WO2016011254A1 - Combinaisons d'antihistaminiques et d'antagonistes anti-leucotriène et procédés d'utilisation associés - Google Patents
Combinaisons d'antihistaminiques et d'antagonistes anti-leucotriène et procédés d'utilisation associés Download PDFInfo
- Publication number
- WO2016011254A1 WO2016011254A1 PCT/US2015/040752 US2015040752W WO2016011254A1 WO 2016011254 A1 WO2016011254 A1 WO 2016011254A1 US 2015040752 W US2015040752 W US 2015040752W WO 2016011254 A1 WO2016011254 A1 WO 2016011254A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antihistamine
- composition
- pharmaceutically acceptable
- allergic
- acceptable salt
- Prior art date
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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Definitions
- the present invention relates to compositions including an HI antihistamine and a leukotriene receptor antagonist, and optionally an H2 antihistamine, and their use for treating inflammatory and allergic conditions.
- Allergic rhinitis affects an estimated 10-30% of the world's population. Roughly 8% of adults over the age of 18 and 10% of children suffer from allergic rhinitis in the US as of 2010. Allergic rhinitis is a disease that is largely preventable.
- Allergic urticaria has a lifetime prevalence of over 20% worldwide. It affected 13% of children in the US under 18 years of age in the previous 12 months in 2010. It can range from a mild nuisance to a debilitating disease that affects every aspect of an individual's quality of life.
- mast cells are immune cells that are present in almost every tissue in the body (eg: brain, lung, heart, intestines, and skin). They start as precursor cells in the bone marrow and enter the blood stream as MC progenitor cells. They travel to the target organ and compete their maturation once inside the organ tissue.
- MCs are filled with granules that contain mediators that cause allergic reactions and inflammation.
- the MCs can become activated and release their mediators through a process called degranulation.
- the two most important types of chemicals to be released are histamine and the cysteinyl leukotrienes (cys-leukotrienes).
- the predominant symptoms of allergic asthma, rhinitis and urticaria, not to mention numerous other allergic and inflammatory diseases, are caused by these mediators.
- Therapies are being developed to block the histamine and/or cys- leukotriene effect, or stabilize the mast cell and prevent its degranulation.
- the MCs are involved in uncommon diseases such as Mastocytosis and Mast Cell Activation Disorder.
- mast cells can abnormally release their effector chemicals under little or no provocation. These abnormal mast cells may invade the skin or other organs. Patients can have devastating reactions such as swelling, flushing, chest pain, shortness of breath, abdominal pain, and loss of consciousness. Histamine and the cys-leukotrienes are the predominant chemicals involved in these reactions. Current treatments are aimed at blocking mediators (histamine and cys-leukotrienes) released from mast cells.
- Histamine is a chemical that is naturally made in the body. It is synthesized from the amino acid histidine by L-histidine decarboxylase. Histamine acts through four subtypes of receptors (HI, H2, H3, and H4). When histamine acts through the HI receptor, it contributes to the regulation of cell differentiation, embryonic development, hematopoiesis, wound healing, and plays an important role in neurotransmission in the central nervous system. When it acts via the H2 receptor it contributes to gastric parietal cell function, intestinal function, and helps to regulate cell growth and differentiation. Additionally, there is growing evidence that mast cells worsen the inflammation of ischemic events such as myocardial infarction, cerebral and kidney ischemic disease, and reperfusion mediation or delayed inflammatory reactions that can occur after thermal (hot or cold) or chemical burns.
- ischemic events such as myocardial infarction, cerebral and kidney ischemic disease, and reperfusion mediation or delayed inflammatory reactions that can occur after thermal (hot or cold) or chemical burn
- Leukotrienes are biologically active chemicals released from metabolizing arachidonic acidl6.
- Arachidonic acid is oxygenated by a lipoxygenase to 5-hydroperoxy-6,8,l l,14- eicosatetraenoic acid.
- This product is further converted to leukotrienes by elimination of the 10- pro-R hydrogen and OH from the hydroperoxy group to give 5,6-oxido-7,9,l l, 14- eicosatetraenoic acid (leukotriene A4).
