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1. 发明授权

US5219553A Composition of a n-carboxymethylated tetraazacyclododecane chelating agent, a paramagnetic metal and excess calcium ions for MRI 失效
标题翻译： N-羧甲基化四氮杂环十二烷螯合剂，顺磁金属和过量钙离子的组成
公开(公告)号：US5219553A
公开(公告)日：1993-06-15
申请号：US743212
申请日：1991-08-09
申请人： Karl F. Kraft , Steven C. Quay , Scott M. Rocklage , Dilip Worah
发明人： Karl F. Kraft , Steven C. Quay , Scott M. Rocklage , Dilip Worah
IPC分类号： A61K49/06 , C07D259/00 , C07F5/00 , C07F9/38 , C07F13/00 , G01R33/28
CPC分类号： G01R33/5601 , A61K49/06 , C07D259/00 , C07F13/005 , C07F5/003 , C07F9/3817 , Y10S424/90 , Y10S436/806 , Y10S514/836 , Y10S514/922 , Y10T436/24
摘要： Magnetic resonance imaging contrast media used to affect the relaxation times of atoms in body tissues undergoing NMR diagnosis are disclosed. Such media comprise (1) a paramagnetic, physiologically compatible complex of (a) a chelant consisting of a N-carboxy methylated tetraazacyclododecane, and (b) a paramagnetic ion of a lanthanide element of atomic numbers 59-70, or of a transition metal of atomic numbers 21-29, 42 or 44, or a physiologically compatible salt of such a complex, and (2) a toxicity-reducing amount of labile calcium ions. The labile calcium ions can be derived from a source other than a salt of said chelant, e.g. an inorganic or organic calcium salt. NMR image-enhancing compositions comprising NMR image-enhancing effective amounts of said contrast media and pharmaceutically acceptable diluents are also disclosed.
摘要翻译：公开了用于影响经历NMR诊断的身体组织中的原子的弛豫时间的磁共振成像造影剂。这种培养基包括（1）由（a）由N-羧基甲基化四氮杂环十二烷组成的螯合剂和（b）原子序数59-70的镧系元素的顺磁离子或过渡金属的原子序数21-29,42或44，或这种络合物的生理上相容的盐，和（2）不稳定的钙离子的毒性减少量。不稳定的钙离子可以衍生自除所述螯合剂的盐之外的来源，例如，无机或有机钙盐。还公开了包含NMR图像增强有效量的所述造影剂和药学上可接受的稀释剂的NMR图像增强组合物。

2. 发明授权

US5091169A Dipyridoxyl phosphate NMRI contrast agent compositions 失效
标题翻译：磷酸二吡啶酯NMRI造影剂组成
公开(公告)号：US5091169A
公开(公告)日：1992-02-25
申请号：US370429
申请日：1989-06-23
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K49/06 , C07F9/58 , C07F13/00 , G01R33/28
CPC分类号： C07F13/005 , A61K49/06 , C07F9/582 , G01R33/5601 , Y10T436/24
摘要： N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-arylenediamines, and the corresponding monophosphate compounds.
摘要翻译： N，N'-二 - （吡哆醛-5-磷酸） - 亚烷基二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸酯）-1,2-环烷二胺-N，N' - 二乙酸和N，N'-二 - （吡哆醛-5-磷酸）-1,2-芳基二胺-N，N'-二乙酸，相应的单磷酸酯化合物和单乙酸化合物，其盐和酯形成稳定，具有顺磁金属离子的高度可溶性螯合物，是高效的NMRI造影剂。优选的造影剂是N，N'-双 - （吡哆醛-5-磷酸）乙二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸）反式-1的顺磁离子螯合物， 2-环己二胺-N，N'dia cetic酸，N，N'-双 - （吡哆醛-5-磷酸）反式-1,2-芳基二胺-N，N'-二乙酸及其可溶性钙盐。用于形成这些化合物的新型中间体是N，N'-双（吡哆醛-5-磷酸）亚烷基二亚胺，N，N'-双（吡哆醛-5-磷酸）亚烷基二胺，N，N'-双（吡哆醛-5-磷酸酯） 1,2-环烷基二亚胺，N，N'-双（吡哆醛-5-磷酸）-1,2-环烷基二胺，N，N'-双（吡哆醛-5-磷酸）-1,2-亚芳基二胺，和相应的单磷酸盐化合物。

