PMID- 11748110
OWN - NLM
STAT- MEDLINE
DCOM- 20020111
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 104
IP  - 25
DP  - 2001 Dec 18
TI  - Conjugation of low-molecular-weight heparin and deoxycholic acid for the 
      development of a new oral anticoagulant agent.
PG  - 3116-20
AB  - 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.
FAU - Lee, Y
AU  - Lee Y
AD  - Department of Materials Science and Engineering, Kwangju Institute of Science and 
      Technology, Chonnam National University, Gwangju, Korea.
FAU - Nam, J H
AU  - Nam JH
FAU - Shin, H C
AU  - Shin HC
FAU - Byun, Y
AU  - Byun Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 005990WHZZ (Deoxycholic Acid)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Anticoagulants/chemistry/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Chemistry, Pharmaceutical/methods
MH  - Chromatography, High Pressure Liquid/methods
MH  - Deoxycholic Acid/chemistry/*pharmacokinetics
MH  - Heparin, Low-Molecular-Weight/chemistry/*pharmacokinetics
MH  - Male
MH  - Molecular Weight
MH  - Partial Thromboplastin Time
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2001/12/19 10:00
MHDA- 2002/01/12 10:01
CRDT- 2001/12/19 10:00
PHST- 2001/12/19 10:00 [pubmed]
PHST- 2002/01/12 10:01 [medline]
PHST- 2001/12/19 10:00 [entrez]
AID - 10.1161/hc5001.100627 [doi]
PST - ppublish
SO  - Circulation. 2001 Dec 18;104(25):3116-20. doi: 10.1161/hc5001.100627.