From Farm to Pharma: An Overview of Industrial Heparin Manufacturing Methods

Abstract

The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for commercial heparin production in industry. Heparin purification methods are closely guarded industrial secrets which are not available to the general (scientific) public. However by reviewing the academic and patent literature, we aim to provide a comprehensive overview of the general methods used in industry for the extraction of heparin from animal tissue.

A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer’s Disease

“…The P. pelagicus GAG of the present study largely circumvents the anticoagulant limitations of mammalian heparins while maintaining comparable, low IC 50 BACE1 inhibition values. Additional advantages with marine-derived GAGs is that they offer sources, derived from waste material of otherwise very low economic value, that are free from contamination with mammalian pathogens (e.g., BSE) and avoid many of the religious and social issues associated with mammalian products [72]. Interestingly, the mechanism by which the present product from P. pelagicus inhibits BACE1 is complex, concentration dependent and appears to be distinct from that of mammalian heparin, suggesting marine GAGs as a potential starting point for future drug development.…”

Incomplete understanding of biogas chemical hazards — Serious gas poisoning accident while unloading food waste at biogas plant

“…We note that this is similar to our hypothesis for generation of H₂S in food waste: protein degradation and the action of sulfate reducing bacteria. We further comment, that during industrial heparine extraction, intestinal mucosa is often preserved using an oxygen scavenger such as sodium hydrogen sulfite [27], some of which may have been reduced and contributed to the high sulfide content. The German investigation stated that whey concentrate and animal by-products had been offloaded into the pit the day before.…”

Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity

“…Difficulties/hurdles related to sourcing, isolation, and purification of heparin continue to be faced in order to obtain a pharmaceutical-grade drug or intermediates with guaranteed safety and efficacy. To circumvent some manufacturing problems, as well as the risk of contamination with pathogens (e.g., mammalian prionic proteins and viruses) or other dangerous polysaccharides (e.g., oversulfated chondroitin sulfate), intensive efforts were made to identify alternative sources of heparin-like compounds, as well as synthetic derivatives endowed with similar biological activities but devoid of side effects [ 212 , 213 , 214 ].…”