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
  • 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
  • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
• • 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
  • A61P27/16—Otologicals

Definitions

• Topical nasal antiinflammatory preparations are known in the art for the treatment of inflammatory conditions of the nasal mucous membranes, and in particular for relief of the symptoms of nasal and sinus conditions such as rhinitis.
• nasal and sinus conditions may be characterized by diverse symptoms requiring treatment with multiple therapeutic agents.
• allergic rhinitis may be characterized by rhinorrhea, nasal itching, sneezing, congestion and postnasal drip and treatment may require antihistamines, decongestants, antiallergics and anesthetics in addition to antiinflammatories.
• the use of multiple topical nasal preparations to administer multiple therapeutic agents suffers from significant disadvantages.
• the volume of liquid that can effectively be applied nasally is limited by the surface area of the nostril and the bioadhesiveness of the liquid.
• a sufficient contact time between topical preparations and the surface area of the nostril is required to assure adequate dosing of a therapeutic agent.
• spray formulations require a threshold surface tension to form droplets.
• the delivery volume per actuation is limited to the volume that will be retained in the nostril without premature drainage.
• multiple topical nasal preparations cannot be effectively administered simultaneously.
• Another disadvantage of the administration of multiple topical nasal preparations is patient inconvenience. Patient compliance may be compromised by the inconvenience of applying multiple spray products or nose drops. Patients complain when excess spray drains into their throats where it can be tasted, resulting in a need for flavor masking of bitter medicaments.
• the present invention provides topically applicable nasal compositions comprising a therapeutically effective amount of a topical antiinflammatory agent and a therapeutically effective amount of at least one agent suitable for topical nasal administration and selected from the group consisting of a vasoconstrictor, a neuramidinase inhibitor, an anticholinergic agent, a leukotriene inhibitor, an antihistamine, an antiallergic agent, an anesthetic, and a mucolytic agent.
• the present invention provides topically applicable nasal compositions comprising a topical antiinflammatory agent and at least one additional therapeutic agent.
• the present compositions are useful for the treatment of nasal and sinus conditions, for example allergic rhinitis or the common cold.
• the topical antiinflammatory agents in the compositions of the present invention are corticosteroids known in the art to suppress inflammation.
• the topical antiinflammatory agent is beclomethasone diproprionate, budesonide, dexamethasone, mometasone furoate, fluticasone proprionate or triamcinolone acetonide.
• the compositions contain a therapeutically effective amount of the selected antiinflammatory agent. Those of ordinary skill in the art can determine an amount that is therapeutically effective for the suppression of inflammation. The precise amount will depend upon the method of administration and the age, weight and condition of the subject to be treated. Generally the antiinflammatory agents are utilized in dosages known in the art to be therapeutically effective upon nasal administration.
• compositions of the invention further comprise at least one additional therapeutic agent, and thus allow the convenient administration of an antiinflammatory agent and at least one additional therapeutic agent in a single topical nasal composition.
• the additional therapeutical agent is suitable for topical nasal administration and is selected from the group consisting of a vasoconstrictor, a neuramidinase inhibitor, a leukotriene inhibitor, an anticholinergic agent, an antihistamine, an antiallergic agent, a local anesthetic and a mucolytic agent.
• the use of an additional therapeutic agent in combination with an antiinflammatory agent provides additive and synergistic effects in the treatment of nasal and sinus conditions.
• Vasoconstrictors suitable for topical nasal administration in the compositions of the present invention are oxymetazoline naphazoline, xylometazoline, and phenylephrine.
• Leukotriene inhibitors include zafirlukast, a selective, competitive receptor antagonist of the three leukotrienes C4, D4, and E4; pranlukast, a selective, competitive receptor antagonist of D4; and zileuton, a leukotriene inhibitor.
• A. neuramidinase inhibitor includes zanamivir (GG-167).
• Suitable antihistamines are diphenhydramine, chlorpheniramine, cetirizine terfenadine, fenofexadine, astemizole norastemizole, azelastine, and azatidine.
• Antiallergic agents include cromolyn sodium and nedocromil levocabastine.
• An anticholinergic agent useful in the compositions of the present invention is ipratropium bromide.
• Local topical anesthetics include dyclonine, pramoxine, and benzocaine.
• Mucolytic agents suitable for topical nasal administration are acetylcysteine, guaifenisin and mucocysteine. The therapeutically effect amount of foregoing agents can be determined by the ordinarily skilled artisan with regard to the known use of these agents in the art and taking into account the method of administration and the age, weight and condition of the subject to be treated.
• compositions of the present invention are formulated as aqueous solutions comprising an antiinflammatory agent and at least one additional therapeutic agent and further comprising a pharmaceutically acceptable nasal carrier.
• the formulation of pharmaceutical compositions is generally known in the art and reference can be conveniently made to standard text such as Remington's Pharmaceutical Sciences, 1985, 17th ed., Mack Publishing Co., Easton, Pennsylvania.
• Preferred nasal formulations are nose drops or nasal sprays containing a water buffered aqueous solution as a carrier.
• the compositions are preferably isotonic. Isotonic agents such as a sugars and sodium chloride are known in the art and may be included in the subject compositions.
• compositions of the present invention may also contain a humectant to increase viscosity and effect moisturization and ciliary vitality.
• Suitable humectants include glycerin, polyethylene glycol, propylene glycol and mixtures thereof.
• compositions including pharmaceutically acceptable preservatives, stabilizers, flavoring agents, and pH adjusters are known in the art and may be included in the present compositions.
• Another embodiment of the present invention provides preservative- free compositions comprising an anti-inflammatory agent and at least one additional therapeutic agent. Preservative-free compositions are preferred due to reduced sensitivity and increased patient acceptance. These can be prepared in unit dose or in systems which prevent contamination of the reservoir of solution.
• the compositions of the present invention can be conveniently administered nasally to a human subject in dosage unit form to elicit the desired therapeutic effect of the antiinflammatory agent and the additional therapeutic agents described above.
• the compositions may be administered in the form of a nasal spray or nose drops.
• Nasal sprays may be provided as squeeze bottles or metered dose manual nasal spray pumps designed to deliver the desired dose in one or two sprays, for example.
• the composition may also be administered as aerosol spray formulations, for example as metered dose pressurized aerosols containing propellants such as halogenated hydrocarbons.

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

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Publications (1)

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• 1998
  • 1998-04-02 EP EP98914420A patent/EP0979105A1/en not_active Withdrawn
  • 1998-04-02 CN CN98804579A patent/CN1253508A/zh active Pending
  • 1998-04-02 JP JP54699898A patent/JP2001524108A/ja active Pending
  • 1998-04-02 WO PCT/US1998/006483 patent/WO1998048839A1/en not_active Application Discontinuation
  • 1998-04-02 CA CA002281789A patent/CA2281789A1/en not_active Abandoned
  • 1998-04-02 IL IL13149298A patent/IL131492A0/xx unknown
  • 1998-04-02 BR BR9809022-4A patent/BR9809022A/pt not_active Application Discontinuation
  • 1998-04-02 AU AU68780/98A patent/AU6878098A/en not_active Abandoned

Non-Patent Citations (1)

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