Recent Patents on Inflammation & Allergy Drug Discovery - Volume 9, Issue 2, 2015

Chronic Rhinosinusitis (CRS), one of the commonest chronic inflammatory disorders, is encountered daily in all healthcare settings. In its refractory form, CRS seems to prevail over most up-to-date surgical interventions and systemic medical remedies, owing to our poor understanding of its perplexing pathophysiology. Although several systemic influences impinge on the progression of inflammation, the true interplay between offensive and defensive factors takes place on-site, i.e. across the sinonasal epithelial coating. Therefore, current treatment strategies shift the weight of CRS management toward topical modalities, which combine the benefits of surgical approach with the healing effect of conventional medications. An explosive emergence of relevant patents is still in progress, emphasizing the need for classification and comparison. Novel delivery methods of medications into the sinus cavities include modifications of traditional rinses, state-of-the-art nebulizing devices, and the revolutionary concept of sustained drug application utilizing carrier gels or nasal implants. As far as the introduction of new medications is concerned, recent patents propose alterations to the physical and chemical properties of irrigating solutions, as well as the local use of antiseptics, hydragogues, and anti-biofilm agents. This review focuses on the local pathophysiologic events of CRS and the most exciting innovations regarding its topical management.

Background: Alcohol is one of the etiological factors of chronic pancreatitis and there is evidence that acute pancreatitis is the first episode of preexisting chronic pancreatitis and is sometimes not evident from a clinical point of view. The diagnosis of acute pancreatitis is based on the presence of abdominal pain, serum increase of pancreatic enzymes or their presence in urine and/or the presence of alterations of the pancreas imaging. Aims: To revise actual knowledge on the relationship between alcohol use and pancreatic diseases benign as well as malignant. Results: In occasional drinkers, levels of serum amylase were found to be abnormally high in approximately 13% of subjects, while pancreatic isoamylase and lipase were found to be abnormally high in serum in only 2%. The reason might be related to the fact that alcohol can affect the salivary glands. In chronic alcoholics without abdominal pain, amylase and lipase in serum are elevated in 14% of subjects and, in patients with alcoholic acute pancreatitis, pancreatic amylase and isoamylase are elevated in 94% of cases and lipase is generally more sensitive (100% of cases). Conclusions: Chronic abuse of alcohol, but not occasional alcoholic intoxication, causes pancreatic damage. Regarding pancreatic neoplasms, the role of alcohol is under debate in ductal pancreatic adenocarcinoma as well as in pancreatic neuroendocrine tumors. Few relevant patents are also described in this review.

Allergic rhinitis (AR) is a common respiratory disease affecting both adults and children worldwide. Affected patients may experience nasal congestion/stuffiness, rhinorrhea (anterior and/or posterior), nasal/ nasopharyngeal itching and sneezing. Allergen avoidance is the principal step in the management. Nasal saline irrigation to remove allergen (s) in the nose is a useful adjunctive therapy in the management of moderate to severe AR. Symptomatic relief and improved quality of life may be achieved in the majority of patients with appropriate pharmacotherapy. Mild-to-moderate cases are usually managed with either an oral second generation antihistamine or an intranasal corticosteroid. More severe cases may require treatment with an intranasal corticosteroid in combination with various oral medications. Patients who require medications for more than 6 months per year or have intolerable side effects from pharmacotherapy can be considered for immunotherapy. A wide range of complementary and alternative medicines (CAM) have also been proposed. This overview evaluates the evidence of use of CAM for AR. Some methods including acupuncture and herbal medicine have supportive evidence, but the efficacy of other CAM is controversial. Conversely, possible side effects of different modalities are often inadequately documented. The herbal formulae include Butterbur, Nigella sativa, Shi-Bi-Lin, Polyherbal formula, Grapeseed extract, Rosmarinic acid, Spirulina, Biminne, and Bhu-zhong-yi-qi-tong. Further research is needed to assess the efficacy and safety before they are employed in treating AR. This review article also discusses recent CAM patents for use in AR, which are exclusively traditional Chinese medicine (TCM) concoctions primarily for oral consumption but two as topical spray. Only 8 pertinent patents, all TCM compositions for treating AR and registered in 2014, were obtained. Description about their efficacy is impressive but objective outcome evaluation tools are lacking.

Tuberculosis is a major public health concern. The present article reviews the current updates on the usage of nanoparticles against tuberculosis and recent patents that could develop into novel therapeutics available to the clinical armamentarium for the TB management. The drug delivery systems involving nanoparticles are suitable against chronic diseases such as tuberculosis. Polymers in many forms like liposomes, dendrimers, Nanoemulsions can be used as synthetic and natural carriers for first line and second line drugs employed for chemotherapy. Not only are the drugs sustainably released in organs and plasma, but also their dosages as well as adverse effects have been reduced, the drug interaction has increased and the drug resistant bacteria have been targeted. The hurdles in the development of anti-tuberculosis have made Nano medicines to act as a silver lining.

