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    Specifically crosslinked hemoglobin with free functionality
    1.
    发明授权
    Specifically crosslinked hemoglobin with free functionality 失效
    具有自由功能的具有交联性的血红蛋白

    公开(公告)号：US5399671A

    公开(公告)日：1995-03-21

    申请号：US978418

    申请日：1992-11-18

    申请人： Ronald Kluger ,  Yonghong Song

    发明人： Ronald Kluger ,  Yonghong Song

    IPC分类号： A61K38/16 ,  A61K38/00 ,  A61K47/48 ,  A61P7/08 ,  C07C69/86 ,  C07K1/113 ,  C07K14/805 ,  C07C103/52 ,  A61K35/14 ,  C07K13/00

    CPC分类号： C07K14/805 ,  A61K47/48307 ,  C07C69/76 ,  A61K38/00

    摘要： Hemoglobin is site-specifically crosslinked into its tetrameric form by reaction with a trifunctional reagent which combines electrostatic effects, steric effects and the presence of functional groups so that two of the functional groups react with specific sites on the hemoglobin whilst the third site is left free for reaction with endogenous nucleophilic compounds. A specific example of such a crosslinking reagent is trimesoyl tris(3,5-dibromosalicylate), TTDS, which effects specific crosslinking between the amino groups of lysine-82 on each respective .beta. sub-unit. While the crosslinking reagent TTDS has three available carboxyl groups for the crosslinking reaction, only two so react, leaving one free carboxyl for reaction with exogenous nucleophiles, e.g. to render the hemoglobin product useful as a carrier for nucleophilic compounds through the body's circulatory system.

    摘要翻译： 血红蛋白通过与三官能试剂反应进行位置特异性交联成四聚体形式，其结合了静电效应，空间效应和功能基团的存在，使得两个官能团与血红蛋白上的特定位点反应，而第三位点保持游离 用于与内源性亲核化合物反应。 这种交联试剂的具体实例是均苯三甲酸三（3,5-二溴水杨酸酯）TTDS，其在每个相应的β子单元上影响赖氨酸-82的氨基之间的特异性交联。 虽然交联剂TTDS具有三个用于交联反应的可用羧基，但仅有两个反应，留下一个游离羧基用于与外源亲核试剂反应，例如， 以使血红蛋白产物通过身体的循环系统用作亲核化合物的载体。

    Pharmaceutical composition and treatment
    4.
    发明授权
    Pharmaceutical composition and treatment 失效
    药物组成和治疗

    公开(公告)号：US4738985A

    公开(公告)日：1988-04-19

    申请号：US841214

    申请日：1986-03-19

    申请人： Ronald Kluger ,  Mortimer Mamelak

    发明人： Ronald Kluger ,  Mortimer Mamelak

    IPC分类号： A61K31/22 ,  A61K31/23 ,  A61K31/235

    CPC分类号： A61K31/235 ,  A61K31/22 ,  A61K31/23

    摘要： Sleep disorders in mammals, such as insomnia and narcolepsy, are treated by administering an effective amount of ethyl 4-acetoxybutanoate, or a closely related homolog thereof. The compounds may also be administered to mammals to cause muscle relaxation and as animal anaesthetics. Moreover the compounds appear to inhibit the release of dopamine in the brain, and are hence useful also in treatment of conditions which are associated with abnormalities of dopamine release and dopamine sensitivities, such as Parkinson's disease, schizophrenia and tardive dyskenesia.

    摘要翻译： 通过施用有效量的4-乙酰氧基丁酸乙酯或其密切相关的同系物来治疗哺乳动物的睡眠障碍，例如失眠和发作性睡病。 化合物还可以施用于哺乳动物以引起肌肉松弛和作为动物麻醉剂。 此外，化合物似乎抑制脑中多巴胺的释放，因此也可用于治疗与多巴胺释放异常和多巴胺敏感性相关的病症，例如帕金森病，精神分裂症和迟发性失眠症。

    CROSS-LINKING REAGENTS FOR HEMOGLOBIN AND HEMOGLOBIN PRODUCTS CROSS-LINKED THEREWITH
    5.
    发明申请
    CROSS-LINKING REAGENTS FOR HEMOGLOBIN AND HEMOGLOBIN PRODUCTS CROSS-LINKED THEREWITH 审中-公开
    HEMOGLOBIN和HEMOGLOBIN产品的交联试剂与其交联

    公开(公告)号：US20070142626A1

    公开(公告)日：2007-06-21

    申请号：US11608466

    申请日：2006-12-08

    申请人： Ronald Kluger ,  Dongxin Hu

    发明人： Ronald Kluger ,  Dongxin Hu

    IPC分类号： C07K14/805 ,  C07F9/02

    CPC分类号： C07F9/096 ,  A61K38/00 ,  A61K47/548 ,  A61K47/6445

    摘要： A process for efficiently preparing bis-tetrameric hemoglobin in which the tetramers are specifically linked at predetermined sites on the β-sub-units and in which the tetramers themselves are effectively bonded to prevent dissociation into dimeric αβ-hemoglobin sub-units therefrom is provided. The process uses as cross-linking reagent a hexafunctional aromatic acyl phosphate containing amide groups, The concept is to use a cross-linking reagent which has an excess of site-specific hemoglobin reacting groups, namely six acyl phosphate groups, so that at least four of them will react site specifically to form the bis-tetrameric product of particular therapeutic interest.

    摘要翻译： 提供了一种有效制备双四聚体血红蛋白的方法，其中四聚体在β-亚单元上的预定位点特异性连接，并且其中四聚体本身有效结合，以防止从其分离成二聚体字母a-血红蛋白亚单元。 该方法用作交联试剂为含有酰胺基团的六功能芳族酰基磷酸酯，其概念是使用具有过量的位点特异性血红蛋白反应基团（即六个酰基磷酸酯基团）的交联试剂，使得至少四个 的它们将特异性地反应位点以形成具有特定治疗兴趣的双 - 四聚体产物。