Development and use of sulodexide in vascular diseases: implications for treatment

Abstract

Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium. For this reason, in preclinical studies, SDX administered parenterally displays an antithrombotic action similar to that of HPs but associated with fewer alterations of the blood clotting mechanisms and tests, thus being much less conducive to bleeding risk than HPs. When given orally, SDX is associated with minimal changes in classic coagulation tests, but maintains a number of important effects on the structure and function of endothelial cells (EC), and the intercellular matrix. These activities include prevention or restoration of the integrity and permeability of EC, counteraction versus chemical, toxic or metabolic EC injury, regulation of EC–blood cell interactions, inhibition of microvascular inflammatory and proliferative changes, and other similar effects, thus allowing oral SDX to be considered as an endothelial-protecting agent. The best available clinical evidence of the efficacy of SDX administered orally with or without an initial parenteral phase is the following: alleviation of symptoms in chronic venous disease and especially acceleration of healing of venous leg ulcers; prevention of cardiovascular events in survivors after acute myocardial infarction; marked improvement of intermittent claudication in patients with peripheral occlusive arterial disease; and abatement of proteinuria in patients with diabetic nephropathy that may contribute to the amelioration or stabilization of kidney function. Although further clinical trials are warranted, SDX is presently widely accepted in many countries as an effective and safe long-term, endothelial-protecting drug.

Therapeutic Restoration of Endothelial Glycocalyx in Sepsis

“…Therefore, this relatively high dose was used in the subsequent experiments. Based on the available data on the pharmacokinetics of SDX in humans (Coccheri and Mannello, 2014), the dose used should be sufficient for the duration of the experiments (16 hours after induction of sepsis and 14 hours after SDX administration)…”

Correction of Vascular Disturbances in Patients With Chronic Obstrucive Pulmonary Disease in Combination With the Hypertonic Disease: New Directions of Pathogenetic Therapy

“…Помимо этого, гепариноиды, к которым относится сулодексид, благодаря двухкомпонентному составу, содер-жащему высокоподвижную фракцию гепарина и дерматан-сульфата, обладают комплексным антикоагулянтным дей-ствием. Двойной механизм антитромботического дей-ствия сулодексида состоит в замедлении образования [13,14]. Клиническая эффективность сулодексида не ограничивается только влиянием на свертываемость крови, фибринолиз и реологические свойства крови.…”

“…Клиническая эффективность сулодексида не ограничивается только влиянием на свертываемость крови, фибринолиз и реологические свойства крови. Положительное воздействие на вазоактивную функцию эндотелия, приводящее к повышению его защитных и противовоспалительных свойств, было продемонстриро-вано в ряде исследований [11,13,14]. Препарат блокиро-вал выброс ЭТ-1, стимулировал выработку эндотелиально-го фактора релаксации -оксида азота, способствуя вос-становлению поврежденной базальной мембраны сосу-дов и улучшению бета-адренергической регуляции тонуса легочных артерий [3].…”

The role of sulodexide in chronic venous insufficiency

“…The heparin (HP) fraction of sulodexide has a mean molecular weight of 7 KDa [17]. This fraction has properties similar to LMWH, which allows the drug to achieve a longer half-life, oral bioavailability, as well as decreased pro-haemorrhagic effects [16,17].…”

“…This fraction has properties similar to LMWH, which allows the drug to achieve a longer half-life, oral bioavailability, as well as decreased pro-haemorrhagic effects [16,17]. The DS fraction of sulodexide has a mean molecular weight of 25 kDa.…”