PMID- 27044828
OWN - NLM
STAT- MEDLINE
DCOM- 20161226
LR  - 20161230
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 79
DP  - 2016 Apr
TI  - Preparation and evaluation a new generation of low molecular weight heparin.
PG  - 194-200
LID - S0753-3322(15)30476-5 [pii]
LID - 10.1016/j.biopha.2016.02.021 [doi]
AB  - 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 beta-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.
CI  - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved.
FAU - Zhao, Dan
AU  - Zhao D
AD  - Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical 
      Science, Shandong University, Jinan 250012, China.
FAU - Sang, Qing
AU  - Sang Q
AD  - Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical 
      Science, Shandong University, Jinan 250012, China.
FAU - Cui, Huifei
AU  - Cui H
AD  - Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical 
      Science, Shandong University, Jinan 250012, China. Electronic address: 
      cuihuifei@sdu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160309
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Anticoagulants)
RN  - 0 (Antithrombins)
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Protamines)
SB  - IM
MH  - Animals
MH  - Anticoagulants/pharmacology
MH  - Antithrombins/pharmacology
MH  - Disease Models, Animal
MH  - Enoxaparin/pharmacokinetics/pharmacology
MH  - Factor Xa Inhibitors/pharmacokinetics/pharmacology
MH  - Heparin, Low-Molecular-Weight/*chemical 
      synthesis/chemistry/pharmacokinetics/*pharmacology
MH  - Male
MH  - Protamines/pharmacology
MH  - Rabbits
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Anti-thrombus
OT  - Anticoagulation
OT  - Low molecular weight heparin (LMWH)
OT  - Pharmacokinetic
OT  - Protamine sulfate
OT  - Rational design
EDAT- 2016/04/06 06:00
MHDA- 2016/12/27 06:00
CRDT- 2016/04/06 06:00
PHST- 2015/12/11 00:00 [received]
PHST- 2016/02/25 00:00 [revised]
PHST- 2016/02/25 00:00 [accepted]
PHST- 2016/04/06 06:00 [entrez]
PHST- 2016/04/06 06:00 [pubmed]
PHST- 2016/12/27 06:00 [medline]
AID - S0753-3322(15)30476-5 [pii]
AID - 10.1016/j.biopha.2016.02.021 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2016 Apr;79:194-200. doi: 10.1016/j.biopha.2016.02.021. Epub 
      2016 Mar 9.