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1. 发明授权

US5958373A Polychelants as contrast enhancing agents 失效
标题翻译： Polychelants作为对比增强剂
公开(公告)号：US5958373A
公开(公告)日：1999-09-28
申请号：US615241
申请日：1996-06-13
申请人： Martha Garrity , Shaun Paul Crofts , Joan Carvalho , Per Strande , Harald Dugstad
发明人： Martha Garrity , Shaun Paul Crofts , Joan Carvalho , Per Strande , Harald Dugstad
IPC分类号： A61K31/395 , A61K49/00 , A61K49/04 , A61P39/02 , C07D257/02 , C07D519/00 , A61B5/055
CPC分类号： A61K49/0002 , C07D257/02 , Y10S514/836
摘要： The present invention provides a polychelant compound of formula (VII), (wherein each X which may be the same or different is NZ, O or S, at least two Xs being NZ; B is (CR.sup.1 Y) or --N(CR.sup.1.sub.2 Y)--; each Z is a group R.sup.1 or a group CR.sup.1.sub.2 Y, at least one Z being a group CR.sup.1.sub.2 Y; each Y is a group CO.sub.2 H, PO.sub.3 H, SO.sub.3 H, CONR.sup.1.sub.2, CON(OR.sup.1)R.sup.1, CNS or CONR.sup.1 NR.sup.1.sub.2 ; m is 0 or 1 or 2; each n is 2 or 3; q is 0 or 1 when B is (CR.sup.1 Y) and 2 when B is N(CR.sup.1.sub.2 Y); p is an integer having a value of at least 2; each R.sup.1 which may be the same or different is a hydrogen atom or an alkyl, aryl or aralkyl group optionally substituted by one or more hydroxy or alkoxy groups, or two R.sup.1 groups on ring atoms or in Z groups together represent a linker group L; each L which may be the same or different represents a bond or an organic linker group having a molecular weight of less than 1000 and salts and chelates thereof. These compounds, especially the diand trichelates with paramagnetic or heavy metal ions are especially useful as diagnostic imaging contrast agents.
摘要翻译： PCT No.PCT / GB94 / 01931 Sec。 371日期：1996年6月13日 102（e）日期1996年6月13日PCT 1994年9月6日PCT公布。公开号WO95 / 07270 日期：1995年3月16日本发明提供了式（VII）所示的聚合物化合物，其中每个X可以相同或不同，为NZ，O或S，至少两个X为NZ; B为（CR1Y）或 - N（CR12Y） - ;各Z为基团R1或基团CR12Y，至少一个Z为基团CR12Y;每个Y为CO 2 H，PO 3 H，SO 3 H，CONR 12，CON（OR 1）R 1，CNS或CONR1NR 12; m 是0或1或2;每个n是2或3;当B是（CR1Y）时，q是0或1，当B是N（CR12Y）时，q是2; p是具有至少2的整数;每个R1 可以相同或不同的是氢原子或任选被一个或多个羟基或烷氧基取代的烷基，芳基或芳烷基，或在环原子上或Z基团中的两个R 1基团一起表示连接基团L;每个L 可以相同或不同，表示分子量小于1000的键或有机连接基团及其盐和螯合物，这些化合物，特别是具有顺磁性或重金属离子的二联体三聚体是特别的作为诊断成像造影剂有效。

2. 发明授权

US07696381B1 Alternative dimerisation reagents for synthesis of iodixanol 有权
标题翻译：用于合成碘克沙醇的替代二聚试剂
公开(公告)号：US07696381B1
公开(公告)日：2010-04-13
申请号：US12565785
申请日：2009-09-24
申请人： Arne Berg , Harald Dugstad , Michel Gacek , Trygve Gulbrandsen , Per Strande
发明人： Arne Berg , Harald Dugstad , Michel Gacek , Trygve Gulbrandsen , Per Strande
IPC分类号： C07C233/65 , C07C233/05
CPC分类号： C07C231/12 , C07C237/46
摘要： This invention relates generally to non-ionic X-ray contrast agents. It further relates to the synthesis of iodixanol. In particular, it relates to alternative dimerisation reagents in the conversion of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (“Compound A”) to iodixanol.
摘要翻译：本发明一般涉及非离子X射线造影剂。它还涉及碘克沙醇的合成。特别地，它涉及将5-乙酰氨基-N，N'-双（2,3-二羟丙基）-2,4,6-三碘间苯二酰胺（“化合物A”）转化成碘克沙醇的替代二聚试剂。

