EP0954318A1 - Aerosol nasal contenant un steroide intranasal et un antihistaminique - Google Patents

Aerosol nasal contenant un steroide intranasal et un antihistaminique

Info

Publication number
EP0954318A1
EP0954318A1 EP97926878A EP97926878A EP0954318A1 EP 0954318 A1 EP0954318 A1 EP 0954318A1 EP 97926878 A EP97926878 A EP 97926878A EP 97926878 A EP97926878 A EP 97926878A EP 0954318 A1 EP0954318 A1 EP 0954318A1
Authority
EP
European Patent Office
Prior art keywords
mixtures
safe
effective amount
acceptable salts
present
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Withdrawn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
EP97926878A
Other languages
German (de)
English (en)
Inventor
Patricia Elaine Koochaki
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.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
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 Procter and Gamble Co filed Critical Procter and Gamble Co
Publication of EP0954318A1 publication Critical patent/EP0954318A1/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Withdrawn legal-status Critical Current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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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

Definitions

  • the present invention relates to novel nasal spray compositions comprising a safe and effective amount of a glucocorticosteroid and an antihistamine.
  • Allergic disorders remain a leading cause of both acute and chronic illnesses the world over. These illnesses are often times present in the form of acute or chronic rhinitis.
  • the symptoms of allergic rhinitis are nasal, ocular and palatial irritation, sneezing and hypersecretion. These symptoms occur following exposure to allergens.
  • the main allergens are usually grass and/or tree pollens, hence, allergic rhinitis is common during the spring and summer months.
  • the symptoms of allergic rhinitis are believed to be due to the stimulation of H-l receptors by histamine, followed by reflexive activation of parasympathetic nerves causing increases in nasal secretion and obstruction. Histamine is initially released from the tissue mast cells upon sensitization of the mast cells. This sensitization results when airborne allergens combine with specific IgE antibodies attached to mast cell membranes.
  • Antihistamines and/or decongestants have traditionally been the drugs of choice in treating allergic rhinitis.
  • Other forms of therapy include the use of cromolyn sodium, hypertonic salt solutions or immunotherapy.
  • Hagen et al. U.S. Patent 4.767.612. discloses nasal corticosteroid therapy as an effective means of treating allergic rhinitis; and is herein incorporated by reference.
  • the effectiveness of these compounds is limited, however, by the slow onset of action characteristic of nasal corticosteroids (activity generally occurring anywhere from 1-3 days) and, occasionally, the occurrence of "break-through" symptoms. For similar reasons, such products also tend to limit consumer compliance.
  • compositions of the present invention also provide improved relief of those symptoms generally associated with either seasonal or perennial allergic rhinitis. Additionally, combining the antihistamine with the nasal steroid results in improved symptom relief (e.g., improved nasal and ocular symptom relief). Furthermore, intranasal administration of antihistamines requires dosage amounts less than those associated with oral administration, thereby reducing potentially annoying side effects (e.g., drowsiness). By addressing such problems, the compositions of the present invention also help in improving overall patient compliance.
  • an object of the present invention to provide pharmaceutical compositions having improved effectiveness in the treatment of symptoms generally associated with either seasonal or perennial allergic rhinitis.
  • Another object of the present invention is to provide an irritant free pharmaceutical composition for use in the treatment of symptoms generally associated with either seasonal or perennial allergic rhinitis.
  • a further object of the present invention is to provide a safe and effective method for treating seasonal or perennial allergic rhinitis.
  • compositions for nasal administration comprising: a) a safe and effective amount of a glucocorticoid selected from the group consisting of beclomethasone, flunisolide, fluticasone, memetasone, budesonide, pharmaceutically acceptable salts thereof and mixtures thereof; b) a safe and effective amount of a fast acting antihistamine selected from the group consisting of acrivastine, carbinoxamine, diphenhydramine, chloropheniramine, brompheniramine, dexchloropheniramine, doxylamine, clemastine, promethazine, trimeprazine, methdilazine, hydroxyzine, pyrilamine, rocastine, tripelennamine, meclizine, triprolidine, azatadine, cyproheptadine, phenindamine pharmaceutically acceptable salts thereof and mixtures thereof; and c.)
