Effect of ultrasonic treatment on aggregation and stability of heparin in aqueous solution

In this paper, dynamic light scattering is employed to investigate the aggregation of heparin in aqueous solution and to reveal the influence of ultrasonic treatment on the aggregation and stability of heparin. The results show that heparin exists in aqueous solution in the form of aggregated species via multiple-molecule cross-linking, with the particle size of the aggregates increasing with the heparin concentration, that the aggregates cannot be completely eliminated though the addition of sodium chloride leads to a reduction of aggregates diameter in a certain degree, and that ultrasonic treatment significantly restrains the heparin aggregation. When ultrasound with 30% of power percentage is applied for 3 min, the aggregates with the diameter of 100~1000 nm change into heparin monomers with the diameter of 1~10 nm, which means that ultrasonic treatment is effective in restraining the heparin aggregation. Moreover, disaggregated heparin powder with the diameter of 1~10 nm can be obtained by the filtration with 100 nm membrane and subsequent freeze drying. The disaggregated heparin remains stable after the storage for more than 64 h at room temperatures.