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Cosmetic Science Meets Sex Appeal

Ingredient makers beef up testing for active ingredients to prove their effectiveness

by Marc S. Reisch
May 12, 2014 | A version of this story appeared in Volume 92, Issue 19

Legend has it that
 Juan Ponce de León trekked the Florida peninsula in 1513 searching for the fountain of youth. He never found it. Five hundred years later, cosmetic ingredient suppliers continue to explore for age-defying tonics.

Model with flawless skin.
Credit: Ashland
Antiaging ingredients promise consumers skin that appears youthful.

But any antiaging ingredients they discover today will likely go through more rigorous testing than in years past. Although such ingredients will come from the same plant, marine, and microbial sources as they did before, the performance they claim will have to be formally substantiated to meet new government guidelines.

Last July, the European Commission released guidelines that are expected to have great influence beyond the borders of the European Union. They require that ingredient performance claims “shall be supported by adequate and verifiable evidence.”

The U.S. Food & Drug Administration also wants more rigorous clinical testing of cosmetic ingredients. In nonbinding recommendations published in September 2013, FDA suggested that ingredients that claim to “cleanse, beautify, promote attractiveness, or alter the appearance” may need an Investigational New Drug (IND) designation.

Previously, the agency required an IND designation, which defines the way drugmakers must test new active compounds for efficacy, only for cosmetic ingredients that act like drugs because they affect the structure or function of the body. For instance, a new sunscreen not on FDA’s approved list needs to get an IND designation to be permitted for use in the U.S.

Chemical companies that make ingredients are taking action in response to both the government moves and requests from customers in the personal care industry for ingredients that really work. To support their hair-raising, wrinkle-erasing, and skin-toning claims—some of which can seem positively miraculous—ingredient makers are conducting more extensive lab and human studies than they have done in the past.

Behind the regulatory agency efforts are concerns that cosmetics make more promises than they can keep. “Consumers want cosmetics that give results,” says Nikola Matic, chemical and materials industry manager at the consulting firm Kline & Co. Whereas drugs require claim substantiation, “cosmetics are a comparative mess,” Matic says.

Even before the European regulations came into effect, ingredient makers were increasing their investment in clinical studies. LubrizolCroda, and BASF all used acquisitions to add active ingredients and testing capabilities to their portfolios. Today those three firms are the largest makers of specialty actives, Matic says. Other major suppliers include Ashland and Germany’s Merck KGaA.

Credit: Shutterstock
Wrinkles develop as collagen and elastin diminish in the dermis of aging skin.

Lubrizol bought botanical extracts maker Active Organics in 2011 and then gained expertise in clinical testing in 2012 with the purchase of Lipotec, a Spanish active ingredient maker. Croda bought Italian biotechnology-derived actives maker Instituto di Ricerche Biotechnologiche in 2012. BASF bought Cognis, which made a variety of personal care ingredients, including actives, in 2010.

Cosmetics company executives agree that more clinical testing of ingredients is a step in the right direction. But ingredient makers’ clinical studies “are just the beginning,” says Erik Schulze zur Wiesche, head of basic development for Henkel’s hair care business. Big brand marketers such as Henkel are putting the actives through their own battery of tests to make sure they have the qualities that are claimed, he points out.

Active ingredients such as sunscreens have been scrutinized closely by regulators for years. In the U.S., for instance, FDA defines how combinations of approved sunscreens are tested and rated according to the sun protection factor (SPF) system. Other ingredients, such as underarm antiperspirants and acne treatments, are regulated as over-the-counter drugs.

Suppliers of peptides, plant extracts, algae extracts, and other specialty active ingredients that are marketed as having youth-enhancing properties realize that greater regulatory scrutiny of their products is in the offing. Yet few people in the industry will go into specifics about how they expect the rules to look.

That may be because they don’t want to jinx a profitable niche in the $16 billion-per-year cosmetic ingredient market. Sales of specialty actives are expected to expand by more than 4% a year in the U.S. and Europe, where combined annual sales are now about $680 million. They’ll grow at a 10% annual rate in China, Kline’s Matic says, from a base of about $80 million.

Euromonitor International, a consumer marketing research firm, says actives are an important ingredient category. Use of such ingredients is on the rise as people age, incomes rise, and “the trend toward more youthful-looking skin” continues, says Anaïs Mirval, an ingredient analyst at the firm.

A recent walk down the aisles of a cosmetics store in New York City confirms the presence of numerous brands promising antiaging ingredients. C&EN found a 2-oz jar of StriVectin TL selling for $90. The cream claims that it “tightens, firms, and returns youthful neck and jawline contours.” The jar identifies the vitamin niacin and “protein tighteners” as active ingredients. StriVectin EV has vitamin C to fight age spots, sun spots, and dark spots on the skin.

Also on store shelves was Neutrogena brand Rapid Wrinkle Repair, which promises to reduce signs of aging in just one week. The line of serums and moisturizers, each of which costs just under $30, advertises the presence of retinol. “Retinol has been around a while, but it is trending now,” a saleswoman said, pointing to a number of brands on the store’s shelves.

Ingredient makers say they have clinical testing results that back up the ambitious claims their customers make on their jars and tubes.

Generally speaking, BASF will test a new ingredient on between 30 and 200 human subjects, according to Tony Jaillot, the firm’s European director for skin care. For its latest active, Perlaura, a water extract from the roots of the meadow bistort plant (Polygonum bistorta), BASF conducted studies on about 45 human subjects between the ages of 25 and 65.