3. 发明授权

US5962626A Surfactants 失效
标题翻译：表面活性剂
公开(公告)号：US5962626A
公开(公告)日：1999-10-05
申请号：US977630
申请日：1997-11-25
申请人： Per Strande , Harald Dugstad , Balin Balinov , Jan Alfheim , Joseph Arukwe
发明人： Per Strande , Harald Dugstad , Balin Balinov , Jan Alfheim , Joseph Arukwe
IPC分类号： A61K8/39 , A61K8/86 , A61K47/14 , A61Q19/00 , B01F17/00 , B01F17/34 , C07C69/96 , C08G65/332 , C08G63/48 , C11D9/00
CPC分类号： C08G65/3322 , A61K47/14 , A61K8/39 , A61K8/86 , A61Q19/00 , B01F17/0028 , C07C69/96
摘要： The present invention provides a polyethylene glycol (PEG) ester surfactant comprising at least one polyethylene glycol moiety and at least one fatty acyl moiety characterized in that said moieties are linked by a linkage incorporating a biodegradable methylene diester unit of formula (I)--CO.O.C(R.sup.1)(R.sup.2).O.CO-- (I)where R.sup.1 and R.sup.2 may, for example, each be a hydrogen atom or a monovalent organic group attached through a carbon atom or R.sup.1 and R.sup.2 together may, for example, form a divalent organic group attached through carbon atoms.
摘要翻译：本发明提供了包含至少一个聚乙二醇部分和至少一个脂肪酰基部分的聚乙二醇（PEG）酯表面活性剂，其特征在于所述部分通过结合有式（I）-CO的可生物降解的亚甲基二酯单元的连接物连接。其中R 1和R 2可以各自为氢原子或通过碳原子连接的一价有机基团，或者R 1和R 2一起可以例如形成OC（R 1）（R 2）通过碳原子连接的二价有机基团。

4. 发明授权

US5869651A Hydrazide derivatives of polyamides and their medical use as chelating agents 失效
标题翻译：聚酰胺的酰肼衍生物及其作为螯合剂的医疗用途
公开(公告)号：US5869651A
公开(公告)日：1999-02-09
申请号：US190143
申请日：1994-08-08
申请人： Richard J. Himmelsbach , P.ang.l Rongved , Jo Klaveness , Per Strande , Harald Dugstad
发明人： Richard J. Himmelsbach , P.ang.l Rongved , Jo Klaveness , Per Strande , Harald Dugstad
IPC分类号： A61K51/00 , C07C243/34 , C07C259/06 , C07C311/31 , C07C317/28 , C07D257/02 , C07D259/00 , C07F5/00 , C07F9/24 , C07F9/6524 , C09K3/00 , C07D498/08 , C07F15/02
CPC分类号： C07C243/34 , C07C259/06 , C07D257/02
摘要： The invention relates to certain substituted derivatives of aminopolycarboxylic acids and metal chelates thereof. The compounds are particularly suitable for use as diagnostic agent. For example, the compounds can be used as radiodiagnostic agents, detoxification agents and contrast agents for diagnostic imaging processes. In particular, the high relaxivity paramagnetic metal chelates of substituted aminopolycarboxylic acids are especially suited for use as magnetic resonance imaging contrast agents.
摘要翻译： PCT No.PCT / EP92 / 01598 Sec。 371日期1994年8月8日 102（e）日期1994年8月8日PCT提交1992年7月16日PCT公布。公开号WO93 / 08045 日期：1993年2月4日本发明涉及某些取代的氨基多羧酸衍生物及其金属螯合物。该化合物特别适合用作诊断剂。例如，化合物可用作诊断成像过程的放射诊断剂，解毒剂和造影剂。特别地，取代的氨基多羧酸的高弛豫顺磁性金属螯合物特别适合用作磁共振成像造影剂。

