WO2002019995A2 - Utilisation d'une combinaison pharmaceutique - Google Patents

Utilisation d'une combinaison pharmaceutique Download PDF

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Publication number
WO2002019995A2
WO2002019995A2 PCT/GB2001/004001 GB0104001W WO0219995A2 WO 2002019995 A2 WO2002019995 A2 WO 2002019995A2 GB 0104001 W GB0104001 W GB 0104001W WO 0219995 A2 WO0219995 A2 WO 0219995A2
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WO
WIPO (PCT)
Prior art keywords
salmeterol
fluticasone propionate
rhinitis
physiologically acceptable
acceptable salt
Prior art date
Application number
PCT/GB2001/004001
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English (en)
Other versions
WO2002019995A3 (fr
Inventor
Smithkline Glaxo
Original Assignee
Glaxo Group Limited
Smithkline Glaxo
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 Glaxo Group Limited, Smithkline Glaxo filed Critical Glaxo Group Limited
Priority to AU2001284287A priority Critical patent/AU2001284287A1/en
Publication of WO2002019995A2 publication Critical patent/WO2002019995A2/fr
Publication of WO2002019995A3 publication Critical patent/WO2002019995A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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

Definitions

  • the present invention relates to the use of salmeterol and fluticasone propionate combinations for the treatment of rhinitis.
  • beta-2 adrenergic agonist salmeterol or a physiologically acceptable salt thereof has been described in GB 2 235 627 for use in the treatment of asthma and other respiratory disorders.
  • Fluticasone propionate is itself known from GB 2 088 877 to have anu- inflammatory activity and to be useful for the treatment of allergic and inflammatory conditions of the nose, throat, or lungs such as asthma and rhinitis, including hay fever.
  • Salmeterol is known from GB 2 140 800 and is used clinically in the form of its xinafoate salt for the treatment of asthma. There is no precedent for the use of a beta-2 adrenergic agonist, in particular salmeterol in combination with a corticosteroid as an effective therapy for rhinitis.
  • Rhinitis is characterised by a combination of sneezing, nasal discharge and blockage lasting at least ah hour on most days.
  • rhinitis includes allergic rhinitis which may be seasonal as in hay fever, or perennial, and non-allergic rhinitis.
  • the present invention also relates to the treatment of sinusitis.
  • rhinitis also includes sinusitis whether present as a complication of rhinitis or not.
  • the present invention relates to treatment of allergic rhinitis, meaning rhinitis caused by an allergen to which the patient is exposed such as pollen, dust, danders, food, and mould.
  • Allergic rhinitis is characterised by sudden attacks of sneezing, swelling of the nasal mucosa with watery discharge, itching of the eyes and lacrimation.
  • the present invention provides a method for prophylaxis or treatment of rhinitis in a mammal, such as a human, which comprises administering an effective amount of a combination of salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and fluticasone propionate.
  • a method for prophylaxis or treatment of allergic rhinitis in a mammal, such as a human which comprises administering an effective amount of a combination " of salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and fluticasone propionate.
  • a combination of salmeterol or a physiologically acceptable salt thereof such as the xinafoate salt, and fluticasone propionate for the manufacture of a medicament for the prophylaxis or treatment of rhinitis.
  • a combination of salmeterol or a physiologically acceptable salt thereof such as the xinafoate salt, and fluticasone propionate for the manufacture of a medicament for prophylaxis or treatment of allergi ⁇ rhinitis.
  • treatment means the improvement of clinical outcome, for example, alleviation of the symptoms of rhinitis, in particular reduction of sneezing, itching nose, runny nose, nasal blockage, and/or itching eyes.
  • treatment of rhinitis includes a reduction of complications such as sinusitis and otitis media.
  • the compounds of the salmeterol and fluticasone propionate combination may be administered simultaneously, either in the same or different pharmaceutical formulations, or sequentially. Where there is sequential administration, the delay in administering the second and any subsequent active ingredient should not be such as to lose the beneficial therapeutic effect of the combination of the active ingredients.
  • the salmeterol or its physiologically acceptable salt and the fluticasone propionate are administered as a combined pharmaceutical formulation.
  • the weight/weight ratio of salmeterol to fluticasone administered according to the invention is preferably in the range 4:1 to 1 :20.
  • the amount of salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and fluticasone propionate which is required to achieve a therapeutic effect will, of course, vary with the particular salt form, the route of administration, the subject under treatment, and the particular disorder or disease being treated.
  • the combination of the invention may be administered intranasally to an adult human at a dose of from 50 ⁇ g to 2000 ⁇ g per day, suitably 50 ⁇ g to 500 ⁇ g per day, more suitably 100 ⁇ g to 400 ⁇ g per day of fluticasone propionate and 50 ⁇ g to 200 ⁇ g per day, suitably 50 ⁇ g to 10O ⁇ g per day of salmeterol.