Jaillot says Perlaura makes the skin appear more radiant by reanchoring the junction of the topmost epidermis skin layer and the dermal skin layer just below it. The antiaging active also restores the integrity of the skin, making it appear brighter and smoother within four weeks, he adds.

A sugar-based derivative of red seaweed is the basis for another BASF active ingredient called Slim-Excess. The derivative targets spermidine and spermine, two compounds important in fat metabolism, Jaillot explains. By blocking those compounds, Slim-Excess “redesigns the face contours within four weeks,” he says.

Sonia Dawson, marketing manager at Instituto di Ricerche Biotechnologiche (IRB), now part of Croda’s Sederma active ingredients unit, says her firm also conducts clinical evaluations, although “not to the same extent as a drugmaker.” For Sebuless, a concentrated extract from lilac intended to prevent the oily buildup on the skin that can lead to visible blemishes, IRB and its new parent company combined their expertise.

IRB developed the tissue culture techniques used to grow a lilac cell line and the methods for extracting the active ingredients. Sederma tested the lilac extract’s efficacy using proprietary “predictive cell models,” Dawson says. A consumer evaluation involving 100 panelists followed the in vitro tests, she notes.

Sederma and IRB similarly combined efforts to introduce Senestem, a derivative of the plantain plant (Plantago lanceolata), which is known for its anti-inflammatory activity, according to Dawson. Sederma tested compounds IRB extracted from the plant cells for their ability to mitigate certain microRNA activity in skin cells. That activity is in part responsible for loss of elasticity, wrinkles, and age-spot formation in mature skin, according to Sederma.

“We were able to show a visible cosmetic benefit for panelists aged 50 plus by minimizing microRNA’s impact,” Dawson says.

To test the activity of its newest active ingredient, Actigym, the Lipotec unit of Lubrizol drew on 60 human volunteers. Actigym consists of peptides and sugars isolated from a microbe living on the Dysidea etheria sea sponge gathered off the coast near Bermuda. The peptides and sugars trigger the release of adiponectin from fat cells, increasing mitochondrial activity and thus burning off fat, says Elena Cañadas, Lipotec’s marketing director.

In the test, one group of volunteers applied a cream containing Actigym, then some of them exercised regularly and others did not. Compared with a control group that exercised but rubbed a placebo cream on their bodies, both groups of Actigym users showed improvements in thigh and arm contours, Cañadas says.

Because Lipotec has the expertise to test cosmetic ingredients for their activity, it can also test new ingredients that sister firm Active Organics had previously tested at third-party labs. Patrick Bentley, Active Organics’ sales manager, says Lipotec helped with in vitro and in vivo studies of his newest product, ActiGuard S, an extract from sorghum bran.

Those studies, Bentley says, showed that the polyphenols in ActiGuard S could reduce skin inflammation. The in vitro studies helped Active Organics tweak its process to better extract the polyphenols most effective in modifying inflammatory pathways in the skin. Follow-up testing at Lipotec with volunteers confirmed that the extract could reduce skin inflammation, he says.

Clinical studies are also important at Merck, according to Michael Weiden, the firm’s vice president for pigments and cosmetics. “We don’t launch a product without proving efficacy,” he says. The firm typically tests its new cosmetic actives on 20 to 40 volunteers.

Although Merck has a pharmaceuticals business, “we don’t approach studies of cosmetic actives in the same way as we would studies of drugs,” Weiden explains. After all, he points out, cosmetic ingredients and pharmaceuticals are not the same.

But the actives sector is attractive to Merck. “We made the decision two years ago to strengthen our actives business and go for products with real efficacy,” Weiden says. Unlike acquisitive competitors such as Lubrizol and Croda, Merck has decided to beef up its business through licensing agreements with other firms and through its own in-house research.

At the end of March, Merck signed an agreement with the California-based biotech firm Laboratory Skin Care to license Hydroxysomes Calcium. The new active delivers calcium into the skin through a microcarrier delivery system. Merck says the calcium helps skin retain moisture and prevents wrinkles. The firm also signed an agreement last July with contract research organization Greenpharma to license a poppy seed extract with skin-firming abilities.

One product of Merck’s internal research is a new tanning ingredient, dihydroxy methylchromonyl palmitate, that supports melanin production in the skin without exposure to the sun. Merck describes it as a biological tanner and calls it Bronzyl. “It is not like dihydroxyacetone,” a chemical that causes skin to brown by reacting with amino acids, points out Anja-Martina Bohlmann, Merck’s cosmetics marketing manager.

Also working on internal development of active ingredients is Ashland, whose France-based Vincience unit developed a biofunctional skin pentapeptide, Neomatrix, to repair wrinkles. Joel Mantelin, Ashland’s global marketing director for skin care, says Neomatrix is a combination of five amino acids.

In vitro studies show that Neomatrix optimizes keratinocyte-fibroblast cross-communication leading to “dermal remodeling,” Mantelin says. A clinical study of 12 volunteers “showed highly statistically significant reductions in the number and average depth of facial wrinkles.”

Today such studies are the rule rather than the exception and are getting larger and more sophisticated. Compared with five years ago, “we are being asked to provide more clinical information” for active ingredient claims, Lubrizol’s Bentley says.

After all, some of those lofty claims can raise eyebrows. And with regulators and retailers looking for evidence that ingredient claims hold up under scrutiny, the pressure is on Bentley and his competitors to do more than just promise a fountain of youth.  


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