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WO2013041696A1 - Spray nasal et gouttes nasales ayant un effet stimulant et tonifiant - Google Patents

Spray nasal et gouttes nasales ayant un effet stimulant et tonifiant Download PDF

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Publication number
WO2013041696A1
WO2013041696A1 PCT/EP2012/068688 EP2012068688W WO2013041696A1 WO 2013041696 A1 WO2013041696 A1 WO 2013041696A1 EP 2012068688 W EP2012068688 W EP 2012068688W WO 2013041696 A1 WO2013041696 A1 WO 2013041696A1
Authority
WO
WIPO (PCT)
Prior art keywords
oil
composition
use according
nasal
extracts
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.)
Ceased
Application number
PCT/EP2012/068688
Other languages
German (de)
English (en)
Inventor
Hyeck-Hee Lee
Ute Steinfeld
Frank Holzer
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.)
F Holzer GmbH
Original Assignee
F Holzer GmbH
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 F Holzer GmbH filed Critical F Holzer GmbH
Publication of WO2013041696A1 publication Critical patent/WO2013041696A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to the use of a composition containing at least one essential oil and at least one stimulating substance for nasal administration.
  • the composition is introduced into the nose, in particular it is formulated as a nasal spray or nose drops, but also suitable for inhalation.
  • compositions comprising essential oils are known in the art.
  • JP 06040906 A relates to a sleep suppression composition comprising essential oils; this composition may be nasal, for example in the form of a spray.
  • EP 1 346 726 A1 relates to a sympathetic nervous system stimulating fragrance composition containing certain essential oils. This composition is used topically.
  • the object of the present invention is to provide a composition which has a particularly high stimulating effect.
  • composition contains at least one essential oil and at least one stimulating substance.
  • the composition contains at least one wound-healing-promoting substance selected from the group consisting of hyaluronic acid, dexpanthenol and chondroitinic acid.
  • the composition is administered nasally and / or inhaled.
  • the present composition combines the following properties:
  • a stimulating substance is understood as meaning a substance or a mixture of substances which excites the sympathetic nervous system of a human or an animal, wherein, for example, there is an increase in cardiac activity, blood pressure, perfusion, and skeletal muscle tone, glycolysis, and metabolism.
  • cardiac activity blood pressure, perfusion, and skeletal muscle tone, glycolysis, and metabolism.
  • perfusion a substance or a mixture of substances which excites the sympathetic nervous system of a human or an animal
  • skeletal muscle tone glycolysis, and metabolism.
  • the lung function can also be increased.
  • a stimulating substance such as caffeine on the nasal route shows, in contrast to oral intake, a much faster effect. This can be explained by the physiological mechanism of action in the brain: the stimulating effect of caffeine results primarily from the binding to adenosine receptors of the Ai and A 2A type. This results in a disinhibition of certain regions in the CNS.
  • the caffeine When administered via the nasal mucosa, the caffeine probably passes directly into the brain via small blood vessels along the olfactory nerve, so that a very fast effect is achieved after just a few minutes, about 5-15 minutes.
  • the caffeine content in cola is about 6-25 mg per 100 ml, which is about 0.006-0.025% by weight, while the caffeine content in coffee is about 20-70 mg per 100 ml, which is about 0.02. 0.07 weight equivalent.
  • a quantity of about 30 ⁇ per spray is applied. Since caffeine administration via the nasal mucosa has a much faster effect than oral administration, as it has been able to reach the brain directly, even smaller amounts are required. Therefore, a preferred caffeine concentration may be between 0.1 to 3 wt%. 2% caffeine in the formulation would correspond to an applied amount of 0.6 mg per 30 ⁇ spray.
  • Guarana powder may also be included as an activating substance; 3g guarana powder dissolved in water, correspond to a caffeine content of
  • a spray of 30 ⁇ would accordingly contain 0.045 mg guarana or caffeine.
  • At least one wound healing promoting agent prevents irritation and damage to the nasal mucous membrane, e.g. through certain essential oils, before. If damage to the nasal mucous membrane should already be present in the application, reliable wound healing can be ensured despite the use of irritating oils if necessary.
  • the at least one essential oil is selected from the group consisting of menthol-containing essential oils, camphor-containing essential oils, cajuput oil, grapefruit oil, eucalyptus oil, lime oil, rosemary oil, orange oil, lime-containing essential oils, citron oil, pine oil, Bergamot oil, clove oil, ginger oil, peppermint oil, aniseed oil, mint oil, lemongrass oil, cedarwood oil, niaouli oil, jasmine oil, lineol, eugenoil, a-
  • Pinene spearmint oil, blood orange oil, lavender oil, clary sage oil, mountain pine oil, as well as mixtures and / or combinations thereof.
  • the stimulating substance is selected from the group consisting of xanthines, in particular caffeine (teein), theophylline, theobromine, extracts of cola seeds, exacerbations. from leaves of Erythroxyium species and / or extracts of
  • Guarana species taurine; Mono- and / or oligosaccharides, in particular glucose and / or dextrose; Nicotine; Ginko extracts, extracts of green tea, L-carnitine, creatine, lecithin, ginseng extracts, orotic acid and / or salts thereof, in particular magnesium orotate, choline, nicotinamide,
  • Dimethylaminoethanol (Deanol), omega-3 fatty acids, Icelandic moss extract, capsiacin and / or mixtures and / or combinations thereof.
  • the concentration of the at least one essential oil, based on the total composition is from 0.01 to 2.5% by weight, preferably from 0.05 to 2% by weight, particularly preferably from 0 , 2 to 1% by weight and / or of the at least one stimulating substance, based on the total composition, of 0.005 to 5% by weight.
