Recent Patents on Inflammation & Allergy Drug Discovery - Volume 7, Issue 1, 2013

COPD is pathogenically associated with oxidative stress, which originates not only from cigarette smoke, but also from hypoxia, infection, inflammation, and ageing. It is the reason that therapeutic strategies aim at attenuation of oxidative stress, its sources, or intracellular signals and pro-inflammatory network of its downstream. This review discusses the pathogenesis of COPD and its current therapy in viewpoint of oxidative stress and further provides the perspectives for new treatment strategies in COPD and recent patents that could develop into novel therapeutics.

Atopic eczema or dermatitis (AD) is a chronically relapsing dermatosis associated with pruritus, sleep disturbance and impaired quality of life. AD affects 10 to 20% of school-aged children. The prevalence has increased two to three folds over the past three decades in industrialized countries and there is evidence to suggest that this prevalence is increasing. AD is frustrating to both patients and caregivers and can impose considerable financial impact on the families. The pruritus and sleep disturbance can be intractable and the disease has important physical and psychological implications. Filaggrin (filament-aggregating protein) has an important function in epidermal differentiation and barrier function. Null mutations within the filaggrin gene cause ichthyosis vulgaris and are major risk factors for developing AD. The affected skin of atopic individuals is deficient in natural moisturizing factors (derived from deiminated filaggrin peptides filaggrin) or ceramides (a family of lipid molecules, composed of sphingosine and a fatty acid, found in high concentrations within the cell membrane of cells in the stratum corneum). Avoidance of triggering factors, optimal skin care and topical corticosteroids are the mainstay of therapy for AD. There are two important dermatologic facets to its management, namely, preventive and therapeutic measures. Preventive measures refer to the frequent and proper application of skin moisturizers. When these preventive measures fail to control the disease exacerbation, therapeutic measures such as topical/systemic corticosteroids, antibiotics and immunomodulating agents may be required to control the skin inflammation. Proper moisturizer therapy can reduce the frequency of flares and the demand of topical corticosteroids or topical calcineurin inhibitors. Regular topical application of a moisturizer is the key in the management of patients with AD. Moisturizer therapy of childhood-onset AD is significantly complicated by the diversity of disease manifestations and by a variety of complex immune abnormalities. Recent advances in the understanding of the pathophysiological process of AD leads to the production of new moisturizers and topical skin products targeted to correct reduced amount of ceramides in the skin with ceramide and pseudoceramide products. However, many cosmetic products claimed to have these ingredients have no or limited studies to document their clinical efficacy. Recent studies have shown the therapeutic efficacy of several new compounds. This review provides an update on recent patents that could develop into novel therapeutics available to the clinical armamentarium for the management of the disease.

This review provides an update on histamine, on diamine oxidase (DAO) and on their implications in allergy and various conditions or affections, such as food histaminosis, ischemia and inflammatory bowel diseases (IBD). The review also presents, in brief, patent coverage on therapies for allergy and IBD with the focus on histamine-related treatments.

The increasing epidemic of diabetes mellitus around the globe is increasing the risk of various other chronic diseases i.e. coronary artery diseases, myocardial infarction, hypertension, dyslipidemia and number of other complicated disorders. Diabetes mellitus is clinically characterized by a marked increase in blood glucose levels and is associated with mild hyperlipidemia. Although the prevalence of this health ailment is increasing dramatically, various therapeutic compounds have been developed to treat this disease that is available in the market as synthetic, formulated and combined forms. Recently, various compounds have come through preclinical studies and shown the therapeutic efficacy of using multiple/ specific drug targets. Recent research approaches have been based on receptors targeting, islet cell transplantation, gene expression profiling, glucagon-like peptide-1, dipeptidyl peptidase IV inhibitors, insulin therapy, modulators of peroxisome proliferator-activated receptors (PPAR), glucagon receptor antagonists, insulin analogues, sensitizers and combination therapies. Furthermore various, latest findings claimed to identifying new anti-diabetic regimens with novel mechanism of action are being developed. This review provides an update on the use of approaches to the development of preventive and therapeutic strategies against diabetes and recent patents that could develop into novel therapeutics available to the clinical success for the management of the disease.

Particle engineering is the prime focus to improve pulmonary drug targeting with the splendor of nanomedicines. In recent years, submicron particles have emerged as prettyful candidate for improved fludisation and deposition. For effective deposition, the particle size must be in the range of 0.5-5 μm. Inhalers design for the purpose of efficient delivery of powders to lungs is again a crucial task for pulmonary scientists. A huge number of DPI devices exist in the market, a significant number are awaiting FDA approval, some are under development and a large number have been patented or applied for patent. Even with superior design, the delivery competence is still deprived, mostly due to fluidisation problems which cause poor aerosol generation and deposition. Because of the cohesive nature and poor flow characteristics, they are difficult to redisperse upon aerosolization with breath. These problems are illustrious in aerosol research, much of which is vastly pertinent to pulmonary therapeutics. A technical review is presented here of advances that have been utilized in production of submicron drug particles, their in vitro/in vivo evaluations, aerosol effects and pulmonary fate of inhaled submicron powders.

Inflammation, allergy and asthma are the manifestation of multitude reactions of biological, cellular and immunological events. The various associated biological, cellular, and molecular events with inflammation, allergy and asthma participate to induce increased vascular permeability, vasodilatation, cellular migration, increased mucus secretion, broncho- constriction, structural changes of airway architecture, decline in pulmonary functions, release of intracellular mediators, increased formation of reactive oxygen species, cartilage degradation and loss of function. The participation of variety of effector cells viz. leukocytes, neutrophils, eosinophils, basophils, monocytes, macrophages, mast cells, dendritic cells, T-cells, B-cells, NK-cells, lead to cascade of events trigger of intracellular mediators (cytokines, chemokines etc.) activating diverse biological effects and immune responses. Eicosanoids are major precursors in cyclooxygenase and lipooxygenase pathways and play an important role in inflammation, allergy and asthma. Such biological and cellular events are further enhanced by stress related effects. The wide varieties of synthetic and natural compounds have been showed to act on different molecular targets (receptor, enzymes, mediators, and cells) involved in inflammation, allergy and asthma and to alter produce specific/definite therapeutic activity. The present review describes pathogenesis and etiological aspects of inflammation, allergy and asthma with few relevant patents which would be immensely useful for researchers in the field of immunology and molecular pharmacology to explore new avenues/strategies for development of new generation of therapeutically active agents for treatment of inflammation and allergic disorders.

Several patents of methods for diagnostic work-up of IgE-mediated disease have recently been acclaimed. The aim of the present study was to assess the diagnostic usefulness of the Multiple allergen simultaneous testchemiluminescent assay® (MAST CLA) as compared to the Phadia Immunocap® (Phadia CAP) allergen-specific IgE test panel system. The design was a prospective, observational study in which MAST CLA and Phadia CAP test panels were assessed in 105 children aged 1 to 17 years (46 girls and 59 boys) with a suspected diagnosis of rhinoconjunctivitis, asthma, eczema or food allergy. The MAST CLA screening panel included 23 and 13, the Phadia CAP 10 inhalant and 6 food allergens. The MAST CLA screening panel found 353 sensitizations which were not detected by Phadia CAP, 93 (26.3%) of which were class 3 or 4 results. The sensitizations gave clinically useful information in 7 patients (6.6%). As compared to the Phadia CAP the MAST CLA screening test panel adds little to the diagnostic work-up of IgE mediated disease in children and adolescents.