The owners of Central Brasileira de Comercialização e Distribuição de Rã (Brazilian Center for Frog Commercialization and Distribution) have always heard stories about the healing and anti-inflammatory power of the so-called “frog oil”, which is extracted from the bags of fat found in the intestines of the Rana catesbeiana Shaw species. Francisco Hikichi, one of the company owners, has a friend in the State of Rio Grande do Norte, in northeastern Brazil, who calls the oil “asmarana” and used to prescribe it for treating respiratory diseases such as asthma and bronchitis. Onessi Rolim de Freitas, the other partner, has a friend who treats sunburns by spreading it on the skin. He himself has something to say about it: diabetic, he has used the oil on wounds that wouldn’t heal and assures the results were “encouraging.”

Determined to investigate the pharmacological properties of frog oil, Hikichi and Rolim resorted to the Technological Innovation in Small Businesses Program (Programa Inovação Tecnológica em Pequenas Empresas, PIPE), the program of the State of São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo, Fapesp) that gives support to small innovating companies. The research project funded by the program had two phases and lasted a total of two and a half years. When it ended the partners had the answer they were hoping for: frog oil indeed helps treating wounds and inflammations. Enthusiastic with the results, they requested a patent for the technique used to extract the oil and proceeded to sell it as raw material for medicines and cosmetics. In one of the sales, to a manufacturer of hair products from Campinas, in the State of São Paulo, they got about US$ 280 for two liters (a little more than half a gallon) of the oil; they sell the kilogram (2.2 lbs) of frozen frog meat, the company’s core business, for about US$ 15.50. Two get a liter of oil 220 frogs are necessary, compared to an average of just eight frogs to get a kilogram of meat. But considering that the oil would otherwise be simply discarded, its commercialization – and of its by-products – becomes quite attractive.

The benefits of frog oil are many: as the research funded by PIPE showed, the substance is not toxic and can be easily and cheaply extracted. Those characteristics led Hikichi and Rolim to submit one more project to Fapesp – this time for PIPE’s Phase III, to be funded by the agency in partnership with the venture capital company Imprimatur. If the project is approved, Central Rã is going to use the resources from the program to develop its own products from the oil, such as sunscreens, for instance.

The beginning

Rolim started to raise frogs in his farm in 1999, when he retired from Telefônica, one of Brazil’s private phone companies. With a degree in computer science from the State University of Campinas (Universidade Estadual de Campinas, Unicamp), he had worked in the company’s computing area. “Then one day I realized I had 8,000 frogs,” he recalls. Even though he was familiar with the difficulties of selling frog meat in Brazil – a delicacy that is still not very popular in the country – he created a company with two other partners to sell his production. Called Max Rã (Max Frog), the company headquarters were in Campinas and its slaughterhouse in neighboring Atibaia, from where the frozen meat was distributed.

Business began to prosper and attracted the attention of large frog producers from the State of São Paulo, among them Hikichi, who had owned a frog farm in Ubatuba, on the São Paulo coast, for more than 30 years. In 2001 several producers joined Rolim to form Central Rã. The partners, however, left the company one by one – some moved to other cultures, such as mushrooms; another left because of problems with sanitary surveillance – until finally only Hikichi and Rolim stayed on.

Central Rã operates today in Hikichi’s own residence in the city of São Paulo. The company is established in the Butantã neighborhood, not far from the University of São Paulo (Universidade de São Paulo, USP) campus, and is limited to one secretary and three large freezers, in which the meat is stored – autonomous salesmen are in charge of the sales. The slaughterhouse in Atibaia has been discontinued. When they need to renew their stock of frog oil, the partners ask their suppliers – one of them from Tucunduva, in the State of Rio Grande do Sul – to set apart the animals’ fat in packs of approximately two kilograms each.

PIPE is discovered

In 2003 Rolim and Hikichi went to USP to check into the possibility of using frog skin to manufacture objects. “The young woman we talked to had a bruise in a finger,” Rolim recalls. When he saw the bruise, Hikichi recommended that she treated her finger with frog oil. “Spread some of the oil on it,” he said. A week later, when they went back to the same office, the young lady showed them her healed finger. She then suggested that they conducted extensive research on the oil’s pharmacological properties and told them about the Centro Incubador de Empresas Tecnológicas (Incubating Center for Technology Companies, Cietec), located on campus.

