Abstract：
Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.
摘要：
低分子量肝素（LMWHs）已被确定用于预防和治疗血栓性疾病。由于其可预测的药代动力学和皮下生物利用度，可替代普通肝素（UFH）。LMWH是通过各种解聚方法从UFH生产的，导致具有相似生化和药理特性的异质化合物。然而,UFH的微妙供应链和来自动物来源的潜在污染需要LMWH的新制造方法。各种LMWH制备方法不断涌现,如化学合成，酶或化学解聚和化学酶合成。为了在创新者和通用LMWH产品中建立活性成分的一致性，美国食品和药物管理局实施了严格的基于理化性质的等效性科学方法，肝素源材料和解聚技术，二糖组成和寡糖图谱，生物和生化特性，和体内药效学谱。在这次审查中,我们讨论当前可用的LMWH，潜在的制造方法，以及这些LMWH的制造质量控制的最新进展。