5. 发明申请

US20050201942A1 Contrast agents 审中-公开
标题翻译：对比剂
公开(公告)号：US20050201942A1
公开(公告)日：2005-09-15
申请号：US11073027
申请日：2005-03-04
申请人： Harald Dugstad , Jo Klaveness , Pal Rongved , Roald Skurtveit , Jorunn Braenden
发明人： Harald Dugstad , Jo Klaveness , Pal Rongved , Roald Skurtveit , Jorunn Braenden
IPC分类号： A61K49/00 , A61K47/24 , A61K49/04 , A61K49/22
CPC分类号： A61K49/22 , A61K49/223 , A61K49/227 , Y10T428/2982
摘要： Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful as efficacious contrast agents. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.
摘要翻译：主要由包含单独具有整体净电荷的分子的磷脂稳定的微泡分散体显示出有利的稳定性，使其成为有效的造影剂。还公开了一种用于制备含微泡的造影剂的改进方法，其包括将由一种或多种形成膜的脂质稳定的气体微泡的水性分散体冻干以产生可在可注射载体液体中重构以产生微泡的干燥产物含有造影剂。

6. 发明授权

US06221337B1 Microbubbles surrounded by a monolayer of negatively charged phospholipids as contrast agents 有权
标题翻译：由单层带负电荷的磷脂包围的微泡作为造影剂
公开(公告)号：US06221337B1
公开(公告)日：2001-04-24
申请号：US09136410
申请日：1998-08-19
申请人： Harald Dugstad , Jo Klaveness , Pål Rongved , Roald Skurtveit , Jorunn Brænden
发明人： Harald Dugstad , Jo Klaveness , Pål Rongved , Roald Skurtveit , Jorunn Brænden
IPC分类号： A61B800
CPC分类号： A61K49/22 , A61K49/223 , A61K49/227 , Y10T428/2982
摘要： Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful as efficacious contrast agents. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.
摘要翻译：主要由包含单独具有整体净电荷的分子的磷脂稳定的微泡分散体显示出有利的稳定性，使其成为有效的造影剂。还公开了一种用于制备含微泡的造影剂的改进方法，其包括将由一种或多种形成膜的脂质稳定的气体微泡的水性分散体冻干以产生可在可注射载体液体中重构以产生微泡的干燥产物含有造影剂。

7. 发明授权

US06310243B1 Iodinated x-ray contrast media 失效
标题翻译：碘化x射线造影剂
公开(公告)号：US06310243B1
公开(公告)日：2001-10-30
申请号：US09217625
申请日：1998-12-22
申请人： Torsten Almen , Sven Andersson , Lars-Goran Wistrand , Klaes Golman , Oyvind Antonsen , Rune Fossheim , Unni Nordby Wiggen , Hakan Wikstrom , Tomas Klingstedt , Ib Luenbach , Arne Berg , Harald Dugstad
发明人： Torsten Almen , Sven Andersson , Lars-Goran Wistrand , Klaes Golman , Oyvind Antonsen , Rune Fossheim , Unni Nordby Wiggen , Hakan Wikstrom , Tomas Klingstedt , Ib Luenbach , Arne Berg , Harald Dugstad
IPC分类号： C07C23303
CPC分类号： C07C33/46 , A61K49/0433 , A61K49/0452 , C07C33/483 , C07C235/16 , C07C237/46
摘要： The invention provides low viscosity iodinated aryl compounds, useful as X-ray contrast agents, of formula C6R6 wherein three non-adjacent R groups are iodine and the remaining R groups are non-ionic, hydrophilic moieties, said compound being water soluble at 20° C. to a concentration of at least 350 mgl/ml and which in aqueous solution at 20° C. at a concentration of 350 mgl/ml has a viscosity no greater than 13.8 mPas.
摘要翻译：本发明提供低粘度的碘化芳基化合物，其可用作式C6R6的X射线造影剂，其中三个不相邻的R基团是碘，其余的R基团是非离子的亲水部分，所述化合物在20°时是水溶性的至浓度至少为350mg / ml，在浓度为350mg / ml的20℃的水溶液中的粘度不大于13.8mPa·s。