  • the present invention also relates to a method for the treatment of symptoms associated with seasonal or perennial allergic rhinitis comprising the administration of a safe and effective amount of the intranasal pharmaceutical compositions of the present invention.
  • symptoms associated with seasonal or perennial allergic rhinitis is meant ocular and palatial irritation, sneezing, mucoid hypersecretion, nasal congestion and itching.
  • safety and effective amount is an amount that is effective to mitigate and/or treat the symptoms for which the active ingredient is indicated in a human without undue adverse side effects commensurate with a reasonable risk/benefit ratio.
  • fast acting refers to an onset of action which occurs within 15-30 minutes after administration.
  • the pH of the compositions is preferably from about 5 to about 9, more preferably from about 5.5 to about 7.
  • compositions of the present invention contain the essential components as well as various optional components as indicated below.
  • compositions of the present invention are for nasal administration and contain a therapeutically safe and effective amount of the pharmaceutical agents described herein. They are preferably provided as isotonic aqueous solutions, suspensions or viscous compositions which may be buffered to a selected pH.
  • Glucocorticoid agents most useful to the present invention include those selected from the group consisting of beclomethasone, flunisolide, fluticasone, memetasone, budesonide, pharmaceutically acceptable salts thereof and mixtures thereof.
  • the glucocorticoid component is preferably present at a concentration of from about 0.001% to about 0.1%, more preferably from about 0.01 % to about 0.1 %.
  • Antihistamines most useful to the present invention are histamine H-l receptor antagonists which are fast acting.
  • H-l receptor antihistamines may be selected from among the following groups of antihistamines: alkylamines, ethanolamines, ethylenediamines, piperazines, phenothiazines, piperidines.
  • Examples of useful fast acting antihistamines include acrivastine, carbinoxamine, diphenhydramine, chloropheniramine, brompheniramine, dexchloropheniramine, doxylamine, clemastine, promethazine, trimeprazine, methdilazine, hydroxyzine, pyrilamine, tripelennamine, meclizine, triprolidine, azatadine, cyproheptadine, rocastine, phenindamine or pharmaceutically acceptable salts and mixtures thereof.
  • the antihistamine additionally improves the delivery of the glucocorticoid, improving the glucocorticoid's onset of action.
  • the antihistamine component is preferably present at a concentration of from about 0.01% to about 3.0%, more preferably from about 0.01% to about 1%.
  • the nasal composition is isotonic, i.e., it has the same osmotic pressure as blood and lacrimal fluid.
  • the desired isotonicity of the compositions of this invention may be accomplished using, for example, the sodium chloride already present, or other pharmaceutically-acceptable agents such as dextrose, boric acid, citric acid, sodium tartrate, sodium phosphate, potassium phosphate, propylene glycol or other inorganic or organic solutes.
  • Sodium chloride is preferred particularly for buffers containing sodium ions. Further examples of sodium choride equivalents are disclosed in Remington's Pharmaceutical Sciences pp. 1491-1497 (Alfonso Gennaro 18th ed. 1990), which is herein inco ⁇ orated by reference.
  • aqueous, isotonic saline solution carriers are aqueous, isotonic saline solution carriers. These solutions which generally contain sodium chloride as the salt are fully described in Remington's Pharmaceutical Sciences, 17th edition (1985) p. 835, which is herein incorporated by reference.
  • the salt is present in the solution at a level of about 0.01% to about 2%, preferably from about 0.5% to about 1.0% and most preferably from about 0.5% to about 0.75%.
  • any of the above described antihistamines and glucocorticoids can be conveniently administered nasally to warm-blooded animals to elicit the desired therapeutic response by formulating it into a nasal dosage form, together with a nontoxic pharmaceutically-acceptable nasal carrier.
  • Suitable nontoxic pharmaceutically-acceptable nasal carriers are known to those skilled in the art and are also fully disclosed in Remington's Pharmaceutical Sciences, 17th edition, 1985. Obviously, the choice of suitable carrier forms will depend on the exact nature of the particular nasal dosage form required, e.g., whether the drug is to be formulated into a nasal solution (for use as drops or as a spray), a nasal suspension, a nasal ointment, a nasal gel or another nasal form.