- Nucleophilic opening of the epoxide at C-6 by the sulfhydryl group of glutathione gives leukotriene C4.
- leukotriene B4 This is metabolized to leukotrienes D4 and E4 by sequential elimination of glutamic acid and glycine.
- water may add at C-12 of leukotriene A4, leading also to opening of the epoxide at C-6 with formation of 5,12- dihydroxy-6,8,10,14-eicosatetraenoic acid (leukotriene B4).
- Leukotrienes induce smooth muscle cell contraction (particularly the airways), vascular permeability, and recruitment of leukocytes.
- the leukotrienes are three to four orders of magnitude more potent than histamine and their effects have a longer duration.
- Histamine and leukotrienes play a vital role in the development of inflammation and allergic reactions. Histamine increases antigen-presenting cell capacity, down-regulates the immune response, and increases the release of additional histamine and other mediators from MCs and basophils when acting through the HI receptor. Histamine via the H2 receptor causes release of stomach acid, while performing similar functions to the HI receptor. Leukotrienes are potent bronchoconstrictors and play an additional role in mucociliary clearance and eosinophilic inflammation, which is a hallmark of allergic asthma.
- Antihistamines have been used for decades to treat allergies and inflammatory conditions. HI and H2 antihistamines have been used successfully in allergic rhinitis, allergic conjunctivitis, asthma, urticaria, atopic dermatitis, pruritis, diarrhea, anaphylaxis, mastocytosis, and mast cell activation disorder. Leukotriene receptor antagonists have been used to improve allergic rhinitis, asthma, and urticaria. There have been a multitude of studies showing a synergistic effect when using both antihistamines and leukotriene receptor antagonists to treat these conditions. The main issue when using these medications is compliance.
- An individual being treated with an HI antihistamine, H2 antihistamine and leukotriene receptor antagonist may have to take a medication every 6 hours to achieve symptom relief. At times, they may be asked to take two to four pills/tablets each dosing period for a total of 10 or more pills/tablets per day. This is difficult for most patients to accomplish, especially when asked to do this for months or even years.
- a simple pill/tablet that contains an HI antihistamine and an H2 antihistamine, or HI antihistamine, H2 antihistamine, and leukotriene receptor antagonist taken once to twice a day would improve compliance and hence treatment
- composition comprising an HI antihistamine and a leukotriene receptor antagonist.
- the composition may also comprise an H2 antihistamine.
- the HI antihistamine may be ethylenediamine, ethanolamine, alkylamine, piperazine,
- the leukotriene receptor antagonist may be montelukast, zafirlukast, pranlukast, zileuton, or a pharmaceutically acceptable salt thereof.
- the H2 antihistamine may be cimetidine, ranitidine, famotidine, nizatidine, or a pharmaceutically acceptable salt thereof.
- the composition may further comprise a mast cell stabilizer, which may be cromolyn sodium or ketotifen.
- the composition may be an oral formulation.
- a method for treating an inflammatory or allergic condition comprising administering the composition to a subject in need thereof.
- the inflammatory or allergic condition may be allergic asthma, allergic rhinitis, conjunctivitis, a dermatological condition, atopic dermatitis, mastocytosis, a mast cell activation disorder, allergic urticaria (hives), anaphylaxis, diarrhea, nausea, vomiting, pruritis, or inflammation due to a mast cell mediator, which may be a histamine or cys-leukotriene.
- the combination of an HI antihistamine and leukotriene receptor antagonist, and optionally an H2 antihistamine effectively treats inflammatory and allergic conditions.
- this combination may be particularly advantageous when administered during the acute phase of one of these conditions.
- the patient can experience a more beneficial treatment through the synergistic effects of the combination.
- the chronic phase of these conditions can be more readily treated by the improved compliance of taking fewer doses of the combined treatment agent.
- Treatment when referring to protection of an animal from a disease, means preventing, suppressing, repressing, or completely eliminating the disease.
- Preventing the disease involves administering a composition of the present invention to an animal prior to onset of the disease.
