Labrude P
Laboratoire d'Hématologie et Physiologie, Faculté des Sciences pharmaceutiques et biologiques, Nancy.
Ann Pharm Fr. 1992;50(5-6):250-66.
Although products currently under study are usually called "artificial blood" or "blood substitutes", it concerns only, for the moment, to achieve preparations able to carry and release oxygen to tissues while allowing also a temporary restoration of "blood" volume. The most advanced scopes are related to hemoglobin solutions and fluorocarbons emulsions. The limitations of free hemoglobin impose to modify it. The reestablishment of a normal, even reduced, affinity for oxygen is obtained by the fixation on hemoglobin of a 2,3-DPG substitute whose most known example is pyridoxal phosphate. The enhancement of vascular retention may be achieved by intramolecular cross-linking, intermolecular polymerization or covalent binding of hemoglobin on macromolecules. The two modifications of hemoglobin must be performed successively et numerous possibilities have been proposed. Bovine and recombinant hemoglobins are also promising. Originally and logically, fluorocarbons are synthetic compounds derived from hydrocarbons by an important or maximal substitution of hydrogen by fluorine. The physical properties of these molecules, impose, for transfusion, their emulsification in an aqueous physiological solution. They need an oxygen enriched atmosphere and their storage in tissues is often extended. At present, the most known emulsion is Fluosol DA, a mixture of perfluorodecalin and perfluorotripropylamine. It allowed to realize numerous researches and the proposal of the multiple possible employment for this category of oxygen carriers. The limitations of Fluosol DA led to fluorocarbons under investigation such as F dimethyl bicyclononanes, F methyladamantane, bis (F-butyl) ethene or F-octylbromide. The new hemoglobin solutions and fluorocarbons emulsions start to meet the requirements of potential users.
尽管目前正在研究的产品通常被称为“人造血液”或“血液替代品”,但目前它只涉及制备能够向组织输送和释放氧气,同时还能暂时恢复“血液”容量的制剂。最先进的研究方向与血红蛋白溶液和氟碳化合物乳液有关。游离血红蛋白的局限性促使人们对其进行改性。通过在血红蛋白上固定2,3 - 二磷酸甘油酸(2,3-DPG)的替代品来恢复对氧气的正常亲和力,即使是降低的亲和力,其最著名的例子是磷酸吡哆醛。通过分子内交联、分子间聚合或血红蛋白与大分子的共价结合,可以提高血管滞留性。血红蛋白的这两种改性必须相继进行,并且已经提出了许多可能性。牛血红蛋白和重组血红蛋白也很有前景。从本质和逻辑上讲,氟碳化合物是由烃类通过氢被氟大量或最大程度取代而衍生出的合成化合物。这些分子的物理性质要求在生理水溶液中对其进行乳化以便用于输血。它们需要富氧环境,并且在组织中的储存时间通常较长。目前,最知名的乳液是氟碳乳剂DA,它是全氟萘烷和全氟三丙胺的混合物。它使得人们能够进行大量研究,并提出了这类氧载体的多种可能用途。氟碳乳剂DA的局限性促使人们对正在研究中的氟碳化合物进行探索,例如F - 二甲基双环壬烷、F - 甲基金刚烷、双(F - 丁基)乙烯或F - 辛基溴。新型血红蛋白溶液和氟碳化合物乳液开始满足潜在用户的需求。