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Extracting synergistic mixtures from plants for the booming skin care market
Ancient botanicals meet new technologies to produce novel ingredients
By Malorye Allison Branca,
C&EN BRANDLAB Contributing Writer
Credit: Shutterstock

Antiaging products are one of the world’s most vibrant markets, expected to reach over $10 billion by 2018. It’s also a competitive field, often buoyed by trends. Soy, green tea, pomegranate, and other various botanicals have been popular ingredients in personal care products that have come and gone out of favor over time.

One of the key questions, however, has always been whether scientists can truly capture the potential impact of any whole plant—essentially, reproducing the synergistic effects of multiple ingredients found together in nature.

The allure of plants as skin care ingredients is that they are natural. Some contain compounds proven to have certain benefits. Soy, for example, contains the isoflavone genistein, which is considered to improve skin tone and brightness. Many cultures also have age-old traditions of using plants for healing. But scientists wonder if there are real effects behind those beliefs. The challenge for chemists is to extract those compounds and to create ingredients that truly provide benefits.

Getting from the plant to the end-use product often brings up the issue of synergy. “Most botanical ingredients rich with various types of phytochemicals actually act synergistically,” explains Sreenivasan Sasidharan, associate professor at the Institute for Research in Molecular Medicine at Universiti Sains Malaysia.

“The ‘synergy hypothesis’ is that optimal fractions of mixtures can hit multiple biological pathways,” says Thomas Dawson, an independent consultant at Beauty Care Strategies, Singapore. Since biology is complex, he adds, “when hitting a biological system at multiple points, it becomes possible to impact it in a more effective manner.”

To get those optimal fractions, scientists need to have a way to pull out mixtures of active ingredients from fresh plant matter. But this is easier said than done.

The Traditional Process

To get active compounds out of plants, scientists usually turn to high-performance liquid chromatography, gas chromatography/mass spectroscopy, and liquid chromatography/mass spectroscopy. Multiple solvents are used to draw out particular compounds.

Using solvents means degassing them to make certain the process takes place under inert conditions. Solvents also are believed to restrict the ability to measure synergies because they disassociate different ingredients into different extracts. “Protecting antioxidative compounds from autoxidation during isolation is one of the most important steps,” says Sung Hoon Kim of the department of chemistry at Konkuk University. Further, simply identifying the correct solvent that can “extract the target phytochemicals” is often a major step, Sasidharan says.

Another big issue is that most plant ingredients are derived from dried plant matter. The drying process initiates osmotic shock and oxidative stress, which can trigger effects such as decompartmentalization in plant cells, disruption of enzymes, hydrolysis, and microbial contamination.

The extraction process can also be affected by variability in growth, harvest, and drying conditions. Even if variability is low, these factors can impact reproducibility, making it hard to evaluate the extract, let alone establish a proper usage dose.

Ashland’s Zeta Fraction process requires proprietary equipment and begins with separation of the fresh plant into a relatively stable intracellular colloidal dispersion and fiber-enriched material. The dispersion is then separated into fractions. The plant’s important ingredients are captured in a serum fraction containing the continuous phase of the intracellular colloidal dispersion.

“The Zeta Fraction technology is unique in its use of fresh, living plants,” says Miri Seiberg of Seiberg Consulting. “As a plant dries, numerous changes occur at the molecular level, which change its composition. Using fresh plants immediately at harvest preserves the natural composition of the plant material and enables the capture of all metabolic activities of the plant that could otherwise be modified or destroyed.”

“From a strict ‘biofunctional activity’ view, Zeta fractions have more opportunity to preserve the natural activity of a plant,” says consultant Thomas Dawson. “The fraction isolation from live plant material and from particular parts of live plants is unique among natural isolates.” This feature, he adds, makes it possible to extract specific mixtures from a single plant specimen. “Hence, you can screen many subtly different isolation fractions and quickly narrow to the activity of interest.”

