Acylated non-α-amino acids as novel agents for the oral delivery of heparin sodium, USP

Ten N-acylated, non-α-amino acids have been prepared as oral delivery agents and used to demonstrate the oral delivery of heparin in vivo in rats and primates. Following the oral administration of solutions containing a combination of heparin and a delivery agent to rats or primates, significant plasma heparin concentrations were evidenced by APTT and anti-Factor Xa assays. The estimated pharmacodynamic equivalence for an oral dosing solution containing heparin and a delivery agent is 39% in primates. In vitro experiments based on heparin affinity chromatography or heparin/methylene blue complexation were also performed to begin investigation of the mechanism by which these compounds facilitate heparin oral delivery. Results of in vitro studies suggest that absorption of the drug across the gastrointestinal membrane is the result of a non-covalent interaction between heparin and the delivery agent.