EP1119372A1 - Composition et procede pour le traitement d'allergies - Google Patents

Composition et procede pour le traitement d'allergies

Info

Publication number
EP1119372A1
EP1119372A1 EP99951477A EP99951477A EP1119372A1 EP 1119372 A1 EP1119372 A1 EP 1119372A1 EP 99951477 A EP99951477 A EP 99951477A EP 99951477 A EP99951477 A EP 99951477A EP 1119372 A1 EP1119372 A1 EP 1119372A1
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
antagonist
pharmaceutically acceptable
alkyl
acceptable derivative
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99951477A
Other languages
German (de)
English (en)
Inventor
Neng-Yang Shih
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme Corp
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Corp filed Critical Schering Corp
Publication of EP1119372A1 publication Critical patent/EP1119372A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention generally relates to compositions and methods for treating allergic rhinitis and other respiratory diseases. It specifically discloses compositions which comprise (i) combinations of antagonists of neurokinin receptors and antagonists of leukotriene receptors, and (ii) combinations of antagonists of neurokinin receptors and inhibitors of 5- lipoxygenase, as well as methods for treating the above-noted diseases using such compositions.
  • NK receptors such as the N ⁇ and the NK 2 receptors are found in the central nervous system and the circulatory system and the peripheral tissues of mammals, and are involved in a variety of biological processes. Antagonists of the neurokinin receptors are, therefore, expected to be useful in the treatment or prevention of various mammalian diseases such as, for example, pulmonary disorders such as asthma, cough, bronchospasm, chronic obstructive pulmonary diseases, and airway hyperactivity; skin disorders and itch, for example, atopic dermatitis, and cutaneous wheal and flare; neurogenic inflammatory diseases such as, arthritis, migraine, nociception; CNS diseases such as anxiety, emesis, Parkinson's disease, movement disorders and psychosis; convulsive disorders, renal disorders, urinary incontinence, ocular inflammation,, inflammatory pain, and eating disorders such as food intake inhibition; allergic rhinitis, neurodegenerative disorders, psoriasis, Huntington's disease
  • N ⁇ receptors have been reported to be involved in microvascular leakage and mucus secretion, and NK 2 receptors have been associated with smooth muscle contraction, making NK 1 and NK 2 receptor antagonists especially useful in the treatment and prevention of asthma.
  • NK 1 and NK 2 receptor antagonists have been reported such as, for example, in U.S. patents 5,798,359; 5,795,894; 5,789,422; 5,783,579; 5,719,156; 5,696,267; 5,691 ,362; 5,688,960; 5,654,316 (all assigned to Schering-Plough Corporation, Madison, New Jersey); and in "Recent Advances in Neurokinin Receptor Antagonists", by C. J. Ohnmacht Jr., et al, Annual Reports in Medicinal Chemistry, A. M. Doherty Ed., 33, 71-80 (1998).
  • 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism, particularly the leukotrienes, can mediate bronchoconstriction, mucous secretion, airway mucosal edema, chemotaxis and mobilization of cells into the airway in the inflammatory process of asthma. Therefore, inhibition of 5-LO should help cure, reduce or prevent such diseases.
  • leukotriene (“LK”) antagonists play a role in treating the multitude of symptoms associated with diseases of the respiratory tract, such as season allergic rhinitis, perennial allergic rhinitis, common colds, sinusitis and concomitant symptoms associated with allergic asthma.
  • the symptoms of such diseases may include sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, and coughs associated with postnasal drip.
  • a discussion of leukotriene receptors may be found in R. Robertson, Prostaglandins, 31, 395 (1986), and a discussion of leukotriene antagonists can be found in J. Musser et al, Agents and Actions, 1J3, 332 (1986), J. Piwinski et al, Annual Reports in Medicinal Chemistry, 22, 73-76 (1987), and R. Bell et al, Annual Reports in Medicinal Chemistry, 32, 91 (1997).
  • the afore-mentioned objective and other objectives and desires are addressed by the present invention which, in one embodiment, provides a composition for treating and preventing allergic rhinitis and other respiratory diseases such asthma, cough, wheezing and the like.
  • the inventive composition comprises, in combination, a therapeutically effective amount of at least one neurokinin antagonist and a therapeutically effective amount of at least one leukotriene antagonist.
  • One or more of the antagonists may be substituted by a pharmaceutically acceptable derivative such as salt, ester, and the like.
  • the composition may additionally contain a pharmaceutically acceptable carrier, a decongestant (such as, for example, pseudoephedrine), a cough suppressant (such as, for example, dexrtomethorphan), expectorant (such as, for example, guaifenesin), analgesics (such as, for example, aspirin, ibuprofen and acetaminophen) or mixtures thereof.
