Alfa Wassermann S.p.a.

Alfa Wasserman S.p.a.

Gianfranco Tamagnone

Egidio Marchi

Silvano Piani

Maria R Milani

Raul R Alpino

Fabrizio Ungarelli

Agostino Fracasso

Giorgio Bazzato

Bruno Baggio

Marinella Fantuz

Giovanni Gambaro

The use of some glycosaminoglycans like sulodexide, low molecular weight heparin and low molecular weight dermatan sulfate and of the medicines by parenteral use that contain them in the treatment of patients suffering from chronic renal insufficiency subjected to peritoneal dialysis is described. The effectiveness of this use has been shown both by pharmacological studies carried out in nephrectomized rats to whom a peritoneal damage has been caused and by clinical studies carried out in patients suffering from chronic renal insufficiency subjected to CAPD and treated by intraperitoneal route (i.p.) with 2 ml vials of VESSEL DUE F.RTM. containing 50 mg of sulodexide. A significant increase of the peritoneal transports of urea and of creatinine joined to a significant decrease of the protein-loss in the peritoneal effluent has been observed. Significant changes of the ultrafiltration capacity and of haemorrhagic-coagulative complications have not been observed during the study.

Use of some glycosaminoglycans in the peritoneal dialysis

The use of sulodexide, a glycosaminoglycan of natural origin extracted from mammalian intestinal mucosa, and of medicines containing it in the treatment of patients suffering from nephropathy of diabetic origin constitutes the object of the present invention. The effectiveness of sulodexide has been shown by the significative decrease of the albuminuria in microalbuminuric and macroalbuminuric diabetic patients treated with pharmaceutical compositions administered by oral or intramuscular route containing therapeutically effective amounts of drug.

Method of treatment of diabetic nephropathy by means of sulodexide of

New heparin and heparan sulfate derivatives having antithrombotic activity, also endowed with reduced haemorrhagic and anticoagulant activity, are obtained by nucleophilic addition to heparin and heparan sulfate derivatives containing 2,3-anhydrogulonic acid residues. The compounds have the formula IV ##STR1## The glycosaminoglycan derivatives obtained through this treatment show a structural modification in the unit of .alpha.-L-iduronic acid 2-O-sulfate with the partial or total selective substitution of the O-sulfate group in position 2 with a nucleophilic residue. The structural modifications produce an improvement of the biological properties of the heparin and heparan sulfate, substantially keeping the antithrombotic activity while diminishing the haemorragic effect in vivo and the anticoagulant activity in vitro.

Semi-synthetic glycosaminoglycans with heparin or heparan structure of

New heparinic derivatives having anticalculous activity, devoid of the anticoagulant and antithrombotic activity characteristic of the heparins, obtained by treating commercial or purified or low molecular weight heparins in a basic medium, optionally in the presence of alkali metal salts and of a reducing agent. The heparinic derivatives obtained through this treatment show significant chemical-physical characteristics, in particular they present a .sup.13 C-NMR spectrum different from that of the starting heparins especially in the zone between 102 and 92 p.p.m. with a characteristic signal at 101.3 p.p.m., a specific rotatory power at 546 nm between about +15.degree. and about +40.degree. in aqueous solution, a sulfur content between about 6% and about 9%, a sulfate/carboxyl ratio between about 1.20 and about 1.70 and a content of free amino groups between about 0.4% and about 2.1%. These heparin derivatives can be useful in the treatment of the nephrolithiases.

Heparin derivatives and process for their preparation

New heparin derivatives having antithrombotic activity, also endowed with reduced hemorrhagic and anticoagulant activity, obtained by treating in a basic medium heparins of various origin, optionally in the presence of alkali metal salts and of a reducing agent. The heparin derivatives obtained through this treatment show peculiar chimico-physical characteristics, like new signals at about 53 and 54 p.p.m. in the .sup.13 C-NMR spectrum and an increase of the specific rotatory power, compared to that of the starting heparins, to values between +50.degree. to +90.degree.. Said structural modifications produce an improvement of the biological properties of the heparin, substantially keeping the antithrombotic activity while diminishing the hemorrhagic effect in vivo and the anticoagulant activity in vitro.

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Casalecchio di Reno, Italy

Gianfranco Tamagnone