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WO1996000071A1 - 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 - Google Patents

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 Download PDF

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Publication number
WO1996000071A1
WO1996000071A1 PCT/US1995/007425 US9507425W WO9600071A1 WO 1996000071 A1 WO1996000071 A1 WO 1996000071A1 US 9507425 W US9507425 W US 9507425W WO 9600071 A1 WO9600071 A1 WO 9600071A1
Authority
WO
WIPO (PCT)
Prior art keywords
caffeine
nicotine
composition
treatment
pharmaceutically
Prior art date
Application number
PCT/US1995/007425
Other languages
English (en)
Inventor
Satyanarayana Majeti
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 AU27036/95A priority Critical patent/AU2703695A/en
Publication of WO1996000071A1 publication Critical patent/WO1996000071A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—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
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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

Definitions

  • Nicotine appears to be the most pharmacologically active substance in tobacco smoke, yet it seems not to be as significant from a health standpoint as the tars and carbon monoxide. However, nicotine is the reinforcing substance in tobacco which maintains the addiction.
  • composition can be formulated which provides the combination of nicotine and caffeine or caffeine equivalent in a single
  • compositions may offer the advantage of providing treatment and/or relief of nicotine craving and/or smoking withdrawal symptoms to a broader spectrum of smokers who wish to break the smoking habit. It has further been discovered that these compositions may also curb the appetite which may aid in reducing the weight gain that is commonly experienced by
  • the present invention relates to a liquid composition suitable for nasal administration for the treatment of nicotine craving and/or smoking withdrawal symptoms comprising nicotine and caffeine or caffeine equivalent, wherein the composition delivers from about O.Olmg to about 3mg of nicotine, and from about lmg to about 30mg of caffeine or caffeine equivalent.
  • the present invention also relates to a method for providing treatment and/or relief of nicotine craving and/or smoking withdrawal symptoms to a human or lower animal in need of such treatment comprising the administration of a safe and effective amount of a liquid composition comprising nicotine and caffeine or caffeine equivalent.
  • the subject invention comprises nicotine, caffeine or caffeine equivalent, and preferably one or more pharmaceutically-acceptable carriers suitable for nasal administration. These compositions are useful for the treatment and/or relief of nicotine craving and/or smoking withdrawal symptoms.
  • nicotine craving and “smoking withdrawal symptoms” as used herein both refer to any physical or psychological reaction relating to breaking the habit of smoking tobacco or using any tobacco product or decreasing the frequency or intensity of smoking tobacco or using any tobacco product.
  • pharmaceutically-acceptable is used herein to describe materials that are non-toxic and suitable for administration to humans and/or lower animals.
  • pharmaceutically-acceptable carrier as used herein means any material safe and effective for use in the compositions of the present invention.
  • Such materials include pH adjusters, emollients, emulsifiers, buffering agents, solvents, preservatives, agents for regulating isotonicity, water, wetting agents, thickening agents, humectants, surfactants, aromatic compounds, bioadhesive compounds, agents for aiding the film-forming properties and substantivity of the formulations, antimicrobials for maintaining the antimicrobial integrity of the compositions, an tioxidants, agents suitable for aesthetic purposes such as fragrances, pigments, and colorings, non-soluble ingredients, and mixtures thereof.
  • safe and effective amount mean a sufficient amount of material to provide the desired benefit without undue adverse side effects commensurate with a reasonable benefit/risk ratio when used in the manner of this invention.
  • the specific safe and effective amount will vary with such factors as the particular condition that is being treated, the severity of the condition, the duration of the treatment, the physical condition of the patient, the nature of concurrent therapy (if any), and the specific formulation and optional components hereinafter.
