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WO1994005330A1 - Produits pour pulverisateur nasal - Google Patents

Produits pour pulverisateur nasal Download PDF

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Publication number
WO1994005330A1
WO1994005330A1 PCT/US1993/007554 US9307554W WO9405330A1 WO 1994005330 A1 WO1994005330 A1 WO 1994005330A1 US 9307554 W US9307554 W US 9307554W WO 9405330 A1 WO9405330 A1 WO 9405330A1
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WO
WIPO (PCT)
Prior art keywords
nasal
composition
weight
product according
spray product
Prior art date
Application number
PCT/US1993/007554
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English (en)
Inventor
Patricia Elaine Koochaki
Roderick Peter Hafner
Original Assignee
The Procter & Gamble Company
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 The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to AU58922/94A priority Critical patent/AU5892294A/en
Publication of WO1994005330A1 publication Critical patent/WO1994005330A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles

Definitions

  • This invention relates to a nasal pharmaceutical product.
  • a nasal pharmaceutical product in sprayable form whereby upon contact with the mucous linings of the nasal cavity the viscosity of the composition increases so as to form a gel.
  • the composition which comprises a carboxyl-containing polymer, a surfactant and a pharmaceutically-acceptable nasal medicament has higher patient compliance, provides a high availability of active ingredient and minimizes the common problem of "roll-back" associated with drops and non-gellable nasal formulations where the liquid runs down the back of the throat or out of the front of the nose causing a nasty, medicinal aftertaste, irritation, and inaccurate dosing of the decongestant.
  • WO92/00044 discloses an ophthalmic suspension or emulsion with a viscosity of from 1,000 to 30,000 mPa.s and a pH of from about 3.0 to about 6.5 containing lightly crosslinked polymers which is administrable in drop form.
  • a viscosity of from 1,000 to 30,000 mPa.s and a pH of from about 3.0 to about 6.5 containing lightly crosslinked polymers which is administrable in drop form.
  • the viscosity of the suspension rapidly increases so that a gel is formed.
  • nose drops are difficult to administer and therefore have low patient compliance.
  • dosing is not always accurate when drugs are administered in drop form.
  • W091/19481 discloses aqueous compositions which reversibly gel in response to simultaneous variations in at least two physical parameters such as temperature, pH or ionic strength.
  • the compositions disclosed start with a pH in the range of from 2.5 to 6.5 and transform to visco-elastic gels when exposed to a pH of about 7.4 and a temperature of about 37 °C.
  • the compositions can be formulated to incorporate a pharmaceutical composition for utilization as droppable or injectable drug delivery systems.
  • compositions which are stable to long term storage, which can be administered to the nasal cavity in controlled sprayable form, and which are effective for preventing or minimizing "roll-back".
  • a need also exists for sprayable nasal compositions having improved drug release characteristics.
  • a nasal spray product comprising a pump-actuated nasal dispenser equipped with a reservoir, spray head and liquid/air mixing means, wherein the reservoir contains a topical nasal medicament composition in the form of a sprayable liquid comprising:
  • composition of a carboxyl-containing polymer prepared by polymerizing one or more carboxyl-containing monoethyleneically unsaturated monomers and from about 0.1 % to about 5 % by weight of the polymer of a crosslinking agent
  • composition of a surfactant selected from anionic, nonionic, cationic, amphoteric and zwitterionic surfactants and mixtures thereof, and
  • composition of a pharmaceutically-acceptable nasal medicament from about 0.005 % to about 5 % by weight of composition of a pharmaceutically-acceptable nasal medicament
  • composition has a low shear viscosity (measured with a Brookfield RVT Viscometer, Spindle 7, 1 r.p.m., 25 °C) of from about 0 to about 300,000 mPa.s, a high shear viscosity (measured with a Brookfield RVT Viscometer, Spindle 7, 100 r.p.m., 25 °C) of from about 0 to about 10,000 mPa.s and a pH in the range of from about 2.5 to about 6 and wherein the composition is administrable to the nasal cavity in sprayable form, whereby upon contact with the nasal linings of the nasal cavity the viscosity of the composition increases so as to form a viscous gel.
  • a low shear viscosity measured with a Brookfield RVT Viscometer, Spindle 7, 1 r.p.m., 25 °C
  • high shear viscosity measured with a Brookfield RVT Viscometer, Spindle 7, 100 r.p.m.