  • the daily dose may be administered as several sub-doses, for example, twice daily, but will preferably be administered once daily
  • salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and fluticasone propionate it is preferable to present each of them as a pharmaceutical formulation.
  • a pharmaceutical formulation for the prophylaxis or treatment of rhinitis comprising salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and fluticasone propionate, and a pharmaceutically acceptable carrier or excipient, and optionally one or more other therapeutic agents.
  • the pharmaceutical formulation is in a form which is suitable for intranasal administration.
  • active ingredient means salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and/or fluticasone propionate.
  • Suitable formulations include those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous and intraarticular), inhalation (including fine particle dusts or mists which may be generated by means of various types of metered dose pressurised aerosols, nebulisers or insufflators), rectal and topical (including dermal, buccal, sublingual and intraocular) administration although the most suitable route may depend upon for example the condition and disorder of the recipient.
  • the formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing the active ingredient into association with the carrier which constitutes one or more accessory ingredients. In general the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.
  • the pharmaceutical formulations used in accordance with the present invention are suitable for intranasal administration.
  • Intranasal formulations may be in the form of powder compositions which will preferably contain lactose, or spray compositions which may be formulated, for example, as aqueous solutions or suspensions or as aerosols delivered from pressurised packs, with the use of a suitable propellant, e.g. dichlorodifluoromethane, trichlorofluoromethane, dichlorotetra-fluoroethane, 1 ,1 ,1 ,2,3,3,3-heptafluoro- propane, 1 ,1 ,1 ,2-tetrafluoroethane, carbon dioxide or other suitable gas.
  • Suitable aerosol spray compositions for use in accordance with the invention are described in WO 93/11743.
  • Intranasal sprays may be formulated with aqueous or non-aqueous vehicles with the addition of agents such as thickening agents, buffer salts or acid or alkali to adjust the pH, isotonicity adjusting agents or anti-oxidants.
  • agents such as thickening agents, buffer salts or acid or alkali to adjust the pH, isotonicity adjusting agents or anti-oxidants.
  • Capsules and cartridges of for example gelatin, or blisters of for example laminated aluminium foil, for use in an inhaler or insuflator may be formulated containing a powder mix of a compound of the invention and a suitable powder base such as lactose or starch.
  • Solutions for inhalation by nebulisation may be formulated with an aqueous vehicle with the addition of agents such as acid or alkali, buffer salts, isotonicity adjusting agents or antimicrobials. They may be sterilised by filtration or heating in an autoclave, or presented as a non-sterile product.
  • the formulations used according to the invention may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavouring agents.
  • the combination of salmeterol or a physiologically acceptable salt thereof, such as the xinafoate salt, and fluticasone propionate used according to the present invention may be used in combination with a further active ingredient, for example an antihistamine such as terfenidine, astemizole, cetirizine, loratidine, chlorpheniramine, clemastine, hydroxyzine, cyproheptadine, ketotifen, levocabastinem or azelastine, a decongestant such as ephidrine, pseudoephidrine, or phenylpropanolamine, an anticholinergic such as ipratropium, tiotropium or oxitropium, another anti- inflammatory agent such as cromogly
  • Example 1 25/50 salmeterol/fluticasone propionate metered dose inhaler
  • micronised active ingredients are weighed into an aluminium can, 1 ,1 ,1 ,2- tetrafluoroethane is then added from a vacuum flask and a metering valve is crimped into place.
  • Example 2 25/125 salmeterol/fluticasone propionate metered dose inhaler
  • a randomised , placebo-controlled, double-blind, cross-over study was conducted which compared the effects of the nasal fluticasone propionate (FP, data not shown), fluticasone propionate and salmeterol combination (FSC) and placebo, on nasal clinical symptoms and nasal blockage following intranasal allergen challenge.
  • the study was conducted in 47 subjects with a history of allergic rhinitis to grass pollen, outside the grass pollen season. Subjects were treated for 7 days with either FP (200mcg/day), FSC (200/1 OOmcg/day; FP/salmete ' rol) or placebo, delivered via a metered-dose inhaler (MDI) with a nasal actuator. On Day 7, subjects were challenged with timothy grass pollen extract.
  • MDI metered-dose inhaler
  • CAT categorical nasal symptom score
  • VAS visual analogue score
  • PNIF peak inspiratory nasal flow
  • Nasal symptoms and PNIF were recorded at intervals over a 10.5h period post challenge and the mean total symptom score determined.

