (CHR )wCO2R; each R independently is hydrogen, benzyl or C1-C4 alkyl; with the proviso that at least two of the sum of Q and Q must be other than hydrogen; each R independently is hydrogen; C1-C4 alkyl or (C1-C2 alkyl)phenyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p is 1 or 2; r is 0 or 1; w is 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon to carbon bond, and the sum of r and w is 0 or 1; L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula (1) wherein s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; R is an electrophilic or nucleophilic moiety which allows for covalent attachment to an antibody or fragment thereof, or synthetic linker which can be attached to an antibody or fragment thereof, or precursor thereof; and Cyc represents a cyclic aliphatic moiety, aromatic moiety, aliphatic heterocyclic moiety, or aromatic heterocyclic moiety, each of said moieties optionally substituted with one or more groups which do not interfere with binding to an antibody or antibody fragment; with the proviso that when s, t, m, r, and n are 0, then R is other than carboxyl; their pharmaceutically acceptable salts, their conjugates and the use thereof for radioimmunotherapy is disclosed.
摘要翻译：吖啶-225（225Ac）与式（I）的官能化螯合剂络合，其中：每个Q独立地为氢或（CHR 5）pCO 2 R; Q 1是氢或（CHR 5）wCO 2 R; 每个R独立地为氢，苄基或C 1 -C 4烷基; 条件是Q和Q 1的总和中的至少两个必须不是氢; 每个R 5独立地为氢; C1-C4烷基或（C1-C2烷基）苯基; X和Y各自独立地为氢或可以与相邻的X和Y一起形成额外的碳 - 碳键; n是0或1; m是从0到10的整数，包括0和10; p是1或2; r是0或1; w是0或1; 条件是当X和/或Y形成另外的碳 - 碳键时，n仅为1，并且r和w之和为0或1; L是与其所连接的碳原子中的一个碳原子共价键合并且取代其中一个碳原子的一个氢原子的连接基团/间隔基团，所述连接基团/间隔基团由式（1）表示，其中s是0或1的整数 ; t是0〜20的整数， R 1是允许共价连接至抗体或其片段或可以连接至抗体或其片段或其前体的合成连接体的亲电或亲核部分; 并且Cyc表示环状脂族部分，芳族部分，脂族杂环部分或芳族杂环部分，所述部分中的每一个任选地被一个或多个不干扰与抗体或抗体片段结合的基团取代; 条件是当s，t，m，r和n为0时，则R 1不是羧基; 其药学上可接受的盐，它们的缀合物及其用于放射免疫疗法的用途。

2. 发明申请

WO0128567A3 AMINOALKYLENEPHOSPHONATES FOR TREATMENT OF BONE DISORDERS 审中-公开
标题翻译：用于治疗骨质疏松症的氨基磷酸酯
公开(公告)号：WO0128567A3
公开(公告)日：2001-11-29
申请号：PCT/US0028713
申请日：2000-10-17
申请人： DOW CHEMICAL CO , FRANK R KEITH
发明人： FRANK R KEITH
IPC分类号： A61K31/663 , A61K31/662 , A61K31/675 , A61K31/685 , A61P3/14 , A61P19/00 , A61P19/08 , A61P19/10
CPC分类号： A61K31/675 , A61K31/662 , A61K31/685
摘要： A method for preventing or minimizing loss of bone mineral in mammals which method comprises administering to a mammal an amount of an aminoalkylenephosphonate which is effective to prevent or minimize loss of bone mineral density. The aminoalkylenephosphonates of the present invention should have at least one R-N(Alk-PO3H2)2 group or at least two RR´N-Alk-PO3H2 groups wherein R and R´ can be, same or different, aliphatic or cyclic moiety, and Alk is an alkylene group having from 1 to 4 carbon atoms.
摘要翻译：一种用于预防或最小化哺乳动物骨矿物质损失的方法，该方法包括向哺乳动物施用一定量的有效预防或最小化骨矿物质密度损失的氨基亚烷基膦酸盐。本发明的氨基亚烷基膦酸盐应具有至少一个RN（Alk-PO3H2）2基团或至少两个RR'N-Alk-PO3H2基团，其中R和R'可以相同或不同，为脂族或环状部分，Alk 是具有1至4个碳原子的亚烷基。

