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1. 发明授权

US06635235B1 Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy 失效
标题翻译：双功能螯合剂用于设计和开发位点特异性放射性药物和生物分子共轭策略
公开(公告)号：US06635235B1
公开(公告)日：2003-10-21
申请号：US09602487
申请日：2000-06-23
申请人： Kattesh V. Katti , Kandikere R. Prabhu , Hariprasad Gali , Nagavara Kishore Pillarsetty , Wynn A. Volkert
发明人： Kattesh V. Katti , Kandikere R. Prabhu , Hariprasad Gali , Nagavara Kishore Pillarsetty , Wynn A. Volkert
IPC分类号： A61K5100
CPC分类号： A61K49/0002 , A61K51/0478
摘要： There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P2N2-bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the —PR2 containing biomolecules by synthesizing a P2N2-bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a —PR2 containing biomolecule.
摘要翻译：提供了以特异性方式用过渡金属或放射性金属标记生物分子的方法，以通过合成P2N2-双功能螯合剂中间体，将中间体与放射性金属或过渡金属络合来制备诊断或治疗药物化合物，并以特异性方式将所得的金属络合的双功能螯合剂与生物分子共价连接。还提供了通过合成P2N2-双功能螯合剂中间体，使中间体与放射性金属或过渡金属络合，并将所得的放射性金属络合的双功能螯合剂与生物分子共价连接的方法来合成含有-PPR的生物分子的方法现场具体方式。提供包含含有-PR2的生物分子的治疗或诊断剂。

2. 发明授权

US4898724A Organis amine phosphonic acid complexes for the treatment of calcific tumors 失效
标题翻译：有机胺膦酸复合物用于治疗钙化肿瘤
公开(公告)号：US4898724A
公开(公告)日：1990-02-06
申请号：US50263
申请日：1987-05-14
申请人： Jaime Simon , David A. Wilson , Wynn A. Volkert , David E. Troutner , William F. Goeckeler
发明人： Jaime Simon , David A. Wilson , Wynn A. Volkert , David E. Troutner , William F. Goeckeler
IPC分类号： A61K51/04 , C07F9/38
CPC分类号： C07F9/3817 , A61K51/0489 , A61K2121/00
摘要： Particle-emitting radionuclides, e.g. Samarium-153, have been complexed with organic aminoalkylenephosphonic acids wherein the nitrogen and phosphorus are interconnected by an alkylene group or substituted alkylene group. These complexes have been found useful in compositions for the therapeutic treatment of calcific tumors in animals.
摘要翻译：颗粒发射放射性核素，例如钐-153与有机氨基亚烷基膦酸络合，其中氮和磷通过亚烷基或取代的亚烷基相互连接。已经发现这些配合物可用于治疗动物钙化肿瘤的组合物中。

3. 发明授权

US4582698A Process for imaging cardiac infarcts 失效
标题翻译：心脏梗塞成像过程
公开(公告)号：US4582698A
公开(公告)日：1986-04-15
申请号：US533332
申请日：1983-09-19
申请人： Jaime Simon , David A. Wilson , Wynn A. Volkert
发明人： Jaime Simon , David A. Wilson , Wynn A. Volkert
IPC分类号： A61K51/00 , A61K51/04 , C07F9/38 , A61K43/00 , A61K49/00
CPC分类号： A61K51/0478 , A61K51/0489 , C07F9/3817 , A61K2123/00
摘要： The imaging of cardiac infarcts with complexed radioactive metals is improved by employing as the complexing agent a compound of the formula ##STR1## wherein substituents A, B, X and Y are each independently selected from radicals including hydrogen, hydroxyalkyl (wherein the alkyl group contains 2-6 carbon atoms), methylenephosphonic, methylene-, ethylene-, and propylenesulfonic, carboxylic acid radicals (having 2-4 carbon atoms) and the alkali or alkaline earth metal, ammonia and amine salts thereof and wherein at least one A, B, X and Y is methylenephosphonic acid or a salt thereof. In particular Tc-99m complexes have been found useful for imaging damaged cardiac tissue.
摘要翻译：使用复合放射性金属的心脏梗死的成像通过使用式（I）的化合物作为络合剂，其中取代基A，B，X和Y各自独立地选自氢，羟烷基（其中烷基含 2-6个碳原子），亚甲基膦酸，亚甲基 - ，乙烯 - 和 - 丙磺酸 - 羧酸基团（具有2-4个碳原子）和碱金属或碱土金属，其氨和胺盐，并且其中至少一个A，B X和Y是亚甲基膦酸或其盐。已经发现特别是Tc-99m复合物可用于成像损伤的心脏组织。