  • a decongestant such as, for example, pseudoephedrine
  • a cough suppressant such as, for example, dexrtomethorphan
  • expectorant such as, for example, guaifenesin
  • analgesics such as, for example, aspirin, ibuprofen and acetaminophen
  • the amount of the neurokinin antagonist content in the inventive composition per unit dosage form is about 1-1 ,000 milligrams and that of the leukotriene antagonist is about 2-500 milligrams.
  • the respective amounts are about 10-500 milligrams and about 5-500 milligrams, and typically the respective amounts are about 50-200 milligrams and 10-50 milligrams.
  • the present invention additionally provides a composition for treating and preventing allergic rhinitis and other respiratory diseases such asthma, cough, wheezing and the like, the composition comprising, in combination, a therapeutically effective amount of at least one neurokinin antagonist and a therapeutically effective amount of at least one 5-LO inhibitor.
  • a pharmaceutically acceptable derivative such as salt, ester, and the like.
  • the composition may contain a pharmaceutically acceptable carrier, a decongestant, a cough suppressant, and expectorant, or mixtures thereof.
  • the invention further provides methods for treating asthma, chronic obstructive pulmonary disease ("COPD”), and allergic disorders, sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, sinusitis, and coughs associated with postnasal drip symptoms in a mammalian organism in need of such treatment comprising administering the pharmaceutical compositions described above.
  • COPD chronic obstructive pulmonary disease
  • the present invention discloses pharmaceutical compositions that are useful in treating and preventing allergic rhinitis, asthma and related disorders.
  • the composition comprises, in combination, a therapeutically effective amount of at least one neurokinin antagonist and a therapeutically effective amount of at least one leukotriene antagonist.
  • One or more of the antagonists may be substituted by a pharmaceutically acceptable derivative such as salt, ester, and the like.
  • Several neurokinin antagonists that are known currently are useful in the practice of the present invention.
  • Non-limiting examples of such useful neurokinin antagonists include, for example, those belonging to the chemical class of oximes, hydrazones, piperidines, piperazines, aryl alkyl amines, hydrazones, nitroalkanes, amides, isoxazolines, quinolines, isoquinolines, azanorbornanes, naphthyridines, benzodiazepines and the like. Many are disclosed in the U.S. patents cited earlier in this patent application. Preferred NK antagonists are those disclosed in the above- noted U.S.
  • P is R 5 -aryl; or R 5 -heteroaryl
  • X is -0-; -NR 6 -; -N(R 6 )CO-; or -CO-NR 6 -;
  • T is R 4 -aryl; R 4 -heteroaryl; R 4 -cycloalkyl; or R 2 -bridged cycloalkyl;
  • G is H; R 4 -aryl; R 4 -heteroaryl; COR 6 ; C0 2 R 6 ; CONR 6 R 7 ; CN; OCOR 6 ; S0 3 R 2 ;
  • R 2 and R 3 are independently H or C ⁇ C g alkyl;
  • R 4 and R 5 are independently 1 , 2 or 3 substituents independently selected from OR 2 , OC(0)R 2 , OC(0)NR 6 R 7 , C C 6 alkyl, H, halogen, CF 3 , C 2 F 5 , or OCF 3 ; and
  • R 6 and R 7 are independently selected from H or C ⁇ C- g alkyl, with the proviso that when R 6 and R 7 are part of NR 6 R 7 then said NR 6 R 7 may form part of a C 5 - C 6 ring wherein 0-2 ring members are selected from the group consisting of - 0-, -S- and -NR 2 -, with the further proviso that said C 5 -C 6 ring may contain substituents on said ring with said substituents being selected from the group consisting of hydrogen, halogen, -OR 6 and -COOR 6 .
  • Particularly preferred neurokinin antagonists are those disclosed in the above-mentioned U.S. patents, and belonging to the general formula:
  • stereoisomers thereof. More particularly preferred are the stereoisomers with the general formula:
  • R is H; CH 2 CONH 2 ; CH 2 CONHMe; CH 2 CONMe 2 or
  • leukotriene antagonists useful in the practice of the present invention include montelukast (from Merck & Company), pranlukast (from Ono Pharmaceutical Company Limited, CAS Registry Number: 103177-37-3), zafirlukast (from Zeneca Pharmaceuticals; CAS Registry Number: 107753-78-6), CP-195494 (from Pfizer, Incorporated), and the like.
  • montelukast is [R-(E)]-1- [[[1 -[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1 -hydroxy-1 - methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid.
  • the technical name of pranlukast is N-[4-oxo-2-(1 H-tetrazol-5-yl)-4H-1- ' benzopyran-8-yl]-4-(4-phenylbutoxy)-benzamide.
  • zafirlukast is [3-[[2-methoxy-4-[[[2- methylphenyl)sulfonyl]amino]carbonyl]phenyl]methyl]-1-methyl-1 H-indol-5- yl]-carbamic acid, cyclopentylester, disclosed in EP-00199543.