- Suppressing the disease involves administering a composition of the present invention to an animal after induction of the disease but before its clinical appearance.
- Repressing the disease involves administering a composition of the present invention to an animal after clinical appearance of the disease.
- composition comprising an HI antihistamine and a leukotriene receptor antagonist.
- the composition may also comprise an H2 antihistamine.
- the composition may not include a corticosteroid.
- the composition may also comprise a mast cell stabilizer. The composition may increase mast cell stability,
- the HI antihistamine may be a first, second, or third generation HI antihistamine.
- the first generation HI antihistamine may be an ethylenediamine, ethanolamine, alkylamine, piperazine, or tricyclic/tetracyclic antihistamine.
- the ethylenediamine may be mepyramine (pyrilamine), antazoline, or tripelennamine.
- the ethanolamine may be diphenhydramine, carbinoxamine, doxylamine, orphenadrine, bromazine, clemastine, or dimenhydrinate.
- the alkylamine may be pheniramine, chlorphenamine (chlorpheniramine), dexchlorpheniramine, dexbrompheniramine, brompheniramine, triprolidine, or dimetindine.
- the piperazine may be cyclizine, chlorcylizine, hydroxyzine, or meclizine.
- the tricyclic/tetracyclic antihistamine may be promethazine, alimemazine (trimeprazine), cyproheptadine, or azatadine.
- the second generation HI antihistamine may be astemizole, ketotifen, cetirizine, loratadine, rupatadine, mizolastine, acrivastine, ebastine, bilastine, bepotastine, terfenadine, or quifenadine.
- the third generation HI antihistamine may be levocetirizine, desloratidine, fexofenadine, levo-fexofenadine, or des-fexofenadine.
- the HI antihistamine may be a pharmaceutically acceptable salt of an HI antihistamine.
- the HI antihistamine may be fexofenadine, cetirizine, loratadine, levocetirizine, desloratadine, or levo- or des- fexofenadine,
- the leukotriene receptor antagonist may be montelukast, zafirlukast, pranlukast, or zileuton.
- the leukotriene antagonist may also be a pharmaceutically acceptable salt of a leukotriene antagonist.
- the H2 antihistamine may be ranitidine, cimetidine, famotidine, or nizatidine.
- the H2 antihistamine may also be a pharmaceutically acceptable salt of an H2 antihistamine.
- the mast cell stabilizer may be cromolyn sodium or ketotifen.
- the pharmaceutically acceptable salt of the HI antihistamine, H2 antihistamine, or leukotriene receptor antagonist may be a non-toxic acid or base including an inorganic acid or base or organic acid or base.
- the inorganic acid may be hydrochloric, hydrobromic, hydroiodic, sulfuric, or phosphoric.
- the organic acid may be aliphatic, aromatic, carboxylic or a sulfonic class of organic acid.
- the organic acid may be formic, acetic, propionic, succinic, glycolic, glucuronic, maleic, furoic, glutamic, benzoic, anthranilic, salicylic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, pantothenic, benzenesulfonic, stearic, sulfanilic, algenic, or galacturonic.
- the inorganic base may be a metallic salt made from aluminum, calcium, lithium, magnesium, potassium, sodium, or zinc.
- the organic base may be ⁇ , ⁇ -dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumaine (N-methylglucamine), lysine, or procaine.
- the composition may comprise the HI antihistamine, H2 antihistamine, and/or leukotriene receptor antagonist at a dose of about 0.01 mg to about 500 mg.
- the dose may also be about 1 mg to about 500 mg, about 2 mg to about 100 mg, about 5 mg to about 20 mg, about 20 mg to about 200 mg, about 50 mg to about 300 mg, about 150 mg to about 250 mg.
- the dose may be about 1, 5, 20, 40, 60, 80, 100, 180, 225, 350, 400, or 500 mg.
- the composition may comprise about 60 to about 180 mg HI antihistamine, which may be fexofenadine.
- the composition may also comprise about 5 to about 10 mg HI antihistamine, which may be cetirizine or loratidine.