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

Abstract

L'invention concerne l'utilisation de combinaisons de salmétérol et de propionate de fluticasone pour la prévention et le traitement des rhinites.
PCT/GB2001/004001 2000-09-07 2001-09-06 Utilisation d'une combinaison pharmaceutique WO2002019995A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001284287A AU2001284287A1 (en) 2000-09-07 2001-09-06 Pharmaceutical combination containing salmeterol and fluticasone

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0021927.9 2000-09-07
GBGB0021927.9A GB0021927D0 (en) 2000-09-07 2000-09-07 Use of pharmaceutical combination

Publications (2)

Publication Number Publication Date
WO2002019995A2 true WO2002019995A2 (fr) 2002-03-14
WO2002019995A3 WO2002019995A3 (fr) 2002-08-22

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2001/004001 WO2002019995A2 (fr) 2000-09-07 2001-09-06 Utilisation d'une combinaison pharmaceutique

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AU (1) AU2001284287A1 (fr)
GB (1) GB0021927D0 (fr)
WO (1) WO2002019995A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003033000A1 (fr) * 2001-10-12 2003-04-24 Glaxo Group Limited Combinaisons pharmaceutiques comprenant du salmeterol et du propionate de fluticasone pour le traitement de l'asthme

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0416925A2 (fr) * 1989-09-07 1991-03-13 Glaxo Group Limited Utilisation du 4-hydroxy-alpha 1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol ou ses sels dans le traitement de l'allergie et de l'inflammation
WO1997046243A1 (fr) * 1996-06-04 1997-12-11 The Procter & Gamble Company Aerosol nasal contenant un steroide intranasal et un antihistaminique
WO1998017676A1 (fr) * 1996-10-24 1998-04-30 Glaxo Group Limited Nouvelle forme cristalline polymorphe de propionate de fluticasone, son procede de production et des compositions pharmaceutiques la renfermant
WO2001028535A2 (fr) * 1999-10-21 2001-04-26 Glaxo Group Limited Formulations pharmaceutiques
WO2001047493A1 (fr) * 1999-12-24 2001-07-05 Glaxo Group Limited Formulation pharmaceutique en aerosol de salmeterol et de propionate de fluticasone

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0416925A2 (fr) * 1989-09-07 1991-03-13 Glaxo Group Limited Utilisation du 4-hydroxy-alpha 1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol ou ses sels dans le traitement de l'allergie et de l'inflammation
WO1997046243A1 (fr) * 1996-06-04 1997-12-11 The Procter & Gamble Company Aerosol nasal contenant un steroide intranasal et un antihistaminique
WO1998017676A1 (fr) * 1996-10-24 1998-04-30 Glaxo Group Limited Nouvelle forme cristalline polymorphe de propionate de fluticasone, son procede de production et des compositions pharmaceutiques la renfermant
WO2001028535A2 (fr) * 1999-10-21 2001-04-26 Glaxo Group Limited Formulations pharmaceutiques
WO2001047493A1 (fr) * 1999-12-24 2001-07-05 Glaxo Group Limited Formulation pharmaceutique en aerosol de salmeterol et de propionate de fluticasone

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BENINCASA C ET AL: "EVALUATION OF FLUTICASONE PROPIONATE AQUEOUS NASAL SPRAY TAKEN ALONE AND IN COMBINATION WITH CETIRIZINE IN THE PROPHYLACTIC TREATMENT OF SEASONAL ALLERGIC RHINITIS" DRUG INVESTIGATION, ADIS INTERNATIONAL, NZ, vol. 8, no. 4, 1994, pages 225-233, XP000651434 ISSN: 0114-2402 *
MANCINI V ET AL: "FLUTICASONE PROPIONATE OR BUDESONIDE WITH SALMETEROL IN BRONCHIAL SEVERE ASTHMA IN PEDIATRIC AGE" ALLERGY, MUNSKGAARD, COPENHAGEN, DK, vol. 53, no. SUPPL 43, 25 June 1998 (1998-06-25), page 185 XP001013216 ISSN: 0105-4538 *
MARKHAM A ET AL: "INHALED SALMETEROL/FLUTICASONE PROPIONATE COMBINATION A REVIEW OF ITS USE IN PERSISTENT ASTHMA" DRUGS, ADIS INTERNATIONAL LTD, AT, vol. 60, no. 5, November 2000 (2000-11), pages 1207-1233, XP001013660 ISSN: 0012-6667 *
PALMQVIST M ET AL: "ONSET OF BRONCHODILATION OF BUDESONIDE/FORMOTEROL VS SALMETEROL/FLUTICASONE IN SINGLE INHALERS" PULMONARY PHARMACOLOGY AND THERAPEUTICS, ACADEMIC PRESS, NEW YORK, NY, US, vol. 14, no. 1, 2001, pages 29-34, XP001013120 ISSN: 1094-5539 *
PUHAKKA T ET AL: "Sinusitis in the common cold." THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. UNITED STATES SEP 1998, vol. 102, no. 3, September 1998 (1998-09), pages 403-408, XP001079208 ISSN: 0091-6749 *
RATNER P H ET AL: "A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis" JOURNAL OF FAMILY PRACTICE, NEW YORK, NY, US, vol. 47, no. 2, August 1998 (1998-08), pages 118-125, XP002121956 ISSN: 0094-3509 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003033000A1 (fr) * 2001-10-12 2003-04-24 Glaxo Group Limited Combinaisons pharmaceutiques comprenant du salmeterol et du propionate de fluticasone pour le traitement de l'asthme

Also Published As

Publication number Publication date
AU2001284287A1 (en) 2002-03-22
GB0021927D0 (en) 2000-10-25
WO2002019995A3 (fr) 2002-08-22

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