  • a particularly useful leukotriene is montelukast.
  • Montelukast is a leukotriene D4 antagonist capable of antagonizing the receptors for the cysteinyl leukotrienes. This compound is described in EP 480,717.
  • a preferred pharmaceutically acceptable salt of montelukast is the monosodium salt, also known as montelukast sodium (CAS Registry Number: 151767-02-1).
  • this invention discloses other pharmaceutical compositions that are useful in treating and preventing allergic rhinitis, asthma and related disorders.
  • the composition comprises, in combination, a therapeutically effective amount of at least one neurokinin antagonist and a therapeutically effective amount of at least one inhibitor of 5-lipoxygenase.
  • One or more of the compounds may be substituted by a pharmaceutically acceptable derivative such as salt, ester, and the like.
  • Non-limiting examples of useful neurokinin antagonists are those that are disclosed in the above-cited U.S. patents, including, for example, the compounds where R is H; CH 2 CONH 2 ; CH 2 CONHMe; CH 2 CONMe 2 or
  • Useful 5-LO inhibitors include, for example, Zileuton (from Abbott Laboratories, CAS Registry Number: 111406-87-2) and Atreluton (from Abbott Laboratories, CAS Registry Number: 154355-76-7).
  • the technical name of Zileuton is N-(1-benzo[b]thien-2-ylethyl)-N-hydroxy-urea.
  • the technical name of Atreluton is N-[(1 R)-3-[5-[(4-fluorophenyl)methyl]-2- thienyl]-1-methyl-2-propynyl]-N-hydroxyurea.
  • this invention discloses a method for the treatment of asthma, allergic rhinitis, and other allergic disorders, sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, wheezing, sinusitis, and coughs associated with postnasal drip symptoms in a mammalian organism in need of such treatment comprising administering a pharmaceutical composition which comprises the neurokinin antagonist and the leukotriene antagonist as described above.
  • the present invention teaches a method for the treatment of asthma, allergic rhinitis, and other allergic disorders, sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, wheezing, sinusitis, and coughs associated with postnasal drip symptoms in a mammalian organism in need of such treatment comprising administering a pharmaceutical composition which comprises the neurokinin antagonist and the 5-LO inhibitor as described above.
  • the active ingredients will typically be administered in admixture with suitable pharmaceutical diluents, excipients or carriers (collectively referred to herein as carrier materials) suitably selected with respect to the intended form of administration, i.e. oral tablets, capsules (either solid-filled, semi-solid filled or liquid filled), powders for constitution, oral gels, elixirs, dispersible granules, syrups, suspensions, and the like, and consistent with conventional pharmaceutical practices.
  • suitable pharmaceutical diluents, excipients or carriers collectively referred to herein as carrier materials
  • suitable pharmaceutical diluents, excipients or carriers suitably selected with respect to the intended form of administration, i.e. oral tablets, capsules (either solid-filled, semi-solid filled or liquid filled), powders for constitution, oral gels, elixirs, dispersible granules, syrups, suspensions, and the like, and consistent with conventional pharmaceutical practices.
  • the active drug component may be combined with any oral non-toxic pharmaceutically acceptable inert carrier, such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, talc, mannitol, ethyl alcohol (liquid forms) and the like.
  • suitable binders, lubricants, disintegrating agents and coloring agents may also be incorporated in the mixture.
  • Powders and tablets may be comprised of from about 5 to about 95 percent inventive composition.
  • Suitable binders include starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes.
  • lubricants there may be mentioned for use in these dosage forms, boric acid, sodium benzoate, sodium acetate, sodium chloride, and the like.
  • Disintegrants include starch, methylcellulose, guar gum and the like. Sweetening and flavoring agents and preservatives may also be included where appropriate.
  • compositions of the present invention may be formulated in 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, i.e. neurokinin antagonism, leukotriene antagonism, 5- LO inhibition and the like.
  • Suitable dosage forms for sustained release include layered tablets 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.
  • Liquid form preparations include solutions, suspensions and emulsions. As an example may be mentioned water or water-propylene glycol solutions for parenteral injections or addition of sweeteners and opacifiers for oral solutions, suspensions and emulsions. Liquid form preparations may also include solutions for intranasal administration.
  • Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be in combination with a pharmaceutically acceptable carrier such as inert compressed gas, e.g. nitrogen.
