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Successful partnership

Outside researchers help Natura to innovate

YAMADA TARO / GETTY IMAGESCombining academic knowledge with the needs of Natura, Brazil’s largest cosmetics manufacturer, has resulted in encouraging results that benefit both sides. New kinds of aromatic species from the Atlantic coastal rainforest with the potential to yield essential oils and medicinal products, active principles extracted from plants and algae with antioxidant properties for the development of cosmetics, plus new techniques and simpler, cheaper analytical processes for the evaluation of the efficacy of products are among the examples of this successful partnership agreement. “It’s the type of collaboration in which everybody wins,”  says professor Anderson Zanardi de Freitas, from Ipen, the Institute of Energy and Nuclear Research and winner of the Natura Campus 2010 Award for Technological Innovation with the project “Evaluation of the use of optical coherence tomography in dermatology.”   “The company invested in the development of the technique at the Ipen labs with entirely domestic technology in order to conduct product efficacy tests. It has also hired one of my PhD students to work in this field within Natura,”  says Freitas.

The firm’s first contact with Freitas took place in 2006, after a Natura researcher became aware of the technique known as optical coherence tomography during a dermatology congress in the United States. ‘It’s a non-invasive technique that lets you see a real time image of biological tissues with the same resolution of an optical microscope,” explains Freitas, who was doing his PhD in the field at that time. “The result of my doctorate was the first optical coherence tomograph in Brazil,”  he says. Natura contacted the researcher because it wanted to develop a methodology to test the efficacy of its cosmetic products. “The tests used to be conducted in Germany because there was no such technology in Brazil,”  Freitas explains. The project led to developing a methodology and a software program that can assess product efficacy in real time. As a result, the firm sped up the evaluation process and cut costs, as the tests in Germany cost five times as much. “Natura acquired a commercial tomography system and opened a line of optical tomography research, which I think is the project’s chief achievement,”  says Freitas. The researcher believes that placing first in the Natura award, first introduced in 2007 and bestowed every two years, was due to how easily the technique can be used. Though complex, it has no secrets in terms of its industrial applications.

Natura achieved the top slot in the pharmaceutical and cosmetics sector in the ranking of the 25 Brazilian companies chosen for revenue and best performance in the decade, as published in the special issue of the business newspaper Valor Econômico in 2010. The company reached a net revenue of R$5.1 billion in 2010, 21.1% greater than in the previous year, according to the publication. Brazil’s second-ranking cosmetics company, O Boticário, reached a net revenue of R$422.8 million in 2009 , when it grew by 15.8% relative to the previous year, according to the publication.

Brazil ranks third among the 10 largest consumer markets for hygiene, perfume and cosmetic products, with a turnover of US$37.4 billion last year, or 10% of the global figure of US$374.3 billion, according to data from the company Euromonitor International. The United States heads the list, with US$59.8 billion, followed by Japan, with US$43.8 billion.

068_Natura_NOVO_183Daniel das NevesThe development of a standard methodology for in vitro tests used by the dermatological and cosmetic industry to assess the safety of new active principles led professor Maria Vitória Bentley, from the School of Pharmaceutical Sciences in Ribeirão Preto, at the University of São Paulo (USP), to place second in the Natura Campus awards. “In in vitro tests using animal membranes or human skin, we were able to evaluate to what extent a given substance penetrated the skin, in which layer of the skin it was retained, and whether it might even undergo systemic absorption,”  says the researcher, who coordinates the Center for Skin Permeation Research at the university and  has been working in this field for the last 20 years. Three years ago, Natura invited Maria Vitória to conduct an interlaboratories study that involved the USP laboratory, regarded as a benchmark reference in this field of research, a private-sector laboratory and the company itself. “Each party conducted tests in its own lab. These were then compared and, based on the results, we established a standard, validated methodology for cosmetic products to be evaluated in the same way regarding their permeation of the skin.”  The importance of the work had some impact upon Anvisa, the National Sanitary Surveillance Agency, which is now preparing a review of the standards required for products from the pharmaceutical and cosmetic industry for use on the skin, with the collaboration of professor Maria Vitória. The methodology allows one to evaluate, for instance, the efficacy of a controlled release system for active principles using nanotechnology, such as anti-wrinkle creams and other products.

