Italfarmaco Spa

Pietro Cremonesi

Giancarlo Sportoletti

Piergiuseppe Pagella

Moniquet Sarret

Compounds of the general formula I ##STR1## wherein R.sub.1 is hydrogen or methyl;

Cytoprotective guanidine derivatives useful in ischemic diseases

Pharmaceutical compositions are described which have antithrombotic activity suitable for the prevention and for the therapy of cardiac infarcts, cerebral infarcts and venous thrombosis. They contain as the active component a fraction of heparin which has been modified by nitrogen desulfatation and succinylation, which fraction contains less than 10% of the N-sulfate groups of the heparin starting material and more than 0.6 succinyl radicals per disaccharide unit. The method of treatment is described.

Modified glucosaminoglucans having antithrombotic activity

A process for the removal of components having low or no anticoagulant activity from a glucosaminoglucan is described which comprises subjecting said glucosaminoglucan in the form of a salt in an aqueous solution to flow across a membrane suitable for ultrafiltration, hyperfiltration (inverse osmosis) or dialysis with partial passage through said membrane, whereby fractions of low activity go through the membrane and fractions of higher activity do not go through the membrane and are concentrated. The membrane suitable for ultrafiltration may have a nominal molecular cut-off between 1000 and 15,000. The membrane suitable for dialysis may have a nominal molecular cut-off at less than 30,000. The glucosaminoglucan may be heparin in the form of the sodium or calcuium salt.

Process for the purification of glucosaminoglucans

The invention relates to succinylated proteins, with a degree of succinylation of between 20 to 100%, containing from 0.1 to 20% by weight of iron, obtained by treating succinylated proteins with iron salts in suitable pH ranges. The compounds in question, which are completely tolerated, are characterized by an optimum bioavailability of iron.

Bio-available succinylated protein-iron derivatives which do not cause

A process for the preparation of the calcium salt of heparin containing an amount of sodium by weight not in excess of 0.1% and containing an amount of calcium by weight not less than 9.5% is described, which comprises subjecting a solution of sodium heparinate to dialysis, hyperfiltration (inverse osmosis) or ultrafiltration by means of a semi-permeable membrane and isolating the calcium heparinate with anticoagulant activity essentially equal to the anticoagulant activity of the sodium heparinate. For the ultrafiltration, a membrane may be used in the form of a planar sheet or a membrane in the form of a spiral or 'needle' having a molecular nominal cut-off at 20,000 Dalton. For the hyperfiltration (inverse osmosis), a membrane may be used having a rejection of sodium ion between 0 and 75%. For the dialysis, a membrane may be used in the form of multiple sheets or a coiled tube or hollow fibers. A plurality of dialyzers in series or in parallel is used. The process may be carried out continuously or discontinuously.

Method for the preparation of calcium heparinate

Enzyme immobilization is carried out be adding to a suspension of polysaccharide in aqueous medium, a vinyl monomer and an enzyme, then a catalyst comprising a metallic salt, and irradiating the resulting mixture with ultraviolet light to cause polymerization and form a copolymer of the polysaccharide having enzymatic activity. The metallic salt is preferably a ferric salt and the vinyl monomer is preferably methylacrylate, glycidylmethacrylate, acrylonitride, bis-acyloylpiperazine or symmetrical N, N', N'-trisacryloyl-hexahydrotriazine.

Immobilization of enzymes

A novel reactor for enzymatic reactions comprises a flow cell which is constituted by two semi-blocks having a planar surface. The enzyme is immobilized on one of the semi-blocks while a thin channel is provided on the face of the other semi-block. The two semi-blocks are hermetically closed. The substrate solution follows a tangential motion and travels with a laminar flow. The reactor permits to achieve 90% contact with the enzyme and may be used continuously.

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Milan, Italy

Pietro Cremonesi