3. 发明授权

US5008099A Amyloidosis and Alzheimer's disease diagnostic assay and reagents therefor 失效
标题翻译：淀粉样变性和阿尔茨海默病诊断测定及其试剂
公开(公告)号：US5008099A
公开(公告)日：1991-04-16
申请号：US510461
申请日：1990-04-17
申请人： Steven C. Quay , Scott M. Rocklage , Warren K. Miller
发明人： Steven C. Quay , Scott M. Rocklage , Warren K. Miller
IPC分类号： A61K51/04 , C07C309/47 , C07C309/50 , C07D277/66 , C09B29/01 , C09B29/30 , C09B35/08 , C09B35/16 , C09B35/20 , C09B43/40 , G01N33/68
CPC分类号： G01N33/6896 , A61K51/0406 , C07C309/47 , C07C309/50 , C07D277/66 , C09B29/0003 , C09B29/0011 , C09B29/30 , C09B35/08 , C09B35/16 , C09B35/20 , C09B43/40 , A61K2123/00 , G01N2800/2821
摘要： The presence and location of amyloid deposits in an organ or body area of a patient is effected by intravenous administration of novel radioactive iodine-labeled amyloid binding compounds and preferably .sup.123 I-labeled compounds to the patient and sensing radiation emitted from the organ or body area. Novel non-radioactive iodine substituted amyloid binding compounds and amyloid binding compounds which are readily iodinated are further aspects or the invention.
摘要翻译：淀粉样蛋白沉积物在患者的器官或身体区域中的存在和位置通过向患者静脉内施用新的放射性碘标记的淀粉样蛋白结合化合物和优选123I标记的化合物来实现，并感测从器官或身体区域发射的辐射。容易碘化的新型非放射性碘取代的淀粉样蛋白结合化合物和淀粉样蛋白结合化合物是其它方面或本发明。

4. 发明授权

US5130431A Dipyriodoxyl phosphate chelating compound intermediates 失效
标题翻译：二硫代磷酸酯螯合化合物中间体
公开(公告)号：US5130431A
公开(公告)日：1992-07-14
申请号：US550128
申请日：1990-07-06
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K49/06 , C07F9/58 , C07F13/00 , G01R33/28
CPC分类号： G01R33/5601 , A61K49/06 , C07F13/005 , C07F9/582
摘要： N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-arylenediamines, and the corresponding monophosphate compounds.
摘要翻译： N，N'-二 - （吡哆醛-5-磷酸） - 亚烷基二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸酯）-1,2-环烷二胺-N，N' - 二乙酸和N，N'-二 - （吡哆醛-5-磷酸）-1,2-芳基二胺-N，N'-二乙酸，相应的单磷酸酯化合物和单乙酸化合物，其盐和酯形成稳定，具有顺磁金属离子的高度可溶性螯合物，是高效的NMRI造影剂。优选的造影剂是N，N'-双 - （吡哆醛-5-磷酸）乙二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸）反式-1的顺磁离子螯合物， 2-环己二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸）反式-1,2-芳基二胺-N，N'-二乙酸及其可溶性钙盐。用于形成这些化合物的新型中间体是N，N'-双（吡哆醛-5-磷酸）亚烷基二亚胺，N，N'-双（吡哆醛-5-磷酸）亚烷基二胺，N，N'-双（吡哆醛-5-磷酸酯） 1,2-环烷基二亚胺，N，N'-双（吡哆醛-5-磷酸）-1,2-环烷基二胺，N，N'-双（吡哆醛-5-磷酸）-1,2-亚芳基二胺，和相应的单磷酸盐化合物。