  • composition of a carboxyl- containing polymer in a topical nasal medicament composition for preventing or minimizing "roll-back", wherein the carboxyl- containing polymer is prepared by polymerizing one or more carboxyl-containing monoethyleneically unsaturated monomers and from about 0.05 % to about 5 % by weight of the polymer of a crosslinking agent, and wherein the carboxyl-containing polymer is used in combination with from 0% to about 1 % by weight of a surfactant selected from anionic, nonionic, cationic, amphoteric and zwitterionic surfactants and mixtures thereof, and from about 0.005 % to about 5 % by weight of composition of a pharmaceutically- acceptable nasal medicament, and wherein the composition has a pH in the range from about 2.5 to about 6 and is administrable in sprayable form, whereby upon contact with the nasal linings of the nasal cavity the viscosity of the
  • a nasal spray product comprising a pump-actuated nasal dispenser equipped with a reservoir, spray head and liquid/air mixing means.
  • the reservoir comprises a carboxyl-containing polymer, a surfactant and a nasal medicament.
  • the carboxyl-containing polymer is present in an amount of from about 0.05 % to about 5 %, preferably from about 0.25 % to about 2.5 % by weight of composition.
  • Suitable carboxyl-containing polymers for use herein are hydrophilic polymers which can be obtained by the polymerisation or copolymerisation of acrylic acid.
  • hydrophilic polymers include those commercially available under the Registered Trade Mark Carbopol (RTM) 934, 934P, 940, 941 and 974P, 980, 981 and manufactured by B.F. Goodrich Chemical Company, U.S.A. and also Noveon Polycarbophil AA-1.
  • polymers consist essentially of a colloidally water-soluble polyalkenyl polyether- crosslinked polymer of acrylic acid, containing from about 0.75 % to about 2.00 % by weight of the polymer of a crosslinking agent such as for example poly alky 1 sucrose or poly ally 1 pentaerythritol.
  • Carbopol 934 is a water-soluble polymer of acrylic acid crosslinked with about 1 % of a polyallyl ether of sucrose having an average of about 5.8 allyl groups for each sucrose molecule.
  • Preferred polymers for use herein have an average molecular weight in the range from about 1,000,000 to about 4,500,000.
  • a most preferred polymer is Carbopol 974P.
  • acrylic acid is the preferred carboxyl-containing monoethylenenically unsaturated monomer
  • other unsaturated, polymerizable carboxyl-containing monomers such as methacrylic acid, ethacrylic acid, ⁇ - methacrylic acid (crotonic acid), cis - ⁇ - methylcrotonic acid (angelic acid), trans - - methyl - crotonic acid (tiglic acid), - butylcrotonic acid, ⁇ - phenylacrylic acid, ⁇ - benzylacrylic acid, a - cyclohexylacrylic acid, ⁇ - phenylacrylic acid (cinnamic acid), coumaric acid (o- hydrocinnamic acid), umbellic acid (p-hydroxycoumaric acid) and the like can be used in addition to or instead of acrylic acid.
  • Suitable crosslinking agents for use herein include non-polyalkenyl polyether difunctional crosslinking monomers such as di vinyl glycol; 2,3-dihydroxyhexa-l ,5-diene; 2,5-dimethyl-l ,5-hexadiene; divinylbenzene; N,N-diallylacrylamide; N,N-diallylmethacrylamide and the like.
  • an alkenyl halide such as allyl bromide or the like, e.g. polyallyl sucrose, polyallyl pentaerythritol, or the like.
  • Diolefinic non-hydrophilic macromeric crosslinking agents having molecular weights of from about 400 to about 8,000 such as insoluble di- and polyacrylates and methacrylates of diols and polyols, diisocyanate-hydroxyalkyl aery late or methacrylate reaction products, and reaction products of isocyanate terminated prepolymers derived from polyester diols, polyether diols or polysiloxane diols with hydroxyalkylmethacrylates, and the like, can also be used as the crosslinking agents.
  • the crosslinking agent is present at a level in the range of from about 0.05 % to about 5 % , preferably from about 0.75 % to about 2 % by weight of the polymer.
