Bezerra Francisco Felipe, Oliveira Stephan N M C G, Sales Rodrigo A, Piquet Adriana A, Capillé Nina V, Vilanova Eduardo, Tovar Ana M F, Mourão Paulo A S
Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
Pharmaceutics. 2023 Mar 31;15(4):1115. doi: 10.3390/pharmaceutics15041115.
Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. Heparins obtained from different tissues also differ in their structure and activity. Nevertheless, there is an increased demand for more accurate assessments to ensure the similarities of pharmaceutical heparins. We propose an approach to accurately assess the similarity of these pharmaceutical preparations based on well-defined criteria, which are verified with a variety of refined analytical methods. We evaluate six commercial batches from two different manufacturers which were formulated with Brazilian or Chinese active pharmaceutical ingredients. Biochemical and spectroscopic methods and analysis based on digestion with heparinases were employed to evaluate the purity and structure of the heparins. Specific assays were employed to evaluate the biological activity. We observed minor but significant differences between the constitutive units of the heparins from these two manufacturers, such as the content of -acetylated α-glucosamine. They also have minor differences in their molecular masses. These physicochemical differences have no impact on the anticoagulant activity but can indicate particularities on their manufacturing processes. The protocol we propose here for analyzing the similarity of unfractionated heparins is analogous to those successfully employed to compare low-molecular-weight heparins.
来自不同制造商的药用肝素可能由于特定的提取和纯化程序，甚至原材料处理的差异而呈现异质性。从不同组织获得的肝素在结构和活性上也有所不同。然而，为确保药用肝素的相似性，对更精确评估的需求日益增加。我们提出一种基于明确标准准确评估这些药物制剂相似性的方法，该方法通过多种精细分析方法进行验证。我们评估了来自两家不同制造商的六个商业批次，这些批次分别用巴西或中国的活性药物成分配制。采用生化和光谱方法以及基于肝素酶消化的分析来评估肝素的纯度和结构。采用特定检测方法评估生物活性。我们观察到这两家制造商生产的肝素的组成单元之间存在细微但显著的差异，例如乙酰化α-葡萄糖胺的含量。它们的分子量也有细微差异。这些物理化学差异对抗凝活性没有影响，但可以表明其生产过程的特殊性。我们在此提出的用于分析普通肝素相似性的方案与成功用于比较低分子量肝素的方案类似。
