[Effect on low-molecular-weight heparin obtained using a chitinolytic complex on the anticoagulant activity of plasma in rabbits and rats].
The anticoagulant activity of low-molecular-weight heparin with an average molecular weight of 4.7 kD (LMWH-4.7) has been studied. This derivative was prepared from unfractionated heparin with the help of chitinolytic enzyme complex from Streptomyces kurssanovii. The antithrombin activity of LMWH-4.7 (aIla activity) was 72 +/- 9 IU/mg and the activity with respect to the blood coagulation factor Xa (aXa activity) was 200 +/- 33 IU/mg, which corresponded to an aXa/aIIa ratio of 2.8 (necessary for effective antithrombotic drugs). The aIIa and aXa activity exhibited a dose-dependent variation upon intravenous and subcutaneous injections in rabbits, so that a high aIIa/aXa ratio was retained: 5 min after the intravenous injection of a minimum dose (0.3 mg/kg), this ratio was 2, 7, and for a greater dose (3.0 mg/kg) it reached 3.8. Subcutaneous injections were followed by slow elimination of the anticoagulant within 24 h. LMWH-4.7 upon intraperitoneal injections produced a dose-dependent inhibition of a model thrombosis in rats. Complete inhibition was observed for a dose of 3 mg/kg. Thus, it is possible to obtain active LMW heparin with the help of chitinases.
Drozd
N N
NN
Tolstenkov
A S
AS
Makarov
V A
VA
Miftakhova
N T
NT
Bannikova
G E
GE
Sukhanova
P P
PP
Varlamov
V P
VP
Vikhoreva
G E
GE
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002686:Chitin / Q000737:chemistry; D002688:Chitinases / Q000737:chemistry; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011516:Prothrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013302:Streptomyces / Q000737:chemistry; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D002686:Chitin; D011516:Prothrombin; C025337:Factor IIa; D002688:Chitinases; D015951:Factor Xa