4. 发明授权

US07147838B2 Gastrin receptor-avid peptide conjugates 失效
公开(公告)号：US07147838B2
公开(公告)日：2006-12-12
申请号：US11025636
申请日：2004-12-29
申请人： Timothy J. Hoffman , Wynn A. Volkert , Ning Li , Gary Sieckman , Chrys-Ann Higginbotham
发明人： Timothy J. Hoffman , Wynn A. Volkert , Ning Li , Gary Sieckman , Chrys-Ann Higginbotham
IPC分类号： A61K49/00
CPC分类号： A61K51/088 , A61K38/00 , C07F5/003 , C07F15/008 , C07K7/086 , C07K14/57572
摘要： A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

5. 发明授权

US06200546B1 Gastrin receptor-avid peptide conjugates 失效
标题翻译：胃泌素受体 - 狂犬病肽缀合物
公开(公告)号：US06200546B1
公开(公告)日：2001-03-13
申请号：US09064499
申请日：1998-04-22
申请人： Timothy J. Hoffman , Wynn A. Volkert , Ning Li , Gary Sieckman , C. A. Higginbotham
发明人： Timothy J. Hoffman , Wynn A. Volkert , Ning Li , Gary Sieckman , C. A. Higginbotham
IPC分类号： A61K4900
CPC分类号： A61K51/088 , A61K38/00 , C07F5/003 , C07F15/008 , C07K7/086 , C07K14/57572
摘要： A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.
摘要翻译：用作治疗或诊断性放射性药物的化合物包括能够使与能够结合胃泌素释放肽受体的部分连接的医学上有用的金属络合的基团。用于治疗患有肿瘤疾病的受试者的方法包括向受试者施用有效量的具有与螯合基螯合的金属的放射性药物，所述螯合基团连接到能够结合肿瘤细胞上表达的胃泌素释放肽受体的部分，随后内化的细胞。形成治疗或诊断化合物的方法包括使金属合成酶与能够结合胃泌素释放肽受体的部分共价连接的螯合基团反应。

6. 发明授权

US6054115A Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals and method of making same 失效
标题翻译：用作诊断和治疗药物的羟甲基膦化合物及其制备方法
公开(公告)号：US6054115A
公开(公告)日：2000-04-25
申请号：US33928
申请日：1998-03-03
申请人： Kattesh V. Katti , Srinivasa Rao Karra , Douglas E. Berning , C. Jeffrey Smith , Wynn A. Volkert , Alan R. Ketring
发明人： Kattesh V. Katti , Srinivasa Rao Karra , Douglas E. Berning , C. Jeffrey Smith , Wynn A. Volkert , Alan R. Ketring
IPC分类号： A61K51/00 , A61K51/04 , A61K51/08 , A61K51/10 , A61P9/00 , A61P25/00 , A61P31/00 , A61P31/12 , A61P35/00 , C07F7/00 , C07F9/50 , C07F13/00 , C07F15/00 , C07F5/00 , C07F9/00
CPC分类号： C07F15/008 , A61K51/04 , A61K51/0478 , A61K51/0489 , C07F13/005 , C07F9/5004 , C07F9/5022 , C07F9/5027 , A61K2121/00 , A61K2123/00
摘要： A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand.
摘要翻译：制备用作诊断或治疗药物的化合物的化合物和方法包括至少一种官能化羟烷基膦供体基团和一个或多个硫或氮供体和与配体结合的金属。

7. 发明授权

US5601800A New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents 失效
标题翻译：用于设计治疗或诊断性放射性药物成像剂的新的多功能配体
公开(公告)号：US5601800A
公开(公告)日：1997-02-11
申请号：US211905
申请日：1994-07-29
申请人： Kattesh V. Katti , Wynn A. Volkert , Alan R. Ketring , Prahlad R. Singh
发明人： Kattesh V. Katti , Wynn A. Volkert , Alan R. Ketring , Prahlad R. Singh
IPC分类号： A61K51/00 , A61K49/00 , A61K51/10 , C07B59/00 , C07F9/50 , C07F9/6587 , C07F9/80 , C07F13/00 , C07F15/00 , C07F15/02 , A61K51/04
CPC分类号： C07F15/0013 , A61K51/1093 , C07B59/004 , C07F13/005 , A61K2123/00
摘要： A class of diagnostic and therapeutic compounds derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g. .sup.99m Tc or .sup.186 Re/.sup.188 Re) or late transition metals (e.g., .sup.105 Rh or .sup.109 Pd). The complexes with these metals .sup.186 Re/.sup.188 Re, .sup.99m Tc and .sup.109 Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g. Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.
摘要翻译： PCT No.PCT / US92 / 09742 Sec。 371日期1994年7月29日第 102（e）日期1994年7月29日PCT 1991年11月9日PCT PCT。公开号WO93 / 08839 日期1993年5月13日一类衍生自次膦酰亚胺的诊断和治疗化合物，其包括含有单次膦亚胺官能团的配体或膦亚胺基和膦或胂基，或氨基或第二次膦酰亚胺部分。这些膦亚胺配体与早期过渡金属放射性核素（例如99mTc或186Re / 188Re）或后过渡金属（例如，105Rh或109Pd）络合。与这些金属186Re / 188Re，99mTc和109Pd的配合物具有高体外和高体内稳定性。络合物以高产率形成并且可以是中性的或带电的。这些配体也可以用于形成具有顺磁性过渡金属（例如Fe和Mn）的稳定化合物，用于潜在的用作MRI造影剂。还公开了使用配体和制备配体的应用。