8. 发明授权

US5932190A Multinuclear complexes for X-ray imaging 失效
标题翻译：用于X射线成像的多核配合物
公开(公告)号：US5932190A
公开(公告)日：1999-08-03
申请号：US473574
申请日：1995-06-07
申请人： Torsten Almen , Arne Berg , Michael Droege , Harald Dugstad , Jere D. Fellman , Sook-Hui Kim , Jo Klaveness , Scott M. Rocklage , Pal Rongved , Brent Segal , Alan D. Watson
发明人： Torsten Almen , Arne Berg , Michael Droege , Harald Dugstad , Jere D. Fellman , Sook-Hui Kim , Jo Klaveness , Scott M. Rocklage , Pal Rongved , Brent Segal , Alan D. Watson
IPC分类号： A61K49/00 , A61K49/06 , C07C229/16 , C07C237/08 , C07F11/00 , C07F13/00 , C07F15/00 , C07F15/02 , A61K49/04
CPC分类号： C07F11/005 , A61K49/06 , C07F15/025 , Y10S514/836 , Y10S977/903 , Y10S977/928 , Y10S977/929
摘要： An x-ray contrast medium containing a multinuclear complex of the formula (M.sub.6 (.mu..sub.3 B).sub.8 A.sub.v).sub.x L.sub.w, wherein M is Mo, W, Re Tc, V, Nb, Ta, Ru, or Fe; .mu..sub.3 B represent a tridentate bridging atom; A is a non-bridging atom; L is a ligand coordinately bonded to at least one M atom; x is a positive integer; and v and w are independently zero or positive integers.
摘要翻译：含有式（M6（mu 3B）8Av）×Lw的多核配合物的X射线造影剂，其中M为Mo，W，Re Tc，V，Nb，Ta，Ru或Fe; mu 3B代表三齿桥接原子; A是非桥连原子; L是与至少一个M原子配位键合的配体; x是正整数; v和w分别为零或正整数。

