PMID- 30954594
OWN - NLM
STAT- MEDLINE
DCOM- 20191118
LR  - 20191118
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 133
DP  - 2019 Jul 15
TI  - Development of low molecular weight heparin by H(2)O(2)/ascorbic acid with 
      ultrasonic power and its anti-metastasis property.
PG  - 101-109
LID - S0141-8130(18)36833-8 [pii]
LID - 10.1016/j.ijbiomac.2019.04.019 [doi]
AB  - Low molecular weight heparins (LMWHs) are currently used as an anticoagulant 
      agent since unfractionated heparin (UFH) can cause serious adverse drug 
      reactions. LMWHs are commercially prepared using different methods such as 
      nitrous acid cleavage and beta-elimination under strong reaction conditions or with 
      harsh chemicals, which may cause the saccharide units within the polysaccharide 
      backbone to be decomposed and noticeably modified. This study demonstrates an 
      effective method for depolymerizing heparin via the production of large amounts 
      of free radicals from H(2)O(2)/ascorbic acid and ultrasonic power; this results 
      in highly pure products because ascorbic acid can decompose during the reaction, 
      which is different from the previously reported H(2)O(2)/Cu(2+) method. The 
      reaction conditions-including concentration of ascorbic acid, reaction 
      temperature and intensity of ultrasonic power-were investigated and optimized. We 
      found that the degradation behavior of heparin in this combined physicochemical 
      process conformed to first-order reaction kinetics. The chemical composition and 
      structures of different LMWHs were analyzed. The results showed the primary 
      structure and sulfate esters were well preserved after the depolymerization, the 
      major repeat units are (1-4)-linked glucosamine and iduronic acid. The further in 
      vitro assays indicated that the LMWHs produced by H(2)O(2)/ascorbic acid with 
      ultrasonic power have an anti-metastatic effect in A549 cells, which suggested 
      the LMWHs rapidly prepared in this physicochemical way have a potential for 
      anti-tumor metastatic function.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Shen, Xuemin
AU  - Shen X
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China.
FAU - Liu, Zhenfeng
AU  - Liu Z
AD  - Institute of Health Products, Chiatai Qingchunbao Pharmaceutical Co., Ltd., 
      Hangzhou 310023, China.
FAU - Li, Junhui
AU  - Li J
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China.
FAU - Wu, Dongmei
AU  - Wu D
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China.
FAU - Zhu, Meng
AU  - Zhu M
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu 215021, China.
FAU - Yan, Lufeng
AU  - Yan L
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China.
FAU - Mao, Guizhu
AU  - Mao G
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China.
FAU - Ye, Xingqian
AU  - Ye X
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China.
FAU - Linhardt, Robert J
AU  - Linhardt RJ
AD  - Center for Biotechnology & Interdisciplinary Studies, Department of Chemistry & 
      Chemical Biology, Rensselaer Polytechnic Institute, Biotechnology Center 4005, 
      Troy, NY 12180, USA. Electronic address: Linhar@rpi.edu.
FAU - Chen, Shiguo
AU  - Chen S
AD  - Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and 
      Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, 
      China. Electronic address: chenshiguo210@163.com.
LA  - eng
PT  - Journal Article
DEP - 20190404
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Disaccharides)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Sulfates)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - A549 Cells
MH  - Antineoplastic Agents/*chemistry/*pharmacology
MH  - Ascorbic Acid/*chemistry
MH  - Cell Survival/drug effects
MH  - Disaccharides/analysis
MH  - Heparin, Low-Molecular-Weight/*chemistry/*pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/*chemistry
MH  - Molecular Weight
MH  - Neoplasm Metastasis
MH  - Sulfates/chemistry
MH  - Temperature
MH  - *Ultrasonic Waves
OTO - NOTNLM
OT  - Anti-metastasis
OT  - Low molecular weight heparin
OT  - Radical reaction
OT  - Ultrasonic degradation
EDAT- 2019/04/08 06:00
MHDA- 2019/11/19 06:00
CRDT- 2019/04/08 06:00
PHST- 2018/12/09 00:00 [received]
PHST- 2019/02/27 00:00 [revised]
PHST- 2019/04/03 00:00 [accepted]
PHST- 2019/04/08 06:00 [pubmed]
PHST- 2019/11/19 06:00 [medline]
PHST- 2019/04/08 06:00 [entrez]
AID - S0141-8130(18)36833-8 [pii]
AID - 10.1016/j.ijbiomac.2019.04.019 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2019 Jul 15;133:101-109. doi: 
      10.1016/j.ijbiomac.2019.04.019. Epub 2019 Apr 4.