WONG, BING LOU,黄炳鏐,黃炳鏐,KWOK, SUI YI,郭瑞仪,郭瑞儀,BUTT, KWOK CHU,毕国珠,畢國珠
申请号：
TW102123160
公开号：
TWI526218B
申请日:
2012.08.23
申请国别(地区):
TW
年份:
2016
代理人:
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.本發明提供用於製備基於熱穩定血紅素之含氧載體醫藥組成物以便有利於β-β交聯的方法。使用本發明方法可控制所得分子之氧親和力，由此可產生為特定應用定製之基於血紅素之氧載體。較低氧親和力交聯之血紅素適用於需要快速組織氧合之應用(例如出血性休克)而較高氧親和力交聯之血紅素適用於需要較慢氧合速率之應用(例如癌症輔助治療)。本發明產生一種經高度純化且熱穩定交聯的非聚合四聚血紅素，其具有大於40%至60%之β-β交聯且適於在哺乳動物中使用而不造成腎損傷及血管收縮。進行高溫及短時(HTST)熱處理步驟以有效移除任何不合需要之二聚血紅素、非交聯四聚血紅素及血漿蛋白質雜質。