  • a surfactant can be present in the compositions herein in an amount of up to about 1 % by weight of composition, preferably from about 0.4 % to about 0.8 % by weight, selected from anionic, nonionic, cationic, amphoteric and zwitterionic surfactants and mixtures thereof.
  • the presence of a surfactant in the compositions herein serves to increase the stability of the composition at lower pH values.
  • the surfactant is preferably selected from anionic, cationic, amphoteric and zwitterionic surfactants and mixtures thereof, most preferably anionic surfactants.
  • Suitable anionic surfactants include water-soluble salts of C8-C22 alkyl benzene sulphonates, C8-C22 alkyl sulphates, C10-C18 alkyl polyethoxy ether sulphates, C8-C24 paraffin sulphonates, alpha-Ci2-
  • olefin sulphonates alpha-sulphonated C6-C20 fatty acids and their esters, C10-CI8 alkyl glyceryl ether sulphonates, fatty acid monoglyceride sulphates and sulphonates, especially those prepared from coconut oil, C8-C12 alkyl phenol polyethoxy ether sulphates,
  • the anionic surfactant is selected from alkali metal, alkaline earth metal, ammonium, and alkanolammonium salts of alkyl sulphates, alkyl ethoxy sulphates, alkyl benzene sulphonates and mixtures thereof.
  • the alkyl sulphate component is preferably a primary alkyl sulphate in which the alkyl group contains about 10-16 carbon atoms, more preferably an average of 12-14 carbon atoms.
  • the alkyl group may be linear or branched in configuration.
  • Examples of synthetically derived materials include Dobanol 23 (RTM) sold by Shell Chemicals (UK) Ltd, Ethyl 24 sold by the Ethyl Corporation, a blend of C13-C15 alcohols in the ratio 67% C13, 33% C15 sold under the trade name Lutensol by BASF GmbH and Synperonic (RTM) by ICI Ltd, and Lial 125 sold by Liquichimica Italiana.
  • Examples of naturally occurring materials from which the alcohols can be derived are coconut oil and palm kernel oil and the corresponding fatty acids.
  • any alkali metal, alkaline earth metal, ammonium or substituted ammonium cation can be used in association with the alkyl sulphate.
  • the alkyl sulphate can be associated with a source of magnesium ions either introduced as the oxide or hydroxide to neutralise the acid, or added to the composition as a water soluble salt.
  • a preferred alkyl sulphate surfactant for use herein is sodium lauryl sulphate.
  • Alkyl benzene sulphonates preferred for use in compositions of the present invention are those in which the alkyl group, which is substantially linear, contains about 10-16 carbon atoms, preferably about 11-13 carbon atoms, a material with an average chain length of 11.8 being most preferred.
  • the alkyl ethoxy sulphate surfactant component preferably comprises a primary alkyl ethoxy sulphate derived from the condensation products of a C10-C16 alcohol with an average of up to 6 ethylene oxide groups.
  • the C10-C16 alcohol itself can be obtained from any of the sources previously described for the alkyl sulphate component.
  • C12-C13 alkyl ether sulphates are preferred especially those containing an average of from 1 to 3 ethylene oxide moieties per mole.
  • Nonionic surfactants suitable for use herein can be broadly defined as compounds containing a hydrophobic moiety and a nonionic hydrophilic moiety.
  • the hydrophobic moiety can be alkyl, alkyl aromatic, dialkyl siloxane, and polyoxyalkylene alkyls.
  • hydrophilic moieties are polyoxyalkylenes, phosphine oxides, sulfoxides, amine oxides, and amides.
  • Examples of preferred classes of nonionic organic surfactants include:
  • the polyethylene oxide condensates of alkyl phenols, e.g., the condensation products of alkyl phenols having an alkyl group containing from about 6 to about 12 carbon atoms in either a straight chain or branched chain configuration, with ethylene oxide, the said ethylene oxide being present in amounts equal to from about 1 to about 6 moles of ethylene oxide per mole of alkyl phenol.
  • the alkyl substituent in such compounds may be derived from polymerized propylene, diisobutylene, octane or nonane, for example;
  • ethylene oxide e.g., a tallow alcohol ethylene oxide condensate having from about 2 to about 10 moles of ethylene oxide per mole of tallow alcohol, the tallow alcohol fraction having from about 16 to about 18 carbon atoms.