3. 发明申请

WO1995002086A2 PROCESS FOR REMOVING METAL IONS FROM LIQUIDS 审中-公开
标题翻译：从液体中去除金属离子的方法
公开(公告)号：WO1995002086A2
公开(公告)日：1995-01-19
申请号：PCT/US1994007428
申请日：1994-06-30
申请人： THE DOW CHEMICAL COMPANY , MICHALOWSKI, Robert, J. , CHRISTIANSEN, Steven, H. , FRANK, R., Keith , LITTLETON, Teresa , SIMON, Jaime , VAUGHN, Walter , WILSON, David, A.
发明人： THE DOW CHEMICAL COMPANY
IPC分类号： D21C09/10
CPC分类号： D21H21/06 , D21C9/002 , D21C9/1042
摘要： The invention is an improvement in a process for making cellulosic articles said process involving a separation of cellulosic material from a mixture containing a liquid, metal cations, and cellulosic material. The improvement involves adding to the mixture at least one retaining material which binds at least one metal cation and, in the separation, is retained with the cellulosic material. Suitable retaining agents are either organic or inorganic and include chelate-forming polymers, both synthetic and natural, colloidal suspensions of inorganic compounds, and mixed metal hydroxides. In each case, the metal cations remain in the cellulosic article, for example paper, rather going into waste water from which they would otherwise need to be removed.
摘要翻译：本发明是制造纤维素制品的方法的改进，所述方法涉及从含有液体，金属阳离子和纤维素材料的混合物中分离纤维素材料。该改进涉及向混合物中加入至少一种结合至少一种金属阳离子的保留材料，并且在分离中将其与纤维素材料保持在一起。合适的保留剂是有机或无机的，并且包括无机化合物的合成和天然胶体悬浮液和混合金属氢氧化物的螯合形成聚合物。在每种情况下，金属阳离子保留在纤维素制品中，例如纸，而是进入废水，否则它们将需要从中除去它们。

4. 发明申请

WO2005049096A3 PROTEIN AND POLYMER CONJUGATES AS CHELANTS WITH ENHANCED BLOOD RETENTION 审中-公开
标题翻译：蛋白质和聚合物作为具有增强血液保持力的药物
公开(公告)号：WO2005049096A3
公开(公告)日：2005-12-29
申请号：PCT/US2004037769
申请日：2004-11-12
申请人： DOW GLOBAL TECHNOLOGIES INC , ATHEY PHILLIP S , KIEFER GARRY E , SIMON JAIME , FRANK R KEITH , ADAIR CHRISTOPHER , GULYAS GYONGYI
发明人： ATHEY PHILLIP S , KIEFER GARRY E , SIMON JAIME , FRANK R KEITH , ADAIR CHRISTOPHER , GULYAS GYONGYI
IPC分类号： A61K49/08 , A61K49/14 , A61K51/04 , A61K51/06 , A61K51/08
CPC分类号： A61K51/065 , A61K49/085 , A61K49/126 , A61K49/14 , A61K51/0497 , A61K51/088
摘要： The present invention is a pharmaceutical composition that exhibits enhanced IP blood retention, the composition comprising: a biotargeting molecule; and a chelating agent conjugated to the biotargeting molecule; wherein the composition exhibits a half-life in the bloodstream of from 15 minutes to 24 hours. The present invention is also directed to the use of functionalized chelants to modify the pharmacokinetics of radiopharmaceuticals. Compared with non-functionalized chelants, chelants functionalized with bulky and/or lipophilic groups can slow down the renal clearance and enhance the blood retention of metals complexed therewith. This enhanced blood retention leads to increased uptake of metal in target tissue.
摘要翻译：本发明是一种具有增强的IP血液保留性的药物组合物，该组合物包含：生物靶向分子; 和与生物靶向分子缀合的螯合剂; 其中所述组合物在血液中的半衰期为15分钟至24小时。本发明还涉及功能化螯合剂用于改变放射性药物的药代动力学的用途。与非官能化螯合剂相比，用大体积和/或亲脂基团官能化的螯合剂可以减慢肾清除率并增强与其结合的金属的血液保持性。这种增强的血液保留导致靶组织中金属的摄取增加。