9. 发明授权

US5348954A Heterocyclic chelating agents 失效
标题翻译：杂环螯合剂
公开(公告)号：US5348954A
公开(公告)日：1994-09-20
申请号：US690975
申请日：1991-07-24
申请人： Torsten Almen , Arne Berg , Harald Dugstad , Jo Klaveness , Klaus D. Krautwurst , Pal Rongved
发明人： Torsten Almen , Arne Berg , Harald Dugstad , Jo Klaveness , Klaus D. Krautwurst , Pal Rongved
IPC分类号： A61K47/48 , A61K49/00 , A61K49/04 , A61K49/06 , A61K51/00 , A61K51/04 , C07D207/14 , C07D211/42 , C07D211/46 , C07D211/56 , C07D241/04 , C07D241/20 , C07D265/30 , C07D265/32 , C07D279/12 , C07F3/00 , C07F5/00 , C07F9/94 , C07F13/00 , A61K31/15 , C07D211/08
CPC分类号： A61K47/48076 , A61K47/48023 , A61K49/06 , A61K51/0478 , A61K51/0482 , C07D207/14 , C07D211/56 , C07D241/04 , C07D265/30 , C07D279/12 , C07F13/005 , C07F3/003 , C07F5/003 , C07F9/94 , A61K2121/00 , A61K2123/00 , Y10S514/836 , Y10T436/24
摘要： Heterocylic chelating agents and salts thereof of formula I: ##STR1## wherein X represents a bond, O or S, or a group CHR.sup.1 or NR.sup.3 ; R.sup.1 represents H, a group OR.sup.3 or NR.sup.3 R.sup.3, or an alkyl or alkoxyalkyl group optionally substituted by a hydroxyl group or by a group NR.sup.3 R.sup.3 or CON.sup.3 R.sup.3 ;each R.sup.2 represents H, or an alkyl or alkoxy group optionally substituted by a hydroxyl or alkoxy group;each R.sup.3 represents H, an optionally hydroxylated alkyl group or a group CH.sub.2 Y;Y represents a group COZ, CON(OH)R.sup.4, POZ.sub.2 or SO.sub.2 Z;Z represents a group OR.sup.4, NR.sup.4 R.sup.4 or ##STR2## where each R.sup.11 is H, a hydroxyl group or an optionally hydroxylated alkyl group, s is 0, 1 or 2, and W is CHR.sup.11, NR.sup.11 or an oxygen atom; andeach R.sup.4 represents H, or an optionally mono- or poly-hydroxylated alkyl, alkoxyalkyl or polyalkoxyalkyl group;with the provisos that where s is 0 then W is CHR.sup.11 and that where X represents a bond or CHR.sup.1, at least one group R.sup.1 or R.sup.2 represents other than H or an unsubstituted alkyl group. A process for preparing these agents and methods of heavy metal detoxification using these agents are also described.
摘要翻译： PCT No.PCT / EP90 / 00079 Sec。 371日期1991年7月24日 102（e）日期1991年7月24日PCT 1990年1月15日PCT PCT。公开号WO90 / 08138 日本1990年7月26日。式I的杂环螯合剂及其盐：其中X表示键，O或S或CHR1或NR3基团; R1表示H，OR3或NR3R3，或任选被羟基或NR3R3或CON3R3基团取代的烷基或烷氧基烷基; 每个R 2表示H或任选被羟基或烷氧基取代的烷基或烷氧基; 每个R 3表示H，任选羟基化的烷基或基团CH 2 Y; Y代表基团COZ，CON（OH）R4，POZ2或SO2Z; Z表示OR4，NR4R4或，其中每个R11是H，羟基或任选羟基化的烷基，s是0,1或2，W是CHR 11，NR 11或氧原子; 并且每个R 4表示H或任选的单羟基化或多羟基化烷基，烷氧基烷基或聚烷氧基烷基; 条件是其中s为0，则W为CHR 11，并且其中X表示键或CHR，至少一个基团R 1或R 2表示不同于H或未取代的烷基。还描述了使用这些试剂制备这些试剂的方法和重金属解毒的方法。

10. 发明授权

US06217850B1 Method of making lyophilized microbubble compositions useful as contrast agents 失效
标题翻译：制备用作造影剂的冻干微泡组合物的方法
公开(公告)号：US06217850B1
公开(公告)日：2001-04-17
申请号：US09084105
申请日：1998-05-26
申请人： Harald Dugstad , Jo Klaveness , Pål Rongved , Roald Skurtveit , Jorunn Braenden
发明人： Harald Dugstad , Jo Klaveness , Pål Rongved , Roald Skurtveit , Jorunn Braenden
IPC分类号： A61B800
CPC分类号： A61K49/223 , A61K49/227 , Y10T428/2982
摘要： Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful both as efficacious contrast agents per se and as intermediates in the preparation of contrast agents wherein the phospholipids are crosslinked or polymerised. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.
摘要翻译：由主要包含单独具有整体净电荷的分子的磷脂稳定的微泡分散体表现出有利的稳定性，使得它们作为有效的造影剂本身以及作为制备造影剂的中间体是有用的，其中磷脂是交联或聚合的。还公开了一种用于制备含微泡的造影剂的改进方法，其包括将由一种或多种形成膜的脂质稳定的气体微泡的水性分散体冻干以产生可在可注射载体液体中重构以产生微泡的干燥产物含有造影剂。

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