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    METHOD FOR THE PREPARATION OF A HEAT STABLE OXYGEN CARRIER-CONTAINING COMPOSITION FACILATING BETA-BETA CROSS-LINKING
    3.
    发明公开
    METHOD FOR THE PREPARATION OF A HEAT STABLE OXYGEN CARRIER-CONTAINING COMPOSITION FACILATING BETA-BETA CROSS-LINKING 有权
    VERFAHREN ZUR HERSTELLUNG EINER ZUSAMMENSETZUNG ENTHALTEND BETA-BETA-VERNETZTESRINDERHÄMOGLOBIN

    公开(公告)号：EP2750700A2

    公开(公告)日：2014-07-09

    申请号：EP12828756.2

    申请日：2012-08-23

    申请人： Billion King International Limited

    发明人： WONG, Bing Lou. ,  KWOK, Sui Yi. ,  BUTT, Kwok Chu.

    IPC分类号： A61K38/42 ,  A61K35/14 ,  A61K35/12 ,  A61K9/08 ,  A61K47/48

    CPC分类号： A61K38/42

    摘要： Methods for preparation of a heat stable hemoglobin based oxygen-carrier-containing pharmaceutical composition such that beta-beta cross-linking is favored are provided. Using the methods of the present invention, the oxygen affinity of the resultant molecule can be controlled so that hemoglobin based oxygen carriers tailored for specific applications can be produced. Lower oxygen affinity crosslinked hemoglobin is useful for applications requiring rapid tissue oxygenation (e.g. hemorrhagic shock) while higher oxygen affinity cross-linked hemoglobin is useful for applications requiring a slower rate of oxygenation (e.g. cancer adjunct therapy). A highly purified and heat stable crosslinked non-polymeric tetrameric hemoglobin having beta-beta cross-linking of greater than 40-60% and suitable for use in mammals without causing renal injury and vasoconstriction is produced. A high temperature and short time (HTST) heat processing step is performed to effectively remove any undesired dimeric hemoglobin, non-crosslinked tetrameric hemoglobin, and plasma protein impurities.

    摘要翻译： 提供了制备基于热稳定性血红蛋白的含氧载体的药物组合物以使β-β交联成为有利的方法。 使用本发明的方法，可以控制所得分子的氧亲和力，使得可以生产针对具体应用定制的基于血红蛋白的氧载体。 低氧亲和性交联血红蛋白可用于需要快速组织氧合（例如出血性休克）的应用，而较高的氧亲和力交联血红蛋白可用于需要较慢氧合作用的应用（例如癌症辅助治疗）。 产生具有大于40-60％且适用于哺乳动物而不引起肾损伤和血管收缩的β-β交联的高度纯化和热稳定的交联非聚合四聚体血红蛋白。 执行高温和短时间（HTST）热处理步骤以有效地去除任何不期望的二聚体血红蛋白，非交联的四聚体血红蛋白和血浆蛋白质杂质。

    A HEAT STABLE OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION FOR DIFFERENT TREATMENT APPLICATIONS
    4.
    发明公开
    A HEAT STABLE OXYGEN CARRIER-CONTAINING PHARMACEUTICAL COMPOSITION FOR DIFFERENT TREATMENT APPLICATIONS 审中-公开
    热稳定的氧载体含有不同处理的药物组合物

    公开(公告)号：EP2731619A2

    公开(公告)日：2014-05-21

    申请号：EP12811843.7

    申请日：2012-07-11

    申请人： Billion King International Limited

    发明人： Wong, Bing Lou ,  Kwok, Sui Yi ,  Lau, Sze Hang

    IPC分类号： A61K38/42 ,  A61K47/48 ,  A61K47/30 ,  A61P35/00

    CPC分类号： A61K38/42

    摘要： A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. The inventive tetrameric hemoglobin can also be used to prevent tumor metastasis and recurrence following surgical tumor excision. Further the inventive tetrameric hemoglobin can be administered to patients prior to chemotherapy and radiation treatment.

    摘要翻译： 适于在哺乳动物中使用的高度纯化的和热稳定的交联的非聚合的血红蛋白四聚体，而不引起肾损伤和血管收缩设置。 高温和短时（HTST）热加工工序中进行有效地除去血红蛋白的不希望的二聚体形式，未交联的四聚体血红蛋白，与血浆蛋白的杂质。 热处理后并任选地热处理前的N-乙酰基半胱氨酸的加入维持高铁血红蛋白的低水平。 热稳定的交联四聚体血红蛋白可以改善和在正常和缺氧组织延长氧合作用。 如白血病，结肠直肠癌，肺癌，乳腺癌，肝癌，鼻咽癌和食道癌：在另一个方面，所述产物在多种类型的癌症的治疗中使用。 因此，本发明的血红蛋白可用于防止肿瘤转移和复发继外科肿瘤切除。 进一步根据本发明的四聚体血红蛋白可以给予之前化疗和放射治疗的患者。

    METHOD FOR THE PREPARATION OF A COMPOSITION COMPRISING BETA-BETA CROSS-LINKED BOVINE HEMOGLOBIN
    7.
    发明授权
    METHOD FOR THE PREPARATION OF A COMPOSITION COMPRISING BETA-BETA CROSS-LINKED BOVINE HEMOGLOBIN 有权
    制备包含β-β交联牛血红蛋白的组合物的方法

    公开(公告)号：EP2750700B1

    公开(公告)日：2017-12-27

    申请号：EP12828756.2

    申请日：2012-08-23

    申请人： Billion King International Limited

    发明人： WONG, Bing Lou. ,  KWOK, Sui Yi. ,  BUTT, Kwok Chu.

    IPC分类号： A61K38/42

    CPC分类号： A61K38/42

    摘要： Methods for preparation of a heat stable hemoglobin based oxygen-carrier-containing pharmaceutical composition such that beta-beta cross-linking is favored are provided. Using the methods of the present invention, the oxygen affinity of the resultant molecule can be controlled so that hemoglobin based oxygen carriers tailored for specific applications can be produced. Lower oxygen affinity crosslinked hemoglobin is useful for applications requiring rapid tissue oxygenation (e.g. hemorrhagic shock) while higher oxygen affinity cross-linked hemoglobin is useful for applications requiring a slower rate of oxygenation (e.g. cancer adjunct therapy). A highly purified and heat stable crosslinked non-polymeric tetrameric hemoglobin having beta-beta cross-linking of greater than 40-60% and suitable for use in mammals without causing renal injury and vasoconstriction is produced. A high temperature and short time (HTST) heat processing step is performed to effectively remove any undesired dimeric hemoglobin, non-crosslinked tetrameric hemoglobin, and plasma protein impurities.