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21. 发明授权

US5384113A Stabilizers to prevent autoradiolysis of radiolabeled peptides and proteins 失效
标题翻译：稳定剂以防止放射性标记的肽和蛋白质的放射自溶解
公开(公告)号：US5384113A
公开(公告)日：1995-01-24
申请号：US135882
申请日：1993-10-13
申请人： Edward A. Deutsch , Wilhelmus T. Goedemans , Martinus T. Maria de Jong , Kathleen M. Miller , James W. Brodack
发明人： Edward A. Deutsch , Wilhelmus T. Goedemans , Martinus T. Maria de Jong , Kathleen M. Miller , James W. Brodack
IPC分类号： A61K51/00 , A61K51/08 , A61K51/12 , C07K1/00 , C07K7/23 , C07K14/575 , A61K49/02 , A61K43/00
CPC分类号： A61K51/1241 , A61K51/08 , A61K51/083 , A61K51/088 , A61K2123/00
摘要： Gentisic acid and its derivatives substantially inhibit peptide autoradiolysis. Gentisic acid or its derivatives may also be used in combination with other stabilizers such as inositol and ascorbic acid to inhibit autoradiolysis of radiolabeled peptides.
摘要翻译：龙胆酸及其衍生物基本上抑制肽的放射自溶解。龙胆酸或其衍生物也可与其它稳定剂如肌醇和抗坏血酸组合使用以抑制放射性标记的肽的放射自溶解。

22. 发明授权

US4957728A Kit for preparing Tc (III)-99m myocardial imaging agents that are effective in humans 失效
标题翻译：用于制备在人体中有效的Tc（III）-99m心肌显像剂的试剂盒
公开(公告)号：US4957728A
公开(公告)日：1990-09-18
申请号：US463403
申请日：1990-01-11
申请人： Edward A. Deutsch , Karen F. Libson
发明人： Edward A. Deutsch , Karen F. Libson
IPC分类号： A61K51/04
CPC分类号： A61K51/0489 , A61K51/0478 , A61K2123/00
摘要： A myocardial imaging agent for humans is a technetium(III) complex ligated in the planar positions by a tetradentate ligand such as (acac).sub.2 en and in the axial positions by an ether containing phosphine ligand such as tris(3-methoxy-1-propyl)-phosphine. The agent exhibits extremely rapid blood clearance after injection into a human and has a sufficiently high heart/liver and heart/lung ratios to provide effecitve myocardial images. A kit for preparing the above myocardial agent is disclosed.
摘要翻译：用于人的心肌显像剂是通过四齿配体如（acac）2en在平面位置连接的锝（III）复合物，并且在轴向位置通过含醚膦配体如三（3-甲氧基-1-丙基）-膦。注射到人体内后，该药物的血清清除率非常快，并具有足够高的心脏/肝脏和心/肺比，以提供有效的心肌图像。公开了用于制备上述心肌药剂的试剂盒。