  • Preferred nasal dosage forms are solutions, suspensions and gels, which normally contain sodium chloride in a major amount of water (preferable purified water) in addition to the antihistamine and glucocorticoid. Minor amounts of other ingredients such as pH adjusters (e.g., a base such as NaOH), emulsifiers or dispersing agents, buffering agents, preservatives, wetting agents and jelling agents (e.g., methylcellulose) may also be present.
  • pH adjusters e.g., a base such as NaOH
  • emulsifiers or dispersing agents e.g., a base such as NaOH
  • buffering agents e.g., preservatives
  • wetting agents and jelling agents e.g., methylcellulose
  • the composition is applied to the nasal mucosa via topical application of a safe and effective amount of the composition to treat nasal symptoms.
  • the amount of the antihistamine and glucocorticoid combination and frequency of topical application to the nasal mucosa may vary, depending upon personal needs, but it is suggested, as an example, that topical application range from about once per day to about three times daily, preferably twice daily, most preferably once daily.
  • the selected therapeutic compositions will normally be prepared in unit dosage forms or actuations to contain therapeutically effective amounts of the selected antihistamine and glucocorticoid combination. In specific instances fractions of these dosage units or multiple dosage units will be employed.
  • dosage units may be prepared to deliver from about 0.5 meg to about 50 meg of the glucocorticoid agent and from about 5 mg to about 75 mg of the antihistaminic agent per dose (e.g., 50 mg to about 150 mg of the spray composition).
  • a typical dose contains one to three sprays per nostril.
  • An additional antihistamine may be optionally incorporated into the compositions of the present invention.
  • Such antihistamines would preferably include those having a durations of action greater than 6 hours.
  • Examples of such antihistamines include terfenadine, azelastine, cetirizine, astemizole, ebastine, ketotifen, lodoxamide, loratadine, levocabastine, mequitazine, oxatomide, setastine, tazifylline, temelastine or pharmaceutically acceptable salts and mixtures thereof.
  • Active metabolites of the above antihistamines may also be used. Examples of such metabolites are disclosed in U.S.
  • Patents 3,878,217 and 4,254,129 issued April 15, 1975 and March 3, 1981, respectively, to Carr et al.; U.S. Patent 5,375,693, issued December 27, 1994, to Woosley et al.; and European Patent 648759, each of which are herein incorporated by reference in their entirety.
  • Optional ingredients useful in the present invention include decongestants.
  • Decongestants useful to the present invention may be selected from among the class of sympathomimetic agents; examples of which include pseudoephedrine, desoxyephedrine, propylhexedrine, phenylpropanolamine, xylometazoline, phenylephrine, tetrahydrozoline, naphazoline, oxymetazoline, tramazoline and pharmaceutically acceptable salts thereof.
  • Also useful as decongestants are the 5-(2-imidazolinylamino)benzimedazole compounds. Mixtures of these decongestants can also be used.
  • the sympathomimetic agents may be incorporated at concentrations, preferably, of from about 0.01% to about 0.5%, more preferably from about 0.05% to about 0.1 %.
  • compositions of the present invention may also contain a xanthine derivative such as caffeine and methylxanthine and the like.
  • the xanthine derivative may preferably be inco ⁇ orated at concentrations of from about 0.01% to about 1%, most preferably from about 0.1% to about 0.5. Mixtures of xanthine derivatives may also be inco ⁇ orated.
  • the compositions of the present invention may also contain antiallergics. Suitable antiallergics include, but are not limited to, cromolyn, ketotifen, N-allyl-(dichloro-3, 4- benzyl)-2-methylamino-2-propanol-l, AP-582 (Pharmaprojects No.
  • nonopiate analgesics such as oxaprozin.
  • oxaprozin is described in Namiki et al., Studies on improvement of pharmaceutical preparations prescribed in hospitals. VI. oxaprozin nasal sprav. Drug Design and Delivery 1988;2:pp. 311-321, herein incorporated by reference.
  • nonopiate analgesics include, but are not limited to, acetaminophen, acetylsalicylic acid, ibuprofen, etodolac, fen- buprofen, fenoprofen, ketorolac, flurbiprofen, indomethacin, ketoprofen, naproxen, pharmaceutically-acceptable salts thereof, optically active racemates thereof and mixtures thereof.
  • Preferred for use herein are the S(+) isomers of the nonopiate analgesics.