  • suitable for nasal administration refers to any formulation that is suitable for the convenient administration of the composition whereby the composition is placed in contact with mucous membranes of the nose and/or the nasal passages.
  • the present invention comprises nicotine.
  • Nicotine is a tertiary amine composed of a pyridine and a pyrrolidine ring. It is a colorless to pale yellow, which is freely water soluble, strongly alkaline, hygroscopic liquid obtained from the tobacco plant. Nicotine has a characteristic odor and turns brown on exposure to air or light [Physicians Desk Reference. 48th Edition, p. 1306, 1984]. Nicotine is delivered in an amount of from about 0.0 lmg to about 3mg, preferably from about O.lmg to about 2mg, and most preferably from about 0.5mg to about 1.5mg. Nicotine is also described in Remington's Pharmaceutical Sciences. 18th Edition, 1990, p. 891, which is incorporated herein by reference. Caffeine
  • the present inventions also comprise caffeine or a caffeine equivalent.
  • Caffeine is found as white, fleecy masses or long, flexible, silky crystals. It is odorless, bitter tasting, and slightly soluble in water and alcohol. Caffeine may be derived synthetically or by extraction of coffee beans, tea leaves or kola nuts [Hawleys Condensed Chemical Dictionary. Twelfth Edition, 1993]. Examples of suitable sources of caffeine for use in the present invention are pure caffeine, caffeine combined with acetate, citrate, benzoate, phosphate, sulfate or salicylate. Also suitable are any of the xanthine analogues that match caffeine's effectiveness as a central nervous system stimulant, including salts thereof that are compatible.
  • Xanthine derivatives are described in Remington's Pharmaceutical Sciences. 18th Edition, 1990, pp. 1132-34, which is incorporated herein by reference.
  • the caffeine or caffeine equivalent is delivered in an amount of from about lmg to about 30mg, preferably from about 3mg to about 20mg, and most preferably from about 5mg to about lOmg.
  • compositions suitable for nasal administration preferably also contain one or more pharmaceutically-acceptable carriers suitable for nasal administration.
  • Such compositions include (but are not limited to) aqueous nasal solutions for use as drops or as sprays, nasal suspensions, or other liquid formulations suitable administering the present compositions intranasally.
  • Preferred nasal dosage forms are aqueous solutions, emulsions or suspensions which may be administered intranasally as an aerosol or aqueous nasal spray or as nasal drops.
  • Suitable nontoxic pharmaceutically-acceptable carriers are known to those skilled in the art and are also fully disclosed in Remington's Pharmaceutical Sciences. 17th Edition, 1985, which is incorporated by reference herein in its entirety.
  • nasal carrier While the choice of nasal carrier is not critical to the present invention, the carrier or carriers chosen must be suitable for administering the nicotine and caffeine or caffeine equivalent so that the desired blood levels of these compounds are achieved in the body of the recipient.
  • the desired blood level of nicotine is from about lng ml to about lOOng/ml, preferably from about 5ng/ml to about 75ng/ml, and most preferably from about lOng/ml to about 50ng/ ml, preferably within 1 to 4 hours of administration.
  • the desired blood level of caffeine or caffeine equivalent is from about 0.0 lug/ml to about 20ug/ml, preferably from about 0.
  • compositions will normally be prepared in dosage unit form to contain safe and effective amounts of the nicotine and caffeine (or equivalent) to achieve the desired blood levels. Fractions of the dosage units or multiple dosage units may also be utilized.
  • the liquid compositions herein deliver to a human or lower animal from about 0.0 lmg to about 3mg, preferably from about O.lmg to about 2mg, and most preferably from about 0.5mg to about 1.5mg of nicotine; and from about lmg to about 30mg, preferably from about 3mg to about 20mg, and most preferably from about 5mg to about lOmg of caffeine or caffeine equivalent.
  • the present invention may be a liquid composition suitable for nasal administration, for the treatment of nicotine craving or smoking withdrawal symptoms comprising nicotine, caffeine or caffeine equivalent, and one or more pharmaceutically-acceptable carriers suitable for nasal administration, wherein the composition delivers from about O.Olmg to about 3mg of nicotine and from about lmg to about 30mg of caffeine or caffeine equivalent.
