Introduction:
Vascular diseases are among the most widespread diseases in the world. Among them, the chronic venous insufficiency (CVI) of the lower limbs represents one of the diseases with higher incidence and prevalence in the female gender. CVI is a disease characterized by a progressive deterioration in the vascular functionality, especially of the lower limbs, which in the long term determines the onset of pain, aedema, inflammation. Omikron Titalia, S.R.I, US 2025/0295690)
CVI is an “outflow disease”, consequent to structural aminomalies involving the walls of veins, of dilative type (varices) or obstructive type, the latter including, among the varous symptoms, deep vein thromboses (DVT), sueprficial vein thromboses (SVT) and post-thrombotic syndromes. (Omikron Titalia, S.R.I, US 2025/0295690)
CVI clinical pictures are very variegated and the intesity and gravity of the disease can be extremely variable, by determining the onset of alterations at aethetical level only (such as reitcular varices, telangiectasia), until considerable conditions of tissue damage (such as lipodermatosclerosis, trophic ulcers). Omikron Titalia, S.R.I, US 2025/0295690)
CVD is usually described according to the Clinical-Etiology-Anatomy-Pathophysiology classification, which ranges from state CO (no visible or palpable signs of CVD) to C6 (active venous ulcer).
Risk Factors:
Chronic venous disease (CVD) is both prevalent and unavoidable in many people as a result of persistent or unalterable risk factors, the most important of which are advanced age, excess body weight, and family history. (Ulloa, “Micronized purified flavonoid fraction (MPFF) for pateitns suffering from chronic venous disease: a review of new evidence” Adv Ther, 2019).
Treatments:
Introduction:
Compression stockings and venoactive drug therapy are standard frit-line treamtnet options for CVD. Venactive drugs may also be used in conjunciton with interventions such as endevenous ablation and other surgical options as the disease progresses.
Once a correct anamnestic collection and specific diagnsotics, including instrumental analysis (for example, hemodynamic cartography with eco-colour doppler) have been performed, the currently available main strategies for therapeutically treating CVI provide to adopt adquate stands of conduct aimed at guaranteeing a better lifesyle to the patient. The use of a graduated and decreasing elastic compression, especially to face the moments of obliged sedentary lifestyle together with supporting medical therapy with the prupose of obtianing a clinical and hemodynamic stabilization of the disease. Omikron Titalia, S.R.I, US 2025/0295690)
CVI can be treated surgically or conservatively (non-surgically). The mainstay of conservative treatment is compression with elastic stockings or elastic bandages. Another commonly used form of conservative treatment is the use of oral enoactive drugs, made from plants or synthetically. These medications fall into four groups: benzopyrones, saponins, other plant extracts and synthetic drugs. They act at two levels, in the macrocirculation, they induce changes in the vein walls that prevent the development of venous hypertension and haemodynamic distrubances and in the microciruclation, they inhibit the inflammation and developmetn of vernous wall damage due to venous hypertension. The increase in venous tone is acheived by ost compositions (including diosmin). Zsuga (US 2025/0332185A1)
Diosmin/ Diosmetin:
Diosmetin is the aglycone/active metabolite of diosmin to which diosmin is converted following oral admiistration and other routes of delivery. The compound is known chemically as 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenol-4H-1-benzopyran-4-on, with a MW of 300.266 g/ml.
–Micronized purified flavnoid fraction (MPFF) is the most widely prescribed and well-studied venoactive drug available for the treatment of CVD. Diosmin is the predominant component of the micronized purified flavonoid fraction, or MPFF (DAFLON). MPFF includes 90% disomin and 10% other active favonoids (hesperidin, diosmetin, linarin, and isorhoifolin). MPFF has anti-inflammatory activiteis, reduces endothelial activaiton and leukocyte adhsion, and increases capillary resistance and ntegrity. (Guvn, “Effect of Micronized purified flavonoid fraction on venous hemodynamics evaluated using digital photoplethysmography in patietns with chronic venous dsiease” (2024)
—-Daflon is an oral medication containing micronized purified flavonoid fractions (typically 450 mg of diosmin and 50 mg of hesperidin) used to protect small blood vessels and improve blood circulation.
—Sulodexide + Favlones: US 2025/0295690, to virrno discloses a composition for oral use for the treatment of vascular diseases which includes sulodexide and one or more flavonoids selected among diosmin, hesperidin, troxerutin, oxerutin, quercitin and hesperidin. Sulodexide is a biological drug of natural original purfied by porcine iterstinal mucosa, consisting of glycosaminoglycans (GAGs) consisting by 80% of heparin with low MW and the remaining 20% of dermatan sulfate (DS). It is characterized by a complex pharmacological profile with several effects on the vascular system: antithrombotic, profibrinolytic, direct ani-inflammatory on the MMP-2 and MMP-9, structural for reintegration of glycocayx and prtoective for endothelium. Favonoids represtn a lass of chompounds of natural original which include a skelton C15 consisting of two aromatic rings and one heterocyclic ring. The Diosmin, hesperidin and/or troxerutin usable can by of synthetic or natural origin such as foundplant extracts.
Zsuga (US 2025/0332185A1) discloses treatment of venous insufficiency using a combiantion of diosmin, folic acid and vitamin B6.