Recent Patents on Inflammation & Allergy Drug Discovery - Volume 10, Issue 1, 2016

Abstract: Background: Allergen avoidance, pharmacotherapy; with antihistamines, anti-leukotrienes, corticosteroids and bronchodilators as well as monoclonal antibodies; and allergen specific immunotherapy stand as confirmed approaches for the management of allergic disorders as asthma, allergic rhinitis/rhinoconjunctivitis, atopic dermatitis, food allergies and anaphylaxis. Galectins are members of animal lectin protein family, with binding specificity for β-galactoside sugars. These highly conserved proteins are known to be expressed in various effector cells of the immune system, exert immuno-regulatory activities, and enroll in tissue inflammation and regulation of immune homeostasis. Objective: This review aims to explain the galectin family and influence of galectins in the immune mechanisms of allergic disorders. Results: Galectins have multiple roles in innate and adaptive immunity. Intense research in the field of immunology related with galectins have given rise to several patent applications. Those, increasing in vivo efficacy of galectins for therapeutic applications, utilizing galectins for immune stimulation and prolongation of immune responses, utilization of them as disease markers are pioneers. As immune cells can be targeted by galectins, cells containing these molecules can be used for immune intervention. Regulation of cytokine productions by immune cells as IL-1β and IL-10 as well as dendritic cell functions by galectins may be efficient in limitation of some immune-mediated disorders. Conclusion: Taken all together, better learning of galectin biology together with detailed revealing of galectin-immune system interactions have great potential for immune interventions targeting allergy-related disorders.

Background: Despite adequate adherence and completion of anti-asthmatic treatment, many patients remain poorly controlled or uncontrolled. Asthma management is based on the use of medication to reverse the bronchial obstruction and eliminate the airway inflammation. New drug development is expected in the future as a consequence of discoveries in the pathophysiology and mechanisms of asthma. Currently, a good and effective set of treatments is available for these diseases. However, the search for new treatment modalities to improve the currently available is especially important for those patients unresponsive to current therapy. Objective: In this review, we summarize new anti-cytokines therapies, anti-leucotrienes molecules, immunomodulatory and anti-inflammatory agents, researched for treatment of asthma. Method: Database patents were used for searching new patents from 2015 and from the beginning of 2016 about treatment of asthma. Conclusion: Pharmacogenomic point of view is now being considered by most major pharmaceutical companies as line of investigation without end in the nearest horizon. Pharmacogenomics has the potential to notably improve the safety and effectiveness of medications.

Background: Plant derived products are not only served as dietary components but also used to treat and prevent the inflammatory associated diseases like cancer. Among the natural products pentacyclic terpenoids including ursolic acid and oleanolic acid are considered as the promising anti-inflammatory therapeutic agents. Objectives: The current review extensively discusses the anti-inflammatory therapeutic potential of these pentacyclic moieties along with their proposed mechanisms of action. Furthermore, the relevant patents have also been listed to present the health benefits of these promising therapeutic agents to pin down the inflammatory diseases. Expert opinion: Pentacyclic terpenoids are known to negatively down-regulate a variety of extracellular and intracellular molecular targets associated with disease progression. The major anti-inflammatory effects of these molecules have been found to be mediated via inactivation of NF, STAT3/6, Akt/mTOR pathways. A number of patents on UA & OA based moieties have been reported between 2010 and 2016. Still there have been only a few compounds which meet the need of sufficient hydro solubility and bioavailability along with higher anti-inflammatory activities. Thus, it is essential to develop novel derivatives of terpenpoids which may not only overcome the solubility issues but also may improve their therapeutic effects. In addition, scientific community may utilize nanotechnology based drug delivery systems so as to increase the bio-availability, selectivity and dosages related problems.

Background: Etiologic diagnosis of pediatric chronic urticaria is quite challenging, as few cases can be associated to specific triggers. Thus, more than 50% of chronic urticaria in children are labeled as idiopathic. Several evidences supported an autoimmune pathogenesis in 30-40% of patients with idiopathic (or spontaneous) chronic urticaria in adults, where the diagnosis of autoimmune chronic urticaria included in vivo and in vitro tests, revealing the presence of autoantibodies against high-affinity IgE receptors mainly. Objective: This review aimed at collecting and analyzing all the available evidences on the diagnosis and treatment of autoimmune chronic urticaria in children, including most recent developments and patents. Results and conclusion: Most pediatric studies relied on autologous serum skin test only, in order to evidence autoimmune urticaria. A complete diagnostic assessment of pediatric autoimmune chronic urticaria, demonstrating an antibodymediated mechanism of disease, might ameliorate the therapeutic management of spontaneous (autoimmune) chronic urticaria in children, supporting the use of omalizumab rather than immuno-suppressive therapy in cases resistant to the firstline treatments.

