Semisynthesis of linarin, acacetin, and 6-iodoapigenin derivatives from diosmin.

Semisynthesis of linarin and acacetin from the Citrus flavonoid diosmin was performed via, as first intermediate, the 3'-O-phenyltetrazolyl ether of diosmin. This paper relates also a semisynthetic access to 6-iodoapigenin derivatives, which are key compounds in the synthesis of some biflavonoids such as robustaflavone.

[Evaluation of clinical efficacy of a venotonic drug: lessons of a therapeutic trial with hemisynthesis diosmin in "heavy legs syndrome"]. / Evaluation de l'efficacité clinique d'un médicament veinotrope: les enseignements d'un essai thérapeutique avec la diosmine d'hémisynthèse dans le syndrome des jambes lourdes.

Venous-type symptoms, i.e. painful sensation of heavy, swollen or restless legs, influenced by orthostatism and warm environment, significantly alters quality of life of a large proportion of women. Although the condition is frequently associated with chronic venous insufficiency, no demonstrable hemodynamic abnormality of the superficial as well as deep venous systems of the lower limbs can be found in many patients. The pathogenesis of this syndrome remains unknown, and there is no objective measurement of any biological nor hemodynamic parameters that can be used for its assessment. Diosmine and other flavane derivatives have been shown beneficial in this condition using various discomfort indexes. The aim of this work was to compare the therapeutic efficacy of two formulations of the same compound diosmine. In the analysis, particular attention was paid to the signification and usefulness of discomfort scales. This study was a double-blind, placebo-controlled therapeutic trial, comparing the efficacy of a new formulation, hemisynthesis diosmine 600 mg, one tablet per day taken in the morning, versus the usual tablet formulation of 300 mg taken twice a day (morning and evening). Treatment blindness was assured by the double placebo method. Two parallel groups were treated 28 days with one or the other treatment. Randomization was performed with stratification by center. The main evaluation criteria were a composite scale of venous type symptoms (i.e. the sum of individual score 0-4 of each symptom), and a visual analog auto-evaluation scale quoted each week by the patient. The global opinion of the physician on treatment adequacy to the clinical situation, and the degree of patient satisfaction (four grade scales) were used as subsidiary criteria. In order to increase the homogeneity of the study sample, inclusion was restricted to non-menopaused women aged 18 years and over, having given written informed consent, complaining of distressing sensation of heavy legs, without history of venous thrombosis, varicose veins, superficial or deep venous reflux at the duplex-scan examination. Patients with other causes of pain in the lower limbs, taking analgesic medications or requiring elastic stocking were not included. 255 patients participated in the trial. Eighteen withdrew, equally distributed in both groups (6 lost, 5 interfering diseases, and two dropouts for side effects, namely headache and gastric pain). Twenty additional patients complained of detrimental events not requiring treatment withdrawal, equally distributed between both groups, and mainly involving digestive functions. The results confirmed a similar efficacy of the two drug regimens, and a small but significantly better improvement of the patients' auto-evaluation of their discomfort on the analogic scale (p = 0.021) for hemisynthesis diosmine 600 mg, mainly during the first two weeks; for all four criteria, the gamma risk showed that the once-a-day 600 mg preparation at least as effective as 300 mg twice daily (p < 0.001). On a methodological point of view, the comparison of evaluation criteria showed that the composite scale, although giving the feeling of a comprehensive and quantitative appraisal of the discomfort in the legs, was almost equivalent to a standard four grade rating of heaviness, which appeared as the central symptom of this condition. Auto-evaluation through an analogic scale proved to be more informative, more sensitive, less influenced by the physician's feelings and allow easier assessment of the time-course of the drug's effects. Global evaluations by the patient and the physician did not give additional information but could be used as quality criteria, assessing the coherence of the results obtained with the scales. This study demonstrated a similar efficacy of the two drug regimens, with a more rapid effectiveness of the 600 mg preparation taken once a day. Auto-evaluation on the analog scale proved to be the most informative and effe

[Randomized study of the use of synthetic diosmin in premenstrual and vascular dysplastic mastodynia]. / Studio randomizzato sull'impiego della diosmina sintetica nella mastodinia displasica premestruale e vascolare.

The antalgic effect of synthetic diosmin in 120 patients suffering from vascular and premenstrual mastodynia is studied compared to the same number of non-treated cases. The therapy has been carried out for one consecutive year. For the same period the course of the painful symptomatology, both in the cases treated and in the controls, has been checked. For the treated cases a significant decrease of the painful symptomatology has been obtained and this decrease was maintained.