Relative Pharmacological Properties
Bleeding risk. Bleeding risk has been the main problem in the
application of anticoagulants. Herein, the effect of dHG-5 on bleeding
was assessed by the mice tail bleeding model. At 10 times
anti-thrombosis ED50 doses, dHG-5 did not significantly
increase the blood loss compared with control group (Figure 6C).
f.XII and platelets activation. Native FG had the undesired
activation on f.XII and platelets (J. Z. Li, Bao et al. , 1985),
which may result in proinflammation or thrombocytopenia, respectively.
Therefore, the activation of dHG-5 and its containing oligosaccharides
(oHG-8, oHG-14 and oHG-29) on f.XII and platelets were analyzed.
The results showed that dHG-5 and its containing oligosaccharides had no
obvious activation on f.XII at the concentrations up to 10 µM (Figure
7A). At the peak concentrations of the bleeding tolerance doses (Figure
S28) dHG-5, oHG-8, oHG-14 and oHG-29 showed no obvious activation on
platelets, either in human PRP or rat WP, whereas FG could induce
platelet aggregation (Figure 7B-C).
Preliminary pharmacodynamics. After administrating
subcutaneously to mice, the effect of dHG-5 on plasma APTT was
determined (Figure 8). And the pharmacodynamic parameters were
calculated according to noncompartmental procedure model (Table S3). The
the maximum APTT-prolonging effect (Emax) and
AUC0-8h (the area under the time-effect curve within 8
h) increased in a dose-proportional manner, while the half-life
(T1/2) did not obviously change (Figure 8 and Table S3).