Recent Patents on Inflammation & Allergy Drug Discovery - Volume 8, Issue 2, 2014

The hepatitis C virus (HCV) is a prevalent human pathogen that causes persistent liver infections in most infected individuals; thus, efforts to develop a safe vaccine, preventive and therapeutic, are urgently needed. Current approaches for the vaccine include the use of recombinant E1 and E2 proteins, synthetic peptides, viral particles, viral vectors, DNA vaccines, dendritic cells, and prime-boost strategies. However, several problems have been encountered: restricted humoral and cell mediated responses, the low delivery of potentially protective viral epitopes, and the low effectiveness of the adjuvants used in the different protocols. Strong neutralizing antibodies and powerful cellular immune responses are required for an effective vaccine against HCV. New patents are being developed to enhance both immune responses. The high prevalence of global HCV infection obliges the development of new efforts in primary prevention; therefore, a safe and efficient vaccine to confer protection against HCV is urgently needed.

Arsenic (As) contaminates drinking water worldwide, and As exposure, hypersensitivity and deficiency are involved in the immunopathogenesis of various health problems. Its chemoprevention thus has a high health impact. Given its oxidative potential, antioxidant compounds are good candidates to counteract arsenic's deleterious effects on humans. Phytochemicals (e.g., phenolics, carotenoids, etc.) act through free radical chelation activity and regulation of cellular targets. Consequently, they are appropriate for developing anti-As strategies derived from plants, and Argentinean flora is rich in useful species. Several molecular pathways involved in immune regulation are at the same time targets of exogenous agents, and oxidative stress itself is a modulating phenomenon of immunity. Since xenohormesis has been described as the organic enhancement of resistance to stress conditions (e.g., oxidation, pollution, etc.) by consuming xenobiotics, immunoxenohormesis implies also defense improvement. This review focuses on recent patents on the development of vegetable redox-related immunomodulating agents, which might be applied in As-induced dysfunctions, with their scientific basis being reviewed.

Acute inflammation is the result of a complex signal transduction pathway that protects and heals our body and is necessary for our good health and normal wellbeing. Whereas, chronic inflammation can be correlated well with the onset of a plethora of autoimmune disorders; rheumatoid arthritis, systemic lupus and polymyalgia, rheumatic and other diseases like asthma, inflammatory bowel diseases, cardiovascular disorders, ulcerative colitis and Crohn’s disease. Also, it has been reported to be associated with the onset of various cancers. An effective anti-inflammatory drug should be able to inhibit the development of chronic inflammation without interfering in normal homeostasis. A number of herbal drugs have been identified in the past that can target inflammatory cytokines. Among these, Ganoderma lucidum: a powerful medicinal mushroom has been found to possess immune-modulating and immune-potentiating capabilities and has been characterized as a wonder herb. This review mainly focuses on the molecular mechanism of anti-inflammatory and antiallergic action of this mushroom and also sheds light on various patent studies related to its pharmacological action.

Glia-mediated or glia-propagated inflammation, which acts as the central component in the progression of several brain diseases, is a milestone in the pathophysiological process contributing to the onset or progression of neurodegeneration. Excessive and prolonged neuroinflammation compromises cell and brain function, resulting in fatal brain anomalies. Glial research has garnered attention recently following breakthroughs in neuroinflammation-targeting therapeutics. Activation of microglia and astrocytes, and the attendant expression of proinflammatory cytokines and chemokines, is often associated with disease-, trauma-, and toxicant-induced damage to the central nervous system. A cause-andeffect relationship exists between neuroinflammation and neurotoxic outcomes. In clinical settings, pharmacological antagonists and immunosuppressive regimens can be used to prevent proinflammatory responses and attenuate subsequent neurotoxicity. Current research is focused on the exploration of existing drugs approved for other clinical purposes and on the development of novel synthetic compounds that may selectively downregulate neuroinflammation. The development of innovative therapeutic classes based on targeted selection of glial activation pathways and glia-mediated pathophysiology seems to be a promising approach, and may lead to more effective prevention and treatment of neuroinflammation and resulting maladies. This review focuses on recent patents and emerging therapeutics related to the management of glia-mediated neuroinflammation.

