![]() In addition, heparin has been shown to exert favourable bioactivities through a number of pathophysiological pathways involved in the disease processes of Alzheimer's Disease including inflammation, oxidative stress, tau phosphorylation and amyloid peptide generation. The clinically important anticoagulant heparin, a member of the glycosaminoglycan family of carbohydrates that is extracted predominantly from porcine and bovine tissue sources, has previously been shown to inhibit the β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), a key drug target in Alzheimer's Disease. The protocol we propose here for analyzing the similarity of unfractionated heparins is analogous to those successfully employed to compare low-molecular-weight heparins. These physicochemical differences have no impact on the anticoagulant activity but can indicate particularities on their manufacturing processes. They also have minor differences in their molecular masses. We observed minor but significant differences between the constitutive units of the heparins from these two manufacturers, such as the content of N-acetylated α-glucosamine. Specific assays were employed to evaluate the biological activity. Biochemical and spectroscopic methods and analysis based on digestion with heparinases were employed to evaluate the purity and structure of the heparins. We evaluate six commercial batches from two different manufacturers which were formulated with Brazilian or Chinese active pharmaceutical ingredients. 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. Nevertheless, there is an increased demand for more accurate assessments to ensure the similarities of pharmaceutical heparins. Heparins obtained from different tissues also differ in their structure and activity. Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. ![]()
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