- the composition may comprise about 5 to about 10 mg leukotriene receptor antagonist, which may be montelukast.
- the composition may also comprise about 10 to about 20 mg leukotriene receptor antagonist, which may be zafirlukast.
- the composition may comprise about 10 to about 40 mg H2 antihistamine, which may be famotidine.
- the composition may also comprise about 50 to about 150 mg H2 antihistamine, which may be ranitidine.
- the composition may comprise about 100 to about 300 mg mast cell stabilizer, which may be cromolyn sodium.
- the composition may also comprise about 0.5 to about 2 mg mast cell stabilizer, which may be ketotifen.
- the composition may comprise doses that allow for adequate HI receptor blockade, are well tolerated (that is, have few anticholinergic side effects from the HI antihistamine), and are not generally considered hepatotoxic (due to the H2 antihistamine and leukotriene receptor antagonist).
- the composition may comprise about 60 mg fexofenadine, about 20 mg famotidine, and about 5 mg montelukast, and may be orally administered twice daily.
- the composition may also comprise about 60 mg fexofenadine, about 20 mg famotidine, and about 10 mg montelukast, and may be orally administered once daily.
- the composition may comprise about 180 mg fexofenadine, about 20 mg famotidine, and about 5 mg montelukast, and may be orally administered twice daily.
- the composition may also comprise about 180 mg fexofenadine, about 20 mg famotidine, and about 10 mg montelukast, and may be orally administered once daily.
- the composition may comprise about 180 mg fexofenadine, about 40 mg famotidine, and about 10 mg montelukast, and may be orally administered once daily.
- the composition may comprise about 5 mg cetirizine, about 75 mg ranitidine, and about 5 mg montelukast, and may be orally administered twice daily.
- the composition may also comprise about 5 mg cetirizine, about 75 mg ranitidine, and about 10 mg montelukast, and may be orally administered once daily.
- the composition may comprise about 10 mg cetirizine, about 75 mg ranitidine, and about 5 mg montelukast, and may be orally administered twice daily.
- the composition may comprise about 10 mg cetirizine, about 150 mg ranitidine, and about 10 mg montelukast, and may be administered once daily.
- the combination of a second or third generation HI antihistamine with a leukotriene receptor antagonist may provide a significant benefit as compared to the use of a first generation HI antihistamine.
- the combination of a second or third generation HI antihistamine, H2 antihistamine, and leukotriene receptor antagonist may provide a superior effect both in potency and in length of time of symptoms relief, as compared to the use of a first generation HI antihistamine and to the use of the combination of a second or third generation HI antihistamine with a leukotriene receptor antagonist.
- the composition may comprise about 10 mg cetirizine or about 180 mg fexofenadine, and about 10 mg montelukast; and may also comprise about 40 mg famotidine or about 150 mg ranitidine.
- the composition may also comprise about 180 mg fexofenadine, about 40 mg famotidine, and about 10 mg montelukast.
- the dosages may block multiple targets of mast cell and basophil degranulation while simultaneously providing better control of symptoms and medication compliance by requiring fewer pills to be administered to a subject.
- the famotidine dosage may result in decreased toxicity in comparison to a composition comprising ranitidine
- the fexofenadine dosage may result in decreased somnolence in comparison to a composition comprising cetirizine.
- the composition may be included in a formulation, which may be an oral, topical, ocular, intranasal, or inhaled formulation.
- the formulation may also not be a topical formulation, including an intranasal, pulmonary, or intraocular formulation, and may not contain a mucosal adjuvant.
- the formulation may also not be a parenteral formulation, and may not be formulated for injection, such as intravenous, subcutaneous, or intramuscular.
- the formulation may be as described in U.S. Patent No. 6,224,907; 6,120,803; 6,451,815; 5,007,790; 5,456,918; 5,407,687; or 6,383,471; the contents of which are incorporated herein by reference.
- the formulation may be a sustained release form to provide the rate controlled release of any one or more of the components or active ingredients to optimize the therapeutic effects.