8. 发明授权

US07060247B2 Gastrin receptor-avid peptide conjugates 失效
公开(公告)号：US07060247B2
公开(公告)日：2006-06-13
申请号：US09847134
申请日：2001-05-02
申请人： Timothy J. Hoffman , Wynn A. Volkert , Gary Sieckman , Charles J. Smith , Hariprasad Gali
发明人： Timothy J. Hoffman , Wynn A. Volkert , Gary Sieckman , Charles J. Smith , Hariprasad Gali
IPC分类号： A61K49/00
CPC分类号： A61K51/088 , A61K38/00 , C07F5/003 , C07F15/008 , C07K7/086 , C07K14/57572
摘要： A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a-moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

9. 发明授权

US5855867A Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals and method of making same 失效
公开(公告)号：US5855867A
公开(公告)日：1999-01-05
申请号：US818080
申请日：1997-03-14
申请人： Kattesh V. Katti , Srinivasa Rao Karra , Douglas E. Berning , C. Jeffrey Smith , Wynn A. Volkert , Alan R. Ketring
发明人： Kattesh V. Katti , Srinivasa Rao Karra , Douglas E. Berning , C. Jeffrey Smith , Wynn A. Volkert , Alan R. Ketring
IPC分类号： A61K51/00 , A61K51/04 , A61K51/08 , A61K51/10 , A61P9/00 , A61P25/00 , A61P31/00 , A61P31/12 , A61P35/00 , C07F7/00 , C07F9/50 , C07F13/00 , C07F15/00 , C07C233/00 , C07F5/00 , C07F9/02
CPC分类号： C07F15/008 , A61K51/04 , A61K51/0478 , A61K51/0489 , C07F13/005 , C07F9/5004 , C07F9/5022 , C07F9/5027 , A61K2121/00 , A61K2123/00
摘要： A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand.

10. 发明授权

US5478474A Method for treating liquid wastes 失效
标题翻译：液体废物处理方法
公开(公告)号：US5478474A
公开(公告)日：1995-12-26
申请号：US165373
申请日：1993-12-10
申请人： Kattesh V. Katti , Wynn A. Volkert , Prahlad Singh , Alan R. Ketring
发明人： Kattesh V. Katti , Wynn A. Volkert , Prahlad Singh , Alan R. Ketring
IPC分类号： B01D15/08 , C22B3/20 , G21C19/46 , G21F9/12
CPC分类号： G21F9/12 , C22B3/205 , C22B3/42 , G21C19/46 , Y02P10/234 , Y02W30/883
摘要： The method of treating liquid waste in a media is accomplished by exposing the media to phosphinimines and sequestering .sup.99 Tc from the media by the phosphinimine (PN) functionalities. The system for treating the liquid waste in the media includes extraction of .sup.99 TcO.sub.4.sup.- from aqueous solutions into organic solvents or mixed organic/polar media, extraction of .sup.99 Tc from solutions on a solid matrix by using a container containing PN functionalities on solid matrices including an inlet and outlet for allowing flow of media through an immobilized phosphinimine ligand system contained within the container. Also, insoluble suspensions of phosphinimine functionalities on solid matrices in liquid solutions or present on supported liquid membranes (SLM) can be used to sequester .sup.99 Tc from those liquids.
摘要翻译：通过将介质暴露于次膦酰亚胺并通过膦亚胺（PN）官能团从介质中螯合99Tc来实现处理介质中废液的方法。用于处理介质中的液体废物的系统包括将99TcO4-从水溶液中萃取到有机溶剂或混合有机/极性介质中，通过使用在包括入口的固体基质上含有PN官能团的容器从固体基质上的溶液中提取99Tc 和用于允许介质流过包含在容器内的固定化膦酰亚胺配体系统的出口。此外，膦酰亚胺功能性在液体溶液中固体基质上的不溶性悬浮液或存在于载体液膜（SLM）上的不溶性悬浮液可用于从这些液体中螯合99Tc。

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