Anesthesia is defined as a total or partial loss of sensation and it may be general, local or topical, depending on the method of drug administration and area of the body affected. General anesthesia is a reversible state of unconsciousness produced by anesthetic agents, characterized by amnesia, muscle relaxation and loss of sensitivity to pain of the whole body. General anesthetic drugs can be classified into two main groups according to their predominant molecular pharmacological effects: volatile and intravenous agents. Local anesthesia produce a reversible loss of sensation in a portion of the body and it reversibly block impulse conduction along nerve axons and other excitable membrane. All local anesthetics (LA) are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes. They act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The main local anesthetic (LA) agents for skin anesthesia are benzocaine (aminoester), prilocaine and lidocaine (aminoamides) which are commercially available as gels, ointments and creams (benzocaine and eutectic mixture of lidocaine and prilocaine) or as a bioadhesive (lidocaine) with different compositions (vehicles and excipients) for adults or pediatric use. Topical anesthetics decrease anxiety, pain and discomfort during cutaneous procedures and provide effective analgesia with rapid onset, prolonged duration and minimal side effects. This article outlines the different classes of topical anesthetics available and gives an overview of the mechanism of action, metabolism of each different class, of the possible complications that can occur because of their use and their possible treatment options and new patents.

An increasing body of evidence shows the importance of the chemokine (C-X-C motif) receptor (CXCR)3 and cognate chemokines (C-X-C motif) ligand (CXCL)9, CXCL10 and CXCL11 in the T helper 1 immune response, and in inflammatory diseases such as bowel inflammatory disorders, allograft rejection, thyroid autoimmune disorders, vascular and renal inflammation, and others. Peroxisome proliferator-activated receptor (PPAR)-γ agonists show a strong inhibitory effect on the expression and production of CXCR3 chemokines in vitro, in various kinds of cells, such as denditric cells, monocytes, macrophages, endothelial and vascular smooth muscle cells, intestinal cells, thyrocytes, fibroblasts, preadypocytes and mesangial cells, and in vivo in animal models. As rosiglitazone has recently been linked to a higher risk of heart failure, stroke, and all-cause mortality in old patients, it has been interrupted from the European market. On the contrary, the safety profile of pioglitazone seems favorable. However, further studies are ongoing to explore the use of new PPAR-γ agonists in the treatment of the above mentioned inflammatory disorders, and many interesting patents have been recently applied.

Seasonal and perennial allergic conjunctivitis are IgE-mediated, hypersensitivity conditions characterized by ocular pruritus, epiphora, and hyperemia. Proper diagnosis is usually made clinically based on history and physical examination. Diagnostic procedures are rarely necessary. Non-pharmacological measures, such as environmental modification and proper eye care, should be considered for all patients with allergic conjunctivitis. Pharmacological interventions may also be required. Milder cases can be treated with short-term topical ophthalmic therapy such as a decongestant/ antihistamine combination, a mast cell stabilizer, or a multi-action agent. Moderate to severe cases may require longer usage of the above agents and/or the addition of an oral antihistamine. Refractory cases may necessitate the use of topical ophthalmic corticosteroids and topical NSAIDs. Immunotherapy, whether via the subcutaneous route or the intranasal route, should be considered in the treatment of persistent severe cases refractory to conventional treatment. Despite all the available therapeutic agents, there continues to be a constant need to discover more effective ways to treat seasonal and perennial allergic conjunctivitis. This article also discusses recent patents related to the field.

We have revised the literature data on the various substances having antioxidant properties used to cure acute pancreatitis. We have also evaluated the data according to two main topics: the effects of antioxidant substances in experimental studies and the effects of antioxidant substances in human acute pancreatitis. At present, the only convincing data on the benefits of antioxidant treatment in acute pancreatitis comes from the studies on animals in whom the experimental variables are well defined and do not change overtime. In human studies, the benefits of antioxidants are still not convincing due to limited number of the patients studied. Finally, we need to know which antioxidant substances should be used and their optimal dosage. Further clinical randomized controlled trials need to be carried out before the use of antioxidants can be recommended for human acute pancreatitis. Some patents relevant to treatment of acute pancreatitis have also been reviewed in this article.