Synthetic Pork-based Blood Coagulant Now Achievable

Currently, an anticoagulant called heparin is widely used. Collected from the intestines of 1 trillion pigs a yearThis means there is a risk of infection as well as accidental or intentional contamination. Now, methods of creating it synthetically have the potential to eliminate most of these risks.

“We think it could be sold within the next four to five years, maybe even less,” he says. Jonathan Dordick At New York’s Rensselaer Polytechnic Institute, the team developed a process to make heparin from scratch.

The drug was discovered in 1916 and has been used to prevent blood clotting since the 1930s. It is used to treat a wide range of conditions, as well as during kidney dialysis and various surgeries.

A major advantage of heparin is that it can be safely administered in large doses. “It’s very difficult to take an excessive dose,” Dordik says. And if someone takes too much, another drug can reverse the effect.

In contrast, other anticoagulants, such as warfarin, can be fatal if given in excess, and there is no antidote, which is why warfarin is used as a rat poison, he says.

A major disadvantage of heparin is that, unlike most drugs, heparin is not a single small molecule but a diverse mixture of large chains of sugars. “Heparin doesn’t have a specific size or a specific structure,” Dordik says. Heparin is derived from pigs because complex sugars are difficult to produce.

Ideally, animal-based medicines would be sourced from small herds that are isolated to prevent viral transmission. But extracting the 100 tons of heparin used around the world each year requires processing so many pig intestines that the only way to obtain enough intestines is through regular pig farming. It is to collect them from the field. Most heparin comes from China because heparin is the largest pork. producer.

As a result, the early stages of heparin production are unregulated as pharmaceutical manufacturing standards are not applicable to regular farms. There is a risk of accidental contamination or the deliberate addition of counterfeit heparin analogs to increase profits. In the worst case in 2008, about 800 people in the United States suffered side effects and at least 81 died. This risk remains, Dordik says. “That’s always possible.”

Despite all precautions, products of animal origin also carry the risk of contracting diseases caused by viruses and pathogens called prions. However, Dordik said there is no known case of this happening with heparin.

Dependence on pigs also causes shortages when pig farms are hit by conditions such as swine fever. Some people object to the use of pig-derived products for ethical or religious reasons.

Therefore, although synthetic heparin should have many advantages, its production has proven to be extremely difficult. The first task is to create a branched sugar chain that will serve as the backbone. The four enzymes then make various additional modifications to the chain, which must be done in a precise order.

After years of research, Dordik’s team has now licensed the process they developed to a pharmaceutical company to scale up for commercial production. One of the things that took him the most time was isolating and manufacturing the enzymes involved, Dordik says.

Since first producing a few micrograms 20 years ago, the team says they have successfully scaled up production a million times. Kuberan Balagulnathan He was involved in this early study but is no longer part of the team. “The next major challenge will be to increase the scale another million times, from grams to metric tons,” he says.

Balagurunathan believes this is achievable with sufficient investment. “We hope that synthetic heparin will replace heparin in animals in the same way that recombinant insulin replaces bovine and porcine insulin.”

but Jiang Liu A professor at the University of North Carolina at Chapel Hill isn’t so sure. “It remains to be seen whether this process can be translated to synthesis on the scale of thousands of kilograms.”

Many other companies are working on making synthetic heparin, but commercial confidentiality makes it difficult to gauge their progress, Balagulnathan said.