  • a pharmaceutically acceptable carrier such as inert compressed gas, e.g. nitrogen.
  • a low melting wax such as a mixture of fatty acid glycerides such as cocoa butter is first melted, and the active ingredient is dispersed homogeneously therein by stirring or similar mixing. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool and thereby solidify.
  • solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for either oral or parenteral administration.
  • liquid forms include solutions, suspensions and emulsions.
  • the compounds of the invention may also be deliverable transdermally.
  • the transdermal compositions may take the form of creams, lotions, aerosols and/or emulsions and can be included in a transdermal patch of the matrix or reservoir type as a re conventional in the art for this purpose.
  • the compound is administered orally.
  • the pharmaceutical preparation is in a unit dosage form.
  • the preparation is subdivided into suitably sized unit doses containing appropriate quantities of the active components, e.g., an effective amount to achieve the desired purpose.
  • the quantity of the inventive active composition in a unit dose of preparation may be generally varied or adjusted from about 0.01 milligrams to about 1 ,000 milligrams, preferably from about 0.01 to about 750 milligrams, more preferably from about 0.01 to about 500 milligrams, and typically from about 0.01 to about 250 milligrams, according to the particular application.
  • the actual dosage employed may be varied depending upon the patient's age, sex, weight and severity of the condition being treated. Such techniques are well known to those skilled in the art.
  • the human oral dosage form containing the active ingredients can be administered 1 or 2 times per day. The amount and frequency of the administration will be regulated according to the judgment of the attending clinician.
  • a generally recommended daily dosage regimen for oral administration may range from about 0.04 milligrams to about 4,000 milligrams per day, in single or divided doses.
  • Capsule - refers to 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.
  • Tablet- refers to 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.
  • Oral gels refer to the active ingredients dispersed or solubilized in a hydrophil ⁇ c semi-solid matrix.
  • Powders for constitution refers to powder blends containing the active ingredients and suitable diluents which can be suspended in water or juices.
  • Diluent - refers to substances that usually 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, com 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%.
  • Disintegrants refers to materials 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; 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.
  • Binders - refers to substances that bind or "glue” 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 carboxymethylcellulose and hydroxypropylmethylcellulose; polyvinylpyrrolidone; and inorganics such as magnesium aluminum silicate.
  • 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.
  • Lubricant - refers to a substance added to the dosage form to enable the tablet, granules, etc. 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. 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.
  • 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.
  • Coloring agents - excipients that provide coloration to the composition or the dosage form.
  • 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%.
  • Bioavailability - refers to the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed into the systemic circulation from an administered dosage form as compared to a standard or control.
  • Conventional methods for preparing tablets are known. Such methods include dry methods such as direct compression and compression of granulation produced by compaction, or wet methods or other special procedures. Conventional methods for making other forms for administration such as, for example, capsules, suppositories and the like are also well known.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Otolaryngology (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Cette invention concerne une composition pharmaceutique permettant de traiter la rhinite allergique, l'asthme ainsi que les troubles apparentés. Dans un mode de réalisation, cette composition comprend une combinaison des éléments suivants dans des quantités suffisantes pour avoir un effet thérapeutique: au moins un antagoniste de neurokinine, et au moins un inhibiteur de 5-lipoxygénase.
EP99951477A 1998-10-09 1999-10-06 Composition et procede pour le traitement d'allergies Withdrawn EP1119372A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US16960998A 1998-10-09 1998-10-09
US169609 1998-10-09
PCT/US1999/021438 WO2000021564A1 (fr) 1998-10-09 1999-10-06 Composition et procede pour le traitement d'allergies