  • the concentration of the at least one wound-healing-promoting substance can be from 0.001 to 6% by weight, preferably from 0.1 to 5% by weight, particularly preferably from 0.5 to 3% by weight.
  • the composition contains as at least one stimulating substance at least one of the following substances and / or combinations thereof:
  • the composition comprises at least one adjuvant selected from the group consisting of viscosity boosters, in particular hyaluronic acid, carboxymethylcellulose, hydroxypropylmethylcellulose and / or glycerol; at least one solubilizer, in particular polyvinylpyrrolidone (polyvidone), emulsifiers, in particular macrogol-25-cetostearyl ether (Cremophor A25), macrogolglycerol ricinoleate (Cremophor EL) and / or lecithin; Polysorbates, in particular TWEEN; Osmoregulators, in particular glycerol, sorbitol, sodium or potassium or citrate salts and / or mixtures thereof; Antioxidants, especially coenzyme Q10, Vitamin A, rosemary oil, tocophenol, ascorbyl palmitate, Vitamin E, Vitamin C and / or combinations thereof; and mixtures and / or combinations of the aforementioned substances. Substances that have hyaluronic acid,
  • Tocotrienols algae oil, perilla oil, poppy seed oil, singer oil, evening primrose oil, etc. may also be included in the composition.
  • composition in a further preferred embodiment, is a composition
  • Preservative included In addition, however, it is also preferred that the composition be free of preservatives.
  • composition is free of quaternary ammonium compounds, in particular benzalkonium chloride. It has been shown that such compounds can damage the nasal mucosa, so that in their absence an extremely gentle nasal spray is obtained.
  • the composition comprises ad 100% by weight of a liquid carrier phase, in particular water, oils, triglycerides and / or fatty acid esters.
  • composition is particularly preferably in the form of an emulsion, in particular an irkoemulsion.
  • Formulation of the essential oils as an emulsion and especially as a microemulsion avoids the problem of o durability
  • Volatile substances such as essential oils, are sensitive to external factors such as atmospheric oxygen, light and heat, as well as oxidative degradation processes mediated by metal ions, which are found in trace amounts in excipients.
  • alcoholic co-solvents or by quaternary ammonium compounds such as benzalkonium chloride.
  • Alcohols and quaternary ammonium compounds irritate and damage the nasal mucosa.
  • the present invention enhances the stability and compatibility of the essential oils by formulation in microemulsions.
  • the microemulsion contains a dispersion of nanoscale oil droplets in the aqueous continuous phase.
  • the ethereal oil droplets are enveloped by adsorbed emulsifier / solvent mediator, which protects the droplets in a protective way and stabilizes them. This forms a protection against degradation by oxidation.
  • the rate of evaporation of the dispersed oil droplets is reduced relative to the rate of un emulsified oil. Also a beautiful effect of the essential oils themselves, when applied to the
  • the nasal application can be achieved by atomizing the composition and / or by dribbling the nasal mucous membranes with the composition.
  • a sputtering or the formation of an aerosol can be made from the composition.
  • the nasal application is carried out 1 to 10, preferably 2 to 4 times per day.
  • the number of Applikattonen is preferably situation-dependent and vote on the case of need; ie it can be used mainly in special stress and stress situations and thus not regularly.
  • the composition is for stimulating and / or stimulating the sympathetic nervous system; before, during and / or after exercise; before, during, and / or after situations requiring increased attention; to increase concentration; to increase mental performance; before, during and / or after driving; for the prophylaxis and / or treatment of jet lag; used for the prophylaxis and / or treatment of fatigue, fatigue and / or fatigue and / or to improve well-being and / or smoking cessation.
  • a method for non-therapeutic stimulation and / or activation of the sympathetic nervous system is also specified, in which the composition described above is administered nasally and / or inhaled.
  • the composition described above is administered nasally and / or inhaled.
  • a nasal spray and nasal drops which each contain at least one essential oil, at least one stimulating substance and at least one wound healing substance.
  • the nasal spray and the nasal drops are based on the composition described above. With regard to preferred embodiments of this composition, reference is also made to the above-mentioned referenced.
  • composition is used according to the invention for invigorating, refreshing, stimulating and increasing the concentration and / or performance of a human or an animal.
  • the composition can also be used for smoking cessation.
  • the concentration of the oils is in the range of 0.01 to 5 wt .-%, preferably in the range of 0.05 to 2.5 parts by weight, particularly preferably in the range of 0.1 to 1 wt .-%.
  • the oil consists mainly (50-60%) of cineole; additionally L-pinene, terpineol and several aldehydes are included;
  • Caffeine has a narrowing effect on vessels in the brain, widening to those in the periphery; Due to the cerebral vasoconstrictive effect, there is a reduced blood flow velocity in the brain.
  • Taurine is a simple sulfur-containing free amino acid; often in electrically excitable tissues such as the brain, retina, heart, skeletal muscles; it is involved in many physiological processes, e.g. Osmoregulation, lipid metabolism; intracellular calcium regulation, neuronal development, neuromodulation and cell protection.
  • Theophylline theobromine
  • Extract of leaves of erythroxylum species or high caffeine guarana species Extract of leaves of erythroxylum species or high caffeine guarana species
  • Herbal extracts that promote mental performance / concentration > NADH / NADPH.
  • Viscosity enhancers e.g., hyaluronic acid, hydroxypropylmethylcellulose, glycerin
  • Solvents e.g., Polyvidone, Tween, SPAN, PEG castor oil, PEG-hydrogenated castor oil, polyoxyethylene stearate, etc.
  • Antioxidants e.g., Q10, Vitamin E, Vitamin C, Vitamin A, taurine, etc.
  • Macrogolglycerol ricinoleate (Cremophor 0.3-0.6 EL)