- the sustained release formulation may be a layered tablet containing layers of varying disintegration rates or controlled release polymeric matrices impregnated with the active components and shaped in tablet form or capsules containing such impregnated or encapsulated porous polymeric matrices.
- the composition may be formulated to provide optimum effects and provide benefit to multiple types of subjects.
- the composition may be formulated to provide long-lasting coverage at a constant concentration that extends through the day and night from a single dose.
- the composition may be formulated as a controlled release capsule or tablet, by providing zero order release kinetics of the HI antihistamine, leukotriene receptor antagonist, and/or H2
- composition may also be formulated as a sustained release capsule or table, which may provide a slower increase in therapeutic drug concentrations, with a gradual but more persistent dosing compared with quick release formulations.
- the composition may be formulated for a child subject, who may be younger than about 7 years old, and may be about 5 to 7 years old.
- the subject may be incapable of swallowing a pill, tablet, or gel tablet.
- the composition may thus be formulated as a liquid solution or suspension.
- the composition may also be formulated as a disintegrating pill or chewable tablet.
- the formulation may comprise a pharmaceutical excipient, adjuvant, or carrier.
- the pharmaceutical excipient may be a starch, sugar, lactose, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, talc, mannitol, ethyl alcohol, microcrystalline cellulose, diluent, granulating agent, lubricant, binder, or disintegrating agent.
- composition provided herein may be a solid formulation in the form of capsules, sprinkle formulation, tablets or lozenges formulated in a conventional manner.
- tablets and capsules for oral administration may contain conventional excipients including, but not limited to, powders, diluents, binders, fillers, lubricants, disintegrants, glidents, coloring agents, and wetting agents.
- Fillers include, but are not limited to, lactose, sugar, microcrystalline cellulose, maize starch, calcium phosphate, and sorbitol.
- Wetting agents include, but are not limited to, sodium lauryl sulfate. Tablets may be coated according to methods well known in the art.
- the capsule may be a special container or enclosure made of methyl cellulose, polyvinyl alcohols, or denatured gelatins or starch for holding or containing compositions comprising the active ingredients.
- Hard shell capsules are typically made of blends of relatively high gel strength bone and pork skin gelatins.
- the capsule itself may contain small amounts of dyes, opaquing agents, plasticizers and preservatives.
- the tablet may be a compressed or molded solid dosage form containing the active ingredients with suitable diluents.
- the tablet can be prepared by compression of mixtures or granulations obtained by wet granulation, dry granulation or by compaction.
- the powder may be a powder blend containing the active ingredients and suitable diluents which can be suspended in water or juices.
- the diluent may be a substance that may make up the major portion of the composition or dosage form.
- Suitable diluents include sugars such as lactose, sucrose, mannitol and sorbitol; starches derived from wheat, corn rice, and potato; and celluloses such as microcrystalline cellulose.
- the amount of diluent in the composition can range from about 10 to about 90% by weight of the total composition, preferably from about 25 to about 75%, more preferably from about 30 to about 60% by weight, even more preferably from about 12 to about 60%.
- the disintegrant may be a material added to the composition to help it break apart (disintegrate) and release the medicaments.
- Suitable disintegrants include starches; "cold water soluble” modified starches such as sodium carboxymethyl starch, potato starch, and sodium starch glycollate; natural and synthetic gums such as locust bean, karaya, guar, tragacanth and agar; cellulose derivatives such as methylcellulose and sodium carboxymethylcellulose;
- microcrystalline celluloses and cross-linked microcrystalline celluloses such as sodium croscarmellose; alginates such as alginic acid and sodium alginate; clays such as bentonites; and effervescent mixtures.
- the amount of disintegrant in the composition can range from about 2 to about 15% by weight of the composition, more preferably from about 4 to about 10% by weight.
- the binder may be a substance that binds or "glues" powders together and make them cohesive by forming granules, thus serving as the "adhesive" in the formulation. Binders add cohesive strength already available in the diluent or bulking agent. Suitable binders include sugars such as sucrose; starches derived from wheat, corn rice and potato; natural gums such as acacia, gelatin and tragacanth; derivatives of seaweed such as alginic acid, sodium alginate and ammonium calcium alginate; cellulosic materials such as methylcellulose and sodium
- the binder may be syrup, sorbitol, or mucilage of starch.
