Oral low-molecular weight heparin and delivery agent prevents jugular venous thrombosis in the rat.

Abstract

Sodium N-[10-(2-hydroxybenzoyl)amino]decanoate (SNAD) is a novel carrier that allows the gastrointestinal absorption of low-molecular weight heparin (LMWH). The purpose of this experiment was to evaluate oral LMWH with SNAD for the prevention of deep venous thrombosis. Sixty Sprague-Dawley rats were equally assigned to five experimental groups: group 1 (control), oral saline solution; group 2, oral LMWH (15 mg/kg); group 3, oral SNAD (300 mg/kg); group 4, subcutaneous LMWH (5 mg/kg); and group 5, oral LMWH (15 mg/kg) and SNAD (300 mg/kg). After treatment, the jugular vein was isolated, occluded, and bathed in an ethanol and formalin solution for 2 minutes. Two hours later, the vessel was examined for patency, presence of thrombus, and thrombus weight. Serum measurement of anti-factor Xa activity was performed in a separate set of 30 rats, which were placed into the following four groups: group A, LMWH (5 mg/kg); group B, oral LMWH (15 mg/kg) and SNAD (300 mg/kg); group C, oral LMWH (15 mg/kg); and group D, SNAD (300 mg/kg). The animals that underwent oral LMWH/SNAD therapy had a statistically significant decrease in visible thrombi. The thrombus weight of the oral LMWH/SNAD group was significantly less than the weights of all other groups, except the subcutaneous LMWH group. Anti-factor Xa levels were significantly elevated in the LMWH/SNAD group. There was no statistically significant difference between the data for the oral LMWH/SNAD group and the subcutaneous LMWH group. The combination of oral LMWH and SNAD prevented deep venous thrombosis. The oral LMWH and SNAD therapy effected an increase in levels of anti-factor Xa.