Heparin, a high-molecular weight acidic polysaccharide, has raised much interest in the field of biomedical research due to its multiple bio-functions. The anticoagulant application of heparin in routine clinical practice, however, has been limited as the large molecular size of heparin can reduce its subcutaneous bioavailability and lead to severe adverse consequences such as thrombocytopenia. Here, we report a highly efficient and convenient method to depolymerize high-molecular weight, unfractionated heparin (UFH), into low molecular weight heparin (LMWH) by combining physical ultrasonic treatment with the chemical Fenton reaction, referred to as sono-Fenton. We found that this combination treatment synergistically degraded UFH into a LMWH of 4.87 kDa within 20 min. We characterized the mechanism of sono-Fenton heparin degradation through multiple approaches, including HPLC-SAX, disaccharide composition, FT-IR, NMR and top-down analysis, and found that the uronic acid residue in heparin was the most susceptible site attacked by ·OH radicals produced in the sono-Fenton process. Importantly, the LMWH prepared by this method had significantly higher anticoagulant activity than UFH and other LMWHs. This approach represents an effective method to produce heparin with improved activity and should be potentially useful for heparin production in the pharmaceutical industry.

肝素是一种高分子量的酸性多糖，由于其多种生物功能，在生物医学研究领域引起了人们的极大兴趣。肝素在常规临床实践中的抗凝应用受到限制，因为大分子肝素会降低其皮下生物利用度并导致严重的不良后果，如血小板减少症。在这里，我们报告了一种高效便捷的方法，通过将物理超声处理与化学芬顿反应（称为声芬顿）相结合，将高分子量的普通肝素（UFH）解聚为低分子量肝素（LMWH）。我们发现这种联合治疗在20分钟内将UFH协同降解为4.87 kDa的LMWH。·声音-芬顿过程中产生的OH自由基。重要的是，用这种方法制备的LMWH具有比UFH和其他LMWH更高的抗凝活性。这种方法代表了一种生产具有改进活性的肝素的有效方法，并且对于制药业中肝素的生产应该具有潜在的用途。