23. 发明授权

US4778672A Method of isolating radioactive perrhenate or pertechnetate from an aqueous solution 失效
标题翻译：从水溶液中分离放射性高铼酸盐或高锝酸盐的方法
公开(公告)号：US4778672A
公开(公告)日：1988-10-18
申请号：US802779
申请日：1985-11-27
申请人： Edward A. Deutsch , Jean-Luc Vanderheyden
发明人： Edward A. Deutsch , Jean-Luc Vanderheyden
IPC分类号： A61K51/04 , C07B59/00 , G21G4/08 , A61K43/00 , C01G47/00 , C01G57/00
CPC分类号： G21G4/08 , A61K51/04 , C07B59/004 , A61K2123/00
摘要： Pure perihenate is isolated from a aqueous crude solution of perrhenate by first associating the perrherate with a lipophilic counter ion such as tetrabutyl ammonium. This is added to the solution in a form such as tetrabutyl ammonium bromide. Tetrabutyl ammonium perrhenate is formed. The aqueous mixture is then added to a reverse phase separation column such as a C.sub.18 Sep Pak filter which has been previously loaded with the lipophilic counter ion. The aqueous portion of the crude mixture is eluted from the column with water. Subsequently the purified perrhenate associated with the lipophilic counter ion is removed with a less polar solvent such as ethanol. Pertechnetate can also be separated from an aqueous mixture in the same manner. These procedures are particularly suited for isolating relatively pure radioactive forms of perrhenate and pertechnetate such as Re.sup.186 O.sub.4.sup.-, Re.sup.188 O.sub.4.sup.-, and .sup.99m TcO.sub.4.sup.-.
摘要翻译：通过首先将苦参碱与亲脂性抗衡离子如四丁基铵缔合，从硬质酸水溶液的粗水溶液中分离出纯的过氧化钙。将其以诸如四丁基溴化铵的形式加入到溶液中。形成高铼酸四丁基铵。然后将含水混合物加入到反相分离柱如C18 Sep Pak过滤器中，其已经预先装载了亲脂性抗衡离子。粗制混合物的水溶液部分用水从柱中洗脱出来。随后，用极性较小的溶剂如乙醇除去与亲油性抗衡离子缔合的纯化的高铼酸盐。高锝酸盐也可以以相同的方式从含水混合物中分离出来。这些方法特别适用于分离相对纯的放射性形式的高铼酸盐和高锝酸盐，如Re186O4-，Re188O4-和99mTcO4-。

24. 发明授权

US5330742A Methods and compositions for magnetic resonance imaging 失效
标题翻译：磁共振成像的方法和组成
公开(公告)号：US5330742A
公开(公告)日：1994-07-19
申请号：US862865
申请日：1992-04-03
申请人： Edward A. Deutsch , Dennis A. Moore
发明人： Edward A. Deutsch , Dennis A. Moore
IPC分类号： A61K47/30 , A61K49/00 , A61K49/04 , A61K49/06 , A61K49/18 , C01B25/32 , C07F13/00 , G01N31/00
CPC分类号： A61K49/1818 , A61K49/04 , A61K49/0433 , A61K49/06 , A61K49/1887 , Y10S436/806 , Y10S514/836 , Y10T436/24
摘要： Methods and diagnostic compositions are disclosed for enhancing magnetic resonance imaging which utilize a paramagnetic metal cluster. Magnetic resonance contrast media containing Z+[Mn.sub.12 X.sub.12 (OYR).sub.16 (L).sub.4 ], where OYR is an oxyacid such as benzoic acid, acetic acid, methyl sulphonic acid, methyl phosphonic acid; L is a neutral donor such as water, alcohol, pyridine, or other amines; X is a chalcogen, such as O or S; and Z is a pharmaceutically acceptable counterion are disclosed. Z may also be a paramagnetic counter ion, such as a high spin metal cluster. The paramagnetic cluster may optionally be complexed or conjugated to a carrier compound capable of altering the paramagnetic metal cluster's biodistribution, increasing its selectivity of tumor localization, and amplifying its proton relaxivity.
摘要翻译：公开了用于增强利用顺磁金属簇的磁共振成像的方法和诊断组合物。含有Z + [Mn12X12（OYR）16（L）4]的磁共振造影剂，其中OYR是含氧酸，例如苯甲酸，乙酸，甲基磺酸，甲基膦酸; L是中性给体，例如水，醇，吡啶或其它胺; X是硫属元素，如O或S; 并且Z是药学上可接受的抗衡离子。 Z也可以是顺磁抗衡离子，例如高自旋金属簇。顺磁簇可以任选地复合或缀合到能够改变顺磁性金属簇的生物分布，增加其对肿瘤定位的选择性和扩增其质子弛豫性的载体化合物。