  • Still further examples of such drugs are disclosed in U.S. Patent No. 4,522,828, to Sunshine et al., issued June 11, 1985; this patent being inco ⁇ orated herein by reference in its entirety.
  • Synthetic opiate analgesics such as buto ⁇ hanol may also be inco ⁇ orated into the compositions of the present invention.
  • the intranasal use of buto ⁇ hanol is described in Baumel, Migraine: A pharmacologic review with newer options and delivery modalities. Neurology 1994;44(supp):pp. sl3-sl7, herein inco ⁇ orated by reference.
  • Further examples of preferred synthetic opioid analgesics include alfentanil, bupreno ⁇ hine, fentanyl, meperidine, methadone, nalbuphine, natrexone, propoxyphene, pentazocine, sufenanil, pharmaceutically-acceptable salts thereof and mixtures thereof.
  • Leukotriene receptor antagonists may also be incorporated into the compositions of the present invention. Suitable examples include, but are not limited to, experimental agents such as Zafirlukast (Accolate, Zeneca), MK-571 (Merck, Sha ⁇ and Dohme), LY171883, Wy-45,911, LY163443, ONO-RS-411 and ONO-RS-347 and ICI 198,615.
  • Zafirlukast Acolate, Zeneca
  • MK-571 Merck, Sha ⁇ and Dohme
  • LY171883, Wy-45,911, LY163443, ONO-RS-411 and ONO-RS-347 and ICI 198,615.
  • a more detailed discussion of leukotriene receptor antagonists is found in European Patent Application 318093, and Fleisch, J. H., Development of Cysteinyl Leukotriene Receptor Antagonists. Vol. 12 Advances in Inflammation Research 173-189 (A. Lewis et al. ed
  • Lipoxygenase inhibiting compounds may also be inco ⁇ orated into the compositions of the present invention. Suitable examples are discussed in U.S. Patent 4,873,259, to Summers et al., issued October 10 1989 and U.S. Patent 5,037,853, to Brooks et al., issued August 6, 1991, both of which are herein inco ⁇ orated by reference in their entirety.
  • aromatic components e.g., aldehydes and esters
  • aromatics include, for example, menthol, camphor, eucalyptol, benzaldehyde (cherry, almond); citral (lemon, lime); neral; decanal (orange, lemon); aldehyde C-8, aldehyde C-9 and aldehyde C-12 (citrus fruits); tolyl aldehyde (cherry, almond); 2,6-dimethyl-octanal (green fruit); and 2-dodecenal (citrus, mandarin).
  • Additional aromatic components suitable for use in the present invention include those described in U.S. Patent 4.136.163 to Watson et al., U.S. Patent 4.459.425 to Amano et al., and U.S. Patent 4.230.688 to Rowsell et al.; all of which are herein incorporated by reference. Mixtures of these aromatics can also be used.
  • Viscosity of the compositions may be maintained at the selected level using a pharmaceutically-acceptable thickening agent.
  • Methyl cellulose is preferred because it is readily and economically available and is easy to work with.
  • Other suitable thickening agents include, for example, xanthan gum, microcrystalline cellulose, carboxymethyl cellulose, chitosan, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, carboxyvinyl polymer, carbomer, and the like or pharmaceutical salts thereof. Mixtures of such thickening agents may also be used. The preferred concentration of the thickener will depend upon the agent selected. The important point is to use an amount which will achieve the selected viscosity. Viscous compositions are normally prepared from solutions by the addition of such thickening agents.
  • compositions within the scope of this invention will contain from about 0.01% to about 5% of a humectant to inhibit drying of the mucous membrane and to prevent irritation.
  • a humectant to inhibit drying of the mucous membrane and to prevent irritation.
  • Any of a variety of pharmaceutically-acceptable humectants can be employed including, for example sorbitol, propylene glycol, polyethylene glycol, glycerol or mixtures thereof.
  • the concentration will vary with the selected agent, although the presence or absence of these agents, or their concentration is not an essential feature of the invention.
  • Enhanced abso ⁇ tion across the nasal membrane can be accomplished employing a therapeutically acceptable surfactant.
  • Typical useful surfactants for these therapeutic compositions include polyoxyethylene derivatives of fatty acid partial esters of sorbitol anhydrides such as Polysorbate 80, Polyoxyl 40 Stearate, Polyoxylethylene 50 Stearate and Octoxynol, as well as Oxyethylated tertiary octyl phenol formaldehyde polymer (available from Sterling Organics as tyloxapol) or mixtures thereof.
  • the usual concentration is from 0.5% to 10% based on the total weight.
  • a pharmaceutically-acceptable preservative is generally employed to increase the shelf life of the compositions of the present invention.