5. 发明授权

US5089644A Preparation of oxamine complexes 失效
标题翻译：制备恶木复合物
公开(公告)号：US5089644A
公开(公告)日：1992-02-18
申请号：US61933
申请日：1987-06-11
申请人： Steven C. Quay , Scott M. Rocklage
发明人： Steven C. Quay , Scott M. Rocklage
IPC分类号： A61K49/06 , C07F13/00 , C07F15/02
CPC分类号： C07F13/005 , A61K49/06 , C07F15/025 , Y10T436/24
摘要： A process for making a solution of a complex of an oxamine and a polyvalent paramagnetic metal comprising contacting a solution of the oxamine with (a) the insoluble hydroxide of the polyvalent paramagnetic metal in water, or (b) an alkoxide of the metal is a non-aqueous solvent, thereby to form a solution of a complex of the oxamine and the metal. The complex, preferably ferrioxamine, is an improved NMR image enhancer compared even with ferrioxamine made conventionally, characterized by a high LD.sub.50.
摘要翻译：制备含有胺和多价顺磁性金属络合物的方法，包括将该胺的溶液与（a）多价顺磁金属的不溶性氢氧化物在水中接触，或（b）金属的醇盐是非水溶剂，从而形成了木胺和金属络合物的溶液。复合物，优选铁草胺，是一种改进的NMR图像增强剂，与常规制备的铁三胺相比，其特征在于高LD 50。

6. 发明授权

US4933456A Dipyridoxyl phosphate NMRI contrast agents 失效
标题翻译：磷酸二吡啶酯NMRI造影剂
公开(公告)号：US4933456A
公开(公告)日：1990-06-12
申请号：US47614
申请日：1987-05-08
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K49/00 , A61B5/055 , A61B10/00 , A61K49/06 , C07F1/00 , C07F1/08 , C07F5/00 , C07F9/58 , C07F11/00 , C07F13/00 , C07F15/00 , C07F15/02 , C07F15/04 , C07F15/06 , G01R33/28
CPC分类号： G01R33/5601 , A61K49/06 , C07F13/005 , C07F9/582
摘要： N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylene-diamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate(-1,2-arylenediamines, and the corresponding monophosphate compounds.

7. 发明授权

US4842845A Radioactive metal chelates for dipyridoxyl phosphate 失效
标题翻译：磷酸二吡啶酯的放射性金属螯合物
公开(公告)号：US4842845A
公开(公告)日：1989-06-27
申请号：US47616
申请日：1987-05-08
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K51/00 , A61B5/055 , A61K51/04 , C07B59/00 , C07F1/00 , C07F9/58 , C07F13/00
CPC分类号： C07F13/005 , A61K51/0478 , C07F9/582 , A61K2123/00
摘要： Radioactive metal ion chelates of N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective agents for radiopharmaceutical imaging. Preferred contrast agents are radioactive metal ion such as technetium-99m and indium-111 ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylene-diamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.

8. 发明授权

US5039512A NMR imaging with paramagnetic polyvalent metal salts of poly-(acid-alkylene-amino)-alkanes 失效
标题翻译：聚（亚烷基 - 氨基） - 烷烃的顺磁多价金属盐的NMR成像
公开(公告)号：US5039512A
公开(公告)日：1991-08-13
申请号：US057709
申请日：1987-06-15
申请人： Karl F. Kraft , Steven C. Quay , Scott M. Rocklage , Dilip Worah
发明人： Karl F. Kraft , Steven C. Quay , Scott M. Rocklage , Dilip Worah
IPC分类号： A61K49/06 , C07D259/00 , C07F5/00 , C07F9/38 , C07F13/00 , G01R33/28
CPC分类号： G01R33/5601 , A61K49/06 , C07D259/00 , C07F13/005 , C07F5/003 , C07F9/3817 , Y10S424/90 , Y10T436/24
摘要： In a method of imaging body tissue in a patient, comprising administering to the patient an effective amount of a pharmaceutical agent for effecting the relaxation times of atoms in body tissues undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to effect such relaxation times, of a paramagnetic, physiologically compatible salt of a physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 57-70, or of a transition metal of atomic numbers 21-29, 42, or 44; and a pharmaceutically acceptable carrier, and subjecting the patient to NMR tomography, the improvement wherein said salt of said chelate complex is the calcium or magnesium salt. Such salts are new as are some of the complexing chelates.
摘要翻译：在患者体内成像身体组织的方法中，包括向患者施用有效量的用于进行经历核磁共振诊断的身体组织中的原子的松弛时间的药剂，由此增强图像对比度，所述药剂包含有效量实现这样的松弛时间，原子序数为57-70的镧系元素离子的生理上相容的螯合络合物的顺磁性生理上相容的盐或原子序数21-29,42或44的过渡金属; 和药学上可接受的载体，并对患者进行NMR层析成像，其中所述螯合络合物的所述盐是钙盐或镁盐。这些盐是一些新的络合螯合物。