- the amount of binder in the composition can range from about 2 to about 20% by weight of the composition, more preferably from about 3 to about 10% by weight, even more preferably from about 3 to about 6% by weight.
- the lubricant may be a substance added to the dosage form to enable the solid dosage form after it has been compressed, to release from the mold or die by reducing friction or wear.
- Suitable lubricants include metallic stearates such as magnesium stearate, calcium stearate or potassium stearate; stearic acid; high melting point waxes; and water soluble lubricants such as sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and d'l- leucine.
- the lubricant may be talc, polyethylene glycol, or silica.
- Lubricants are usually added at the very last step before compression, since they must be present on the surfaces of the granules and in between them and the parts of the tablet press.
- the amount of lubricant in the composition can range from about 0.2 to about 5% by weight of the composition, preferably from about 0.5 to about 2%, more preferably from about 0.3 to about 1.5% by weight.
- the glident may be a material that prevents caking and improve the flow characteristics of granulations, so that flow is smooth and uniform. Suitable glidents include silicon dioxide and talc.
- the amount of glident in the composition can range from about 0.1% to about 5% by weight of the total composition, preferably from about 0.5 to about 2% by weight.
- the coloring agent may be an excipient that provides coloration to the composition or the dosage form. Such excipients can include food grade dyes and food grade dyes adsorbed onto a suitable adsorbent such as clay or aluminum oxide.
- the amount of the coloring agent can vary from about 0.1 to about 5% by weight of the composition, preferably from about 0.1 to about 1%.
- compositions provided herein may also be liquid formulation including, but not limited to, aqueous or oily suspensions, solutions, emulsions, syrups, oral gels, and elixirs.
- the compositions may also be formulated as a dry product for constitution with water or other suitable vehicle before use.
- Such liquid preparations may contain additives including, but not limited to, suspending agents, emulsifying agents, nonaqueous vehicles and preservatives.
- Suspending agent include, but are not limited to, sorbitol syrup, methyl cellulose, glucose/sugar syrup, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminum stearate gel, and hydrogenated edible fats.
- Emulsifying agents include, but are not limited to, lecithin, sorbitan monooleate, and acacia.
- Nonaqueous vehicles include, but are not limited to, edible oils, almond oil, fractionated coconut oil, oily esters, propylene glycol, and ethyl alcohol.
- Preservatives include, but are not limited to, methyl or propyl p-hydroxybenzoate and sorbic acid.
- the oral gels may contain the active ingredients dispersed or solubilized in a hydrophillic semi-solid matrix.
- the pH of the formulation may be about 6.5 to about 7.5, about 6 to about 9, or about 5 to about 10.
- the composition may be administered according to evidence-based guidelines.
- the dosages for the HI antihistamine, leukotriene receptor antagonist, and/or H2 antihistamine may adhere to established dosages already used in clinical practice, which may be approved by the Food and Drug Administration.
- the composition may not be administered or co-administered with a corticosteroid.
- the composition may be selectively delivered to provide the HI antihistamine, leukotriene receptor antagonist, and/or H2 antihistamine at a dosage rate of 0.08 mg/hr up to 20 mg/hr, thereby providing proportional to the administered dose a plasma concentration of 0.01 ⁇ g/ml to 75 ⁇ g/ml.
- the composition may be administered in single or divided doses.
- the composition may be administered about every 6, 8, 12, or 24 hours.
- the composition may be administered once or twice daily.
- a method for treating a disease or condition comprising administering a composition described herein to a subject in need thereof.
- the subject may be a mammal, such as a pig, horse, cow, dog, cat, monkey, ape, or human.
- the subject may not have cardiovascular disease.
