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1. 发明申请

WO1992008984A1 ASSAY FOR GLYCATED BLOOD PROTEINS 审中-公开
标题翻译：血糖测定蛋白质
公开(公告)号：WO1992008984A1
公开(公告)日：1992-05-29
申请号：PCT/EP1991002163
申请日：1991-11-13
申请人： COCKBAIN, Julian, Roderick, Michaelson , AXIS RESEARCH AS , SUNDREHAGEN, Erling , FRANTZEN, Frank
发明人： COCKBAIN, Julian, Roderick, Michaelson , AXIS RESEARCH AS
IPC分类号： G01N33/68
CPC分类号： G01N33/6842 , G01N33/68 , G01N33/723 , Y10S436/815 , Y10S436/824 , Y10T436/25125 , Y10T436/25375
摘要： There is provided a method of assessing a glycated blood protein in a sample, said method comprising the steps of a) optionally hemolysing said sample to liberate cell bound glycated protein; b) separating said glycated blood protein and the corresponding non-glycated blood protein from said sample; c) contacting said sample before or during separation of said glycated and non-glycated proteins therefrom or contacting said separated proteins with a first signal forming agent capable of binding to said glycated protein but not to the corresponding non-glycated protein; d) optionally, contacting said sample before or during separation of said glycated and non-glycated proteins therefrom or contacting said separated proteins with a second signal forming agent capable of binding to said glycated protein and to said corresponding non-glycated protein; and e) assessing the signal forming agents which have bound to said separated proteins and/or which have not bound to said glycated protein or said corresponding non-glycated protein; with the proviso that where said glycated protein comprises glycated hemoglobin said first signal forming agent is a chromophore labelled boronic acid or salt thereof having an absorption maximum at above 600 nm. In this method the glycated protein which is labelled by the first signal forming agent may be any one, or indeed any set, of the blood proteins. By appropriate selection of the proteins under assay an indication may be obtained of the history of the patient's blood glucose control over the short, medium and long (up to 3 months) term.
摘要翻译：提供了一种评估样品中糖化血液蛋白质的方法，所述方法包括以下步骤：a）任选地溶血所述样品以释放细胞结合的糖基化蛋白质; b）从所述样品中分离所述糖化血液蛋白质和相应的非糖化血液蛋白质; c）在分离所述糖化糖基化蛋白质和非糖化蛋白质之前或期间使所述样品接触或使所述分离的蛋白质与能够结合所述糖基化蛋白质但不与相应的非糖基化蛋白质结合的第一信号形成剂接触; d）任选地，在从所述糖基化和非糖化蛋白质分离之前或期间使所述样品接触，或使所述分离的蛋白质与能够结合所述糖基化蛋白质和所述相应的非糖基化蛋白质的第二信号形成剂接触; 和e）评估与所述分离的蛋白质结合的信号形成剂和/或不结合所述糖基化蛋白质或所述相应的非糖基化蛋白质的信号形成剂; 条件是所述糖化蛋白质包含糖化血红蛋白的所述第一信号形成剂是在600nm以上具有吸收最大值的发色团标记的硼酸或其盐。在该方法中，由第一信号形成剂标记的糖化蛋白质可以是血液蛋白质中的任何一种，或者甚至是任意组合的。通过适当选择测定中的蛋白质，可以获得关于短期，中期和长期（至多3个月）期患者血糖控制史的指示。

2. 发明申请

WO1992008722A1 LABELLING AGENTS COMPRISING BORONIC ACID CONJUGATES 审中-公开
标题翻译：包含硼酸结合物的标签试剂
公开(公告)号：WO1992008722A1
公开(公告)日：1992-05-29
申请号：PCT/EP1991002160
申请日：1991-11-13
申请人： COCKBAIN, Julian, Roderick, Michaelson , AXIS RESEARCH AS , FRANTZEN, Frank , SUNDREHAGEN, Erling
发明人： COCKBAIN, Julian, Roderick, Michaelson , AXIS RESEARCH AS
IPC分类号： C07F05/02
CPC分类号： G01N33/587 , C07F5/025 , G01N33/533
摘要： Labelling agents comprising non-proteinaceous boronic acid conjugates having absorption maxima at not less than 600 nm, said label being provided by e.g. an azine, triphenylmethane, cyanine or phthalocyanine dye, are useful in the estimation and quantification of cisdiols such as glycosylated haemoglobin, by virtue of the substantially total absence of overlap with the absorption spectrum of haemoglobin. Oxazine and thiazine dyes exhibiting similar absorption characteristics and containing other activated moieties are similarly useful labelling agents, especially in the presence of haemoglobin.
摘要翻译：包含非蛋白质硼酸缀合物的标记试剂，其吸收最大值不小于600nm，所述标记由例如，吖嗪，三苯甲烷，花青或酞菁染料，由于与血红蛋白的吸收光谱基本完全不存在重叠，可用于估计和定量顺式二糖如糖基化血红蛋白。表现出相似吸收特性并含有其它活化部分的恶嗪和噻嗪染料也是类似地有用的标记试剂，特别是在血红蛋白存在下。

