Micronized purified flavonoid fraction (MPFF; e.g., Daflon) consists of 90% diosmin and 10% other active concomitant flavonoids (hesperidin, diosmetin, linarin, and isorhoifolin), and is currently one of the most widely available and prescribed venoactive drugs, and the best studied. Diosmin is synthesized from hesperidin, which is extracted from a particular type of small immature orange, and the mixture is micronized to particles of 2 µm diameter to improve bioavailability. The effects of MPFF have been demonstrated in both clinical and nonclinical studies, with reported improvements in venous tone and contractility, microcirculation, trophic disorders, and venous ulcer healing, and reductions in edema, inflammation, leukocyte adhesion and activation, and inflammatory mediator production. A recent meta-analysis of randomized, double-blind, placebo-controlled clinical trials investigating the effectiveness of MPFF treatment in improving the symptoms, signs, and QoL in CVD patients identified seven studies involving 1692 patients. The following results were observed: Most of leg pain, heaviness, and feeling of swelling [risk factors (RR) of 0.35–0.53; P.0001]; cramps (RR 0.51, P=.02); paresthesia (RR 0.45, P=.03); skin changes (RR 0.18, p.0001); and burning sensation (standard mean difference –0.59, 95% CI –1.15 to –0.02).

Clinical and nonclinical studies support the notion that MPFF generally improves venous tone and contractility. Nonclinical studies in isolated rat veins found that diosmin directly enhanced sympathetic-mediated venous contractility and increased calcium sensitivity and contractility. In similar studies in varicose human saphenous veins, the reported mechanisms of action were different, although with similar results, since diosmin potentiated dose-dependent norepinephrine-induced contractility. Regarding the clinical efficacy of MPFF in improving venous tone, two controlled clinical trials are particularly important. Barb et al., in a study of women with various grades of CVD, demonstrated that MPFF treatment was associated with improvements in venous distension, capacitance, and tone. In addition to its venotonic effects, MPFF has demonstrated various antiinflammatory properties. In several animal models, MPFF treatment was shown to reduce leukocyte adhesion to vascular endothelium. In a hamster ischemia–reperfusion model, neutrophil adhesion in postcapillary venules was lower in animals pretreated with MPFF than in control animals. Similar findings were obtained in two rat ischemia–reperfusion models employing the cremaster muscle and mesentery vein.

One mechanism by which MPFF may prevent leukocyte adhesion to damaged epithelium is by inhibiting the production of the surface molecules that mediate adhesion and activation. In CVD patients, MPFF was found to selectively reduce the expression of l-selectin/CD62-L on monocytes and neutrophils after treatment for 60 days. In a rat model of chronic venous hypertension initiated by local venous occlusion followed by reperfusion (which also results in leukocyte adhesion and activation), MPFF treatment significantly mitigated these inflammatory processes and CD62-L expression in neutrophils in a dose-dependent manner.