  • Amide surfactants which include the ammonia, monoethanol, diethanol, and other alkanol amides of fatty acids having an acyl moiety of from about 8 to about 22 carbon atoms and represented by the general formula:
  • Rj is a saturated or unsaturated, aliphatic hydrocarbon radical having from 7 to 21, preferably from 11 to 17 carbon atoms
  • R2 represents a Cj_4 alkylene group
  • m is 1, 2 or 3, preferably 1.
  • Specific examples of said amides are monoethanol coconut fatty acids amide and diethanol dodecyl fatty acid amide.
  • acyl moieties may be derived from naturally occurring glycerides, e.g., coconut oil, palm oil, soybean oil and tallow, but can be derived synthetically, e > g- > by the oxidation of petroleum, or by hydrogenation of carbon monoxide by the Fischer-Tropsch process.
  • the monoethanol amides and diethanolamides of C 18-22 fatty acids are preferred.
  • Suitable cationic surfactants are generally quaternary ammonium compounds such as the alkylarylether dimethylbenzylammonium chlorides, for example, 2-[2-(p-octylcres ⁇ xy) ethoxy] ethyl dimethylbenzylammonium chloride. This is commercially available under the name methylbenzethonium chloride or Hyamine(RTM) 10X. The corresponding p-octylphenoxy derivative of this compound is commercially available as benzethonium chloride, and is also suitable for the present purpose, as are the alkyldimethylbenzylammonium chlorides available under the name benzalkonium chloride.
  • alkyltrimethylammonium chlorides of which cetyltrimethylammonium chloride is commercially available under the trade name Cetab(RTM); alkyldimethylethylammonium halides; alkylpyridinium chloride, for example, cetylpyridinium chloride; alkylimidazolinium chloride such as alkylhydroxyethylimidazolimum chloride; alkyldimethyldichlorobenzylammonium chlorides; acylcolaminoformylinethyl pyridinium chlorides available under the trade name of Emulsept(RTM); and alkylarylmethylpyridinium chlorides such as polyalkylnaphthalene methylpyridinium chloride available under the trade name Emcol(RTM).
  • Cetab(RTM) alkyldimethylethylammonium halides
  • alkylpyridinium chloride for example, cetylpyridinium chloride
  • alkyl in the aforementioned anionic surfactants refers to alkyl radicals containing from eight to eighteen carbon atoms, preferably from ten to sixteen carbon atoms, and mixtures thereof, this being the range in which quaternary ammonium compounds are considered to have good germicidal activity.
  • Zwitterionic surfactants can be broadly described as derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, in which the aliphatic radical may be straight chain or branched, and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic water solubilizing group, e.g. carboxy, sulfo, sulfato, phosphato, or phosphono.
  • Examples of compounds falling within this definition are 3-(N,N-dimethyl-N-hexadecylammonio) propane- 1-sulfonate and 3-(N , N-dimethy 1-N-hexadecy lammonio)-2-hydroxy propane- 1 - sulfonate.
  • Amphoteric surfactants can be broadly described as derivatives of aliphatic secondary and tertiary amines, in which the aliphatic radical may be straight chain or branched and wherein one of the aliphatic substituents contains from about 8 to 18 carbon atoms and one contains an anionic water solubilizing group, e.g., carboxy, sulfo, sulfato, phosphato, or phosphono. Examples of compounds falling within this definition are sodium-3-dodecylaminopropionate and sodium-3-dodecylaminopropane sulfonate.
  • a pharmaceutically-acceptable nasal medicament i.e. a drug suitable for application via the nasal cavity, in an amount in the range of from about 0.005 % to about 5 % , preferably from about 0.01 % to about 2 % by weight of composition.
  • Drugs suitable for use in the compositions herein can be selected appropriately according to the disease to which the composition is to be applied.
  • the drug is preferably an agent for treating or preventing a nasal or upper respiratory disease, preferably a vasoconstrictor or other nasal decongestant.
  • the drug should not react with either the carboxyl-containing polymer or the anionic surfactant.
  • Suitable drugs may be in solid or liquid form, preferably liquid form.
  • drugs include antipyretic and analgesic agents, antiphlogistics, antiarrhythmics, hypotensors, vasodilators, anticholinergics, antiarteriosclerotics, agents for circulatory systems, antitussives, expectorants, ulcer preventives, enzyme preparations, anti-malignants, chemotherapeutic agents, antihistamine agents, enzyme preparations, local anaesthetic agents, steroidal anti- inflammatory agents, non-steroidal anti-inflammatory agents, anti ⁇ allergic agents, vasoconstrictors, and mixtures thereof.
