Ethanol precipitation for the purification of herbal medicines

By Jillian Jastrzembski

What is ethanol precipitation?

Ethanol precipitation is a process used for the purification of traditional medicine herbal formulas. This process represents a simple and efficient way to increase potency, remove impurities, and even improve safety.

In this article, we’ll discuss how ethanol precipitation works, and the advantages it offers to traditional herbal preparations.

The role of herbal medicine

Herbal formulas are a heavy component of Traditional Chinese Medicine (TCM). Unlike many other herbal traditions which focus on single herbs, TCM herbalism uses formulas composed of multiple substances. The classical formulas are elegantly designed so that the herbs work synergistically, as well as balance each other out. The purpose of this is to minimize, or ideally eliminate, side effects and toxicity of individual herbs.

Historically, these formulas were prepared by decocting the raw herbs in boiling water to make a medicinal tea. While many practitioners and patients still prefer to use herbs in this way, it is nonetheless impractical and inconvenient for most modern-day people. It requires keeping an up-to-date dispensary of raw herbs, which have a short shelf-life and take up a lot of storage space. The decoction itself is time-consuming to prepare and needs to be consumed quickly.

Today, there is a widespread preference among the TCM community for alternatives such as tablets and granules. These are designed to deliver the same herbal formula in a more convenient form. They take up less space, have a longer shelf life, and require minimal preparation on the patient side with minimal instructions on the practitioner side

The processing of these herbal tablets and granules often involves ethanol precipitation. Ethanol precipitation can refine the herbal mixtures to enhance the concentration of bioactive compounds and increase efficacy at a lower dosage, while also improving safety. Let’s take a closer look at how the process works.

How ethanol precipitation works

Ethanol precipitation technology works on the principal that certain compounds will be more or less soluble depending on the concentration of ethanol in an ethanol-water mixture. In other words, as the ethanol concentration increases, certain compounds will become less soluble. At the same time, other compounds will become more soluble. In this way, ethanol precipitation allows for the selection of certain compounds and the removal of others.

Another way to help manipulate solubility is to influence temperature and/or pH. Ethanol precipitation technology takes advantage of multiple parameters in addition to ethanol concentration in order to remove “impurities” and thereby concentrate bioactive compounds.

For example, crude herbal decoctions may contain polysaccharides like inulin and dextran. These sugar components are considered impurities in the sense that they are not physiologically active. In other words, they are not involved in the healing mechanism of the formula actions. These sugars are easy to precipitate out of the mixture by increasing the ethanol concentration and lowering the temperature. Branched chain polysaccharides are the easiest to remove.

On the other hand, this process is only useful if the biologically active components of the formula are retained during the purification step. That means that the bioactive compounds have to remain soluble, or preferably increase in solubility, as the ethanol concentration increases and the sugars precipitate out of solution. In fact, this is generally found to be the case. Bioactive compounds are usually moderately polar, which means they solubilize better in ethanol compared to water alone.

Bioactive compounds that are retained and enhanced during ethanol precipitation include: phenolic acids, phenols, flavonoids, and alkaloids.

Advantages of ethanol precipitation

Ethanol precipitation is an efficient, simple, and non-toxic way to remove biologically inactive components from herbal concentrates while simultaneously enhancing the concentration of pharmacologically relevant compounds.

The result of this is that a lower dosage of the herbal formula can now achieve the same biological benefits.

Disadvantages of ethanol precipitation

Despite the many advantages of ethanol precipitation, there are some factors that need to be considered in order to avoid loss of medicinal potency. Specifically, bioactive compounds can be lost during the purification process due to incomplete mixing, undesired precipitation, and degradation.

Although many research studies have demonstrated that potency increases and required medicinal dosage decreases following ethanol precipitation, sometimes the opposite can also happen. For this reason, it is important to carefully optimize the purification parameters, and perform studies to ascertain the efficacy of the purified mixture.

Conclusion

Ethanol precipitation is a simple, efficient process that allows for the purification of traditional medicine herbal formulas. This technology operates on the principal that most bioactive compounds are increasingly soluble in higher ethanol concentrations, while compounds that are irrelevant or unsafe are usually less soluble. Increasing the ethanol concentration allows for impurities to precipitate out of solution while bioactive compounds remain. The result is a potent, bioactive concentrate that can be used to make tablets or granules in place of the less convenient, traditional decoction.

References

Tai, Y., Shen, J., Luo, Y. et al. Research progress on the ethanol precipitation process of traditional Chinese medicine. Chin Med 15, 84 (2020). https://doi.org/10.1186/s13020-020-00366-2

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