Background: Actinic keratosis is a common premalignant skin lesion. Because of its increasing incidence, several efforts have been made to earlier detectection and to improve knowledge on photocarcinogenic pathways of keratinocytes. As a consequence, recently new discoveries have been done in this field. Objective: Starting from our previous review on actinic keratosis, we reviewed the literature focusing on pathogenesis and new patents in order to highlight the most recent progresses in diagnosis and therapeutic approach. Conclusion: Although several efforts have been done in the field of photodamaged skin, new upgrades in diagnosis and therapy are needed to detect superficial actinic keratosis earlier, to improve the disease free survival of patient and to better treat the field cancerization.

Context: Immunity related disorder is one of the leading causes of disease in the world. Oxidative stress and microbial infections play a major role in inflammation-induced diseases. Bovine colostrum (BC) contains immunoglobulins and lactoferrins which help in building the immunity and protect against the bacterial proliferation and growth. Aim: This study was designed to investigate the antimicrobial and antiinflammatory activities of BC. Materials and Methods: Antimicrobial activity was determined by the pour-plate method using five different strains of bacteria (Gram -ve and +ve), and carrageenan-induced rat paw edema method was used for the evaluation of antiinflammatory activity in adult Wistar rats. Diclofenac was used as standard antiinflammatory drug, and amoxicillin was used as standard antimicrobial agent. Results: BC showed significant antimicrobial activity against Escherichia. coli, Staphylococcus. aureus, Proteus. vulgaris, Enterobacter. aerogenes and Salmonella. typhi. At 100 μg/mL of BC, the inhibition zones were found to be 13mm, 11mm, 12mm, 12mm, and 11mm, respectively. The BC zones were comparatively smaller than those of amoxicillin at 10μg/mL, where the inhibition zones were 16mm, 30mm, 23mm, 22mm and 23mm, respectively. In the BC treated animals, the percentage edema inhibition was found to be 67.94% at the third hour, suggesting high antiinflammatory activity of BC in rats. Conclusion: BC may be beneficial in reducing the risks of inflammation associated diseases. Further studies are needed before BC can be recommended for therapeutic interventions in humans.

Background: Grip muscle force has always been used to assess functional limitations in elderly. Its use as a tool to assess work capacity has never been described in the literature. Objective: To describe the patent determinants of grip strength and the usefulness of its measurement in assessing workability index in the healthcare sector. Methods: This is a cross-sectional study conducted in a sample of 293 healthcare workers representative of 1181 based on a comprehensive questionnaire about socio-professional characteristics and on an 8-item work capacity evaluation (WAI). Besides, Body mass index was measured and muscle strength was assessed by JAMAR hydraulic dynamometer. Results: Handgrip Strength was stronger in male nurses (p < 0.001), with low perceived physical load (p = 0.0001) and working on a night shift (p = 0.001). It decreased with a greater duration of household work (p < 0.0001) and increased with a greater BMI (p = 0.015) and a better workability index (p < 0.0001). After removal of all the variables that were not independently associated with the muscle strength force, factors accounting for 52.6% of the variance in nurses handgrip strength were gender (p < 0.001), workability index (p < 0.001), duration of household work (p = 0.021), BMI (p = 0.002), perceived physical load (p < 0.001) and work schedule (p = 0.002). Conclusion: Grip Strength Test is a useful tool to assess strength and functional capacity at work in healthcare workers. Further longitudinal studies are required to confirm this hypothesis.

Background: Naproxen is a non-steroidal anti-inflammatory drug (NSAID), belonging to propionic acid group, and its chemical structure is a 6-metoxi-metil-2-naftalenoacetic acid. Fixed drug eruptions (FDE) have been rarely reported. Objective: A 38-year-old woman referred that after 2 hours of taking 2 tablets of naproxen for a headache, she developed several edematous and dusky-red macules, one on right forearm and the other two in both thighs and she was diagnosed with FDE probably due to naproxen. Methods: We performed patch testing (PT) (Nonweven Patch Test Strips Curatest^®; Lohman & Rauscher International, Rangsdorf, Germany), with ibuprofen (5% Petrolatum), ketoprofen (2.5% Petrolatum), naproxen and nabumetone (both 10% in DMSO) on the residual lesion of the forearm with naproxen and in both thighs with ibuprofen, ketoprofen and nabumetone. Results: Readings at day 1 (D1) and day 2 (D2) showed negative results to ibuprofen, ketoprofen and nabumetone, but were positive to naproxen in D1. A single blind oral challenge test (SBOCT) with other propionic acid derivates were performed in order to check for crossreactivity between them: ibuprofen, ketoprofen and nabumetone were administered and all drugs were well tolerated. Conclusion: In our patient PT confirmed the diagnosis and allowed us to study the cross-reactivity between NSAIDs of the same group, and confirmed by SBOCT. Cross-reactivity between propionic acid derivatives was studied. This is a case of hypersensitivity to naproxen with good tolerance to other propionic acids NSAIDs (ibuprofen and ketoprofen) and nabumetone, confirmed by PT and SBOCT. Some relavent patents for fixed drug eruption are discussed.