The impacts of air pollution on human health and disease have been attracting attention, especially in industrialized countries and areas with heavy traffic burdens. Fine particulate matters (PMs) are considered as an important air pollutant, since it was reported that there was a significant relationship between PM2.5 levels and mortality by cohort studies in 1990s. Epidemiological and toxicological studies have strongly suggested a causative relationship between fine particulate air pollution and increased incidence as well as exacerbations of asthma, and other respiratory disorders. Recent advances in research have elucidated that PMs primarily and secondarily induce oxidative stresses which result both in pro- and antiinflammatory activities. It has been demonstrated that gene polymorphisms of antioxidant enzymes might change responses to particulate air pollution exposures. To prevent health hazardous effects of particles, it is crucial to screen susceptible subpopulations and establish chemoprevention strategies in the world. Novel techniques and modalities are patented for future progress on better control of air pollution.

Recently, the improvement of innovative medications named focused treatments represents the consequence of a superior knowledge of the procedures implicated in the modification of physiological tissues in tumor. Focused treatment is known as the therapy which uses specific substances that affect selective mechanisms implicated in tumorigenesis and tumor development. Angiogenesis is important for tumor development and distant metastatic disease and represents a significant aim for modern biological substances. Bevacizumab belongs to humanized recombinant antibody family which obviates vascular endothelial growth factor (VEGF) receptor fastening, and suspending genesis of new vessels and tumor development. Bevacizumab represents the primary antiangiogenic treatment authorized for usage in tumor and has FDA authorization to treat the recurrent glioblastoma multiform since 2009. Bevacizumab’s efficiency for treating malignant brain gliomas along with correlated patent appliances related to this agent is discussed below.

The present paper reviews pharmacokinetics and systemic activity of a new patent of fluticasone fumarate/vilanterol trifenatate and summarises the efficacy data in children, adolescents and adults with asthma. Bioavailability of oral deposition of fluticasone furoate is approximately 1%, of oral and pulmonary deposition 15%. Fluticasone furoate 400, 600 and 800μg have been associated with reductions in 24h urine cortisol excretion in adults, whereas several studies on fluticasone furoate/ vilanterol trifenatate 100/25μg and 200/25μg once daily found no suppressive effects. Bronchodilation was detected in adults with asthma from 5 minutes after vilanterol trifenatate was inhaled and up to 24 hours after. Five large clinical trials which were sponsored by the manufacturer GlaxoSmithKline provided evidence that dry powder fluticasone furoate/vilanterol trifenatate 100/25μg and 200/25μg once daily are efficacious in asthma in patients ≥ 12 years of age. It remains to be proven, however, that once daily dosing may improve asthma control as compared to twice daily dosing. Efficacy and the systemic activity potential for hypothalamic-pituitary-adrenal and growth suppression of fluticasone furoate have not been established in children. The potential for systemic acitivity of fluticasone furoate in children may be assessed by knemometry.

Aims: The aim of this study is to assess the neuropsychological manifestations of mercury exposure in dentists. Methods: A cross-sectional study was carried out including 64 dentists matched to a control group according to age and gender. This study protocol included a neurological evaluation, a questionnaire assessing the study groups’ general characteristics and personal factors that may affect mercury urinary excretion in both groups. EUROQUEST questionnaire and Hospital Anxiety and Depression scale (HADS) were used to evaluate the neuropsychological symptoms reported during the last 12 months. In both groups, mercury impregnation was assessed by monitoring urinary mercury. Results: In the exposed group, scores of neurological symptoms, memory disturbances and anxiety were found to be significantly higher than those in controls (p < 0.01). Mean scores of HAD Depression’s scale were higher in the exposed group than in controls. Most of the neurotoxic manifestations were correlated to the levels of urinary mercury excretion in the exposed group. Mean levels of urinary mercury were significantly higher in the dentists group than in controls, with respective values of 21.1 ± 19.6μg/g of creatinine and 0.05 ± 0.9μg/g of creatinine. In nine dentists having urinary mercury levels higher than 35μg/g of creatinine, neurological examination showed a bilateral and symmetric intentional tremor in both upper limbs. In the exposed group, the neuropsychological manifestations and levels of urinary mercury were found to be significantly correlated. Conclusion: Increased levels of urinary mercury observed in dentists suggest that exposure to mercury vapour emissions adversely affects dental professionals, therefore prevention measures should be strengthened, with a special medical supervision program of dentists exposed to mercury vapours should be implemented. We have also outlined some relevant patents in this article.