Monique Mauzac

Anticoagulant activity of dextran derivatives. Part I: Synthesis and characterization

Substituted dextrans bearing carboxymethyl and benzylsulphonate groups have been prepared. These materials exhibit an antithrombic activity correlated with the ratio of each substituent. The highest activity is obtained when the dextran derivative contains more than 50% of carboxylic acid groups and simultaneously about 15% of benzylsulphonate functions.

Antithrombic activity of some polysaccharide resins

Crosslinked dextrans (Sephadex) bearing essentially carboxymethyl, benzylsulphonate and alpha-amino acid groups have been synthesized. The antithrombic activity of the resins may be the result of a cooperative effect between the functional groups. The binding of benzylsulphonate to carboxymethylated Sephadex endows these materials with activity. However the highest activity is obtained when the resins contain simultaneously benzylsulphonate, alpha-amino acid and carboxylic acid groups.

Anticoagulant activity of dextran derivatives. Part II: Mechanism of thrombin inactivation.

The mechanism of anticoagulant activity of dextrans substituted with carboxylic and benzylamide sulphonate groups is studied by various coagulation tests. These derivatives exhibit a heparin-like antithrombic activity which requires the presence of antithrombin III; however they are less effective than heparin on a weight basis. They also exert a direct antithrombic activity by an antithrombic III independent pathway; but this action is negligible compared to the thrombin inhibition observed in the presence of antithrombin III. Dextran derivatives have been prepared with antithrombic properties similar to those of heparin.

Anticoagulant hydrogels derived from crosslinked dextran. Part I: synthesis, characterization and antitithrombic activity

Hydrogels have been prepared by binding various amino acids to Sephadex derivatives bearing carboxymethyl and sulphonated benzylamide groups. Depending on the chemical nature and content of the amino acid substituent, these insoluble strongly hydrophilic materials may absorb 7 to 19 volumes of buffer per volume of dry material. These hydrogels present antithrombic activity in relation to their swelling ratio. The adsorption of thrombin might partially explain the anticoagulant effect as shown by the evaluated affinity constants between the hydrogels and the enzyme i.e. 1 to 2 X 10(6) I/M.

Anticoagulant hydrogels derived from crosslinked dextran. Part II: mechanism of thrombin inactivation

Sephadex derivatives bearing carboxymethyl, sulphonated benzylamine and amino acid groups exhibit heparin-like behaviour as demonstrated by the kinetic study of the thrombin inactivation in the presence of antithrombin III. Furthermore, whatever the chemical composition of these hydrogels, the diffusion coefficient of thrombin remained approximately constant and could not be connected with the variation of the antithrombin activity of the resins. Hence, in the heparin-like mechanism, the diffusion rate of thrombin inside the beads of hydrogels was not the limiting step. In fact, the swelling ratio (varying according to the chemical composition of these biomaterials) was involved in the anticoagulant properties of the resins.