  • Benzyl alcohol is suitable, although a variety of preservatives including, for example, parabens, phenylethyl alcohol, thimerosal, chlorobutanol, phenylmecuric acetate or benzalkonium chloride may also be employed.
  • the most preferred preservative system for use herein comprises a combination of benzalkonium chloride, chlorhexidine gluconate and disodium EDTA.
  • a suitable concentration of the preservative will be from 0.001% to 2% based on the total weight, although there may be appreciable variation depending upon the agent selected Mixtures of these preservatives may also be used.
  • Optional Components may be added to the emulsion compositions of the present invention. These additional ingredients include various polymers for aiding the film-forming properties and substantivity of the formulation, preservatives for maintaining the antimicrobial integrity of the compositions, antioxidants, and agents suitable for aesthetic purposes such as fragrances, pigments, and colorings.
  • compositions can also contain low levels of insoluble ingredients added, for example for visual effect purposes, e.g. thermochromic liquid crystalline materials such as the microencapsulated cholesteryl esters and chiral nematic (nonsterol) based chemicals such as the (2-methylbutyl) phenyl 4-alkyl(oxy)benzoates available frorr Hallcrest, Glenview, Illinois 60025, U.S.A., Mixtures of these and the above ingrediem. may also be used.
  • thermochromic liquid crystalline materials such as the microencapsulated cholesteryl esters and chiral nematic (nonsterol) based chemicals
  • nonsterol chiral nematic
  • Example I The intranasally administered pharmaceutical composition of the present invention is prepared by combining the following components utilizing conventional mixing techniques similar to that described below.
  • Component Wgt % beclomethasone diproprionate, monohydrate 0.042 chlo ⁇ heniramine 0.500 avicel RC - 591 1 1.200 dextrose 5.100 polysorbate 80 0.050 benzalkonium chloride 0.020 phenylethyl alcohol 0.025 distilled water q.s. 100ml
  • microcrystalline cellulose and sodium carboxymethyl cellulose, supplied FMC Co ⁇ oration microcrystalline cellulose and sodium carboxymethyl cellulose, supplied FMC Co ⁇ oration.
  • the above listed ingredients are added one at a time to water with mixing, allowing each to dissolve before adding the next. After all the ingredients have been added, purified water is used to bring the batch to the appropriate weight.
  • composition is used for topical nasal application to provide relief from allergy or allergy-like symptoms.
  • Example II The intranasally administered pharmaceutical composition of the present invention is prepared by combining the following components utilizing conventional mixing techniques similar to that described in Example I.
  • composition is used for topical nasal application to provide relief from allergy or allergy-like symptoms.
  • Example III The intranasally administered pharmaceutical composition of the present invention is prepared by combining the following components utilizing conventional mixing techniques similar to that described in Example I.
  • composition is used for topical nasal application to provide relief from allergy or allergy-like symptoms.
  • Example IV The intranasally administered pharmaceutical composition of the present invention is prepared by combining the following components utilizing conventional mixing techniques similar to that described in Example I.
  • substantially similar results are also obtained using, in whole or in part, equivalent amounts of other glucocorticoid agents such as fluticasone, mometasone, budesonide, pharmaceutically acceptable salts thereof and mixtures thereof or by using, in whole or in part, equivalent amounts of other fast acting antihistamines such as carbinoxamine, diphenhydramine, brompheniramine, dexchloropheniramine, doxylamine, clemastine, promethazine, rocastine, trimeprazine, methdilazine, hydroxyzine, pyrilamine, tripelennamine, meclizine, triprolidine, azatadine, cyproheptadine, phenindamine, pharmaceutically acceptable salts thereof and mixtures thereof.
  • other fast acting antihistamines such as carbinoxamine, diphenhydramine, brompheniramine, dexchloropheniramine, doxylamine, clemastine, promet
  • compositions may also contain a sympathomimetic amine such as pseudoephedrine, phenylpropanolamine, phenylephrine, tetrahydrozoline, naphazoline, oxymetazoline, tramazoline, 5-(2-imidazolinylamino)benzimedazoles, pharmaceutically acceptable salts thereof and mixtures thereof.
  • a sympathomimetic amine such as pseudoephedrine, phenylpropanolamine, phenylephrine, tetrahydrozoline, naphazoline, oxymetazoline, tramazoline, 5-(2-imidazolinylamino)benzimedazoles, pharmaceutically acceptable salts thereof and mixtures thereof.