3. 发明申请

WO1993015220A1 HOMOCYSTEINE ASSAY 审中-公开
标题翻译：同位素测定
公开(公告)号：WO1993015220A1
公开(公告)日：1993-08-05
申请号：PCT/GB1993000138
申请日：1993-01-22
申请人： COCKBAIN, Julian, Roderick, Michaelson , AXIS RESEARCH AS , SUNDREHAGEN, Erling
发明人： COCKBAIN, Julian, Roderick, Michaelson , AXIS RESEARCH AS
IPC分类号： C12Q01/34
CPC分类号： C12Q1/48 , C07H15/14 , C07H15/26 , C07H19/16 , C12Q1/34 , G01N33/542 , G01N33/5735 , G01N33/68 , G01N33/6815
摘要： There is provided a method for assaying homocysteine in a sample, e.g. blood, plasma or urine, which comprises the steps of contacting said sample with a homocysteine converting enzyme and at least one substrate for said enzyme other than homocysteine, and without chromatographic separation assessing a non-labelled analyte selected from a homocysteine co-substrate and the homocysteine conversion products of the enzymic conversion of homocysteine by said enzyme.
摘要翻译：提供了在样品中测定同型半胱氨酸的方法，例如血液，血浆或尿液，其包括以下步骤：使所述样品与高半胱氨酸转化酶和至少一种用于除同型半胱氨酸以外的酶的底物接触，并且不进行色谱分离，评估选自同型半胱氨酸共底物的非标记分析物和所述酶对同型半胱氨酸进行酶转化的同型半胱氨酸转化产物。

4. 发明申请

WO1997009633A1 A METHOD OF DETERMINING OXYGEN CONCENTRATION IN A SAMPLE 审中-公开
标题翻译：在样品中测定氧气浓度的方法
公开(公告)号：WO1997009633A1
公开(公告)日：1997-03-13
申请号：PCT/GB1996002198
申请日：1996-09-06
申请人： NYCOMED IMAGING A/S , COCKBAIN, Julian, Roderick, Michaelson , ARDENKJAER-LARSEN, Jan, Henrik , LEUNBACH, Ib
发明人： NYCOMED IMAGING A/S , COCKBAIN, Julian, Roderick, Michaelson
IPC分类号： G01R33/62
CPC分类号： A61K49/20 , G01R33/281 , G01R33/62
摘要： A method for determining the oxygen concentration of a sample using electron spin resonance enhanced magnetic resonance imaging.
摘要翻译：使用电子自旋共振增强磁共振成像确定样品的氧浓度的方法。

5. 发明申请

WO1995026754A1 SEGMENTED CHELATING POLYMERS AS IMAGING AND THERAPEUTIC AGENTS 审中-公开
公开(公告)号：WO1995026754A1
公开(公告)日：1995-10-12
申请号：PCT/GB1995000742
申请日：1995-03-31
申请人： NYCOMED IMAGING A.S , COCKBAIN, Julian, Roderick, Michaelson , BUTTERFIELD, Dennis, Earl , FUJII, Dennis, Kiyoshi , LADD, David, Lee , SNOW, Robert, Allan , TAN, Julia, Shieh , TONER, John, Luke
发明人： NYCOMED IMAGING A.S , COCKBAIN, Julian, Roderick, Michaelson
IPC分类号： A61K49/00
CPC分类号： C08G65/329 , Y10S530/815 , Y10S530/816
摘要： A segmented polymer suitable for use in diagnostic imaging or as a cell killing agent comprising a chelating agent residue linked via an amide linkage to a poly(alkylene oxide) moiety, said polymer having a molecular weight of at least 4,500.
摘要翻译：适用于诊断成像的分段聚合物或作为细胞杀伤剂的分段聚合物，其包含通过酰胺键与聚（环氧烷）部分连接的螯合剂残基，所述聚合物的分子量至少为4500。

