Hill S E
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Can J Anaesth. 2001 Apr;48(4 Suppl):S32-40.
In an effort to develop agents that enhance the oxygen-delivery capability of blood without the risks associated with allogeneic blood transfusions, several products are undergoing development and clinical trials. These oxygen transport agents can be divided into two main groups, perfluorocarbon (PFC) emulsions and modified hemoglobin solutions.
Articles from the literature on the development and clinical trials of oxygen therapeutic agents were reviewed.
PFCs are synthetic fluorinated hydrocarbons that increase dissolved oxygen in the fluid phase of the blood without binding the oxygen molecule. They enhance oxygen delivery significantly and may be used to augment the technique of intraoperative autologous donation. Two PFC products have been tested in Phase III clinical trials. Hemoglobin-based oxygen carriers (HBOCs) are either cross-linked or microencapsulated hemoglobin molecules. Modification of the human hemoglobin molecule with intra- and inter-molecular cross-linking eliminates renal toxicity and improves the oxygen dissociation characteristics of the molecule. These modifications are necessary because stroma-free hemoglobin (Hb) does not release oxygen in the physiologic range and dissociates into dimers which can be rapidly filtered by the kidney, leading to renal toxicity. In addition to human Hb, bovine hemoglobin is another source of raw material for HBOC products. Recombinant human Hb has also been produced, using an E. coli expression system, for HBOC manufacturing. Four cross-linked hemoglobin products have been tested in Phase III clinical trials.
While no product has yet been approved for clinical use, preliminary studies with oxygen therapeutics show promising results, with effective oxygen carrying capacity and acceptable side effect profiles. In the future, the formation of a hybrid product which combines the best features from several of the products currently undergoing development may yield the ideal oxygen therapeutic agent.
为开发能增强血液输氧能力且无异体输血相关风险的药物，多种产品正在研发和进行临床试验。这些氧转运药物可分为两大类，即全氟碳（PFC）乳剂和改良血红蛋白溶液。
回顾了有关氧治疗药物研发和临床试验的文献文章。
全氟碳是合成的氟化烃，可增加血液液相中的溶解氧而不与氧分子结合。它们能显著增强氧输送，可用于增强术中自体输血技术。两种全氟碳产品已进入Ⅲ期临床试验。基于血红蛋白的氧载体（HBOC）是交联或微囊化的血红蛋白分子。通过分子内和分子间交联对人血红蛋白分子进行修饰可消除肾毒性并改善分子的氧解离特性。这些修饰是必要的，因为无基质血红蛋白（Hb）在生理范围内不释放氧且会解离成二聚体，而二聚体可被肾脏迅速滤过，导致肾毒性。除人血红蛋白外，牛血红蛋白是HBOC产品的另一种原料来源。还利用大肠杆菌表达系统生产了重组人血红蛋白用于制造HBOC。四种交联血红蛋白产品已进入Ⅲ期临床试验。
虽然尚无产品获批用于临床，但氧治疗药物的初步研究显示出有前景的结果，具有有效的携氧能力和可接受的副作用情况。未来，结合目前正在研发的几种产品最佳特性的混合产品可能会产生理想的氧治疗药物。