25. 发明授权

US5026829A Cyclo substituted propyleneamine oxime and its use as a brain imaging agent 失效
标题翻译：环取代的丙烯胺肟及其用作脑显像剂
公开(公告)号：US5026829A
公开(公告)日：1991-06-25
申请号：US453696
申请日：1989-12-20
申请人： Edward A. Deutsch
发明人： Edward A. Deutsch
IPC分类号： A61K51/04 , C07F13/00
CPC分类号： C07F13/005 , A61K51/0478 , A61K2123/00
摘要： A useful brain perfusion imaging agent comprises ##STR1## wherein R completes a four or five member ring. The agent is stable in vitro permitting its use up to six to eight hours after preparation.
摘要翻译：有用的脑灌注成像剂包括其中R完成四或五个成员环的。该试剂在体外稳定，允许其在制备后六至八小时使用。

26. 发明授权

US4895960A Cyclo substituted propyleneamine oxime and its use as a brain imaging agent 失效
标题翻译：环取代的丙烯胺肟及其用作脑显像剂
公开(公告)号：US4895960A
公开(公告)日：1990-01-23
申请号：US300617
申请日：1989-01-23
申请人： Edward A. Deutsch
发明人： Edward A. Deutsch
IPC分类号： A61K51/04 , C07F13/00
CPC分类号： C07F13/005 , A61K51/0478 , A61K2123/00
摘要： A useful brain perfusion imaging agent comprises ##STR1## wherein R completes a four or five member ring. The agent is stable in vitro permitting its use up to six to eight hours after preparation.

27. 发明授权

US4839467A Radioactive rhenium complexed to 2-hydroxy isobutyric acid 失效
标题翻译：放射性铼与2-羟基异丁酸络合
公开(公告)号：US4839467A
公开(公告)日：1989-06-13
申请号：US206880
申请日：1988-06-15
申请人： Edward A. Deutsch
发明人： Edward A. Deutsch
IPC分类号： A61K51/04 , C07C51/41 , C07C59/01 , C07F13/00 , G01N33/60
CPC分类号： A61K51/0476 , A61K51/0478 , C07C51/418 , C07C59/01 , C07F13/005 , G01N33/60 , A61K2123/00
摘要： A composition of matter having the following general formula ##STR1## wherein L represents 2-hydroxy isobutyric acid. This composition of matter is useful in improving the reaction efficiency or yield when bonding rhenium to a chelating ligand preferably a polydentate sulfur, selenium, phosphorous or nitrogen ligand. This provides a method to bond radioactive rhenium to various chelating ligands for a radiopharmaceutical. Further, this also provides a method to bond a radioactive rhenium to a protein such as a monoclonal antibody. This in turn provides a method to provide beta emitting radiation to cancer cells.
摘要翻译：一种具有以下通式的物质组合物，其中L代表2-羟基异丁酸。当将铼结合到螯合配体（优选多齿硫，硒，磷或氮配体）时，这种物质组合物可用于提高反应效率或产率。这提供了将放射性铼与放射性药物的各种螯合配体结合的方法。此外，这也提供了将放射性铼与蛋白质如单克隆抗体结合的方法。这又提供了向癌细胞提供β发射辐射的方法。

28. 发明授权

US4795626A .sup.99m Tc.sup.(III) myocardial imaging agents which are non-reducable in vivo 失效
标题翻译： 99mTc（III）在体内不可还原的心肌显像剂
公开(公告)号：US4795626A
公开(公告)日：1989-01-03
申请号：US172969
申请日：1988-03-11
申请人： Edward A. Deutsch , Jean-Luc Vanderheyden
发明人： Edward A. Deutsch , Jean-Luc Vanderheyden
IPC分类号： A61K51/04 , C07F13/00 , A61K49/02
CPC分类号： C07F13/005 , A61K51/0476 , A61K2123/00
摘要： A cationic .sup.99m Tc.sup.III myocardial imaging agent is disclosed which has a relatively negative redox potential. This prevents in vivo reduction of the Tc(III) to Tc(II). The redox potential of the Tc(III) is controlled by complexing the Tc with both hard and soft atoms. Preferably four of the atoms complexed to the Tc(III) are hard atoms such as nitrogen or oxygen and the remaining two are soft atoms such as phosphorous or arsenic. These imaging agents are particularly useful in imaging the human heart.
摘要翻译：公开了具有相对负的氧化还原电位的阳离子99mTcIII心肌显像剂。这可以防止Tc（III）体内还原为Tc（II）。 Tc（III）的氧化还原电位通过使Tc与硬原子和软原子相互配合来控制。优选与Tc（III）络合的四个原子是诸如氮或氧的硬质原子，剩下的两个是诸如磷或砷的软原子。这些成像剂在人心脏成像中特别有用。

