US 20070003580A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0003580 A1 Loria et al. (43) Pub. Date: Jan. 4, 2007 (54) ANTI-ALLERGIC PHARMACEUTICAL (30) Foreign Application Priority Data COMPOSITION CONTAINING AT LEAST ONE ALLERGEN AND AT LEAST ONE Mar. 30, 2001 (FR)............................................ O1/O437O ANTHSTAMINE COMPOUND May 3, 2001 (FR)............................................ O1/O5929 (76) Inventors: Emile Loria, La Jolla, CA (US); Publication Classification Gaetan Terrasse, Saint-Valier (FR); Yves Trehin, Toulouse (FR) (51) Int. Cl. A6IR 39/36 (2006.01) Correspondence Address: A6II 3L/495 (2006.01) MANDEL & ADRANO A61K 31/4172 (2006.01) SS SOUTH LAKEAVENUE A6II 3/473 (2006.01) SUTE 710 (52) U.S. Cl. ................ 424/275.1: 514/255.04: 514/400; PASADENA, CA 91101 (US) 514/290 (21) Appl. No.: 11/413,489 (57) ABSTRACT (22) Filed: Apr. 28, 2006 The present invention relates to an anti-allergic pharmaceu tical composition containing at least two active agents Related U.S. Application Data chosen from: (i) one allergen, (ii) one antihistamine com pound, and (iii) one inhibitor of histamine synthesis, said (63) Continuation-in-part of application No. 09/867,159, active agents being associated in said composition with a filed on May 29, 2001, now Pat. No. 7,048,928. pharmaceutically acceptable vehicle. US 2007/0003580 A1 Jan. 4, 2007 ANT-ALLERGIC PHARMACEUTICAL seen in atopic persons in whom allergic reactions are severe COMPOSITION CONTAINING AT LEAST ONE owing to the high level of Th2 clones promoting the Syn ALLERGEN AND AT LEAST ONE thesis of IgE. ANTHSTAMINE COMPOUND 0015 The general reaction observed subsequent to the 0001. This application is a continuation-in-part of U.S. penetration of the new allergen is not due to its toxicity but application Ser. No. 09/867,159, filed May 29, 2001, which simply to the fact that the triggering level of allergic claims the priority of French Application No. 01/04370 filed phenomena is very low, helped by other sensitizations. Mar. 30, 2001 and French Application No. 01/05929 filed May 3, 2001, the contents of which are hereby incorporated 0016. An allergy is a reaction due to hypersynthesis of by reference, in their entirety, into this application, and from IgE immunoglobulins. The inflammatory reaction chiefly which priority is hereby claimed. affects the respiratory and ENT spheres, with pathological focalization at the nose, lungs and skin. Pathologies asso 0002 Throughout this application various publications ciated with the allergy are invalidating and suffer from the are referenced. The disclosures of these publications in their lack of efficacy of conventional treatment. There is no entireties are hereby incorporated by reference into this preventive strategy and curative means are insufficient or ill application in order to more fully describe the state of the art used. to which the invention pertains. 0017. The usual treatment of allergic disease consists, BACKGROUND OF THE INVENTION during a first phase, of identifying the allergen responsible: 0003. The present invention relates to new pharmaceuti dust mites, pollen, mold, food. The second phase comprises cal compositions for the prevention and treatment of aller removal measures. The third treatment phase focuses on the gies. Allergies are a scourge which affects 25% of the target organ which appears to be symptomatic: ENT treat world's population. This number is on the increase in ment for rhinitis, anti-asthmatic treatment if the affected connection with growing environmental toxicity (dust, food, sphere is respiratory, dermatological treatment if the affected motor vehicles). In addition, a person’s risk of Suffering areas are skin areas. from allergy is increased if there is a previous family history 0018. In the event of failure of the preceding measures, of allergy. individual or complementary treatment may be offered 0004 The biological mechanism of allergies may be through the choice of a specific immunotherapy (specific described as an abnormally amplified reaction to the entry of pollen, specific acarid, specific mould). The complexity of an allergen into the body. The following events account for the treatment instituted often leads to poor patient compli the reaction: ance, and therefore, failure to the treatment. 