6. 发明申请

WO1995002831A1 METHODS AND COMPOSITIONS FOR IMAGE CONTRAST ENHANCING 审中-公开
标题翻译：图像对比增强的方法和组合
公开(公告)号：WO1995002831A1
公开(公告)日：1995-01-26
申请号：PCT/GB1994001500
申请日：1994-07-11
申请人： COCKBAIN, Julian, Roderick, Michaelson , NYCOMED IMAGING AS , ERICCSON, Anders , FAHLVIK, Anne, Kjersti , HEMMINGSSON, Anders , WIKSTROM, Mats , OKSENDAL, Audun , BACH-GANSMO, Tore
发明人： COCKBAIN, Julian, Roderick, Michaelson , NYCOMED IMAGING AS
IPC分类号： G01R33/28
CPC分类号： G01R33/5601 , A61K49/06 , Y10S514/836
摘要： This invention relates to improvements in and relating to magnetic resonance imaging of the human or non-human body, in particular to a method in which positive and negative contrast agents are administered to enhance image contrast.
摘要翻译：本发明涉及人体或非人体的磁共振成像的改进和涉及，特别涉及其中施用正和负造影剂以增强图像对比度的方法。

7. 发明申请

WO1993002045A1 HYDROXAMATE AND HYDRAZIDE DERIVATIVES OF POLYAMINES AND THEIR MEDICAL USE AS CHELATING AGENTS 审中-公开
标题翻译：聚氨酯的氢氧化物和氢化衍生物及其作为螯合剂的医药用途
公开(公告)号：WO1993002045A1
公开(公告)日：1993-02-04
申请号：PCT/EP1992001598
申请日：1992-07-16
申请人： COCKBAIN, Julian, Roderick, Michaelson , NYCOMED SALUTAR, INC. , HIMMELSBACH, Richard, J. , RONGVED, Pål , KLAVENESS, Jo , STRANDE, Per , DUGSTAD, Harald
发明人： COCKBAIN, Julian, Roderick, Michaelson , NYCOMED SALUTAR, INC.
IPC分类号： C07C243/34
CPC分类号： C07C243/34 , C07C259/06 , C07D257/02
摘要： The present invention provides a compound of formula (I): A[X(CR R )n]mXA or a chelate complex of salt thereof, for use as therapeutic or diagnostic agent wherein in formula (I), each of the groups R and R may independently represent a hydrogen atom or an alkyl or alkoxy group, optionally carrying one or more substituents selected from hydroxy, alkoxy and aryl groups; each X independently represents an oxygen or sulphur atom or a group NA; each A independently represents a hydrogen atom or an alkyl group optionally substituted by a group Y; each Y represents a hydrogen atom, or a group Z, COZ, SO3R , CSZ, PO2Z or B; or one or more pairs of A groups on different X moieties may together form a group [(CR R )nX ]p (CR R )n or a group A on a mid-chain nitrogen may represent a group [(CR R )nX ]p (CR R )nX A where p represents an integer of 0 to 6, and each X independently represents an oxygen or sulphur atom or a group NA where A is as defined for A but may not form part of a group attached to more than one nitrogen atom; or two adjacent groups R and/or A may together form a homo- or heterocyclic saturated or unsaturated 5-7 membered ring containing 0, 1 or 2 ring heteroatoms selected from oxygen, nitrogen and sulphur; m is an integer of 2 to 8; n is an integer of 2 to 4.
摘要翻译：本发明提供式（I）化合物：A [X（CR 1 R 2）n] m X A或其盐的螯合络合物，其用作治疗或诊断剂，其中式（I）， R 1和R 2中的每一个可以独立地表示氢原子或烷基或烷氧基，任选携带一个或多个选自羟基，烷氧基和芳基的取代基; 每个X独立地表示氧或硫原子或基团NA; 每个A独立地表示氢原子或任选被基团Y取代的烷基; 每个Y表示氢原子，或基团Z，COZ，SO 3 R 6，CSZ，PO 2 Z或B; 或不同X部分上的一对或多对A基团可以一起形成基团[（CR 1 R 2）n X 1] p（CR 1 R 2）n或基团中链氮可以表示基团[（CR 1 R 2）n X 1] p（CR 1 R 2）n X 1 A，其中p表示0至6的整数并且每个X 1独立地表示氧或硫原子或NA <1，其中A 1如对A所定义，但不能形成与多于一个氮原子连接的基团的一部分; 或两个相邻基团R 1和/或A可以一起形成含有0,1或2个选自氧，氮和硫的环杂原子的均聚或杂环饱和或不饱和5-7元环; m为2〜8的整数， n为2〜4的整数。

