Recent Patents on Inflammation & Allergy Drug Discovery - Volume 6, Issue 3, 2012

This overview defines whether anti-irritant agents, in fact, inhibit, prevent or treat irritant contact dermatitis (ICD) in man. We performed a literature search using PubMed, EMBASE, and Scopus via the library at University of California San Francisco, and a hand search of relevant text books to investigate chemicals that can be considered antiirritants in either prevention or treatment. Emphasis was placed on data that included quantitative and qualitative results and that followed evidence-based dermatological guidelines. Related patents were summarized. Conflicting observations summarized here suggest well controlled, but often arduous, field type studies are required for confirmation.

The treatment of dermatitis with conventional dosage forms (ointment, cream, lotion etc.) has many concerns due to side effects especially in long-term therapy. Recent studies focused on strategies to optimize the potency of formulation while minimizing side effects. Several attempts have been made to increase the safety of treatment, including special vehicles (nanoparticle, liposome, patch etc.), combined therapy and new synthesized agents. This review provides major innovations and advances of new approaches for dermatitis treatment based on the published articles and patent applications.

Allergic and irritant skin diseases may be the results of representative inflammatory response in the skin. It has been established that inflammatory response includes reactive oxygen species, reactive nitrogen species, and free radicals. Subsequently, an imbalance between the oxidant and antioxidant components occurs; this is so-called oxidative stress. As various important roles of oxidative stress in contact dermatitis have been reported, controlling oxidative stress in these diseases could be a supplementary and/or novel therapeutic approach. However, there is little convincing clinical evidence that modulation of oxidative stress can be used therapeutically to modulate inflammatory response in allergic and irritant skin diseases. The reason for this discrepancy may be partially due to an insufficient understanding of the dynamics of oxidative stress in allergic and irritant skin diseases. This review introduces the importance of oxidative stress in allergic and irritant skin diseases from basic research to clinical management aspects. This review also introduces recent patents for the methods and compositions for the treatment of skin diseases with antioxidants. These methods may be helpful in treating allergic and irritant skin diseases through topical application of antioxidants.

Due to its high prevalence, allergic contact dermatitis (ACD) has an important economic and occupational health impact on society. ACD presents as an inflammatory response to small molecules and involves both skin resident cells and activated skin infiltrating T cells. Activation of skin resident cells plays an essential role in the initial sensitization phase. A number of different pathways are crucially involved in this phase including the activation of pattern recognition receptors such as TLR, inflammasome activation and production of reactive oxygen species all of which contribute to release of cellular mediators such as IL-1 family members. Chemokines regulate steps in elicitation of adaptive T cell responses including the migration to and presentation of the contact allergen by skin derived antigen presenting cells in the draining lymph node as well as the recruitment of these activated, allergen reactive CD4+ and CD8+ cells back into the skin. The current therapeutic regimens are largely restricted to the avoidance of the contact allergen and the topical use of anti-inflammatory drugs such as glucocorticosteroids. Recent research, as highlighted by current patents, focus on the use of anti-oxidants, the induction of immunological tolerance, interference with cell signaling molecules and blocking of cytokines actively involved in ACD.

Atopic dermatitis is a chronic allergic inflammatory disease of the skin. Its pathophysiology involves an orchestrated sequence of allergic provocation by IgE-mediated and non-IgE-mediated Th2 responses to allergens. Allergen sensitization precedes the immunopathogenesis. Th2 cytokines such as IL-4 and IL-5 play a key role in both the sensitization and effector phases of allergic skin inflammation. Recently, the roles of new cytokines including IL-16, IL-17, IL-21, IL-22, IL-23, IL-27, IL-31, IL-33, IL-35 and thymus stromal lymphopoietin (TSLP), and Th2 polarization in the immunopathogenesis of skin inflammation and physically injured skin have been described, in addition to roles for IL-4, IL- 5, IL-9, IL-13, IFN-γ and TGF-β. Sensitization occurs via the skin for aeroallergen including house dust mites and superantigens and through the gastrointestinal tract for food allergens. Alternatively, food allergens can be sensitized through skin. Atopic dermatitis is described under the structure of sensitization phase and effector phase in this review. Especially, the clinically effective applications of cytokines in AD and relevant patents are updated in this review.

Atopic dermatitis is an immunologic disease that results in allergic inflammations of the skin. Cytokines are involved in the negative regulation of immunopathogenesis of atopic dermatitis. Negative immune regulation is also achieved by immune cells in addition to cytokines which are subsequently regulated by a counter-regulatory mechanism. Allergen tolerance is an important aspect of the treatment of atopic dermatitis. Recently, the IL-27, IL-21, and IL-10 cytokines were found to be important components of the counter regulatory mechanism that terminates immune response, and protects the host from excessive immune responses. IL-10 and TGF-β are well-known to be involved in the immune tolerance. IL-10 and IFN-γ are promising cytokines with respect to the prevention of allergen sensitization and the induction of allergen-specific tolerance. In particular, IFN-γ has unique tolerogenic effects with respect to pre-sensitized allergens, especially in atopic dermatitis. In this review, the role of cytokines in the immune tolerance and relevant patents are reviewed, and therapeutic strategies are presented based on the immunologic architecture of AD.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by therapeutic areas/targets & therapeutic agents related to inflammation and allergy drug discovery.....