Products for the treatment of inflammatory bowel disease: a patent review (2013-2014)

Introduction: Inflammatory bowel disease (IBD) consists of Crohn's disease, ulcerative colitis and an unspecific IBD. The unclear etiology of IBD is a limiting factor that complicates the development of new pharmacological treatments and explains the high frequency of refractory patients to current drugs, including both conventional and biological therapies. In view of this, recent progress on the development of novel patented products to treat IBD was reviewed.Areas covered: Evaluation of the patent literature during the period 2013 - 2014 focused on chemical compounds, functional foods and biological therapy useful for the treatment of IBD.Expert opinion: Majority of the patents are not conclusive because they were based on data from unspecific methods not related to intestinal inflammation and, when related to IBD models, few biochemical and molecular evaluations that could be corroborating their use in human IBD were presented. On the other hand, methods and strategies using new formulations of conventional drugs, guanylyl cyclase C peptide agonists, compounds that influence anti-adhesion molecules, mAbs anti-type I interferons and anti-integrin, oligonucleotide antisense Smad7, growth factor neuregulin 4 and functional foods, particularly fermented wheat germ with Saccharomyces cerevisiae, are promising products for use in the very near future

Pharmacological and toxicological studies of Drimys angustifolia Miers. (Winteraceae)

Drimys angustifolia Miers. (Winteraceae) is a Brazilian medicinal plant used as analgesic, antiulcer and anti-inflammatory without studies to assure its efficacy and safety Leaf and stem bark extracts were evaluated to determine the antiulcer, analgesic, antiinflammatory and antioxidant activities. Preliminary toxic effects and qualitative phytochemical profile were also performed. The antiulcer activity was detected in both extracts. Administration of the leaf extract at 250 mg/kg inhibited total lesion area by 76.50% (p < 0.01 in ethanol/HCl method), while carbenoxolone at 250 mg/kg reduced lesions by 69.48%. Stem bark extract (250 mg/kg) inhibited lesion by 81.42%, while carbenoxolone by 74.10%. Similar effects were observed in the ethanol-induced ulcer method, but no activity was observed in piroxican model. The effects involve nitric oxide in gastric protection, since the L-NAME treatment reversed the protection given by the extracts. Antioxidant effects suggest an involvement against oxidative stress. In the pain (writhing, tail-flick and hot-plate tests) and inflammation (carrageenan-induced paw edema) models, the extracts did not present any effect. The phytochemical studies demonstrated that both extracts contain flavonoids, saponins, glycosilated triterpenoids, fixed acids, cyanogenic glycosides, quinones, tannins, xanthone and steroidal aglycones. Toxicological studies showed that the extracts are safe at the effective antiulcer doses. (c) 2006 Elsevier B.V.. All rights reserved

Mechanism and Effect of Esculetin in an Experimental Animal Model of Inflammatory Bowel Disease

Esculetin is a coumarin derivative with high antioxidant activity. In a rat experimental model of inflammatory bowel disease induced by trinitrobenzenesulfonic acid, esculetin at the dose of 5mg/Kg displayed intestinal anti-inflammatory activity; however, its mechanism of action needs to be elucidated. Our objective was to evaluate the effects of esculetin on the intestinal inflammatory process and to clarify the mechanism of action of this compound. We also compared its effects with prednisolone and sulphasalazine. Our results demonstrate that treatment with esculetin prevented an increase in malondialdehyde content, counteracted the depletion of glutathione content, reduced epithelial cell apoptosis, reduced the secretion of pro-inflammatory cytokines, such as IL-1β, IL-2 and IFN-γ, in vitro , and reduced the colonic levels of TNF-α and IL-1β in vivo . Additionally, esculetin treatment inhibited MPO and AP activities. These results demonstrated that esculetin produced a more effective intestinal anti-inflammatory effect than sulphasalazine because it was used at a 10-fold lower dose, and it produced effects similar to those created by prednisolone. We suggest that esculetin exerts its activity by inhibiting pro-inflammatory cytokine secretion and increasing the defences against reactive oxygen species. This leads to less migration and/or activation of inflammatory cells, resulting in the improvement of lesions and functions in the intestinal epithelium. This study confirms the intestinal anti-inflammatory activity of esculetin and demonstrates that this compound has both antioxidative and immunomodulatory properties. Therefore, esculetin may be an interesting new anti-inflammatory drug for the treatment of inflammatory bowel disease