Prevention effect of orally active heparin derivative on deep vein thrombosis

Sang Kyoon Kim; Dong Yoon Lee; Choong Yong Kim; Hyun Tae Moon; Youngro Byun

doi:10.1160/TH06-02-0077

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(02): 149-153
DOI: 10.1160/TH06-02-0077

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Prevention effect of orally active heparin derivative on deep vein thrombosis

Authors

Sang Kyoon Kim

¹Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
Dong Yoon Lee

²College of Pharmacy, Seoul National University, Seoul, Korea
Choong Yong Kim

³Toxicology Research Center, Korea Research Institute of Chemical Technology, Daejon, Korea
Hyun Tae Moon

⁴Mediplex Corp. , Seoul, Korea
Youngro Byun

²College of Pharmacy, Seoul National University, Seoul, Korea

Abstract

Summary

The use of heparin as the most potent anticoagulant for the prevention of deep vein thrombosis and pulmonary embolism is nevertheless limited, because it is available to patients only by parenteral administration. Toward overcoming this limitation in the use of heparin, we have previously developed an orally active heparin-deoxycholic acid conjugate (LMWH-DOCA) in 10% DMSO formulation. The present study evaluates the anti-thrombogenic effect of this orally active LMWH-DOCA using a venous thrombosis animal model with Sprague-Dawley rats. When 5 mg/kg of LMWH-DOCA was orally administered in rats, the maximum anti-FXa activity in plasma was 0. 35 ± 0. 02, and anti-FXa activity in plasma was maintained above 0. 1 IU/ml [the minimum effective anti-FXa activity for the prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE)] for five hours. LMWH-DOCA (5 mg/kg, 430 IU/kg) that was orally administered reduced the thrombus formation by 56. 3 ± 19. 8%;on the other hand, subcutaneously administered enoxaparin (100 IU/kg) reduced the thrombus formation by 36. 4 ± 14. 5%. Also, LMWH-DOCA was effectively neutralized by protamine that was used as an antidote. Therefore, orally active LMWH-DOCA could be proposed as a new drug that is effective for the longterm prevention of DVT and PE.

Keywords

Low-molecular-weight heparin - deoxycholic acid - chemical conjugate - oral delivery - deep vein thrombosis

Full Text

References

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