  • the amount of nicotine and caffeine or caffeine equivalent and frequency of administration may vary depending on the carrier chosen and the personal needs of the user. However, it is suggested (as an example) that the present invention be administered from about once to about 20 times per day, preferably from about 2 to about 10 times per day and most preferably from about 4 to about 8 times per day.
  • a typical dose for a aqueous nasal spray carrier contains about one to about three sprays per nostril.
  • the present compositions may contain one or more solvents. Suitable solvents include but are not limited to water, alcohol, propylene glycol, glycerin, sorbitol solution and the like, to assist solubilization and incorporation of water- insoluble ingredients. Preferred for use herein are pharmaceutically-acceptable aqueous saline solution carriers.
  • the salt is present in the solution at a level of from 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%.
  • Purified water is present at a level of from about 90% to about 99.99%, preferably from about 95% to about 99.5% , and most preferably from about 98% to about 99.5%, by weight of the composition.
  • compositions of the present invention may be prepared as emulsions.
  • Single emulsion preparations of the oil-in-water type are well-known in the art and are useful in the present invention.
  • multi- phase emulsion compositions such as the water-in-oil-water type, (as disclosed in U.S. Patent No. 4,254,105, Fakuda et al., issued March 3, 1981, incorporated herein by reference), the triple emulsion systems comprising an oil-in-water-in-silicone fluid emulsion and microemulsion systems.
  • such single or multiphase emulsions contain water, emollients and emulsifiers. Emulsions are described in detail in Remington's Pharmaceutical Sciences. 17th Edition, pp. 298-308, which is incorporated herein by reference.
  • compositions may also comprise from about 0% to about 10%, preferably from about 2% to about 5%, of one or more pharmaceutically-acceptable emulsifiers.
  • emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are disclosed in, for example, U.S. Patent 3,755,560, issued August 28, 1973, Dicert et al.; U.S. Patent 4,421,769, issued December 20, 1983, Dixon et al.; and McCutcheon's Detergents and Emulsifiers. North American Edition, pages 317-324 (1986); the disclosures of which are incorporated herein by reference.
  • Preferred emulsifiers are anionic or nonionic, although the other types may also be used.
  • compositions may also comprise from about 0% to about 10% of a pharmaceutically-acceptable emollient.
  • Suitable emollients include volatile silicone oils, non-volatile emollients such as fatty acid and fatty alcohol esters, highly branched hydrocarbons known as the Permethyl 99 through 108 A series (available from Permethyl Corporation), and mixtures thereof.
  • Suitable emollients are disclosed in U.S. Patent No. 5322689, to Hughes et al., issued 6/21/94, incorporated herein by reference.
  • the compositions are isotonic, i.e., they have the same osmotic pressure as blood and lacrimal fluid.
  • sustained release compositions for example, sustained release sprayable solutions and suspensions can be conveniently employed.
  • the desired isotonicity of the compositions of this invention may be accomplished by using, for example, sodium chloride, or other pharmaceutically-acceptable agents such as dextrose, boric 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.
  • 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, carboxymethyl cellulose, hydroxypropyl cellulose, carbomer, and the like. 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 pharmaceutically-acceptable humectant to inhibit drying of the mucous membrane and to prevent irritation.
  • a pharmaceutically-acceptable humectant can be employed including, for example, sorbitol, propylene glycol or glycerol.
  • 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 present invention.
  • Typical useful surfactants for the present compositions include polyoxyethylene derivatives of fatty acid partial esters of sorbitol anhydrides such as Tween 80, Polyoxyl 40 Stearate, Polyoxyethylene 50 Stearate and Octoxynol, as well as Oxyethylated tertiary octyl phenol formaldehyde polymer (available from Sterling Organics as tyloxapol).
  • the usual concentration is from about 0.5% to about 10% based on the total weight.