Landscapes

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

Abstract

Compositions pharmaceutiques d'administration nasale qui comprennent (a) une quantité efficace et sûre d'un glucocorticoïde choisi parmi béclométhasone, flunisolide, fluticasone, mémétasone, budésonide, des sels pharmaceutiquement acceptables et des mélanges desdites substances, (b) une quantité sûre et efficace d'un antihistaminique à action rapide choisi parmi acrivastine, carbinoxamine, diphènhydramine, chlorophéniramine, bromphéniramine, dexchlorophéniramine, doxylamine, clémastine, prométhazine, triméprazine, méthdilazine, hydroxyzine, pyrilamine, rocastine, tripelennamine, méclizine, tripolidine, azatadine, cyproheptadine, phénindamine, des sels pharmaceutiquement acceptables et des mélanges desdites substances et (c) un excipient aqueux intranasal. Ladite composition est exempte de capsaicine et, de préférence, exempte de poudres ou de granules. La présente invention concerne également un procédé de traitement de symptômes associés à la rhinite allergique saisonnière ou apériodique, qui consiste à administrer une quantité sûre et efficace desdites compositions pharmaceutiques intranasales.
EP97926878A 1996-06-04 1997-06-03 Aerosol nasal contenant un steroide intranasal et un antihistaminique Withdrawn EP0954318A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US65750696A 1996-06-04 1996-06-04
US657506 1996-06-04
PCT/US1997/009518 WO1997046243A1 (fr) 1996-06-04 1997-06-03 Aerosol nasal contenant un steroide intranasal et un antihistaminique

Publications (1)

Publication Number Publication Date
EP0954318A1 true EP0954318A1 (fr) 1999-11-10

Family

ID=24637461

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97926878A Withdrawn EP0954318A1 (fr) 1996-06-04 1997-06-03 Aerosol nasal contenant un steroide intranasal et un antihistaminique

Country Status (6)

