Abstract:
BACKGROUND:Heparin administration is usually limited to intravenous or subcutaneous injection. Oral delivery of heparin is an alternative to this and has been in great demand for treating patients who are at a high risk of deep vein thrombosis or pulmonary embolism. In this study, new heparin derivatives were synthesized to enhance the oral absorption of heparin in the gastrointestinal tract. Methods and Results- By using heparin of 3000 Da [LMWH(3 kDa)], heparin of 6000 Da [LMWH(6 kDa)], and unfractionated heparin (UFH), we synthesized 3 kinds of conjugates of heparin and deoxycholic acid (DOCA): LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA. After oral administration of 100 mg/kg of heparin-DOCA, the maximum activated partial thromboplastin times of the LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA were 31.0+/-6.0, 87.8+/-11.1, and 51.0+/-8.7 seconds, respectively. The peak plasma concentrations of LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA were 0.06+/-0.02, 0.76+/-0.15, and 0.41+/-0.13 IU/mL, respectively. The bioavailability of LMWH(6 kDa)-DOCA at the 20-mg/kg dosage was calculated to be 7.8%. CONCLUSIONS:LMWH(6 kDa)-DOCA was found to have a high anticoagulant effect when administered orally and could be used as a new oral anticoagulant agent. Furthermore, the present work proposed a new method for oral delivery of macromolecules and polysaccharide drugs.
journal_name
Circulationjournal_title
Circulationauthors
Lee Y,Nam JH,Shin HC,Byun Ydoi
10.1161/hc5001.100627subject
Has Abstractpub_date
2001-12-18 00:00:00pages
3116-20issue
25eissn
0009-7322issn
1524-4539journal_volume
104pub_type
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