Publications (1)

Publication Number Publication Date
EP1119372A1 true EP1119372A1 (fr) 2001-08-01

Family

ID=22616408

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99951477A Withdrawn EP1119372A1 (fr) 1998-10-09 1999-10-06 Composition et procede pour le traitement d'allergies

Country Status (9)

Country Link
EP (1) EP1119372A1 (fr)
JP (1) JP2002527406A (fr)
CN (1) CN1329505A (fr)
AR (1) AR020741A1 (fr)
AU (1) AU6391199A (fr)
CA (1) CA2346228A1 (fr)
CO (1) CO5140080A1 (fr)
PE (1) PE20001095A1 (fr)
WO (1) WO2000021564A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004091618A1 (fr) * 2003-04-15 2004-10-28 Merck Frosst Canada Ltd. Forme polymorphe de sodium de montelukast
BRPI0513351A (pt) * 2004-07-14 2008-05-06 Inflammation Res Ct Company Lt métodos para inibir metástase de tumor, e inibir adesão de célula de tumor às células endotelias e/ou inibir a permeabilidade capilar na forma de migração transendotelial de células de tumor, método de triagem para um inibidor da permeabilidade capilar para células de tumor, e, uso de um antagonista de leucotrieno ou um sal do mesmo farmaceuticamente aceitável
BRPI0807972A2 (pt) 2007-01-24 2014-06-10 Glaxo Group Ltd Composições farmacêuticas compreendendo 3,5-diamino-6-(2,3-diclofenil)-l,2,4-triazina ou r(-)-2,4-diamino-5-(2,3-diclorofenil)-6-fluorometilpirim idina e uma nk1

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9415997D0 (en) * 1994-08-08 1994-09-28 Merck Sharp & Dohme Therapeutic agents
RU2180852C2 (ru) * 1994-12-12 2002-03-27 Омерос Медикл Системс, Инк. Ингибирующий раствор и способ подавления боли, воспаления или спазма
GB9521781D0 (en) * 1995-10-24 1996-01-03 Merck Sharp & Dohme Therapeutic agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0021564A1 *

Also Published As

Publication number Publication date
AU6391199A (en) 2000-05-01
AR020741A1 (es) 2002-05-29
PE20001095A1 (es) 2000-10-31
CN1329505A (zh) 2002-01-02
WO2000021564A1 (fr) 2000-04-20
CO5140080A1 (es) 2002-03-22
CA2346228A1 (fr) 2000-04-20
JP2002527406A (ja) 2002-08-27

Similar Documents

Publication Publication Date Title
AU758771B2 (en) Composition for treating respiratory and skin diseases, comprising at least one leukotriene antagonist and at least one antihistamine
RU2384333C2 (ru) Применение флибансерина для лечения предменструальных и иных сексуальных расстройств у женщин
JP6827948B2 (ja) 呼吸器疾患の治療
JP2012067134A (ja) 性的障害の治療におけるフリバンセリンの使用
EP2463289A1 (fr) Dérivés imidazo[1,2-b]pyridazine en tant qu'inhibiteur JAK
EP2527344A1 (fr) Dérivés de pyridin-2(1h)-one utiles comme médicaments pour le traitement de maladies myeloproliferatives, de rejets de greffe, de maladies a médiation immune et de maladies inflammatoires
AU6564301A (en) Pharmaceutical combinations for the treatment of stroke and traumatic brain injury
JPH0291068A (ja) 化合物
US6103735A (en) Composition and method for treating allergic diseases
JPH01502186A (ja) 中止症候群の予防の治療薬
US6262077B1 (en) Composition and method for treating allergic diseases
JP2010539130A (ja) 血管運動症状の治療
WO2000021564A1 (fr) Composition et procede pour le traitement d'allergies
EP1429843B1 (fr) Combinaison d'un inhibiteur de pde et d'un antagoniste du recepteur de leukotriene
JP2002527381A (ja) アレルギー性疾患を処置するための組成物および方法
MXPA01003648A (en) Composition and method for treating allergic diseases
WO2005089748A1 (fr) Combinaison pour traitement de maladies inflammatoires
EP1212054A2 (fr) Composes chimiques - ii
JPH04128227A (ja) 医薬組成物
JP2002520364A (ja) 治療方法
JPH05500060A (ja) 置換キノリン類
JP2010518040A (ja) 不眠症を治療するためのフリバンセリンの使用
MXPA00006254A (en) Composition for treating respiratory and skin diseases, comprising at least one leukotriene antagonist and at least one antihistamine
NZ524168A (en) Use of a thrombolytic agent and an NR2B subtype selective NMDA receptor antagonizing compound in combination for the treatment of stroke and traumatic brain injury

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010503

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO PAYMENT 20010503;SI PAYMENT 20010503

17Q First examination report despatched

Effective date: 20010905

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

18W Application withdrawn

Effective date: 20030519

REG Reference to a national code

Ref country code: HK

Ref legal event code: WD

Ref document number: 1034675

Country of ref document: HK