Recent Patents on Inflammation & Allergy Drug Discovery - Volume 7, Issue 2, 2013

Inflammation is the propitious response of vascular tissue to pathogens, damaged cells or irritants. Recent discoveries on the molecular and cellular basis of inflammation and allergy have markedly altered the understanding of these disorders. Although the conventional therapy used for the treatment of autoimmune and inflammatory diseases has improved the condition of patients but it has also placed them at the stake of enormous side effects. In recent times, the usage of Mesenchymal Stem Cell (MSC) therapy in the field of medical science has provided better alternative, concomitant treatment for these diseases as suggested by preclinical studies. Thus, in this review we have summarized the recent findings on MSCs as a therapeutic agent in treating inflammatory disorders using novel methods. This review also outlines the current state of knowledge on the biology of MSCs and their use as a suitable candidate for cell-based therapeutics. In addition, we focus on various patents, in which administration of MSC attenuates inflammation and injury thereby suggesting its integral role in host immune response, immunomodulation and anti-inflammation, which may in turn lead to novel patents in this field in the future.

Current TB regimen involves a combination of first and second line drugs which target only a small number of core metabolic processes such as deoxyribonucleic acid (DNA)/ ribonucleic acid (RNA) synthesis, cell wall synthesis, and energy metabolism pathways. New classes of drugs with additional drug targets that are resistant to mutation are an urgent necessity. Novel targets involved in vital aspects of bacterial growth, metabolism and viability and whose inactivation would lead to bacterial death or an inability to persist need to be investigated. Isocitrate lyase (ICL), which catalyses the first step in the glyoxylate cycle is found to play a pivotal role in persistence of Mycobacterium tuberculosis in mice, can be a potential target for anti-tubercular drug. The current review provides a detailed overview of the therapeutic potential, patents and recent advancements in the investigative studies done on isocitrate lyase (ICL) as an antitubercular drug target. Salicylanilide, benzanilide, 3-nitropropionamide and pthalazinyl derivatives, Pyruvate-isoniazid analogs and its copper complexes are among the synthesized compounds showing a great potential to inhibit mycobacterial ICL and a significant antimycobacterial effect. Some of the relevant patents in the ICL research have been further reviewed and discussed.

Celecoxib, a tricyclic compound having pyrazole ring exhibits an excellent level of antiinflammatory action against COX-2 enzymes and some of its analogs act as anticancer and antibacterial agents. Various efficient routes and different improved processes for the synthesis of this drug have already been disclosed in the literature. However, there is a need for further developments in the present scenario of achieving cost effective synthetic technologies to celecoxib with high purity accompanied by excellent yield. Therefore, an effort has been made to summarize briefly the different methods of preparation of Celecoxib with their advantages or disadvantages that have been reported in various patents up to 2013. The present review would be beneficial for scientific community for further developments in the synthetic methodologies for Celecoxib and to explore some novel celecoxib based biologically active agents.

All organisms are protected by their immune system but occasionally this system overreacts leading to allergic and inflammatory reactions in the body. These reactions are the starting points of various diseases like asthma, eczema and urticaria etc. They involve activation of T cells, release of histamines, toxic chemicals from mast cells and eosinophils respectively. Several chemically and naturally synthesized therapeutic agents are available for the treatment of these immunological diseases. The present review provides a detailed account of mechanism of allergic and inflammatory reactions, its types and various treatment strategies with a special focus on some recent patents in this field.

Advances in the drug development against HIV-1 have lead to the identification of new compounds which could be used to target cellular entry and nuclear integration of virus in addition to drugs that commonly target reverse transcriptase and protease. These additional targets have added a new dimension to fight against HIV. Cellular entry of HIV is a multistep procedure involving a range of cellular and molecular interactions between virus envelope protein and receptors expressed on the surface of the target cells, thus providing many opportunities to block infection. Some of these entry inhibitors are currently being used in the clinic and more compounds are under various stages of development. Integration of the HIV-1 DNA is required and essential to maintain the viral DNA in the infected cell. The design and discovery of integrase inhibitors were first focused at targeting the catalytic site of integrase that selectively acting on strand transfer and thus inhibits integration of virus DNA with host cell genome. Thus, entry and integrase inhibitors present a real added value in combined treatment against HIV infection. This review discusses the recent development in the discovery of inhibitors of HIV entry and integration along with some of recent patents in the field.

Heparanase is an enzyme expressed normally in platelets and in placenta at high levels, and is undetectable in other normal human tissues. Heparanase degrades the heparan sulfate saccharides of the extracellular matrix. The real problem starts when tumor cells express heparanase; this results in increased tumor angiogenesis, aggressiveness, and metastasis. Patents filed on heparanase detection, suppression, and function modulation were not translated yet into products (tested in Phase III trials). The mismatch between researchers, clinicians, and pharmaceutical companies, which identified the first 20 years of heparanase research, is changing and will hopefully foster the arrival of some of these patent inventions for clinical applicability.

Actinic Keratoses (AK) are considered a worldwide problem with continuously increasing incidence. They clinically present as rough or scaly plaques and are histologically characterized by a proliferation of atypical keratinocytes limited to the epidermis. AK are considered as an early step in the continuum of transformation from normal skin to invasive squamous cell carcinoma (SCC). These lesions develop on a background of field cancerization in which chronically UV- damaged-areas accumulate molecular changes, but remain clinically normal for prolonged periods. The presence of certain clinical features of AK, such as large size, ulceration, or bleeding, suggests an increased risk of disease progression. The risk is also increased by evidence of extensive solar damage, advanced age, and immune-suppression. Many treatment modalities are available, although recent developments have focused on the management of the whole actinically damaged field. In this regard, several topical drugs have been approved, differing in efficacy, side effects, application and cost. Research continuingly aims to develop the “ideal” treatment which combines high clearance rates with few side effects, short treatment duration and low costs. Herein, we aim to give an overview on current treatment modalities including their mechanism of action, application scheme and common side effects. Furthermore, recent patents in the field and future aspects are discussed in this review.

Orthopaedic joint implants and osteosynthetic materials are progressively being employed more often. Complications mainly include physical-mechanical problems and infections. Uncommonly, allergic reactions to an alloy metal or a bone cement component have been implicated. Less attention has been paid to the components of bone cement, such as acrylate, catalysers (e.g. peroxide), additive polymers or stabilisers. An important bone cement component is benzoylperoxide (BPO), an initiator of the process enhancement of the bone cement. Vitiligo is an acquired, progressive depigmenting disorder that can induce autoimmune diseases. The occurrence of vitiligo in combination with an infection or allergy is not well described, and this manuscript highlights the possibility of an occurrence of a vitiligo whenever the immunesystem is activated and T-cell activation is observed. The aim of this article was to analyze the diagnosis and management of vitiligo and allergic complications from orthopaedic joint implants due to benzoyl-peroxide and relevant patents.