5. 发明申请

WO9502086A3 PROCESS FOR REMOVING METAL IONS FROM LIQUIDS 审中-公开
标题翻译：从液体中去除金属离子的方法
公开(公告)号：WO9502086A3
公开(公告)日：1995-03-09
申请号：PCT/US9407428
申请日：1994-06-30
申请人： DOW CHEMICAL CO , MICHALOWSKI ROBERT J , CHRISTIANSEN STEVEN H , FRANK R KEITH , LITTLETON TERESA , SIMON JAIME , VAUGHN WALTER , WILSON DAVID A
发明人： MICHALOWSKI ROBERT J , CHRISTIANSEN STEVEN H , FRANK R KEITH , LITTLETON TERESA , SIMON JAIME , VAUGHN WALTER , WILSON DAVID A
IPC分类号： D21C9/00 , D21C9/10 , D21H21/06
CPC分类号： D21H21/06 , D21C9/002 , D21C9/1042
摘要： The invention is an improvement in a process for making cellulosic articles said process involving a separation of cellulosic material from a mixture containing a liquid, metal cations, and cellulosic material. The improvement involves adding to the mixture at least one retaining material which binds at least one metal cation and, in the separation, is retained with the cellulosic material. Suitable retaining agents are either organic or inorganic and include chelate-forming polymers, both synthetic and natural, colloidal suspensions of inorganic compounds, and mixed metal hydroxides. In each case, the metal cations remain in the cellulosic article, for example paper, rather going into waste water from which they would otherwise need to be removed.

6. 发明申请

WO2009045230A1 COMPOSITIONS FOR TREATMENT OF TUMORS BY DIRECT ADMINISTRATION OF A RADIOISOTOPE 审中-公开
标题翻译：通过直接管理放射治疗来治疗肿瘤的组合物
公开(公告)号：WO2009045230A1
公开(公告)日：2009-04-09
申请号：PCT/US2008/002026
申请日：2008-02-15
申请人： ISO THERAPEUTICS GROUP LLC , GABRIEL INSTITUTE, INC. , FRANK, R., Keith , MCMILLAN, Kenneth , SIMON, Jaime , LOY, H., Max , STEARNS, Stanley, D.
发明人： FRANK, R., Keith , MCMILLAN, Kenneth , SIMON, Jaime , LOY, H., Max , STEARNS, Stanley, D.
IPC分类号： A61K51/02 , A61M36/06
CPC分类号： A61K51/0478 , A61K51/025 , A61K51/048 , A61K51/0489
摘要： This invention provides a safer and more effective treatment for undesirable tissue masses, especially bone cancer and soft tissue tumors. The method involves a composition for direct administration of a therapeutic, radioisotope formulation nearby or directly into the tissue mass. Administration of the dose for bone cancer may be done through a hole created in the bone using a miniature drill. Delivery of the dose directly into a tumor may be accomplished using microsyringe or a miniature pump capable of accurately delivering microliter amounts of material. A chelating agent capable of removing activity from the bloodstream is also an aspect of this invention.
摘要翻译：本发明为不希望的组织块，特别是骨癌和软组织肿瘤提供更安全和更有效的治疗。该方法包括用于在组织块附近或直接施用治疗性放射性同位素制剂的组合物。可以通过使用微型钻头在骨头中产生的孔来进行骨癌剂量的施用。可以使用微量注射器或能够精确地递送微量的材料的微型泵来将剂量直接递送到肿瘤中。能够从血液中除去活性的螯合剂也是本发明的一个方面。