8. 发明申请

WO1991014460A1 CONTRAST MEDIA 审中-公开
标题翻译：对比媒体
公开(公告)号：WO1991014460A1
公开(公告)日：1991-10-03
申请号：PCT/EP1991000587
申请日：1991-03-27
申请人： COCKBAIN, Julian, Roderick, Michaelson , NYCOMED AS , BERG, Arne , ALMÉN, Torsten , KRAUTWURST, Klaus, Dieter , KIM, Sook-Hui , RONGVED, Pål , KLAVENESS, Jo , DUGSTAD, Harald
发明人： COCKBAIN, Julian, Roderick, Michaelson , NYCOMED AS
IPC分类号： A61K49/04
CPC分类号： C07F11/005 , A61K49/04 , A61K51/02 , A61K51/04 , A61K51/0482 , A61K2123/00 , Y10S514/836
摘要： The invention relates to the use as contrast enhancing agents in medical imaging, especially X-ray imaging, of multinuclear complexes, i.e. complexes, such as those of W2O2( mu 2O)2, in which the complexed entity comprises at least two contrast enhancing atoms.
摘要翻译：本发明涉及作为多核复合物的医学成像，特别是X射线成像中的对比增强剂的用途，例如复合物，例如W 2 O 2（mu 2 O）2的那些，其中复合实体包含至少两个对比度增强原子。

9. 发明申请

WO1990007719A1 IMPROVEMENTS IN AND RELATING TO MAGNETIC RESONANCE IMAGING 审中-公开
标题翻译：磁共振成像中的改进和相关
公开(公告)号：WO1990007719A1
公开(公告)日：1990-07-12
申请号：PCT/EP1989001611
申请日：1989-12-20
申请人： HAFSLUND NYCOMED INNOVATION AB , COCKBAIN, Julian, Roderick, Michaelson , LEUNBACH, Ib , GOLMAN, Klaes , KLAVENESS, Jo
发明人： HAFSLUND NYCOMED INNOVATION AB , COCKBAIN, Julian, Roderick, Michaelson
IPC分类号： G01R33/28
CPC分类号： G01R33/5601 , G01R33/62
摘要： The invention relates to a modification of electron spin resonance enhanced magnetic resonance imaging (ESREMRI) in which two magnetically responsive materials (contrast agents) are introduced into the sample being investigated, one contrast agent serving as an ESREMRI free induction decay signal enhancing agent and the other as enhancement suppressing agent. In this way image contrast may be enhanced futher for regions in which the suppressing agent distributes poorly or not at all or which the suppressing agent reaches at a later time than the enhancing agent.

10. 发明申请

WO1990003975A1 MANGANESE(II) CHELATES 审中-公开
标题翻译：马来西亚（二）烧烤
公开(公告)号：WO1990003975A1
公开(公告)日：1990-04-19
申请号：PCT/EP1989001122
申请日：1989-09-26
申请人： SALUTAR, INC. , COCKBAIN, Julian, Roderick, Michaelson
发明人： SALUTAR, INC. , COCKBAIN, Julian, Roderick, Michaelson , ROCKLAGE, Scott , CACHERIS, William , JAMIESON, Gene
IPC分类号： C07F09/58
CPC分类号： C07D213/66 , A61K49/06 , C07C229/16 , C07D257/02 , C07D273/00 , C07F9/65583
摘要： A process is provided for the preparation of Mn(II) chelates for use as contrast agents in magnetic resonance imaging, said process comprising reacting insoluble manganese (II) oxide with an aqueous suspension comprising a molar equivalent or molar excess of an insoluble protonated chelating compound conveniently at a temperature of from 20 to 50°C. When the reaction is carried out with a protonated chelating agent in the absence of base, a precipitate of the protonated Mn(II) chelate is formed. A low osmolarity Mn(II) chelate solution can be formed from the precipitates by disssolving them in an aqueous solution of base. When the initial chelate forming reaction is carried out in a solution containing a molar equivalent or excess of base, a low osmolarity solution of the Mn(II) chelate is directly formed with most chelating agents. The Mn(II) chelate precipitates and low osmolarity solutions formed by the above processes are also aspects of this invention.

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