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  • Life Sciences & Earth Sciences (AREA)
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  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Mycology (AREA)
  • Organic Chemistry (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
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  • Dermatology (AREA)
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  • Pulmonology (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne l'utilisation d'une composition qui contient au moins une huile essentielle ainsi qu'au moins une substance à effet stimulant et qui est destinée à une application nasale. A cet effet, ladite composition est introduite dans le nez et elle est plus particulièrement formulée sous forme de spray nasal ou de gouttes nasales mais convient également pour l'inhalation.
PCT/EP2012/068688 2011-09-21 2012-09-21 Spray nasal et gouttes nasales ayant un effet stimulant et tonifiant Ceased WO2013041696A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011114094.1 2011-09-21
DE102011114094A DE102011114094A1 (de) 2011-09-21 2011-09-21 Stimulierendes und belebendes Nasenspray und Nasentropfen

Publications (1)

Publication Number Publication Date
WO2013041696A1 true WO2013041696A1 (fr) 2013-03-28

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Application Number Title Priority Date Filing Date
PCT/EP2012/068688 Ceased WO2013041696A1 (fr) 2011-09-21 2012-09-21 Spray nasal et gouttes nasales ayant un effet stimulant et tonifiant

Country Status (2)

Country Link
DE (1) DE102011114094A1 (fr)
WO (1) WO2013041696A1 (fr)

Cited By (1)

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Publication number Priority date Publication date Assignee Title
WO2014176449A1 (fr) * 2013-04-25 2014-10-30 Rinsenergy LLC Composition de rinçage buccal et procédé d'administration de compléments énergétiques

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Publication number Priority date Publication date Assignee Title
JP2022515021A (ja) * 2018-12-31 2022-02-17 フィリップ・モーリス・プロダクツ・ソシエテ・アノニム 水不混和性溶媒を含む液体ニコチン製剤
EP3991573A1 (fr) * 2020-11-03 2022-05-04 Patrick Faber Compositions a administrer par le nez

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DE202008016517U1 (de) * 2008-12-12 2009-03-05 Ratiopharm Gmbh Wässrige Zusammensetzung enthaltend Dexpanthenol und Natriumchlorid
US20090069433A1 (en) * 2007-09-10 2009-03-12 Wayne Jeffrey Perry Nasal rinse additive
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JP2507445B2 (ja) 1987-06-23 1996-06-12 住友電気工業株式会社 光コネクタコ−ドの製造方法
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Publication number Priority date Publication date Assignee Title
JPH0640906A (ja) 1992-07-22 1994-02-15 Suntory Ltd 眠気抑制剤
WO1996000071A1 (fr) * 1994-06-23 1996-01-04 The Procter & Gamble Company Traitement du besoin de nicotine et/ou des symptomes de manque du fumeur au moyen d'une composition liquide contenant de la nicotine et de la cafeine ou de la xanthine, pour administration par voie nasale
US6350458B1 (en) * 1998-02-10 2002-02-26 Generex Pharmaceuticals Incorporated Mixed micellar drug deliver system and method of preparation
EP1199073A1 (fr) * 1999-07-02 2002-04-24 Nippon Chemical Works Co., Ltd Preparation contenant un acide aminoethane sulfonique
EP1346726A1 (fr) 2000-12-25 2003-09-24 Shiseido Company, Ltd. Composition de parfum stimulant le systeme sympathique
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