9. 发明授权

US5039511A Amyloidosis and alzheimer's disease diagnostic assay and reagents therefor 失效
标题翻译：淀粉样变性和阿尔茨海默病诊断测定及其试剂
公开(公告)号：US5039511A
公开(公告)日：1991-08-13
申请号：US582152
申请日：1990-09-14
申请人： Steven C. Quay , Scott M. Rocklage , Warren K. Miller
发明人： Steven C. Quay , Scott M. Rocklage , Warren K. Miller
IPC分类号： A61K51/04 , C07C309/47 , C07C309/50 , C07D277/66 , C09B29/01 , C09B29/30 , C09B35/08 , C09B35/16 , C09B35/20 , C09B43/40 , G01N33/68
CPC分类号： G01N33/6896 , A61K51/0453 , C07C309/47 , C07C309/50 , C07D277/66 , C09B29/0003 , C09B29/0011 , C09B29/30 , C09B35/08 , C09B35/16 , C09B35/20 , C09B43/40 , A61K2123/00 , G01N2800/2821
摘要： The presence and location of amyloid deposits in an organ or body area of a patient is effected by intravenous administration of novel radioactive iodine-labeled amyloid binding compounds and preferably .sup.123 I-labeled compounds to the patient and sensing radiation emitted from the organ or body area. Novel non-radioactive iodine substituted amyloid binding compounds and amyloid binding compounds which are readily iodinated are further aspects of the invention
摘要翻译：淀粉样蛋白沉积物在患者的器官或身体区域中的存在和位置通过向患者静脉内施用新的放射性碘标记的淀粉样蛋白结合化合物和优选123I标记的化合物来实现，并感测从器官或身体区域发射的辐射。易于碘化的新型非放射性碘取代的淀粉样蛋白结合化合物和淀粉样蛋白结合化合物是本发明的另外的方面

10. 发明授权

US4992555A Certain dipyridylphosphate chelatable compounds capable of forming metal ion chelates 失效
标题翻译：能够形成金属离子螯合物的某些二吡啶磷酸盐螯合化合物
公开(公告)号：US4992555A
公开(公告)日：1991-02-12
申请号：US370428
申请日：1989-06-23
申请人： Scott M. Rocklage , Steven C. Quay
发明人： Scott M. Rocklage , Steven C. Quay
IPC分类号： A61K49/06 , C07F9/58 , C07F13/00 , G01R33/28
CPC分类号： C07F13/005 , A61K49/06 , C07F9/582 , G01R33/5601
摘要： N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof.Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-arylenediamines, and the corresponding monophosphate compounds.
摘要翻译： N，N'-二 - （吡哆醛-5-磷酸） - 亚烷基二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸酯）-1,2-环烷二胺-N，N' - 二乙酸和N，N'-二 - （吡哆醛-5-磷酸）-1,2-芳基二胺-N，N'-二乙酸，相应的单磷酸酯化合物和单乙酸化合物，其盐和酯形成稳定，具有顺磁金属离子的高度可溶性螯合物，是高效的NMRI造影剂。优选的造影剂是N，N'-双 - （吡哆醛-5-磷酸）乙二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸）反式-1的顺磁离子螯合物， 2-环己二胺-N，N'-二乙酸，N，N'-双 - （吡哆醛-5-磷酸）反式-1,2-芳基二胺-N，N'-二乙酸及其可溶性钙盐。用于形成这些化合物的新型中间体是N，N'-双（吡哆醛-5-磷酸）亚烷基二亚胺，N，N'-双（吡哆醛-5-磷酸）亚烷基二胺，N，N'-双（吡哆醛-5-磷酸酯） 1,2-环烷基二亚胺，N，N'-双（吡哆醛-5-磷酸）-1,2-环烷基二胺，N，N'-双（吡哆醛-5-磷酸）-1,2-亚芳基二胺，和相应的单磷酸盐化合物。

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