  • a pharmaceutically-acceptable preservative is generally employed to increase the shelf life of the compositions.
  • Benzyl alcohol is suitable, although a variety of preservatives including, for example, parabens, thimerosal, chlorobutanol, phenylmercuric 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 about 0.001% to about 2% based on the total weight, although there may be appreciable variation depending upon the agent selected.
  • the present invention may also comprise one or more bioadhesive compounds which adhere to moist area of biological membranes.
  • bioadhesive compounds include sodium carboxymethylcellulose, amyopectin, hydroxyethylcellulose, acrylates, gelatins, guar gum karaya gum, tragacanth, agar, alginc acid calcium carboxymethylcellulose, dextrin, methylcellulose, pectin, polyethylene glycol and polyvinylpyrrolidone.
  • the bioadhesive compounds may be present at a level of from about 0.1% to about 30%, and preferably from about 7% to about 25%, by weight of the composition.
  • compositions of the present invention also include microencapsulation of either the nicotine or caffeine (or caffeine equivalent) or both.
  • Techniques and materials for microencapsulation are well known in the art. Microencapsulation is discussed more fully in Kirk and Othmer's Encyclopedia of Chemical Technology. Vol. 13, 2nd Edition, pp.436-456, which is incorporated herein by reference.
  • compositions of the present invention may also contain one or more aromatic components.
  • aromatics include, for example, menthol, 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); 2-dodecenal (citrus, mandarin); thymol; cedar leaf oil, myristica oil, lavender oil, nutmeg oil, turpentine; 3-1-menthoxy propane- 1,2-diol; N-substituted-p-menthane-3-carbox-amides and acyclic carboxamides; and mixtures thereof.
  • Aromatic compounds may be present at a level of from about 0.0001% to about 1%, preferably from about 0.001% to about 1%, and most preferably from about 0.001% to about 0.5%, by weight of the compositions.
  • Aromatic compounds may be present at a level of from about 0.0001% to about 1%, preferably from about 0.001% to about 1%, and most preferably from about 0.001% to about 0.5%, by weight of the compositions.
  • a variety of additional optional pharmaceutically-acceptable ingredients may also be added to the present invention compositions.
  • pH adjusters such as sodium hydroxide
  • buffering agents such as sodium bicarbonate, sodium phosphate, and potassium phosphate
  • various polymers for aiding the film-forming properties and substantivity of the formulations
  • antimicrobials for maintaining the antimicrobial integrity of the compositions
  • antioxidants and agents suitable for aesthetic purposes such as fragrances, pigments, and colorings.
  • compositions may also contain low levels of pharmaceutically-acceptable 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 form Hallcrest, Glenview, Illinois 60025, U.S.A.
  • the pH of the composition is generally from about 5 to about 10, preferably from about 6 to about 9, and most preferably from about 6.0 to about 8.5.
  • the present invention also encompasses a method of treatment.
  • the method of providing treatment and/or relief of nicotine craving and/or smoking withdrawal symptoms to a human or lower animal in need of such treatment comprises the administration of a safe and effective amount of a liquid composition suitable for nasal administration comprising nicotine and caffeine or caffeine equivalent.
  • Such compositions preferably further comprise one or more pharmaceutically-acceptable carriers suitable for nasal administration.
  • a nasal composition is prepared by combining the following components utilizing conventional mixing techniques.
  • Water, Purified QS 87.19 Tyloxapol and water are added to an appropriately sized vessel and completely mixed under low heat. Ingredients are added one at a time with mixing, allowing each to dissolve before adding the next. The aromatic[s] are. blended together in a separate premix before being added to the batch. A separate premix is also made for chlorhexidine gluconate. After all ingredients have been added, purified water is used to bring the batch to the appropriate weight.
  • a nasal spray composition is prepared by combining the following components utilizing conventional mixing techniques.
  • Example II was prepared according the disclosure for Example I.

