College of Pharmaceutical Science & Collaborative Innovation Center for Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, 310014 Hangzhou, China.
College of Pharmaceutical Science & Collaborative Innovation Center for Yangtze River Delta Region Green Pharmaceuticals, Key Laboratory of Marine Fishery Resources Exploitment & Utilization of Zhejiang Province, Zhejiang University of Technology, 310014 Hangzhou, China; Binjiang Cyberspace Security Institute of ZJUT, Hangzhou 310056, China.
Carbohydr Polym. 2024 Sep 1;339:122216. doi: 10.1016/j.carbpol.2024.122216. Epub 2024 May 1.
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.
低分子量肝素（LMWH）因其药代动力学可预测且可皮下给药，已被广泛用于预防和治疗血栓性疾病，并作为未分级肝素（UFH）的替代品。LMWH 是通过 UFH 的各种解聚方法生产的，其结果是具有相似生化和药理学特性的异质化合物。然而，UFH 脆弱的供应链和来自动物源的潜在污染，都需要 LMWH 的新制造方法。各种 LMWH 制备方法正在涌现，如化学合成、酶法或化学解聚以及化学酶合成。为了在创新药和仿制药 LMWH 产品中建立活性成分的等同性，食品和药物管理局已经实施了一种严格的基于物理化学性质、肝素原料和解聚技术、二糖组成和低聚糖图谱、生物和生化特性以及体内药效学特征的等效性科学方法。在这篇综述中，我们讨论了现有的 LMWH、潜在的制造方法，以及这些 LMWH 制造质量控制的最新进展。