7. 发明申请

WO2008060393A2 THE USE OF MATERIALS AND EXTERNAL STIMULI FOR SYNOVECTOMY 审中-公开
标题翻译：材料的使用和外部刺激的概要
公开(公告)号：WO2008060393A2
公开(公告)日：2008-05-22
申请号：PCT/US2007/022536
申请日：2007-10-24
申请人： ISO THERAPEUTICS GROUP LLC , FRANK, R., Keith , McMILLAN, Kenneth , SIMON, Jaime , STRICKLAND, Alan, D.
发明人： FRANK, R., Keith , McMILLAN, Kenneth , SIMON, Jaime , STRICKLAND, Alan, D.
IPC分类号： A61K51/00
CPC分类号： A61K51/1244 , A61K41/0052 , A61K47/6849
摘要： This invention has as one of its aspects a method to provide a safe an effective treatment for synovectomy. The method involves the administration a material to the affected joint, allowing the material to localize in the synovial membrane, and then applying an external stimulus that interacts with the material to provide therapy. The materials of this invention are preferably particles, which are either magnetic or contain a heavy element. The external stimuli of this invention includes an alternating magnetic field to heat magnetic particles, infrared laser to heat heavy elements, or electromagnetic ionizing radiation (X- or gamma-radiation) that interacts with heavy elements to produce a localized radiation dose.
摘要翻译：本发明的一个方面是提供一种安全有效的滑膜切除治疗方法。该方法包括向受影响的关节施用材料，允许材料定位在滑膜中，然后施加与材料相互作用以提供治疗的外部刺激。本发明的材料优选是磁性的或含有重元素的颗粒。本发明的外部刺激包括用于加热磁性颗粒的交变磁场，加热重元素的红外激光或与重元素相互作用以产生局部辐射剂量的电磁离子辐射（X-或γ-辐射）。

8. 发明申请

WO1993011740A1 PHYTATE-ANTIMICROBIAL COMPOSITIONS IN ORAL CARE PRODUCTS 审中-公开
标题翻译：口腔护理产品中的物理 - 抗微生物组合物
公开(公告)号：WO1993011740A1
公开(公告)日：1993-06-24
申请号：PCT/US1992010665
申请日：1992-12-10
申请人： THE DOW CHEMICAL COMPANY , GARLICH, Joseph, R. , MASTERSON, Tipton, T. , FRANK, R., Keith
发明人： THE DOW CHEMICAL COMPANY
IPC分类号： A61K07/16
CPC分类号： A61K8/55 , A61K8/416 , A61K8/49 , A61K8/4926 , A61Q11/00
摘要： Oral compositions containing phytic acid or a physiologically acceptable salt thereof, a cationic antimicrobial compound and a compatibilizing agent are disclosed for controlling dental calculus, dental plaque, gingivitis, periodontitis and/or oral malodor.

9. 发明申请

WO2011149844A1 DELIVERY OF HIGH DOSE THERAPEUTIC RADIOISOTOPES TO BONE 审中-公开
标题翻译：将高剂量治疗放射治疗药物交付给骨骼
公开(公告)号：WO2011149844A1
公开(公告)日：2011-12-01
申请号：PCT/US2011/037575
申请日：2011-05-23
申请人： ISO THERAPEUTICS GROUP LLC , SIMON, Jaime , FRANK, R., Keith
发明人： SIMON, Jaime , FRANK, R., Keith
IPC分类号： A61K9/00
CPC分类号： A61K9/0019 , A61K51/0482
摘要： This invention provides a method of efficiently delivering high amounts of radioactivity to bone and bone tumors of mammals while having lower bone marrow suppression at dosages of about 1 to about 5 mCi per kg and having high retention in the bone at dosages up to about 100 mCi per kg by the administration of chelates of Sm-153 and Lu-177 with DOTMP in a pharmaceutically-acceptable solution. This invention also provides a method of preparing the chelates of this invention that is fast and delivers less radiation dose exposure to the people preparing the chelates.
摘要翻译：本发明提供了一种有效地向哺乳动物的骨骼和骨骼肿瘤输送大量放射性的方法，同时在约1至约5mCi / kg的剂量下具有较低的骨髓抑制，并且以高达约100mCi的剂量在骨中具有高保留性通过在药学上可接受的溶液中施用具有DOTMP的Sm-153和Lu-177的螯合物。本发明还提供了一种制备本发明的螯合物的方法，其快速且对制备螯合物的人们的辐射剂量暴露较少。

