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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2019-04-01
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| Series: | Clinical and Applied Thrombosis/Hemostasis |
| Online Access: | https://doi.org/10.1177/1076029619840701 |
| _version_ | 1818187905768620032 |
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| author | Jianle Chen BS Yanlei Yu PhD Jawed Fareed PhD Debra Hoppensteadt PhD Walter Jeske PhD Ahmed Kouta BS Caijuan Jin MS Yongsheng Jin MS Yiming Yao MS Ke Xia PhD Fuming Zhang PhD Shiguo Chen PhD Xingqian Ye PhD Robert J. Linhardt PhD |
| author_facet | Jianle Chen BS Yanlei Yu PhD Jawed Fareed PhD Debra Hoppensteadt PhD Walter Jeske PhD Ahmed Kouta BS Caijuan Jin MS Yongsheng Jin MS Yiming Yao MS Ke Xia PhD Fuming Zhang PhD Shiguo Chen PhD Xingqian Ye PhD Robert J. Linhardt PhD |
| author_sort | Jianle Chen BS |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T23:18:28Z |
| format | Article |
| id | doaj.art-4f9da34e24724006a321da5be13e1aae |
| institution | Directory Open Access Journal |
| issn | 1938-2723 |
| language | English |
| last_indexed | 2024-12-11T23:18:28Z |
| publishDate | 2019-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical and Applied Thrombosis/Hemostasis |
| spelling | doaj.art-4f9da34e24724006a321da5be13e1aae2022-12-22T00:46:25ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232019-04-012510.1177/1076029619840701Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With EnoxaparinJianle Chen BS0Yanlei Yu PhD1Jawed Fareed PhD2Debra Hoppensteadt PhD3Walter Jeske PhD4Ahmed Kouta BS5Caijuan Jin MS6Yongsheng Jin MS7Yiming Yao MS8Ke Xia PhD9Fuming Zhang PhD10Shiguo Chen PhD11Xingqian Ye PhD12Robert J. Linhardt PhD13 Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA Department of Pathology, Loyola University Medical Center, Maywood, IL, USA Ronnsi Pharma Co, Ltd, Suzhou Industrial Park, Suzhou, China Ronnsi Pharma Co, Ltd, Suzhou Industrial Park, Suzhou, China Ronnsi Pharma Co, Ltd, Suzhou Industrial Park, Suzhou, China Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USAHeparin 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.https://doi.org/10.1177/1076029619840701 |
| spellingShingle | Jianle Chen BS Yanlei Yu PhD Jawed Fareed PhD Debra Hoppensteadt PhD Walter Jeske PhD Ahmed Kouta BS Caijuan Jin MS Yongsheng Jin MS Yiming Yao MS Ke Xia PhD Fuming Zhang PhD Shiguo Chen PhD Xingqian Ye PhD Robert J. Linhardt PhD Comparison of Low-Molecular-Weight Heparins Prepared From Ovine Heparins With Enoxaparin Clinical and Applied Thrombosis/Hemostasis |
| 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 |
| url | https://doi.org/10.1177/1076029619840701 |
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