Orally active desulfated low molecular weight heparin and deoxycholic acid conjugate, 6ODS-LHbD, suppresses neovascularization and bone destruction in arthritis

2012 ◽  
Vol 163 (3) ◽  
pp. 374-384 ◽  
Author(s):  
Seung Rim Hwang ◽  
Dong-Hyun Seo ◽  
Taslim A. Al-Hilal ◽  
Ok-Cheol Jeon ◽  
Jin Hee Kang ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Deoxycholic Acid ◽  
Bone Destruction ◽  
Low Molecular Weight ◽  
Acid Conjugate ◽  
Orally Active

Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant

2011 ◽  
Vol 105 (06) ◽  
pp. 1060-1071 ◽  
Author(s):  
Jin Woo Park ◽  
Ok Cheol Jeon ◽  
Sang Kyoon Kim ◽  
Taslim Al-Hilal ◽  
Kyung-Min Lim ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Administration ◽  
Low Molecular Weight Heparin ◽  
Deoxycholic Acid ◽  
Oral Absorption ◽  
Metabolic Stability ◽  
Oral Dosage ◽  
Low Molecular Weight ◽  
Therapeutic Effects ◽  
Oral Tablet

SummaryThis study was designed to develop a solid oral dosage form of deoxycholic acid (DOCA)-conjugated low-molecular-weight heparin (LMWH) and to evaluate its oral absorption, distribution, and metabolic stability for the prospect of providing an orally bioavailable LMWH. The LMWH derivative (LHD) was synthesised and then formulated with solubilisers and other pharmaceutical excipients to form a solid tablet. Its absorption and distribution after oral administration were evaluated in mice, rats, and monkeys. The in vitro metabolic stability of LHD was examined by liver microsome assays. More than 80% of LHD was released from the tablet within 60 minutes, guaranteeing rapid tablet disintegration after oral administration. Oral bioavailability of LHD in mice, rats and monkeys were 16.1 ± 3.0, 15.6 ± 6.1, and 15.8 ± 2.5%, respectively. After the oral administration of 131I-tyramine-LHD, most of the absorbed drug remained in the blood circulation and was eliminated mainly through the kidneys. LHD was hardly metabolised by the liver microsomes and showed a stable metabolic pattern similar to that of LMWH. In a rat thrombosis model, 10 mg/kg of orally administered LHD reduced thrombus formation by 60.8%, which was comparable to the antithrombotic effect of the subcutaneously injected LMWH (100 IU/ kg). Solid tablets of LHD exhibited high oral absorption and statistically significant therapeutic effects in preventing venous thromboembolism. Accordingly, LHD tablets are expected to satisfy the unmet medical need for an oral heparin-based anticoagulant as an alternative to injectable heparin and oral warfarin.

Orally active heparin and low–molecular-weight heparin

2001 ◽  
Vol 7 (5) ◽  
pp. 344-348 ◽  
Author(s):  
Graham F. Pineo ◽  
Russell D. Hull ◽  
Victor J. Marder
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Orally Active

High antiangiogenic and low anticoagulant efficacy of orally active low molecular weight heparin derivatives

2010 ◽  
Vol 148 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Jin Woo Park ◽  
Ok Cheol Jeon ◽  
Sang Kyoon Kim ◽  
Taslim Ahmed Al-Hilal ◽  
Shun Ji Jin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Heparin Derivatives ◽  
Orally Active
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