ABSTRACT
Quaternized derivatives of chitosan with a substitution degree of 85-98% (highly substituted) synthesized from chitosans with a molecular weight of 5, 10, 20 kDa, with a degree of deacetylation of 89-98%, and the code numbers of QChit 5, QChit 10, QChit 20, respectively, completely neutralize antithrombin activity of unfractionated heparin and partially neutralize aXa activity of low-molecular-weight heparin (clexane), similar to protamine sulfate. The advantages of QChit 5 and QChit 10 over QChit 20 and protamine sulphate are the follows: the effect is achieved at lower concentrations and in greater concentration range; they do not promote platelet aggregation; in a concentration of 0.0072 mg/ml they do not destroy the erythrocyte membranes.
Subject(s)
Anticoagulants/chemistry , Anticoagulants/pharmacology , Chitosan/chemistry , Heparin/chemistry , Heparin/pharmacology , Platelet Aggregation/drug effects , Blood Coagulation Tests , Hemolysis/drug effects , HumansABSTRACT
Nanocrystalline particles of chitin in the form of hydrosol in a concentration of 0.63 mg/ml have no effect on aggregation of human platelets and clotting time of platelet-poor plasma in coagulation tests. ADP-induced aggregation of human platelets was inhibited by these nanoparticles in concentrations of 0.63 and 1.00 mg/ml in comparison with the control. Intravenous administration of nanoparticles in a dose of 1 mg/kg to guinea pigs produced no anticoagulant effect. The nanocrystalline particles of chitin can be of interest as potential drug delivery systems.
Subject(s)
Blood Coagulation/drug effects , Chitin/pharmacology , Drug Delivery Systems/methods , Nanoparticles/chemistry , Adenosine Diphosphate/pharmacology , Animal Shells/chemistry , Animals , Blood Coagulation Tests , Blood Platelets/drug effects , Brachyura , Chitin/chemistry , Chitin/isolation & purification , Crystallization , Female , Guinea Pigs , Humans , Injections, Intravenous , Nanoparticles/ultrastructure , Platelet Aggregation/drug effectsABSTRACT
Sulfation (to 2.8) of dextrans with molecular weight of 150 and 20 kDa was followed by the appearance of anticoagulant activity that increased with decreasing their molecular weight and did not depend on antithrombin, plasma inhibitor of serine proteases of the blood coagulation system. Antithrombin activity of dextran sulfate with a molecular weight of 20 kDa reached 12.6-15.3 U/mg. Dextran sulfates with molecular weights of 20 and 150 kDa did not potentiate ADP-induced human platelet aggregation.
