The latex from the rubber tree, which is the raw material of natural rubber, may now be used to produce an anti-wrinkle gel. This is the result of the integrated work of experts from university and corporate laboratories. A group of researchers from the University of São Paulo/USP in Ribeirão Preto, State of São Paulo and the research and development teams from two companies – São Paulo’s Pele Nova Biotecnologia and the State of Paraná’s O Boticário – have identified, isolated and tested a protein extracted from the raw sap of the Hevea brasiliensis. This protein allegedly softens the signs of aging on the skin: preliminary tests conducted on 60 women at or around the age of 50 indicated an 80% reduction of the wrinkles on the brow and around the eyes, after a month of daily use. A more extensive test, on approximately 300 women from the city of Curitiba, produced similar results. If the final technological development and production stages go smoothly, a new anti-aging gel, able to re-establish the production of the skin´s collagen and elasticity, might be available on the market for women (and men too, of course) this year.
The new anti-aging cream represents one of the latest applications of rubber tree latex, a whitish, milky liquid that has been the object of research studies at USP in Ribeirão Preto since 1994. With the support of chemist Antonio Cesar Zborowski, who works for a natural rubber company located in the region of São José do Rio Preto, two doctors from the university – Joaquim Coutinho Netto and Fátima Mrue – created esophagus prostheses made from natural rubber and implanted them in dogs. They concluded that this material probably contains substances that stimulate the growth of blood vessels and tissues, when they noticed that after nearly one month the dogs expelled the prostheses and their esophagus had been reconstructed. The findings attracted the attention of Ozires Silva, the former president of Embraer airplane manufacturer and of Varig airline company, who at the time was the president of Pele Nova. This company licensed the patent in 2002 and began to produce the latex membrane two years later. The latex membrane was first used to heal injuries, especially on the feet of diabetic patients. This is the only use of the biomembrane, whose trade name is Biocure, and which has already been approved by government regulatory authorities.
“We realized that we did not have the competency to conduct all the necessary tasks”, says Marcos Silveira, president-director of Pele Nova. He outsourced sales and distribution to a company specialized in pharmaceutical products and concentrated his company’s efforts on the research and development department, located in Ribeirão Preto, near the USP campus. Coutinho and Silveira continued working on the project (Fátima Mrue went back to the Federal University of Goiás after getting her doctorate degree in Ribeirão Preto) and agreed that they would have to find the components of latex to prevent the membrane from being treated as a combination of ingredients whose effects could not be explained.
Two years ago, after having extracted and analyzed the compounds of different particles of latex, Coutinho found a protein, which he named F1, and showed it to Silveira, who asked if the protein could work as a cosmetic. The conclusion, after many tests and challenges – for example, how to make the protein pass through the outer layers of the skin – is that the molecule could soften wrinkles and stimulate the formation of blood vessels. Silveira did his part by bringing together the research and development team from Pele Nova; the company had already filed for six patents based on the initial patent, licensed by USP. Pharmacist and biochemist Luiz Kosmiskas was asked to develop protein purification techniques and engineer Katherine David, who had already worked for a French cosmetics company, was asked to head the large-scale production of the F1 at the Pele Nova plant in Ribeirão Preto.
In view of financial limitations, as the research of a new medical drug costs hundreds of millions of dollars, according to estimates of the pharmaceutical industry, Silveira went looking for companies that would be willing to share the risks and the results of the development of products with latex. He finally contacted O Boticário, which tested the F1 protein in vitro and on people. “We verified the safety and efficacy of the product”, says Carlos Praes, the company’s technology products manager. “This was the first time that we had developed a new material with a partner”. Strictly speaking, the work was conducted with two partners, because the experts from the companies and from USP talked and agreed on some important details – for example, the protein should not be purified too much in order to prevent the loss of other useful properties. According to Praes, the final formula contains approximately 30 other components that contribute to the efficiency, sun screening and smearing properties of the product, and provide the pleasant scent of the gel based on the sap of the rubber tree. The next step will be to obtain the approval of the Agência Nacional de Vigilância Sanitária/Anvisa regulatory agency.
The inventors of the gel know that they did not create a long-life product that would produce continuous profits in the manner of aspirin or the BIC pen. “Cosmetics have a short life span, while medical drugs last an average of ten years”, says João Batista Calixto, a researcher at the Federal University of Santa Catarina/ UFSC. Calixto identified anti-inflammatory substances in the Passiflora alata, a passion fruit species. This inspired Natura to create a compound that helps prevent signs of aging. “Of the 750 products in our portfolio”, says Daniel Gonzaga, director of research and development at Natura, “one third are renewed every year”. According to Gonzaga, products such as this one, which entered the women’s beauty care market in 2007, can take up to three to four years of work, cost from R$ 3 million to R$ 4 million and open up perspectives for other uses. “Passiflora could be exploited to a much greater extent by the pharmaceutical industry, because of its anti-inflammatory properties”, says Gonzaga. Natura has the license from the UFSC to use the compound in cosmetics only.
Acting as an anti-wrinkle product is not the only destiny for the F1. Silveira, who has partnered with another company by transferring part of the data assigned by Natura, intends to use this molecule to stimulate hair growth. According to Silveira, the initial tests conducted on thirty men for six months showed that this protein can lead to hair thickening and growth. Coutinho Netto is also exploring the possibility that one of the proteins from the latex sap might stimulate the growth of stem cells for the reconstruction of tissues and organs.
“The rubber tree latex is a powerful material”, says Coutinho Netto. Characterized as a long chain of chemical compounds called isoprenes, which supports the proteins that are slowly released, the membrane has already been used to replace eardrums destroyed by infections in approximately 300 people. It has also been used as the raw material to regenerate the esophagus, bladder, tooth tissues and arteries with a diameter of at least 0.5 centimeters in lab animals. “We lack specialists who can design and build prostheses”, he says. “We have to do everything in the lab”. There are two reasons why latex can be used for many different things: the versatility of the material and Coutinho’s efforts to combine basic and applied research. “The membrane has entered the market, but it hasn’t left the university”.
As a result, the membrane is now an open innovation – explored by many specialists in many different ways at the same time, with shared results and benefits. At the Federal University of Alfenas/Unifal, in the State of Minas Gerais, pharmacist Pablo Gomes Ferreira demonstrated that the membrane stimulates the proliferation of blood vessels, the increase of muscle and collagen fibers, the regeneration of tissues and the production of molecules that stimulate cell growth. These results explain his own experiment – an evaluation of the effect of the latex membrane to induce the recovery of the abdominal wall in rats – and reinforce the argument for the innovative uses, such as the anti-wrinkle gel or potential uses, such as the production of stem cells.
In a preliminary study conducted on 12 people in the city of Goiânia, at the Federal University of Goiás/UFG, nurse Geovana Eloisa Quege verified that the rubber latex film functioned in a similar manner as the most widely used drug, based on fatty acids, to heal infected chronic wounds in patients who had had leprosy. This study also showed an inconvenient property of the membrane: the absence of porosity, which can make the outflow of liquids released by the wounds more difficult. “No dressing solves everything”, says UFG professor Maria Márcia Bachion, Geovana’s academic advisor. Silveira agrees that the lack of porosity is a limitation of the membrane, but he intends to solve this issue by means of a gel with the same properties, the development of which the Pele Nova company expects to conclude this year.Republish