Until then neither of them had ever considered the possibility of commercializing the oil, and were totally unfamiliar with the scientific literature about it. So they went to Cietec – and there they discovered how PIPE operates. Their project’s well-designed structure and Cietec’s physical space encouraged them to lay out their first research and development project.

Phases I and II

Through Cietec’s files Central Rã research plans ended up with Jayme Antônio Sertié, a professor at USP’s Instituto de Ciências Biomédicas (Institute of Bio-medical Sciences, ICB), who was already investigating healing and anti-inflammatory properties from different sources, such as plants. Professor Sertié contacted Hikichi e Rolim and was eventually invited to head the project that the company was going to submit to PIPE.

Fapesp approved the project and gave approximately US$ 22,000 for Phase I, designed for the viability study. With the money Central Rã was able to attest scientifically the efficacy of frog oil to heal wounds and treat inflammations. That ensured the approval of the second phase of the project and funds of about US$ 120,000. The company conducted more thorough tests with the oil and got positive results once again.

Both phases had the participation of USP’s Master’s Degree and PhD candidates, as well as of outsourced professionals. The room at Cietec where the research was conducted is now empty, but Rolim draws in the air the position of each piece of equipment. Next to the counter in the center of the laboratory was the plate where the frog fat was heated until the oil was released. The two freezers used to store the fat were placed against one of the walls. On the other side there was a sterilizer, a centrifugal machine and a precision scale, as well as a number of smaller devices.

If it’s approved, the project’s third phase won’t be coordinated by professor Sertié. According to Rolim, the company was interested in continuing the partnership with him – proof of that is that it invested its own funds to hire the professionals he had asked – but things didn’t work out. Professor Sertié was given the equipment purchased in the first two phases, so now the company will have to set up a new lab in order to carry the project on.

A new coordinator

Hikichi and Rolim called Fabiana Medeiros da Silva, a researcher who is one of the owners of the clinical analyses laboratory Biosíntesis, to replace professor Sertié in PIPE’s Phase III. “I was a pupil of professor Sertié at ICB and was familiar with his work,” she says to justify her being chosen to coordinate the project. Another point in her favor is the fact that Central Rã and Biosíntesis are both at Cietec.

One of the areas in which Silva works at Biosíntesis is the development of efficient methods of analysis using animals as little as possible in clinical essays – the objective is, if possible, the complete elimination of in vivo tests, like what took place with the European Union’s cosmetics industry. This know-how may also be useful to Central Rã, since the research the company has conducted so far has been based on in vitro cell cultures and on essays with mice and rabbits.

Perspectives

In PIPE’s first two phases, Silva explains, Central Rã investigated the oil’s healing power and its activity against inflammations and gastric ulcers. The company also analyzed the toxicity of the substance in topic and oral uses – that is, if there has been irritation on the animal’s skin or cell lesions, in accordance with the amount used and the response obtained, thus establishing an adequate dose. “By the parameters we’ve used toxicity was virtually absent,” she says. “That means that side effects – if there is any – are very low,” completes Silva. But she controls her optimism: “The first two phases are for basic research. Now the time has come for us to think how to turn the oil into a product.”

One thing is certain though: since cosmetics and medicines must go through a long, complicated process of tests determined by Brazil’s National Sanitary Surveillance Agency (Agência Nacional de Vigilância Sanitária, Anvisa) before reaching the market, Central Rã is going to concentrate exclusively on products for topic use for the time being. The company has prepared the business plan required for approval for PIPE’s Phase III, but admits that it is unable to assess the prospects for profits. The tendency is for the final products to be well accepted and have low cost, since frog oil has been proven to cause few side effects and is a cheap raw material.

Because the focus of PIPE’s Phase III is the development of bio-products, and not just research, the owners of Central Rã have already started the process to create a new company. While they wait for Fapesp’s approval of the project, a consultant has been working on negotiating possible alliances with large pharmaceutical laboratories and capital investors as part of the effort to make possible the development of a product and, more than that, to launch it in the market.