Jean T, Bodinier M C
CEREP, Celle l'Evescault, France.
Angiology. 1994 Jun;45(6 Pt 2):554-9.
Each step of an inflammatory reaction is triggered by one or several chemical or biological mediators such as arachidonic acid derivatives (prostaglandins [PG], leukotrienes [LT], or thromboxanes [TX]), vasoactive amines (histamine or serotonin), and oxygen free radicals (superoxide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilatation (histamine), increasing membrane permeability (PGE2, histamine, free radicals) and providing a chemotactic signal for specialized cells, ie, neutrophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The antiinflammatory effects of Daflon 500 mg,* a micronized purified flavonoid fraction (90% diosmin, 10% hesperidin), were studied in different in vivo and in vitro models. In a model of inflammatory granuloma in the rat, Daflon 500 mg (100 mg/kg, orally) reduced edema formation and inhibited the synthesis for PGE2 (78.5%), PGF2 alpha (45.2%) and TXB2 (59.5%) (Damon et al, Arzneim-Forsch/Drug Res 37:1149-1153, 1987). Intravenous injection of Daflon 500 mg (25 and 50 mg/kg) reduced the hyperglycemia induced by injection of alloxan in rat. This effect of Daflon 500 mg was linked to its ability to scavenge active oxygen radicals, demonstrated in vitro using human neutrophils (Lonchampt et al, Arzneim-forsch/Drug Res 39:882-885, 1989) or mouse peritoneal macrophages (Bodinier et al, manuscript in preparation) stimulated by zymosan. The free radical scavenger effect of Daflon 500 mg is observed at concentrations ranging from 10(-7) M to 10(-4) M, with half-maximal effect between 10(-6) M and 10(-5) M. Thus, Daflon 500 mg behaves as a potent protective agent against inflammatory disorders. These properties may explain, at least in part, the clinical activity of Daflon 500 mg and justify its therapeutic use.
炎症反应的每一步都由一种或几种化学或生物介质触发，如花生四烯酸衍生物（前列腺素[PG]、白三烯[LT]或血栓素[TX]）、血管活性胺（组胺或5-羟色胺）和氧自由基（超氧阴离子，O2-，或过氧化氢，H2O2）。在静脉周围炎症中，这些介质在促进血管舒张（组胺）、增加膜通透性（前列腺素E2、组胺、自由基）以及为特殊细胞（即中性多形核粒细胞、巨噬细胞、淋巴细胞）提供趋化信号（白三烯B4、自由基）方面发挥着重要作用。研究了微粒化纯化类黄酮组分（90%地奥司明、10%橙皮苷）达芙通500毫克*在不同体内和体外模型中的抗炎作用。在大鼠炎症性肉芽肿模型中，达芙通500毫克（100毫克/千克，口服）可减少水肿形成，并抑制前列腺素E2（78.5%）、前列腺素F2α（45.2%）和血栓素B2（59.5%）的合成（达蒙等人，《药物研究》37:1149 - 1153，1987年）。静脉注射达芙通500毫克（25和50毫克/千克）可降低大鼠注射四氧嘧啶诱导的高血糖。达芙通500毫克的这种作用与其清除活性氧自由基的能力有关，这在体外用人中性粒细胞（隆尚等人，《药物研究》39:882 - 885，1989年）或经酵母聚糖刺激的小鼠腹腔巨噬细胞（博迪尼尔等人，正在准备的手稿）实验中得到证实。达芙通500毫克的自由基清除作用在浓度范围为10(-7) M至10(-4) M时观察到，半数最大效应在10(-6) M至10(-5) M之间。因此，达芙通500毫克表现为一种针对炎症性疾病的有效保护剂。这些特性至少可以部分解释达芙通500毫克的临床活性，并证明其治疗用途的合理性。
