Enoxaparin is widely used in clinic, but it has some disadvantages. For example, its
anticoagulant activity is weaker compared with
heparin and it can not be effectively neutralizad by
protamine sulfate (PS) in case of
bleeding. Therefore, in this work, a new generation of
low molecular weight heparin (NG-
LMWH) was prepared.The NG-
LMWH was prepared with the method of alkaline β-elimination followed by gel chromatography. Estimating the molecular weight of the NG-
LMWH by GPC-HPLC, it has a remarkably low polydispersity index and narrow molecular weight distribution. The polydispersity index of NG-
LMWH was 1.052, which was lower than
heparin (1.5) and
enoxaparin (1.279). Anti-FXa and anti-
FIIa potency of NG-
LMWH was much higher than that of
Enoxaparin, and close to that of
heparin, which was determined by
chromogenic substrate method. To test the degree of anti-FXa or anti-
FIIa potency neutralized by PS, equivalent anti-FXa or anti-
FIIa activity doses of different
anticoagulant in plasma were titrated with increasing amounts of PS in plasma. The results indicate that NG-
LMWH was more efficiently neutralized by PS than
enoxaparin.The efficacy of anti-
thrombus of NG-
LMWH was superior to
enoxaparin and the effect was dose dependent, which was evaluated with rat
carotid artery thrombosis and inferior vena cava
thrombosis model. The results of pharmacokinetics in New Zealand rabbits showed that the pharmacokinetic characteristics of NG-
LMWH were similar to
enoxaparin. The NG-
LMWH prepared in this work has both advantages of
heparin and
enoxaparin with more effective and safer anticoagulation than
enoxaparin.