Cargando…
Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With Enoxaparin
Heparin and its low-molecular-weight heparin derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications, including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are deri...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714994/ https://www.ncbi.nlm.nih.gov/pubmed/30987427 http://dx.doi.org/10.1177/1076029619840701 |
_version_ | 1783447158092988416 |
---|---|
author | Chen, Jianle Yu, Yanlei Fareed, Jawed Hoppensteadt, Debra Jeske, Walter Kouta, Ahmed Jin, Caijuan Jin, Yongsheng Yao, Yiming Xia, Ke Zhang, Fuming Chen, Shiguo Ye, Xingqian Linhardt, Robert J. |
author_facet | Chen, Jianle Yu, Yanlei Fareed, Jawed Hoppensteadt, Debra Jeske, Walter Kouta, Ahmed Jin, Caijuan Jin, Yongsheng Yao, Yiming Xia, Ke Zhang, Fuming Chen, Shiguo Ye, Xingqian Linhardt, Robert J. |
author_sort | Chen, Jianle |
collection | PubMed |
description | Heparin and its low-molecular-weight heparin derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications, including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine and less frequently bovine intestine and bovine lung. The worldwide dependence on the pig as a single dominant animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including the expanded use of bovine tissues. A number of laboratories are now also examining the similarities between heparin and low-molecular-weight heparins prepared from porcine and ovine tissues. This study was designed to compare low-molecular-weight heparin prepared from ovine heparin through chemical β-elimination, a process currently used to prepare the low-molecular-weight heparin, enoxaparin. Using top-down, bottom-up, and compositional analyses as well as bioassays, low-molecular-weight heparin derived from ovine intestine was shown to closely resemble enoxaparin. Moreover, the compositions of daughter low-molecular-weight heparins prepared from three unfractionated ovine parent heparins were compared. Ovine enoxaparins had similar molecular weight and in vitro anticoagulant activities as Lovenox. Some disaccharide compositional, oligosaccharide composition at the reducing and nonreducing ends and intact chain compositional differences could be observed between porcine enoxaparin and ovine low-molecular-weight heparin. The similarity of these ovine and porcine heparin products suggests that their preclinical evaluation and ultimately clinical assessment is warranted. |
format | Online Article Text |
id | pubmed-6714994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-67149942019-09-04 Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With Enoxaparin Chen, Jianle Yu, Yanlei Fareed, Jawed Hoppensteadt, Debra Jeske, Walter Kouta, Ahmed Jin, Caijuan Jin, Yongsheng Yao, Yiming Xia, Ke Zhang, Fuming Chen, Shiguo Ye, Xingqian Linhardt, Robert J. Clin Appl Thromb Hemost Original Article Heparin and its low-molecular-weight heparin derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications, including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine and less frequently bovine intestine and bovine lung. The worldwide dependence on the pig as a single dominant animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including the expanded use of bovine tissues. A number of laboratories are now also examining the similarities between heparin and low-molecular-weight heparins prepared from porcine and ovine tissues. This study was designed to compare low-molecular-weight heparin prepared from ovine heparin through chemical β-elimination, a process currently used to prepare the low-molecular-weight heparin, enoxaparin. Using top-down, bottom-up, and compositional analyses as well as bioassays, low-molecular-weight heparin derived from ovine intestine was shown to closely resemble enoxaparin. Moreover, the compositions of daughter low-molecular-weight heparins prepared from three unfractionated ovine parent heparins were compared. Ovine enoxaparins had similar molecular weight and in vitro anticoagulant activities as Lovenox. Some disaccharide compositional, oligosaccharide composition at the reducing and nonreducing ends and intact chain compositional differences could be observed between porcine enoxaparin and ovine low-molecular-weight heparin. The similarity of these ovine and porcine heparin products suggests that their preclinical evaluation and ultimately clinical assessment is warranted. SAGE Publications 2019-04-16 /pmc/articles/PMC6714994/ /pubmed/30987427 http://dx.doi.org/10.1177/1076029619840701 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Chen, Jianle Yu, Yanlei Fareed, Jawed Hoppensteadt, Debra Jeske, Walter Kouta, Ahmed Jin, Caijuan Jin, Yongsheng Yao, Yiming Xia, Ke Zhang, Fuming Chen, Shiguo Ye, Xingqian Linhardt, Robert J. Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With Enoxaparin |
title | Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With
Enoxaparin |
title_full | Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With
Enoxaparin |
title_fullStr | Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With
Enoxaparin |
title_full_unstemmed | Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With
Enoxaparin |
title_short | Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With
Enoxaparin |
title_sort | comparison of low-molecular-weight heparins prepared from ovine heparins with
enoxaparin |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714994/ https://www.ncbi.nlm.nih.gov/pubmed/30987427 http://dx.doi.org/10.1177/1076029619840701 |
work_keys_str_mv | AT chenjianle comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT yuyanlei comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT fareedjawed comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT hoppensteadtdebra comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT jeskewalter comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT koutaahmed comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT jincaijuan comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT jinyongsheng comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT yaoyiming comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT xiake comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT zhangfuming comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT chenshiguo comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT yexingqian comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin AT linhardtrobertj comparisonoflowmolecularweightheparinspreparedfromovineheparinswithenoxaparin |