Overcoming Challenges Of Isolation

Ashland’s Zeta Fraction technology (ZFT) overcomes some the efficacy and usability challenges of traditional isolation methods. Developed by Michael Koganov, vice president of BioMaterials, Ashland, and colleagues, ZFT is a solvent-free process that enables the isolation of multiple active ingredients from a whole, fresh, living plant while preserving the natural activity and synergy among biomolecules. Koganov and his team have put the process to work by creating Harmoniance, an antiaging ingredient for skin care products that is based on the sacred lotus plant.

The sacred lotus (Nelumbo nucifera) is both widely grown and steeped in cultural significance in Asia. It is sacred to Buddhists and Hindus and is the national flower of India. Cultivated for over 4,000 years, it is a type of water lily with a stout, creeping rhizome. It is an edible plant that is a mainstay of diet and natural medicines where it has long been cultivated, mainly in southern Asia.

Traditional healers recommend the plant for conditions as varied as gastrointestinal issues to skin conditions, such as inflammation. Although antiaging attributes have not been a priority in traditional medicine, studies of the lotus have suggested it is rich in chemicals (including antioxidants) that could have such effects.

Harmoniance is made by using ZFT to isolate active cellular components from the fresh, whole lotus, including flowers, stem, leaves, and roots. “When we start with the living plant, we have a much better chance of capturing all of its effects,” Koganov says. “The idea here was to bring new technology to the place where plants are grown,” he says, “and as a result, to bring novel plant ingredients into skin care. Ashland is always solving.”

Applied to the lotus plant, ZFT creates a final, complex fraction that includes phenolic compounds, carbohydrates, free amino acids, electrolytes, and microelements. Compounds from all these classes have been used as skin care ingredients before, but it is their unique combination, extracted in one process, that makes Harmoniance different, says Dawson, who has worked with ZFT.

According to Dawson, ZFT produces fractions that demonstrate benefits. “There was measurable synergy in the fractions [we studied]. We were also able to demonstrate biological synergy from specific chemistries combined with plant fractions,” he says.

Another concern with using botanicals for skin care ingredients is consistency in the plant materials. Like many plants, the lotus is affected by where and how it is cultivated. Kim has studied the variations of antioxidant activity and concentration of functional components from extracts of lotus and rhizomes from various regions. “The contents of functional components varied significantly depending on the locations,” he says. “The variation comes from the soil conditions and the climate of the cultured location.” The concentration of various compounds, he points out, also varies significantly depending on the part of the plant being used.

But ZFT can handle the variability in the plant matter. All the materials for Harmoniance come from identifiable and traceable locations. “One of the major problems of botanical ingredients is their reproducibility, as different harvests come from different weather, soil conditions, and storage conditions,” says Miri Seiberg of Seiberg Consulting. “Using the ZFT, it is possible to create reproducible batches of plant material from such nonidentical growth conditions.”

However, turning Harmoniance, which was launched at In-Cosmetics in London in early April, into notable skin care products will take more than good plant extraction and isolation methods. As Dawson points out, “One needs to deliver enough activity to get it to work, and it needs to penetrate the skin and read the desired target.” All that will require appropriate formulation by the manufacturers of personal care products that include Harmoniance.


Traditional plant extraction methods can be time-consuming and require a lot of solvent. “As a result, the traditional methods may have a potential negative effect on the environment and human health,” explains Eng Shi Ong, a lecturer at Singapore University of Technology & Design. In addition, solvent-free approaches make the resulting extracts free from residual solvents and possibly carcinogenic contaminants, such as benzene. It is a particular advantage that ZFT is free of solvents, which are known chemical pollutants. “For the isolation, fractionation, and characterization of chemical compounds in plants, there is a movement to minimize the use of organic solvents,” Ong says.

Besides allowing scientists to create multiple botanical ingredients and capture their synergies, production of Harmoniance via ZFT is a “highly sustainable process,” explains Linda Foltis, Ashland’s vice president of care specialties R&D. “It is a farm-to-product process. We use the entire plant.”

The green attributes of the ingredient will be a selling point. “We see a shift in the attitude of baby boomers, who want graceful aging but are also more concerned about the environmental and ethical impact of their products,” Seiberg says. Millennials too, she adds, “want green and ethical products and perform online research prior to purchasing.”


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