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Climbing the ladder to success

After the anti-bacterial ointment for treating burns, Silvestre Labs makes biomaterial for bone replacement

Miguel BoyayanThe basic material of Extra Graft is hydroxiapatite, one of the components of bone, and a collagen mesh. The product induces cell and bone growth, especially in the case of injuriesMiguel Boyayan

The IBI Brazil innovation index named Silvestre Labs one of the country’s most innovative companies due to its successful track record in the field of research and development, a reputation that has been built up over the last 20 years. A manufacturer of pharmaceutical products in the Bio-Rio technology complex, the company recently launched Extra Graft X-13, a bio-compound that helps cell growth. This compound is used to fill in and replace bone matter in the case of bone injuries. The IBI was established by the Uniemp Institute and by the State University of Campinas (Unicamp), with FAPESP support (see issue 136 of Pesquisa FAPESP).

Extra Graft can, for example, substitute a platinum plate, with the advantage that it does not have to be replaced. It can also induce the growth of bone tissue where it is applied. “The product is the result of a project developed at Unicamp, under the coordination of professor Benedicto Vidal”, says Eduardo Cruz, president of Silvestre Labs. “After a careful analysis of the project, we realized that there was an opportunity to develop a product.”

Hydroxyapatite, a bone component, is one of the bio-material’s raw materials, along with a collagen mesh, both of which come from animal sources. The company and Unicamp own the Extra Graft patent, and the product has already been launched in the Brazilian market. Silvestre Labs is waiting for registration from the FDA (the United States Food and Drug Administration that supervises and regulates foods and drugs), the European Community and China to place the product on the international market. An agreement involving the exchange of knowledge has already been signed with the Chinese. A biotechnology company from Shanghai, created by a group of researchers who graduated from Harvard University, has made significant progress in the field of gene therapy. The Chinese proposed to provide Silvestre Labs with direction regarding gene therapy, acquiring the Extra Graft technology in exchange. Initially, the product was launched for use only in dental injuries, but, as the project progressed, the product was also used in operations involving the reconstitution of facial and skull bones. “When in contact with osteoblasts, the young bone tissue cells, the product induces cell growth, functioning as a matrix for bone growth,” says Cruz.

This is the first bioengineering product launched by the company, which began its activities in 1984 as a pharmacy that prepared prescription drugs. The company currently has over one hundred employees, of whom eight have master’s degrees and four have doctorates. Being ranked as the top company in the average and high technological intensity category by the IBI “was a pleasant surprise, because the company has never received any government support in the last 20 years to fund its research”, says Cruz.

Pharmaceutical industry
The vocation of Silvestre Labs to develop products and become a pharmaceutical company started in 1990, when the Bio-Rio complex was opened on the campus of the Federal University in Rio de Janeiro/UFRJ and the company moved to a new address. At that time, Cruz was at medical school, having previously been a pharmaceutics student at the University of São Paulo. He graduated from UFRJ, where he also specialized in biochemistry. “Something that attracted my attention when I was in medical school was that at the burn treatment center at the Andaraí hospital, many of the patients died because of the lack of an imported drug,” he says.

This is why the company’s first challenge in this new phase was to obtain the molecular synthesis of the main compound of the imported drug used to treat the infections of burn patients whose bodies had been extensively damaged. Data from the Health and Civil Defense Bureau of the State of Rio de Janeiro states that approximately 80% of burn patients’s deaths arise from infections. The result of Silvestre Labs’ research project was obtaining a specific synthetic product patented by a US company and the formula of a pharmaceutical product in the form of an ointment, which was named Dermazine. The product’s main ingredient is silver sulphadiazine, a powerful anti-bacterial agent. “When we started using this product at the Burn Center, we witnessed a 50% drop in the mortality rate of severely burnt patients,” Cruz reports.

Toxic complex
In spite of these positive results, the other 50% of the patients did not respond to the treatment. “Even though we control the bacteria, many of the burn patients die because of immunological causes and inflammations, “explains Cruz. “This is due to the significant immune and inflammatory disturbances related to the formation of toxins in the skin because of thermal energy action.” The thermal energy on the burnt skin produces a type of toxic lipoprotein complex that leads to immunological complications in severely burnt patients. The Silvestre Labs researchers were part of an international group that discovered these toxins. The group included professor Brian Sparkes, from the Canadian Defense Department, professor William Monafo, from Washington University in Saint Louis, and by the team led by professor Frank Allgower, from Switzerland’s Zurich University.

“During our studies, we also discovered that these toxins also form in other kinds of injuries, but for different reasons,” says Cruz. Based on this knowledge, the company developed another compound, based on silver sulphadyazine and cerium nitrate. The combination of cerium nitrate with silver sulphadiazine increases the anti-bacterial action. When the product is applied to the burn, the anti-bacterial ointment, whose commercial name is Dermacerium, removes the toxic proteins that prevent the burn from healing.
Until ten years ago, hospitals were the company’s only sales channel. At that time, the company decided to place its products in drug stores. This decision fueled sales very quickly and took the company to another level. As a result, three years ago the company decided to transfer the promotion and distribution of its products to Farmasa – Laboratório Americano de Farmacoterapia. At the same time as launching its other products onto the market, the company started investing in other lines of research, such as malaria, leprosy, recombining protein, stem cells and bio-engineering.

Stem cell research, one of the research projects, resulted in a spin-off (a smaller company deriving from another company), more specifically, a company named Cryopraxis, the biggest umbilical cord bank in Latin America. Cryopraxis is based in the Bio-Rio complex. The company has a cell manipulation unit, especially of stem cells for heart surgery. Stem cell research resulted in another venture, Cell Praxis, a division focused on cell therapy for the heart muscle, headed by researchers from the Federal University of São Paulo/Unifesp and from the Dante Pazzanese heart institute. In 2001, recombining protein research generated another company, also based at the Bio-Rio complex, called Chron Epigen and focused on the research and development of new drugs.