0005) identification of the allergen by the body, 0019. The purpose of the present invention is precisely to offer new means of treating allergies that are both preventive 0006) secretion of cytokines in response to allergen pen and curative. etration, 0007 conversion of Th1 cells into Th2 cells, with the SUMMARY OF THE INVENTION production of clones specific to the antigen, 0020. The present invention provides pharmaceutical 0008 the Th2 cells synthesize interleukins 4 and 13, compositions (e.g., in a semisolid or liquid dosage form) that responsible for aggravation of the allergic symptoms are, e.g., anti-allergic. In one embodiment, the pharmaceu through an upsurge in IgE synthesis, tical composition comprises an allergen, and an antihista mine compound. In another embodiment, the pharmaceuti 0009 the terminal phase of the reaction is the release cal composition comprises an allergen and an inhibitor of of histamine and serotonin having a recruiting effect on histamine synthesis. In a further embodiment, the pharma the Th2 clones, ceutical composition comprises an antihistamine compound 0010 toxic and inflammatory self-maintaining reac and an inhibitor of histamine synthesis. In a further embodi tion, even without any antigen stimulation. ment, the pharmaceutical composition comprises an aller gen, an antihistamine compound, and an inhibitor of hista 0011. The antigen-presenting cells (APCs: macrophages, mine synthesis. Additionally, said pharmaceutical dendritic cells, B-lymphocytes) take part in the reaction of composition comprises a pharmaceutically acceptable car hypersensitivity through basic cell cooperation carrying the rier or vehicle. immune reaction further. Allergies belong to the nonself class of defense mechanisms. 0021 Additionally, the present invention provides meth ods for inhibiting, preventing, or treating allergic symptoms 0012. The main allergens are acarids (dust mites) (80%) comprising administering: (i) an allergen, and an antihista and pollens (20%). mine compound, (ii) an allergen and an inhibitor of hista 0013 The self-stimulating reactions of specific APC mine synthesis, (iii) an antihistamine compound and an clones have an effect on the general rate of release of inhibitor of histamine synthesis, or (iv) an allergen, an histamine and serotonin leading to an aggravation of the antihistamine compound, and an inhibitor of histamine general clinical symptomatology. synthesis. 0014. The recruitment level of new IgE-secreting cells is 0022. The allergen, antihistamine compound, and inhibi thereby increased facilitating the explosion of clinical signs tor of histamine synthesis can be administered sequentially when a new allergen penetrates inside the body. This can be (in any order) or concurrently. Further, more than one US 2007/0003580 A1 Jan. 4, 2007 allergen, antihistamine compound, and/or inhibitor of his administered to a subject, the composition may be metabo tamine synthesis can be used or administered. lized thus enabling release of peptides from the allergen and other chemical Substances from the composition in an inde DETAILED DESCRIPTION OF THE pendent manner at galenic (i.e., pharmaceutically effective INVENTION dosage) level(s). The peptides so released can be complete or partial amino acid sequences (fragments) that are part of Compositions of the Invention the allergen that can bind MHC molecules and trigger an 0023 The present invention provides pharmaceutical immunological response. compositions (e.g., anti-allergic compositions) containing 0028 Advantageously, said allergen may be chosen from two or more active agents of the invention chosen from among the major antigens or mixture of major antigens of among: (i) an allergen, (ii) an antihistamine compound, and acarids able to induce an immune reaction. Alternatively, the (iii) an inhibitor of histamine synthesis (agents of the allergen may be a nucleic acid that encodes the major invention). Said agents of the invention may be associated in antigens or mixture of major antigens of acarids able to said composition with a pharmaceutically acceptable carrier induce an immune reaction. Indeed, one embodiment of the or vehicle. Pharmaceutically acceptable carrier or vehicle invention involved using ubiquitous antigens of acarids. refers to a non-toxic solid, semisolid (also referred to herein These antigens are present in Substantial quantity in the as Softgel) or liquid filler, diluent, encapsulating material or environment and are the cause of the development of allergic formulation auxiliary of any type. The invention also pro reactions in the world. For example, two acarids, Dermato vides methods for treating or preventing of allergy using said goides Pteronyssinus (DP) and Dermatogoides Farinae compositions. (DF) are the most represented in the world environment. 0024. A first preferred embodiment of an anti-allergic 0029. In accordance with the invention, the allergens pharmaceutical composition according to the invention con used in the compositions of the invention may either be tains (i) at least one allergen and (ii) at least one antihista extracts obtained from crude biological material (e.g., mine compound, in a pharmaceutically acceptable