10. 发明申请

WO0166155A8 ACTINIUM-225 COMPLEXES AND CONJUGATES FOR RADIOIMMUNOTHERAPY 审中-公开
标题翻译： ACTINIUM-225复合物和结合物用于放射治疗
公开(公告)号：WO0166155A8
公开(公告)日：2002-02-07
申请号：PCT/US0105927
申请日：2001-02-23
申请人： MA DANGSHE , MCDEVITT MICHAEL R , SCHEINBERG DAVID A , SIMON JAIME , KIEFER GARRY E , FRANK R KEITH , GULYAS GYONGYI
发明人： MA DANGSHE , MCDEVITT MICHAEL R , SCHEINBERG DAVID A , SIMON JAIME , KIEFER GARRY E , FRANK R KEITH , GULYAS GYONGYI
IPC分类号： A61K51/04 , A61K51/10
CPC分类号： A61K51/1093 , A61K51/0482 , A61K51/0497 , A61K51/1027
摘要： Actinium-225 ( Ac) complexes with functionalized chelants of the formula (I) wherein: each Q is independently hydrogen or (CHR )pCO2R; Q is hydrogen or (CHR )wCO2R; each R independently is hydrogen, benzyl or C1-C4 alkyl; with the proviso that at least two of the sum of Q and Q must be other than hydrogen; each R independently is hydrogen; C1-C4 alkyl or (C1-C2 alkyl)phenyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p is 1 or 2; r is 0 or 1; w is 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon to carbon bond, and the sum of r and w is 0 or 1; L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula (1) wherein s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; R is an electrophilic or nucleophilic moiety which allows for covalent attachment to an antibody or fragment thereof, or synthetic linker which can be attached to an antibody or fragment thereof, or precursor thereof; and Cyc represents a cyclic aliphatic moiety, aromatic moiety, aliphatic heterocyclic moiety, or aromatic heterocyclic moiety, each of said moieties optionally substituted with one or more groups which do not interfere with binding to an antibody or antibody fragment; with the proviso that when s, t, m, r, and n are 0, then R is other than carboxyl; their pharmaceutically acceptable salts, their conjugates and the use thereof for radioimmunotherapy is disclosed.
摘要翻译：与式（I）的官能化螯合剂的锕-265（225Aa）络合物，其中：各Q独立地为氢或（CHR 5）pCO 2 R; Q 1是氢或（CHR 5）w CO 2 R; 每个R独立地是氢，苄基或C 1 -C 4烷基; 条件是Q和Q 1之和中的至少两个必须不是氢; 每个R 5独立地是氢; C 1 -C 4烷基或（C 1 -C 2烷基）苯基; X和Y各自独立地为氢，也可以与相邻的X和Y一起形成附加的碳 - 碳键; n为0或1; m为0〜10的整数，包括0和10; p为1或2; r为0或1; w为0或1; 条件是当X和/或Y形成额外的碳与碳键时，n仅为1，r和w的和为0或1; L是与其连接的一个碳原子上的一个氢原子共价连接并取代其连接的一个氢原子的连接体/间隔基，所述连接体/间隔基由式（1）表示，其中s为0或1的整数 ; t为0〜20的整数， R 1是亲电或亲核部分，其允许共价连接到抗体或其片段，或可以连接到抗体或其片段或其前体的合成接头; Cyc表示环状脂肪族部分，芳香族部分，脂肪族杂环部分或芳香族杂环部分，所述部分中的每一个任选地被一个或多个不干扰与抗体或抗体片段结合的基团取代; 条件是当s，t，m，r和n为0时，R 1不是羧基; 公开了其药学上可接受的盐，它们的缀合物及其用于放射免疫疗法的用途。

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