Avaliação da segurança e eficácia farmacológica não-clínica das Gotas Arthur de Carvalho®: validação do uso medicinal nos distúrbios gastrintestinais

• Autor(a) principal: Bezerra, Suzana Barbosa
• Data de Publicação: 2015
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• dARK ID: ark:/83112/001300002914g
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/22157
• topic: Matricaria; Foeniculum sativum; Gentiana lutea; Toxicidade

The herbal medicine Gotas Arthur de Carvalho® (GAC) produced from Matricaria recutita (chamomile), Gentiana lutea (gentian) and Foeniculum vulgare (fennel) tinctures, has indication use as antispasmodic and stomachic, and despite being on the market more than 70 years, does not have scientific studies proving its quality, stability, safety and therapeutic efficacy in gastrointestinal disorders. This study aims to validate the use of GAC in functional gastrointestinal disorders, determining the safety and efficacy of product, to meet the requirements of ANVISA and thus, contribute to the product registration renovation. Firts, were carried out the preclinical toxicity test (acute and repeated-doses toxicity) in rodents, cytotoxicity on human neutrophils and HepG2 cells and evaluation of the pharmacological activity of the herbal medicine to treat gastrointestinal disorders. Initially, the herbal medicine was standardized on the content of active markers (7-glucosídio apigenin, gentiopicrosídio and anethole) determined by the use of validated analytical method - RE 899 (BRAZIL, 2003) with the aid of Liquid Chromatography System with High Efficiency array detector diiodo (HPLC-DAD). In vitro toxicological evaluations (culture neutrophils and HepG2 cells) was investigated the determination of lactate dehydrogenase activity and / or the MTT test, and GAC (10-200 ug / ml) was shown to be not cytotoxic. Continuing toxicity studies in rodents, the estimated LD50 of the product was above 2 g / kg when administered orally. Moreover, in repeated-doses toxicity study (250-1000 mg / kg, p.o.) in rats confirmed the low toxicity of the product through biochemical, haematological and histopathological evaluations. In pharmacological evaluation, the herbal GAC (100 - 400 mg / kg, p.o.) showed activity on dyspepsia, demosntrated by reduction of intestinal transit induced by bethanechol, besides the laxative effect. Moreover, the antinociceptive effect of GAC founded in visceral pain model induced by mustard oil in mice where both opioid and adrenergic systems, in addition to potassium channels appear to have an important role in action, which is not related to a possible central effect, because sedation or decreased motor activity was not observed. Finally, the herbal medicine Arthur de Carvalho showed a safety standard which confirms its use as medicine, in addition to its potential in the treatment of gastrointestinal disorders, proving its antinociceptive activities / visceral pain and role in dyspepsia. However, further studies are still needed, especially related to determine the pharmacological mechanism of action as well as clinical studies, seeking registration as herbal medicine in Brazil. Also, is important valorize the importance of this study of university-industry partnership / Pharmaceutical Industry, which made work something concretely applied to social and economic needs of the region.