  • compositions to be used for treating or preventing nasal or upper respiratory diseases drugs effective for treatment or prevention of nasal diseases, such as anti-inflammatory agents, antihistamine agents, anticholinergics, anti-allergic agents or vasoconstrictors, are preferred.
  • a highly preferred drug for inclusion in the composition of the present invention is a vasoconstrictor.
  • Suitable vasoconstrictors for use herein include phenylephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphthazoline nitrate, oxymetazoline hydrochloride, xylometazoline hydrochloride and tramazoline hydrochloride, preferably oxymetazoline hydrochloride.
  • compositions can be complemented by various optional ingredients including one or more preservatives, sequestering agents, colouring agents and flavouring agents.
  • Suitable sequestering agents for incorporation herein include polycarboxylates, amino polycarboxylates, polyphosphates, polyphosphonates and aminopolyphosphonates such as ethylenediaminetetra-acetic acid (EDTA), diethylenetriaminepenta- acetic acid, citric acid, gluconic acid, pyrophosphoric acid, etc. as well as their water-soluble salts, especially the alkali metal, ammonium and alkanol ammonium salts.
  • Sequestering agents are generally employed in amounts in the range from about 0.001 % to about 0.2 % , preferably from about 0.01 % to about 0.1 % by weight of the final pharmaceutical composition.
  • the pharmaceutical compositions can additionally include preservatives.
  • DMDM Hydantoin(RTM) ⁇ Germall(RTM) 115, methyl, ethyl, propyl, and butyl esters of hydrobenzoic acid benzoic acid
  • Euxyl(RTM) K400 Bronopol(RTM) (2-bromo-2- nitropropane-l,3-diol)
  • Preferred preservatives for inclusion in the present invention are methyl and propyl parabens. In general, amounts of from about 0.005 % to about 0.5 % are suitable herein with amounts of from about 0.01 % to about 0.1 % being preferred.
  • Suitable flavouring agents for use herein include aromatic flavouring agents such as menthol, camphor and eucalyptol.
  • a carboxyl- containing polymer is used in a topical sprayable nasal medicament composition for preventing or minimizing "roll-back".
  • the carboxyl-containing polymer is present in an amount of from about 0.05 % to about 5 %, preferably from about 0.25 % to about 2.5 % by weight of composition and is prepared by polymerizing one or more carboxyl-containing monoethyleneically unsaturated monomers and from about 0.05 % to about 5 % by weight of the polymer of a crosslinking agent.
  • the carboxyl-containing polymer is used in combination with a surfactant and a pharmaceutically-acceptable nasal medicament.
  • the surfactant is preferably present in an amount of from 0 to about 1 %, preferably from 0.4 % to about 0.8 % by weight of composition.
  • the surfactant is selected from anionic, cationic, amphoteric and zwitterionic surfactants, and mixtures thereof. Said use gives a composition with a pH in the range from about 2.5 to about 6 and is administrable in sprayable form. The viscosity of the composition increases upon contact with the nasal linings of the nasal cavity to form a viscous gel.
  • compositions are preferably provided in the form of a preferably pump-actuated aerosol spray.
  • Compositions herein preferably have a viscosity in the range up to about 300,000 mPa.s, more preferably up to about 20,000 mPa.s under low shear conditions (measured using a Brookfield RVT Viscometer, Spindle 7, 1 rpm, 25 °C) and a viscosity in the range up to about 10,000 mPa.s, more preferably up to about 5000 mPa.s under high shear conditions (measured using a Brookfield RVT Viscometer, Spindle 7, 100 rpm, 25°C).
  • the compositions have a pH in the range from about 2.5 to about 6.
  • the spray pump for use in the administering of unit dosages of pharmaceutical compositions of the present invention is preferably of a finger-actuated pump design.
  • the compositions are applied intra- nasally in a unit dosage containing from about 5 ⁇ g to about 100 ⁇ g, preferably from about 10 ⁇ g to about 50 ⁇ g of oxymetazoline per unit dose.
  • Perfect Valois VP7 there are approximately 1 to 3 sprays per unit dose.
