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ents 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 skintoning 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 ef-
forts are concerns that cosmetics make more promises than they can keep. “Consumers want cosmetics that give results,” says Nikola Matic, chemical and materials FLAWLESS Antiaging industry manager at the consulting firm ingredients promise Kline & Co. Whereas drugs require claim consumers skin that substantiation, “cosmetics are a comparaappears youthful. tive mess,” Matic says. Even before the European regulations came into effect, ingredient makers were increasing their investment in clinical studies. Lubrizol, Croda, and BASF all used acquisitions to add active ingredients Cosmetic ingredient makers embrace testing to and testing capabilities to their portfolios. prove the effectiveness of BIOCHEMICAL ACTIVES Today those three firms are the largest MARC S. REISCH, C&EN NORTHEAST NEWS BUREAU makers of specialty actives, Matic says. Other major suppliers include Ashland and Germany’s Merck KGaA. LEGEND HAS IT THAT Juan Ponce de in September 2013, FDA suggested that Lubrizol bought botanical extracts León trekked the Florida peninsula in 1513 ingredients that claim to “cleanse, beaumaker Active Organics in 2011 and then searching for the fountain of youth. He tify, promote attractiveness, or alter the gained expertise in clinical testing in 2012 never found it. Five hundred years later, appearance” may need an Investigational with the purchase of Lipotec, a Spanish accosmetic ingredient suppliers continue to New Drug (IND) designation. tive ingredient maker. Croda bought Italian explore for age-defying tonics. Previously, the agency required an IND biotechnology-derived actives maker InstiBut any antiaging ingredients they disdesignation, which defines the way drugtuto di Ricerche Biotechnologiche in 2012. cover today will likely go through more rigmakers must test new active compounds BASF bought Cognis, which made a variety orous testing than in years past. Although for efficacy, only for cosmetic ingredients of personal care ingredients, including acsuch ingredients will come from the same that act like drugs because they affect tives, in 2010. plant, marine, and microbial sources as the structure or function of the body. For Cosmetics company executives agree they did before, the performance they instance, a new sunscreen not on FDA’s apthat more clinical testing of ingredients is claim will have to be formally substantiated proved list needs to get an IND designation a step in the right direction. But ingredient to meet new government guidelines. to be permitted for use in the U.S. makers’ clinical studies “are just the beginLast July, the European Commission reChemical companies that make ingredining,” says Erik Schulze zur Wiesche, head leased guidelines that are of basic development expected to have great for Henkel’s hair care WEATHERING Wrinkles develop as collagen and elastin diminish in the influence beyond the business. Big brand dermis of aging skin. borders of the European marketers such as Younger skin Older skin Union. They require that Henkel are putting Deep ingredient performance the actives through wrinkle claims “shall be suptheir own battery of ported by adequate and tests to make sure verifiable evidence.” they have the qualities Epidermis The U.S. Food & that are claimed, he Drug Administration points out. Dermis also wants more rigorActive ingredients ous clinical testing of such as sunscreens Hypodermis cosmetic ingredients. have been scrutinized In nonbinding recomclosely by regulators Elastin Collagen Fibroblast mendations published for years. In the U.S., SHU TTERSTOCK
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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 billionper-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 CEN.ACS.ORG
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(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 sea-
weed 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
FOUNTAINS OF YOUTH Specialty actives are a growing segment of the cosmetic ingredients market. Biotech products Hyaluronic acid; ceramides Botanicals Unsubstantiated extracts; substantiated actives Proteins & peptides Botanical proteins, synthetic peptides Enzymes & coenzymes Coenzyme Q10; free-radical scavenging enzymes Marine ingredients Substantiated algae extracts, chitosan
2013 market in U.S. and Europe:
>4%
$680
Growth rate per year
million
SOURCE: Kline & Co.
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 AnjaMartina 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 crosscommunication 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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