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1. 发明申请

WO2013032828A2 METHOD FOR THE PREPARATION OF A HEAT STABLE OXYGEN CARRIER-CONTAINING COMPOSITION FACILATING BETA-BETA CROSS-LINKING 审中-公开
标题翻译：制备提供β-β交联的热稳定载体组合物的方法
公开(公告)号：WO2013032828A2
公开(公告)日：2013-03-07
申请号：PCT/US2012/051959
申请日：2012-08-23
申请人： WONG, Bing, Lou , KWOK, Sui, Yi , BUTT, Kowk, Chu
发明人： WONG, Bing, Lou , KWOK, Sui, Yi , BUTT, Kowk, 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：提供了制备热稳定血红蛋白基含氧载体药物组合物以使β-β交联更受欢迎的方法。使用本发明的方法，可以控制所得分子的氧亲和力，从而可以生产针对具体应用定制的血红蛋白基氧载体。较低氧亲和力交联血红蛋白可用于需要快速组织氧合（例如失血性休克）的应用，而较高氧亲和力交联血红蛋白可用于需要较慢氧合速率的应用（例如癌症辅助治疗）。产生具有大于40-60％的β-β交联并且适用于哺乳动物而不引起肾损伤和血管收缩的高度纯化和热稳定的交联非聚合物四聚体血红蛋白。进行高温短时间（HTST）热处理步骤以有效除去任何不需要的二聚血红蛋白，非交联四聚体血红蛋白和血浆蛋白杂质。

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