  • At least 95 % by weight of the compositions typically consist of particles having a spray particle size in the range of from about 10 ⁇ m to about 400 ⁇ m.
  • Roll-back testing is carried out using a randomized cross-over design on a minimum base size of 32 people, pre-screened to exclude subjects having colds or taking medication.
  • the dose volume is 100 ⁇ l and is dispensed using a metered dose pump.
  • Each subject uses a product according to the invention and a polymer-free control product, the minimum time between usage of the products being 24 hours. Users are instructed to blow their nose, tilt the head back slightly and spray the product once through each nostril inhaling gently after spraying. The users are then asked to provide favourable/unfavourable comments on a number of in-use characteristics, including roll-back and drop-out from the nasal cavity. Comparison of the two sprays by the subjects shows that the product according to the invention is significantly better at eliminating "roll-back" and drip out from the nasal cavity than the polymer-free control product.
  • Topical nasal medicament compositions of the invention are prepared with the following ingredients:
  • Hot pre-dissolution of methyl and/or propyl parabens in water is carried out at 70 °C followed by addition of Carbopol (RTM) 974P via a sieve to effect thorough wetting of the Carbopol (RTM).
  • RTM Carbopol
  • the remaining ingredients are added to the mixture and the pH is adjusted.
  • compositions are incorporated into Perfect Valois VP7 finger- actuated spray pump dispensers.
  • compositions of the above Examples provide a high availability of active ingredient while significantly reducing "roll-back”.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
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Abstract

L'invention se rapporte à un produit pour pulvérisateur nasal comprenant un distributeur nasal actionné par une pompe et équipé d'un réservoir, une tête et des éléments de mélange de liquide et d'air. Le réservoir contient une composition médicamenteuse nasale à usage local se présentant sous la forme d'un liquide pulvérisable comprenant un polymère contenant du carboxyle, un tensioactif et un médicament nasal pharmaceutiquement acceptable. Le produit permet d'obtenir une grande disponibilité d'ingrédient actif et minimise le problème courant du retour du produit, associé aux gouttes et aux formulations nasales non gélifiables.
PCT/US1993/007554 1992-09-05 1993-08-12 Produits pour pulverisateur nasal WO1994005330A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU58922/94A AU5892294A (en) 1992-09-05 1993-08-12 Nasal spray products

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB929218834A GB9218834D0 (en) 1992-09-05 1992-09-05 Nasal spray products
GB9218834.1 1992-09-05

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Publication Number Publication Date
WO1994005330A1 true WO1994005330A1 (fr) 1994-03-17

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GB (1) GB9218834D0 (fr)
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Cited By (28)

* Cited by examiner, † Cited by third party
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WO1995013810A1 (fr) * 1993-11-19 1995-05-26 Schering-Plough Healthcare Products Incorporated Compositions nasales en nebuliseur contenant de l'oxymetazoline
GB2288734A (en) * 1994-04-29 1995-11-01 Zyma Sa Sprayable pharmaceutical-gel compositions for topical use
EP0666078A3 (fr) * 1994-02-03 1996-01-10 Schering Plough Healthcare Compositions pulvérisables pour l'administration par voie nasale.
EP0704206A1 (fr) * 1994-09-30 1996-04-03 Jürgen Dr. Regenold Composition pharmaceutique
US5897858A (en) * 1994-02-03 1999-04-27 Schering-Plough Healthcare Products, Inc. Nasal spray compositions exhibiting increased retention in the nasal cavity
EP0938345A4 (fr) * 1996-07-03 1999-12-29 Rhone Poulenc Rorer Pharma Composition pharmaceutique a base aqueuse
NL1011016C2 (nl) * 1999-01-13 2000-07-14 Dagra Pharma Bv Neusspray op basis van xylometazoline en kamille-extract.
