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Bank of extracts from Brazilian plants is going to help in the search for new medicines

Extracta Moléculas Naturais, of Rio de Janeiro, has become the first private company to achieve a special authorization to extract plants with a medicinal potential from the Brazilian forests, given at the end of June by the Ministry of the Environment’s Genetic Heritage Management Council (Cgen). “The appreciable collection of plant extracts that we had already built up gains further legitimacy following the recognition of the council that the way it was obtained is technically and ethically correct”, says Antônio Paes de Carvalho, Extracta’s founder and president. With the authorization, the company, created in 1998 at the Polo Bio-Rio Foundation, the incubator of enterprises in biotechnology of the Federal University of Rio de Janeiro (UFRJ), will be able to expand its bank of primary extracts obtained from various parts of the plants (root, stem, leaves and fruit). Today, they add up to 12,000 and originate from about 5,000 different species of plants coming from the Atlantic Rain Forest and the Amazon Forest, which correspond to almost 10% of all the Brazilian flora, estimated at between 55 and 60 thousand species.

These primary extracts have now originated 40,000 compounds, available for customers interested in using substances with a potential for being transformed into new medicines, found in the rich Brazilian biodiversity. One of these customers is the multinational company of British origin, GlaxoSmithKline, which in 1999 signed a contract worth US$ 3.2 million with the biotechnology company. The first part of the agreement, concluded in 2002, involved a search for substances capable of reacting against eight biological targets defined by the multinational.

In the current stage, the choices were directed towards the development of two medicines with an antibiotic activity, one to fight Staphylococcus aureus, a bacterium with great aggressiveness in hospital infections, and the other to inhibit elastase, an enzyme that in chronic obstructive pulmonary diseases acts on the elastic fibers, weakening and destroying them. The company also has contracts with four industrial customers, two Brazilian and two international, which, according to Carvalho, cannot be revealed on account of a confidentiality clause. “The contract with the British multinational was made public during the Parlamentary Investigation on medicines, when Glaxo defended itself from the accusation of only trading in Brazilian territory, without any research, by showing the agreement with Extracta”, says Carvalho, a former director of the Biophysics Institute at UFRJ and today an emeritus professor of the university.

Prior agreements
The process for getting primary extracts begins with incursions by botanists and forestry engineers into private properties located in areas that are still preserved. The search is carried out without any previous choice. But before it begins to be carried out, the company makes prior arrangements with the owners of the land, necessary for defining, in the case of some active ingredient interesting the laboratories of the pharmaceutical industry, the most suitable form of remuneration. Since the country was created until August this year, the research teams have now carried out 179 expeditions, of which about 80% to land located mainly in the state of Rio de Janeiro.

Minas Gerais, São Paulo, Espírito Santo and the south of Bahia collaborated with a small portion of the samples taken from the Atlantic Rain Forest, whereas the contribution of Amazonia to the bank of extracts is in the order of 20%. The analysis of the plants taken from the Amazon Forest is done by the Federal University of Pará (UFPA), which has an extraction center identical to Extracta’s, assembled by the company as an advance on the return of benefits and which now has been incorporated into the institution’s assets. Prospecting for and extracting the samples is done by the researchers from the university.

Each plant extract deposited in the company’s chemical biodiversity bank has a record of the precise geographical location of the plant, determined, at the place, by the GPS (Global Positioning System) satellite identification system. All the plants are with digital images made at the very place of their collection. Attending to the requirements of the Convention on Biological Diversity, of 1992, and of the Brazilian legislation, a sample of each species collected by Extracta is deposited in the herbarium of UFRJ’s Biology Institute. The herbarium provides the company with botanical identification services, and also has a participation in the intellectual property rights over the material identified.

The plants collected are forwarded to the company, where they undergo a process of drying, and then go on to an extraction center, which has 24 rotary evaporators. The extracts are given a bar code and undergo a thin layer and gas chromatography tests and mass spectrometry, techniques that serve to identify the components isolated from the plants. The selection of the active substances that are candidates for generating molecules of interest to the pharmaceutical industry begins with a robotic process called screening, or high speed biological assay, which makes it possible to do 24,000 tests a day. “The number of candidates for generating molecules is very large, because Brazilian nature is extremely rich”, Carvalho says. “We gather only 2.5 kilos of each plant and manage to arrive at a new molecule.” Once the initial triage is done, the chemists’ work begins, taking from four to six months to get active compounds. Each assay in search of a new molecule costs between US$ 300,000 and US$ 400,000.

Antibiotic activity
In 2000, Extracta left the incubator and rented a plot of land of 200,000 square meters, inside UFRJ’s campus, in the space of Polo Bio-Rio intended for industrial lots, where they built 700 meters of laboratories and invested US$ 5 million. At the moment, there are four stockholders responsible for all the decisions taken by the company. The founding partners hold 38% of the shares, a fund managed by Banco Pactual has another 32%, Oxiteno, a company from the Ultra Group, 19%, and the Biominas Foundation, a private non-profit institution, 9%.

A residual amount of less than 2% still belongs to the British company Xenova, which collaborated with the initial organization of Extracta in 1998. The company, which has two patents for substances with antibiotic properties deposited in 14 countries, is betting on a new area, phytotherapics. “Before that, we were focussed only on the search for final molecules. Now, we want to use the resources that we have at our disposal in our extract bank”, Carvalho says. Just with antibiotic activity, the company has 59 extracts already tested in vitro, of which only three are connected with Glaxo.