Oral delivery of new heparin derivatives in rats

Purpose. In this study, conjugates of heparin and deoxycholic acid were syn thesized in order to enhance the heparin absorption in the GI tract. Oral d elivery of heparin is a preferred therapy in the treatment of patients who are at high risk of deep vein thrombosis and pulmonary embolism. Methods. Several different kinds of heparin derivatives were synthesized, a nd their absorption in the GI tract was determined by activated partial thr omboplastin time (aPTT) and factor Xa (FXa) assay. Any histological changes caused by heparin derivatives were examined by hematoxylin and eosin (H&E) stain and transmission electron microscopy (TEM). Results. After administering heparin-DOCA orally, the clotting time in aPTT assay was increased with the increase of the coupled DOCA amount. The maxi mum clotting time of heparin-DOCA was 136+/-33 sec at 200 mg/kg of oral dos e. This value was 7 times higher than the baseline. The absorption of hepar in-cholesterol, heparin-palmitic acid, and heparin-lauric acid conjugates i n the GI tract was lower than that of heparin-DOCA. Histological examinatio n of the GI tract indicated that heparin derivatives did not cause any dama ge to the microvilli and the cell layer. Conclusions. DOCA coupled with heparin greatly enhanced absorption of hepar in in the GI tract, and this enhancing effect was induced without changing the tissue structure of the GI wall.