- the disease or condition may be an inflammatory or allergic condition, which may be allergic asthma, allergic rhinitis, conjunctivitis, a dermatological condition, atopic dermatitis, mastocytosis, a mast cell activation disorder, allergic urticaria (hives), anaphylaxis, diarrhea, nausea, vomiting, pruritis, or inflammation due to a mast cell mediator, which may be a histamine or cys-leukotriene.
- the asthma may be an inflammation in the lungs that leads to reversible airways hyperreactivity, and may present symptoms of wheezing, chest tightness, shortness of breath, or coughing.
- Allergic asthma may be related to allergic rhinitis,
- the disease or condition may have an acute and chronic stage of inflammation involving the lung, nasal passageway, sinuses, eyes, or skin.
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
La présente invention concerne des compositions comprenant un antihistaminique H1 et un antagoniste du récepteur des leucotriènes, et facultativement un antihistaminique H2 et/ou un stabilisateur de mastocytes acide cromoglycique. L'invention concerne également des procédés de traitement d'états inflammatoires et allergiques à l'aide de ces compositions.
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US201462025314P | 2014-07-16 | 2014-07-16 | |
US62/025,314 | 2014-07-16 |
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WO2016011254A1 true WO2016011254A1 (fr) | 2016-01-21 |
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PCT/US2015/040752 WO2016011254A1 (fr) | 2014-07-16 | 2015-07-16 | Combinaisons d'antihistaminiques et d'antagonistes anti-leucotriène et procédés d'utilisation associés |
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Cited By (8)
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US10238625B2 (en) | 2015-08-07 | 2019-03-26 | Respivant Sciences Gmbh | Methods for the treatment of mast cell related disorders with mast cell stabilizers |
US10238628B2 (en) | 2014-02-10 | 2019-03-26 | Respivant Sciences Gmbh | Mast cell stabilizers treatment for systemic disorders |
US10265296B2 (en) | 2015-08-07 | 2019-04-23 | Respivant Sciences Gmbh | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
US10265267B2 (en) | 2016-08-31 | 2019-04-23 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
US10561635B2 (en) | 2016-10-07 | 2020-02-18 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of pulmonary fibrosis |
US10835512B2 (en) | 2014-02-10 | 2020-11-17 | Respivant Sciences Gmbh | Methods of treating respiratory syncytial virus infections |
IT201900012645A1 (it) * | 2019-07-23 | 2021-01-23 | Eros Zanotti | Una composizione farmaceutica per l'uso nel trattamento delle chinetosi |
US11478463B2 (en) * | 2016-10-18 | 2022-10-25 | Emergo Therapeutics, Inc. | Mast cell stabilizers for treatment of chronic inflammatory conditions |
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US10238628B2 (en) | 2014-02-10 | 2019-03-26 | Respivant Sciences Gmbh | Mast cell stabilizers treatment for systemic disorders |
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US10835512B2 (en) | 2014-02-10 | 2020-11-17 | Respivant Sciences Gmbh | Methods of treating respiratory syncytial virus infections |
US10596146B2 (en) | 2015-08-07 | 2020-03-24 | Respivant Sciences Gmbh | Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders |
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US10265267B2 (en) | 2016-08-31 | 2019-04-23 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
US10463613B2 (en) | 2016-08-31 | 2019-11-05 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of chronic cough due to idiopathic pulmonary fibrosis |
US10583113B2 (en) | 2016-10-07 | 2020-03-10 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of pulmonary fibrosis |
US10561635B2 (en) | 2016-10-07 | 2020-02-18 | Respivant Sciences Gmbh | Cromolyn compositions for treatment of pulmonary fibrosis |
US11478463B2 (en) * | 2016-10-18 | 2022-10-25 | Emergo Therapeutics, Inc. | Mast cell stabilizers for treatment of chronic inflammatory conditions |
IT201900012645A1 (it) * | 2019-07-23 | 2021-01-23 | Eros Zanotti | Una composizione farmaceutica per l'uso nel trattamento delle chinetosi |
WO2021014370A1 (fr) * | 2019-07-23 | 2021-01-28 | Zanotti Eros | Composition pharmaceutique destinée à¨être utilisée dans le traitement et la prévention du mal des transports |
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