WO2001017556A1 (fr) * 1999-09-07 2001-03-15 Shionogi & Co., Ltd. Préparations vaccinales administrables par les muqueuses
US6641799B2 (en) 2002-04-03 2003-11-04 Nos Spray, Inc. Nasal spray for decongesting nasal passages
EP1374856A1 (fr) * 2002-06-18 2004-01-02 Impetus AG Aérosol nasal thixotrope huileux
WO2004024187A3 (fr) * 2002-09-13 2004-05-27 Zicam Llc Compositions pouvant reduire la congestion nasale et procedes d'application de ces compositions sur la membrane nasale
US6841146B2 (en) 2000-01-31 2005-01-11 Schering-Plough Healthcare Products Inc. Spray composition
US7067539B2 (en) 2001-02-08 2006-06-27 Schering Corporation Cannabinoid receptor ligands
WO2007059390A1 (fr) * 2005-11-14 2007-05-24 Medtronic Xomed, Inc. Formulation injectable pouvant former un dispositif d’administration de medicament
US7348360B2 (en) * 1998-09-01 2008-03-25 Zicam, Llc Method and composition for delivering zinc to the nasal membrane
EP1450739A4 (fr) * 2001-10-12 2008-12-17 Cns Inc Gel nasal hydratant et applicateur
US7507767B2 (en) 2001-02-08 2009-03-24 Schering Corporation Cannabinoid receptor ligands
US7652030B2 (en) 2001-09-18 2010-01-26 Nycomed Danmark Aps Compositions for treatment of common cold
DE202013000748U1 (de) 2013-01-24 2013-02-19 Merz Pharma Gmbh & Co. Kgaa Sprühbare flüssige Zubereitung zur insbesondere nasalen Anwendung mit erhöhter lokaler Verweilzeit
US8691288B2 (en) 2006-05-10 2014-04-08 Medtronic, Inc. Gallium-containing sealant for medical use
DE102013001151A1 (de) 2013-01-24 2014-07-24 Merz Pharma Gmbh & Co. Kgaa Sprühbare flüssige Zubereitung zur insbesondere nasalen Anwendung mit erhöhter lokaler Verweilzeit
EP2759290A1 (fr) 2013-01-24 2014-07-30 Merz Pharma GmbH & Co. KGaA Composition liquide pulverisable en particulier pour application nasale avec un delai locale retentissant augmente
US8940792B2 (en) 2008-10-06 2015-01-27 Next Science, Llc Antimicrobial composition and methods for using same
US9119896B2 (en) 2007-02-08 2015-09-01 Medtronic Xomed, Inc. Polymeric sealant for medical use
US9629868B2 (en) 2009-04-06 2017-04-25 Joshua D. Levine Method of treating and preventing neuro-olfactory triggered or aggravated illnesses or related conditions
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US10350234B2 (en) 2009-04-06 2019-07-16 Joshua D. Levine Method of treating and preventing neuro-olfactory triggered or aggravated illnesses or related conditions
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WO2000041709A1 (fr) * 1999-01-13 2000-07-20 Dagra Pharma B.V. Aerosol nasal a base de xylometazoline et d'extrait de camomille
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EP1450739A4 (fr) * 2001-10-12 2008-12-17 Cns Inc Gel nasal hydratant et applicateur
US6641799B2 (en) 2002-04-03 2003-11-04 Nos Spray, Inc. Nasal spray for decongesting nasal passages
EP1374856A1 (fr) * 2002-06-18 2004-01-02 Impetus AG Aérosol nasal thixotrope huileux
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WO2004024187A3 (fr) * 2002-09-13 2004-05-27 Zicam Llc Compositions pouvant reduire la congestion nasale et procedes d'application de ces compositions sur la membrane nasale
AU2006315238B2 (en) * 2005-11-14 2012-11-01 Medtronic Xomed, Inc. Injectable formulation capable of forming a drug-releasing device
WO2007059390A1 (fr) * 2005-11-14 2007-05-24 Medtronic Xomed, Inc. Formulation injectable pouvant former un dispositif d’administration de medicament
US8691288B2 (en) 2006-05-10 2014-04-08 Medtronic, Inc. Gallium-containing sealant for medical use
US9119896B2 (en) 2007-02-08 2015-09-01 Medtronic Xomed, Inc. Polymeric sealant for medical use
US9700344B2 (en) 2008-06-12 2017-07-11 Medtronic Xomed, Inc. Method for treating chronic wounds with an extracellular polymeric substance solvating system
US8940792B2 (en) 2008-10-06 2015-01-27 Next Science, Llc Antimicrobial composition and methods for using same
US9629868B2 (en) 2009-04-06 2017-04-25 Joshua D. Levine Method of treating and preventing neuro-olfactory triggered or aggravated illnesses or related conditions
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