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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)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une composition liquide pour administration par voie nasale, destinée au traitement du besoin de nicotine ou des symptômes de manque du fumeur, ladite composition contenant de la nicotine et de la caféine ou un équivalent de la caféine.
PCT/US1995/007425 1994-06-23 1995-06-09 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 WO1996000071A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU27036/95A AU2703695A (en) 1994-06-23 1995-06-09 Treatment of nicotine craving and/or smoking withdrawal symptoms with a liquid nasal composition containing nicotine and caffeine or xanthine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26426294A 1994-06-23 1994-06-23
US08/264,262 1994-06-23

Publications (1)

Publication Number Publication Date
WO1996000071A1 true WO1996000071A1 (fr) 1996-01-04

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PCT/US1995/007425 WO1996000071A1 (fr) 1994-06-23 1995-06-09 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

Country Status (6)

Country Link
AU (1) AU2703695A (fr)
IL (1) IL114129A0 (fr)
MA (1) MA23588A1 (fr)
PE (1) PE33396A1 (fr)
WO (1) WO1996000071A1 (fr)
ZA (1) ZA955032B (fr)

Cited By (16)

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Publication number Priority date Publication date Assignee Title
WO1998003175A1 (fr) * 1996-07-18 1998-01-29 International Diabetes Institute Traitement de l'obesite
US7078016B2 (en) 2001-11-21 2006-07-18 Alexza Pharmaceuticals, Inc. Delivery of caffeine through an inhalation route
US7090830B2 (en) 2001-05-24 2006-08-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7458374B2 (en) 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US7537009B2 (en) 2001-06-05 2009-05-26 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US7540286B2 (en) 2004-06-03 2009-06-02 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US7581540B2 (en) 2004-08-12 2009-09-01 Alexza Pharmaceuticals, Inc. Aerosol drug delivery device incorporating percussively activated heat packages
US7585493B2 (en) 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
US20120022114A1 (en) * 2009-08-29 2012-01-26 Laboratorio Pablo Cassara S.R.L. Low-dose, non-irritating nicotine nasal composition to reduce the desire to smoke
WO2013041696A1 (fr) * 2011-09-21 2013-03-28 F. Holzer Gmbh Spray nasal et gouttes nasales ayant un effet stimulant et tonifiant
US8991387B2 (en) 2003-05-21 2015-03-31 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US9211382B2 (en) 2001-05-24 2015-12-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
WO2017178897A3 (fr) * 2016-04-12 2017-11-23 Arturo Solis Herrera Compositions et méthodes pour le traitement de maladies des muqueuses paranasales à l'aide d'agonistes des récepteurs nicotiniques à l'acétylcholine
WO2019200427A1 (fr) 2018-04-16 2019-10-24 Barista Mist Pty Ltd Compositions de caféine et procédés d'utilisation
US11642473B2 (en) 2007-03-09 2023-05-09 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US12214118B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device

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Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998003175A1 (fr) * 1996-07-18 1998-01-29 International Diabetes Institute Traitement de l'obesite
US7585493B2 (en) 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
US10350157B2 (en) 2001-05-24 2019-07-16 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7090830B2 (en) 2001-05-24 2006-08-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US9440034B2 (en) 2001-05-24 2016-09-13 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US9211382B2 (en) 2001-05-24 2015-12-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US9308208B2 (en) 2001-06-05 2016-04-12 Alexza Pharmaceuticals, Inc. Aerosol generating method and device
US11065400B2 (en) 2001-06-05 2021-07-20 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US9687487B2 (en) 2001-06-05 2017-06-27 Alexza Pharmaceuticals, Inc. Aerosol forming device for use in inhalation therapy
US9439907B2 (en) 2001-06-05 2016-09-13 Alexza Pharmaceutical, Inc. Method of forming an aerosol for inhalation delivery
US8955512B2 (en) 2001-06-05 2015-02-17 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US7537009B2 (en) 2001-06-05 2009-05-26 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
US7078016B2 (en) 2001-11-21 2006-07-18 Alexza Pharmaceuticals, Inc. Delivery of caffeine through an inhalation route
US7488469B2 (en) 2001-11-21 2009-02-10 Alexza Pharmaceuticals, Inc. Delivery of caffeine through an inhalation route
US7458374B2 (en) 2002-05-13 2008-12-02 Alexza Pharmaceuticals, Inc. Method and apparatus for vaporizing a compound
US9370629B2 (en) 2003-05-21 2016-06-21 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US8991387B2 (en) 2003-05-21 2015-03-31 Alexza Pharmaceuticals, Inc. Self-contained heating unit and drug-supply unit employing same
US7540286B2 (en) 2004-06-03 2009-06-02 Alexza Pharmaceuticals, Inc. Multiple dose condensation aerosol devices and methods of forming condensation aerosols
US7581540B2 (en) 2004-08-12 2009-09-01 Alexza Pharmaceuticals, Inc. Aerosol drug delivery device incorporating percussively activated heat packages
US12138383B2 (en) 2007-03-09 2024-11-12 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US11642473B2 (en) 2007-03-09 2023-05-09 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US20120022114A1 (en) * 2009-08-29 2012-01-26 Laboratorio Pablo Cassara S.R.L. Low-dose, non-irritating nicotine nasal composition to reduce the desire to smoke
WO2013041696A1 (fr) * 2011-09-21 2013-03-28 F. Holzer Gmbh Spray nasal et gouttes nasales ayant un effet stimulant et tonifiant
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MA23588A1 (fr) 1995-12-31
AU2703695A (en) 1996-01-19
ZA955032B (en) 1996-03-11
PE33396A1 (es) 1996-08-19
IL114129A0 (en) 1995-10-31

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