Opocrin S.p.a.

Opocrin S.p.a. Laboratorio Farmacobiologico

Opocrin A.p.a.

Pietro Bianchini

Giuseppe Mascellani

Dermatan sulphate possessing a thrombolytic activity, and pharmaceutical

Process for the preparation of oligosaccharides by a controlled chemical depolymerization of natural polysaccharides, such as heparins, heparan sulfates, dermatan sulfates, chondroitinsulfates, hyaluronic acid, by a radicalic reaction in an aqueous solution, at a temperature ranging between 20.degree. and 70.degree. C., in the presence of a catalyst selected in the group consisting of Cu++, Fe++, Cr+++, Cr.sub.2 O.sub.7 - as well as the resulting oligosaccharides and their related pharmaceutical compositions. The products exhibit high antithrombotic activity, little or no anticoagulant activity, high fibinolytic activity an antiinflammatory activity.

Depolymerized dermatan sulfates endowed with an antithrombotic,

Heparin fractions which are a mixture of oligosaccharides containing 6-12 monosaccharides are described. The oligosaccharides contain reducing end groups composed of iduronic acid 2-sulfate or glucosamine N, 6-disulfate. The end group monosaccharides contain the reducing anomeric carbons. The SO.sub.3.sup.- /COO.sup.- ratio is essentially the same as in heparin. The method of preparation is a depolymerization initiated by free radicals. One fraction is a heparin fragment with a molecular weight (MWw) of 2,100 daltons (+10%). The compound contains 6-8 monosaccharides, has the same SO.sub.3.sup.- /COO.sup.- ratio as the parent heparin and has platelet anti-aggregating activity, arterial and venous antithrombotic action, fibrinolytic and antiatherosclerotic activity. It exhibits poor anti factor Xa activity and no anticoagulant action.

Oligosaccharides obtained by heparin depolymerization having

Novel oligosaccharide fractions with valuable pharmacological properties are obtained from heparin. They have the same structural characteristics of heparin. The heparin fraction consists of oligosaccharides which contain end groups consisting of iduronic acid 2-sulfate, or glucosamine N, 6-disulfate. Further the oligosaccharides contain and monosaccharide endowed with reducing anomeric carbon, and are constituted by multiples of monosaccharide units.

Novel oligosaccharides having pharmacological properties by

Process for the preparation of oligosaccharides and oligosaccharide fractions by degradation of heparin, which comprises submitting to incubation an aqueous solution of heparin containing from 5 to 30 g of heparin/liter in the presence of 4-50 m.moles/l of cupric acetate and 50-300 m.moles/l of hydrogen peroxide, at a temperature of 40.degree.-50.degree. C., for 20-24 hours and keeping the pH at a value of 7.8 by means of sodium acetate. The obtained products show a high inhibiting property of the Xa factor, a high antithrombotic activity and a very modest anticoagulant activity; therefore they are very interesting for a possible utilization as drugs in the antithrombotic treatment, practically free from any risk of haemorrhages.

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Corlo, Italy

Pietro Bianchini