Country Link
EP (1) EP0954318A1 (fr)
JP (1) JPH11511758A (fr)
AU (1) AU3153797A (fr)
BR (1) BR9709650A (fr)
CA (1) CA2256721A1 (fr)
WO (1) WO1997046243A1 (fr)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5976573A (en) * 1996-07-03 1999-11-02 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
FR2756739B1 (fr) * 1996-12-05 2000-04-28 Astra Ab Nouvelle formulation de budesonide
EP1041990B1 (fr) * 1997-12-23 2006-06-28 Schering Corporation Composition pour le traitement de maladies respiratoires et cutanees, comprenant au moins un antagoniste de leucotriene et au moins un antihistamine
US6248308B1 (en) 1998-04-14 2001-06-19 Sepracor Inc. Methods of using norastemizole in combination with leukotriene inhibitors to treat or prevent asthma
US6245785B1 (en) * 1998-11-30 2001-06-12 Warner Lambert Company Dissolution of triprolidine hydrochloride
EP1020233A1 (fr) 1999-01-13 2000-07-19 The Procter & Gamble Company Système de dosage et de distribution
DE19924525A1 (de) * 1999-05-28 2000-11-30 Ruediger Scheunemann Kombination eines modernen topischen Glukokortikosteroids mit abschwellenden Nasentropfen
IT1313567B1 (it) * 1999-07-27 2002-09-09 Zambon Spa Uso della n-acetil-cisteina per la preparazione di composizionifarmaceutiche topiche per il trattamento di patologie allergiche delle
GB9918559D0 (en) * 1999-08-07 1999-10-06 Glaxo Wellcome Kk Novel pharmaceutical formulation
DE19947234A1 (de) * 1999-09-30 2001-04-05 Asta Medica Ag Neue Kombination von Loteprednol und Antihistaminika
JP2003511417A (ja) * 1999-10-08 2003-03-25 シェーリング コーポレイション 局所的鼻疾患治療
DE60142043D1 (de) 2000-04-03 2010-06-17 Battelle Memorial Inst Columbu Ausgabevorrichtungen und flüssigformulierungen
US6750210B2 (en) 2000-08-05 2004-06-15 Smithkline Beecham Corporation Formulation containing novel anti-inflammatory androstane derivative
US6759398B2 (en) 2000-08-05 2004-07-06 Smithkline Beecham Corporation Anti-inflammatory androstane derivative
GB0019172D0 (en) 2000-08-05 2000-09-27 Glaxo Group Ltd Novel compounds
US6777400B2 (en) 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6787532B2 (en) 2000-08-05 2004-09-07 Smithkline Beecham Corporation Formulation containing anti-inflammatory androstane derivatives
US6777399B2 (en) 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6858593B2 (en) 2000-08-05 2005-02-22 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6858596B2 (en) 2000-08-05 2005-02-22 Smithkline Beecham Corporation Formulation containing anti-inflammatory androstane derivative
GB0021927D0 (en) * 2000-09-07 2000-10-25 Glaxo Group Ltd Use of pharmaceutical combination
US7776315B2 (en) 2000-10-31 2010-08-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and additional active ingredients
EP1335729A2 (fr) * 2000-10-31 2003-08-20 Boehringer Ingelheim Pharma GmbH & Co.KG Formulation d'une solution d'inhalation contenant un sel de tiotropium
US20020137764A1 (en) 2000-10-31 2002-09-26 Karin Drechsel Inhalable formulation of a solution containing a tiotropium salt
ATE452639T1 (de) * 2000-10-31 2010-01-15 Boehringer Ingelheim Pharma Arzneimittelkompositionen aus tiotropiumsalzen und epinastin zur therapie von atemswegserkrankungen
UA77656C2 (en) 2001-04-07 2007-01-15 Glaxo Group Ltd S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent
GB2389530B (en) 2002-06-14 2007-01-10 Cipla Ltd Pharmaceutical compositions
JP4320217B2 (ja) * 2002-07-10 2009-08-26 剤盛堂薬品株式会社 鼻炎用経口製剤
CN1674916A (zh) 2002-08-30 2005-09-28 奥坦纳医药公司 环缩松与抗组胺药的组合用于治疗变应性鼻炎的用途
US7815924B2 (en) 2002-09-20 2010-10-19 Fmc Corporation Cosmetic composition containing microcrystalline cellulose
PL376970A1 (pl) * 2002-11-12 2006-01-23 Alcon, Inc. Zastosowanie środka przeciwalergicznego i steroidu do leczenia alergicznego nieżytu nosa
US20050192261A1 (en) * 2003-09-15 2005-09-01 Jost-Price Edward R. Methods and reagents for the treatment of immunoinflammatory disorders
WO2005030331A1 (fr) * 2003-09-26 2005-04-07 Fairfield Clinical Trials, Llc Traitement antihistaminique combine
US20070020299A1 (en) 2003-12-31 2007-01-25 Pipkin James D Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid
JP2007533697A (ja) * 2004-04-22 2007-11-22 デュオコート エービー グルココルチコイド救急治療用の医薬組成物
US20050255154A1 (en) 2004-05-11 2005-11-17 Lena Pereswetoff-Morath Method and composition for treating rhinitis
DK2522365T3 (en) 2004-11-24 2017-02-06 Meda Pharmaceuticals Inc Compositions comprising azelastine and methods for its use
US20070020330A1 (en) 2004-11-24 2007-01-25 Medpointe Healthcare Inc. Compositions comprising azelastine and methods of use thereof
SI1919450T1 (sl) * 2005-09-01 2014-10-30 Meda Ab Liposomski sestavek, ki vsebuje antihistaminik in kortikosteroid, in njegova uporaba za izdelavo zdravila za zdravljenje rinitisa in sorodnih motenj
PT2173169E (pt) * 2007-06-28 2014-09-03 Cydex Pharmaceuticals Inc Entrega nasal de soluções de corticosteróide aquosas
EP3943069A1 (fr) 2009-03-17 2022-01-26 Nicox Ophthalmics, Inc. Formulations ophtalmiquesde cetirizine et procedes d'utilisation
US8569273B2 (en) 2009-03-17 2013-10-29 Aciex Therapeutics, Inc. Ophthalmic formulations of cetirizine and methods of use
CN103269687B (zh) * 2011-01-04 2016-09-14 伊斯塔制药公司 贝托斯汀组合物
FR2970180B1 (fr) * 2011-01-06 2013-08-02 Substipharm Dev Procede de preparation de suspensions aqueuses pharmaceutiques comprenant un medicament efficace dans le traitement des rhinites
AU2012291841A1 (en) 2011-08-02 2014-02-06 Cipla Limited Pharmaceutical composition comprising ebastine and fluticasone
CN106074387B (zh) * 2016-08-15 2019-09-13 辽宁大学 具有触变性的曲安奈德鼻喷雾剂及其制备方法
CA3159816A1 (fr) * 2019-02-15 2020-08-20 Gustavo Ferrer Compositions de pulverisation nasale et procedes de traitement associes
WO2020197918A1 (fr) 2019-03-22 2020-10-01 Dbbh, Llc Antihistaminiques administrés par voie intranasale et utilisations associées
CA3179806A1 (fr) * 2020-04-14 2021-10-21 Glaxosmithkline Consumer Healthcare Holdings (Us) Llc Formulation pour pulverisation nasale ayant des bienfaits hydratants
US10874650B1 (en) * 2020-04-24 2020-12-29 Ferrer Medical Innovations, LLC Antiviral and virucidal nasal spray compositions and related treatment methods
WO2023233570A1 (fr) * 2022-06-01 2023-12-07 佐藤製薬株式会社 Composition de gouttes nasales