Essential oils
The partnership agreement between Natura and the outside researchers also encompasses immersion in the biota of the Atlantic rainforest, as was shown by an extensive study conducted by professor Márcia Ortiz, from IAC (the Campinas Institute of Agronomics) in inner-state São Paulo. The study, which took 25 people three years to complete, involved experts from several fields of knowledge as well as from the company, to select essential oils from native species with olfactory potential and biological activity. The research, which had begun timidly within IAC, picked up steam in March 2003, when the first joint public notice was released by Natura and FAPESP for research into biodiversity, with funding provided by Pite (the Technological Innovation Partnership Program). The program has since financed 10 research projects, of which eight have been completed and two are under way. The Foundation’s total investment was R$ 1,374,696.27.

Catiguá-morcego (Guarea macrophylla): olfactory selection

ANDRE BENEDITOCatiguá-morcego (Guarea macrophylla): olfactory selectionANDRE BENEDITO

“Pite was a major landmark and inspired the company to introduce, in 2006, Natura Campus, a continuous flow program,” says the biologist Gilson Manfio, the company’s innovation manager. For this type of grant, the partnership arrangements can be set up in various ways. Some of the themes that are of interest for partnered research projects are posted on the website, but the company also sends its representatives to universities or proposes collaboration with researchers it chooses. “If there’s an interesting line of research, we go after the project to propose a partnership agreement,”  says Manfio. The company may also obtain a license for technologies that are ready. The program focuses on four areas: sustainable technologies, raw materials with sensory properties (smell-related), active principles for skin and hair, and research centered on consumer wellbeing.

“Bioprospection of the aromatic potential of native Atlantic rainforest species involved not only the chemical, olfactory, genetic, taxonomic and plant physiology aspects, but also the propagation of the selected species,”  says Marcia, who ended her project in 2008 and won third place in the aforementioned awards. The proposal she presented aimed to select samples in the native areas preserved by the institution. IAC is part of Apta, the São Paulo Agency of Agribusiness Technology of the São Paulo State Bureau of Agriculture and Supplies, which has more than 20 farms, many of which harbor native areas. Because of its multidisciplinary nature, the study brought together experts from the field of botany, phytochemistry, physiology and genetics. In the first stage, which took seven months, more than 100 species were selected out of various botanical families, based on olfactory criteria. After extraction of the essential oils from all the species, the company conducted an olfactory assessment and IAC verified the chemical composition and the antimicrobial and antioxidant activity of the essential oils.

In the second stage of the project, the researchers went into the field again to collect new samples of the selected species, both at sea level and in the state’s central area. The aim of this was to find out whether the chemical composition of the essential oils was influenced by genetic or environmental factors. “The main doubt was whether the species selected could be found in different places and had different chemical compositions,”  says the researcher. The answer is yes, they did. The study also encompassed identifying species, observing the environments in which they occurred in the field, and assessing their abundance, frequency and demographic dynamics in different populations. At the same time, a chemical and genetic variability study was conducted via a molecular marker for each species.

Sérgio Gallucci, who manages research in the area of the company that focuses on the development of ingredients with sensorial properties, says that the proposal was successful, but that there is still a long path ahead. “For the selected substances to become a product, several complementary studies are needed,”  says Gallucci. Out of the initial 100 species, 11 with potential for cosmetic and medicinal use were selected. “As it’s a new ingredient, we have to be sure about its safety for humans.”

Cachuá (Trichilia elegans): essential oil

IACCachuá (Trichilia elegans): essential oil IAC

Waste reused
Another project involving a native species of the Atlantic rainforest , popularly known as passariúva (Sclerolobium spp.) and used in coal stores, also financed by FAPESP jointly with Natura, showed that the leaves of this tree contain antioxidants and can be used in cosmetic formulations. The plant was chosen because its leaves are discarded waste and also because trials conducted as part of the FAPESP Biota project indicated its antioxidant potential. “We chemically characterized the plant’s extract and demonstrated its antioxidant potential,” says the project’s coordinator, professor Alberto José Cavalheiro, from the Institute of Chemistry of Paulista State University (Unesp) at Araraquara in inner-state São Paulo. “Additional toxicology assays were conducted that proved the safety level was as required for use in skin formulations,”  Cavalheiro tells us. These were unprecedented results and led to a patent. Part of the research was completed in 2007 and delivered to the company, which is in charge of developing the end product. The process may take as long as five years.

“Sometimes plants are not abundant enough for product launches,”  says Gallucci. “In 50% of the cases we have to set up a vegetable supply chain.”  As an example, he mentions certain successful products, such as those made from Brazil nuts, which have an established agronomical chain, or from the pitanga [also known as Surinam cherry], for which it was necessary to establish an agreement with producers in order to get the raw material, which consists of the pitanga tree leaves in sufficient quantity to yield the requisite volume of active ingredient. “The research with the pitanga began in 2002, but the product was only released in 2004,”  he tells us. Even when there is a supply chain already in place and research with promising results, the product may fail to win over the consumer.

