PMID- 30559077
OWN - NLM
STAT- MEDLINE
DCOM- 20190516
LR  - 20200401
IS  - 1873-2828 (Electronic)
IS  - 1350-4177 (Print)
IS  - 1350-4177 (Linking)
VI  - 52
DP  - 2019 Apr
TI  - Preparation of low molecular weight heparin using an ultrasound-assisted 
      Fenton-system.
PG  - 184-192
LID - S1350-4177(18)31207-0 [pii]
LID - 10.1016/j.ultsonch.2018.11.016 [doi]
AB  - Heparin, a high-molecular weight acidic polysaccharide, has raised much interest 
      in the field of biomedical research due to its multiple bio-functions. The 
      anticoagulant application of heparin in routine clinical practice, however, has 
      been limited as the large molecular size of heparin can reduce its subcutaneous 
      bioavailability and lead to severe adverse consequences such as thrombocytopenia. 
      Here, we report a highly efficient and convenient method to depolymerize 
      high-molecular weight, unfractionated heparin (UFH), into low molecular weight 
      heparin (LMWH) by combining physical ultrasonic treatment with the chemical 
      Fenton reaction, referred to as sono-Fenton. We found that this combination 
      treatment synergistically degraded UFH into a LMWH of 4.87 kDa within 20 min. We 
      characterized the mechanism of sono-Fenton heparin degradation through multiple 
      approaches, including HPLC-SAX, disaccharide composition, FT-IR, NMR and top-down 
      analysis, and found that the uronic acid residue in heparin was the most 
      susceptible site attacked by OH radicals produced in the sono-Fenton process. 
      Importantly, the LMWH prepared by this method had significantly higher 
      anticoagulant activity than UFH and other LMWHs. This approach represents an 
      effective method to produce heparin with improved activity and should be 
      potentially useful for heparin production in the pharmaceutical industry.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Zhi, Zijian
AU  - Zhi Z
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 - 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 - Chen, Jianle
AU  - Chen 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; Center for Biotechnology & Interdisciplinary Studies, Department of 
      Chemistry & Chemical Biology, Rensselaer Polytechnic Institute, Biotechnology 
      Center 4005, Troy, NY 12180, USA.
FAU - Li, Shan
AU  - Li 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.
FAU - Cheng, Huan
AU  - Cheng H
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, Donghong
AU  - Liu 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 - 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
GR  - R01 GM038060/GM/NIGMS NIH HHS/United States
GR  - R01 HL094463/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20181120
PL  - Netherlands
TA  - Ultrason Sonochem
JT  - Ultrasonics sonochemistry
JID - 9433356
RN  - 0 (Anticoagulants)
RN  - 0 (Fenton's reagent)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Anticoagulants/chemistry/pharmacology
MH  - Heparin, Low-Molecular-Weight/*chemistry/pharmacology
MH  - Humans
MH  - Hydrogen Peroxide/*chemistry
MH  - Hydrogen-Ion Concentration
MH  - Iron/*chemistry
MH  - Polymerization
MH  - Temperature
MH  - *Ultrasonic Waves
PMC - PMC6475493
MID - NIHMS1516786
OTO - NOTNLM
OT  - Anticoagulant activity
OT  - Depolymerization
OT  - Heparin
OT  - Sono-Fenton
EDAT- 2018/12/19 06:00
MHDA- 2019/05/17 06:00
PMCR- 2020/04/01
CRDT- 2018/12/19 06:00
PHST- 2018/08/08 00:00 [received]
PHST- 2018/11/13 00:00 [revised]
PHST- 2018/11/19 00:00 [accepted]
PHST- 2018/12/19 06:00 [pubmed]
PHST- 2019/05/17 06:00 [medline]
PHST- 2018/12/19 06:00 [entrez]
PHST- 2020/04/01 00:00 [pmc-release]
AID - S1350-4177(18)31207-0 [pii]
AID - 10.1016/j.ultsonch.2018.11.016 [doi]
PST - ppublish
SO  - Ultrason Sonochem. 2019 Apr;52:184-192. doi: 10.1016/j.ultsonch.2018.11.016. Epub 
      2018 Nov 20.