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997001341A1 (fr) * 1995-06-29 1997-01-16 Mcneil-Ppc, Inc. Combinaison d'agents de stabilisation de mastocytes nasaux topiques avec des steroides nasaux topiques
WO1997001337A1 (fr) * 1995-06-29 1997-01-16 Mcneil-Ppc, Inc. Combinaison d'antihistamines et de steroides a application topique par voie nasale
EP0780127A1 (fr) * 1995-12-19 1997-06-25 The Procter & Gamble Company Pulvérisateur nasale contenant un stéréoide et un antihistamine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9746243A1 *

Also Published As

Publication number Publication date
WO1997046243A1 (fr) 1997-12-11
AU3153797A (en) 1998-01-05
CA2256721A1 (fr) 1997-12-11
BR9709650A (pt) 1999-08-10
JPH11511758A (ja) 1999-10-12

Similar Documents

Publication Publication Date Title
EP0954318A1 (fr) Aerosol nasal contenant un steroide intranasal et un antihistaminique
EP0780127A1 (fr) Pulvérisateur nasale contenant un stéréoide et un antihistamine
EP1227812B1 (fr) Traitement nasal topique avec la desloratadine et furoate du mometasone
JP5201795B2 (ja) 掻痒抑制剤
AU669351B2 (en) Method of the treatment of dry nose syndrome
AU5421198A (en) Novel unit dose of budesonide
CA2304162A1 (fr) Utilisation de combinaisons comprenant des antihistaminiques non classiques et des medicaments alpha-adrenergiques destines au traitement local de la rhinite/conjonctivite et du rhume, des symptomes de type refroidissement et/ou grippe
IL151106A (en) A preparation containing azlastin and substances that affect the action of leucotrian for the treatment of rhinitis / otitis media
RU2472499C2 (ru) Лекарственное средство, включающее комбинацию активных веществ, содержащую пантотеновую кислоту или ее производные, для лечения аллергических симптомов
CA2281789A1 (fr) Compositions antiinflammatoires pour application nasale topique
AU2003278962C1 (en) Nasal compositions comprising a mucopolysaccharide and propylene glycol
JPS6034909A (ja) いびき止め剤
US6391282B1 (en) Antihistamine sprays and ointments for relief of delayed contact dermatitis
Law et al. The effect of systemically and topically applied drugs on ultraviolet-induced erythema in the rat.
US20110201582A1 (en) Method and composition for treatment of skin conditions
EP0571670B1 (fr) Compositions pharmaceutiques employés comme stabilisateur des granulocytes basophyles
MXPA98010222A (en) Nasal atomizer containing an intranasal steroid and an antihistam
WO1997001341A1 (fr) Combinaison d'agents de stabilisation de mastocytes nasaux topiques avec des steroides nasaux topiques
Davies et al. Drug treatment for nasal allergy.
JPH05178753A (ja) 皮膚▲そう▼痒症用の外用剤
JP2004075571A (ja) 点鼻剤およびその製造方法
NZ616149A (en) Nasal pharmaceutical formulation comprising fluticasone
MXPA99007597A (en) Topical nasal antiinflammatory compositions
NZ616149B2 (en) Nasal Pharmaceutical Formulation Comprising Fluticasone

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: 19981228

AK Designated contracting states

Kind code of ref document: A1

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

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

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20020102

REG Reference to a national code

Ref country code: HK

Ref legal event code: WD

Ref document number: 1023289

Country of ref document: HK