29. 发明授权

US5382388A Process for the preparation of rhenium-188 and technetium-99m generators 失效
标题翻译：制备铼188和锝-99m发生器的方法
公开(公告)号：US5382388A
公开(公告)日：1995-01-17
申请号：US933385
申请日：1992-08-21
申请人： Gary J. Ehrhardt , Robert G. Wolfangel , Edward A. Deutsch
发明人： Gary J. Ehrhardt , Robert G. Wolfangel , Edward A. Deutsch
IPC分类号： C01G1/00 , C01G39/00 , C01G41/00 , G21G4/08 , C09K11/00 , B01J13/00 , C09K3/00
CPC分类号： G21G4/08
摘要： Process for preparing a radionuclide generator for producing Tc-99m or Re-188. A clear solution containing a metallic cation and an anion comprising W-188 or Mo-99 is provided. The metallic cation is present in the solution as a dissolved complex of the metallic cation and a complexing agent and/or the anion being present in the solution as a dissolved complex of the anion and a complexing agent. The dissolved complex(es) are decomposed to form a slurry containing a precipitate of the metallic cation and the anion. The precipitate is transferred to an elutable container of a radionuclide generator.
摘要翻译：制备Tc-99m或Re-188的放射性核素发生器的方法。提供了含有金属阳离子和包含W-188或Mo-99的阴离子的透明溶液。金属阳离子作为金属阳离子和络合剂和/或阴离子的溶解络合物存在于溶液中，作为阴离子和络合剂的溶解络合物存在于溶液中。溶解的复合物分解形成含有金属阳离子和阴离子沉淀物的浆料。将沉淀物转移到放射性核素发生器的可洗涤容器中。

30. 发明授权

US5002754A Technetium (III/II) imaging agents 失效
标题翻译：锝（III / II）成像剂
公开(公告)号：US5002754A
公开(公告)日：1991-03-26
申请号：US207281
申请日：1988-06-15
申请人： Edward A. Deutsch
发明人： Edward A. Deutsch
IPC分类号： A61K51/00 , A61K51/04 , C07F13/00 , C07H23/00
CPC分类号： A61K51/0476 , C07F13/005 , C07H23/00 , A61K2123/00
摘要： A ligated technetium (III/II) complex is useful as a brain perfusion imaging agent. The complex has a technetium (III/II) center surrounded by six ligating moieties. The complex preferably has a reduction potential Tc(III) to Tc(II) which is less than about +0.6 volts vs Ag/AgCl (3M NaCl) and at least low enough to be oxidized in vivo after crossing the blood brain diffusion barrier. The technetium complex has six ligating moieties, four of which use phosphorous, arsenic, or nitrogen as ligating atoms. The remaining two ligands use sulfur or selenium to complex to the Tc center. These ligands are modified to establish an effective oxidation potential of the Tc(II) thus providing the necessary redox potential for in vivo oxidation.
摘要翻译：连接的锝（III / II）复合物可用作脑灌注成像剂。该复合物具有由六个连接部分包围的锝（III / II）中心。复合物优选具有比Ag / AgCl（3M NaCl）低约+0.6伏特的还原电位Tc（III）至Tc（II），并且至少足够低以在穿过血脑扩散屏障后在体内被氧化。锝络合物具有六个结合部分，其中四个使用磷，砷或氮作为连接原子。剩余的两个配体使用硫或硒与Tc中心复合。这些配体被修饰以建立Tc（II）的有效氧化电位，从而为体内氧化提供必要的氧化还原电位。

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