This was the case with the bush known as pariparoba (Pothomorphe umbellata) from the Atlantic rainforest that, according to studies conducted by the School of Pharmaceutical Sciences at the University of São Paulo, offered protection against UVB ultraviolet rays, which are those that damage the skin the most. The discovery resulted in a patent request and awoke Natura’s interest. The company obtained a license for using the plant’s root extract in cosmetic products (see more about this in Pesquisa FAPESP issue 105). In 2007, Natura launched a facial treatment product made from pariparoba as part of its Ekos line, which is based on Brazilian biodiversity. “The product was discontinued after a while because in was unsuccessful in the marketplace,”  says Manfio.

On the other hand, Chronos Passiflora, an anti-aging cream whose raw ingredient is passion fruit, developed jointly by professor João Batista Calixto, from the Pharmacology Department at the Federal University of Santa Catarina (UFSC), and Natura, has been successful since its launch in 2009. “All the research proving the product’s benefits was conducted by professor Calixto,”   says Manfio. It was up to the company, however, to develop the passion fruit supply chain. Calixto’s research group has also taken part in the development of the first Brazilian phytotherapic anti-inflammatory drug , Acheflan, released in 2005 by the pharmaceutical company Aché.

Biodiversity also involves research with macro algae of the Brazilian coast. “One of the extracts obtained showed excellent potential for use in solar protection formulations,”  says professor Pio Colepicolo Neto, from the Biochemistry Department of the Institute of Chemistry at the University of São Paulo (USP) and coordinator of a Pite project partnered with Natura. One of the substances found in the Brazilian macro algae are mycosporine-like aminoacids, a chemical compound of low molecular weight synthesized by algae and fungi, with a high capacity for absorbing ultraviolet radiation. These aminoacids were isolated and have been characterized by Colepicolo Neto’s group. Natura has conducted stability tests and substance cytotoxity assays on cell cultures, which are required to evaluate the biocompatibility of materials.

External network
Natura currently has partnership arrangements with 18 Brazilian universities in nine states. “There is direct interaction with the researchers and grant holders in the external network, which involves a large number of people.”  The company’s R&D area has 250 in-house researchers. Its largest laboratory, covering an 80 thousand sq. m area, is in Cajamar, in the Greater São Paulo area. The company also maintains a laboratory in the city of Belém, Pará state, which is connected with its soap factory in Benevides, near the sources of raw materials used in its soaps and essential oils. Natura has a third laboratory in Paris, France, which aims to develop new cosmetic technologies. “Over there, the Natura researchers conduct projects jointly with French institutions,”  says Manfio.

The company’s business model, i.e., investing in innovation based on substances from Brazil’s biodiversity, has been undergoing diversification. “This year, we’re going to expand our parterships with new models,”  says Manfio. One example of this is an agreement reached with LNBio (the National Biosciences Laboratory), one of the three laboratories connected with the National Center for Research into Energy and Materials, along with the National Synchrotron Light Laboratory and the Bioethanol Technology Center, in Campinas, inner-state São Paulo. This partnership agreement provides for the establishment of a high performance screening platform to test active principles for skin and hair. Natura sponsors the research center within the laboratory and shares the use of the facilities with LNBio.

The projects
Bioprospection of the aromatic potential of native aromatic species from the Atlantic rainforest biome in the state of São Paulo: occurrence, taxonomy, chemical, genetic and physiological characterization of populations (nº 2003/08896-1); Type Pite Program – Joint Research into Technological Innovation; Coordinator Márcia Ortiz Mayo Marques (IAC); Investment R$ 228,660.74 (FAPESP) and R$ 207,301.34 (Natura)
2. Validation of Sclerolobium spp. as a source of natural cosmetic antioxidants (nº 2003/08863-6); Type Pite Program – Joint Research into Technological Innovation; Coordinator Alberto José Cavalheiro (Unesp); Investment R$ 45,000.00 (Natura) and R$ 45,000.00 (FAPESP)
3. Marine algae from the Brazilian coast: isolation and characterization of bioactive substances with a potential for use in cosmetic formulations (nº 2003/08735-8); Type Pite Program – Joint Research into Technological Innovation; Coordinator Pio Colepicolo Neto (USP); Investment R$ 95,000.00 (Natura) and R$ 95,800.00 (FAPESP)