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WO1996000070A1 - Traitement du besoin de nicotine et/ou des symptomes de manque du fumeur au moyen d'une composition contenant de la nicotine et de la cafeine ou de la xanthine pour administration par voie orale - Google Patents

Traitement du besoin de nicotine et/ou des symptomes de manque du fumeur au moyen d'une composition contenant de la nicotine et de la cafeine ou de la xanthine pour administration par voie orale Download PDF

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Publication number
WO1996000070A1
WO1996000070A1 PCT/US1995/007381 US9507381W WO9600070A1 WO 1996000070 A1 WO1996000070 A1 WO 1996000070A1 US 9507381 W US9507381 W US 9507381W WO 9600070 A1 WO9600070 A1 WO 9600070A1
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WO
WIPO (PCT)
Prior art keywords
caffeine
nicotine
composition
composition according
equivalent
Prior art date
Application number
PCT/US1995/007381
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 AU27708/95A priority Critical patent/AU2770895A/en
Publication of WO1996000070A1 publication Critical patent/WO1996000070A1/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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A61K9/0058—Chewing gums
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • Treatment of nicotine cravi ng and/or smoking withdrawal symptoms with an oral composition containi ng nicotine and caffeine or xanthine
  • Chewing beeswax, eating candy and peppermints as well as cold turkey interruption have been tried without much success.
  • the addition of chemicals designed to sicken the user or render smoking repulsive to the user have also not produced good results.
  • More recent therapies for smoking cessation have focused on the administration of nicotine to the smoker. These therapies allow the individual to satisfy a nicotine habit while minimizing or eliminating side effects caused by absorbing nicotine through the lungs along with the other harmful by-products of combustion of tobacco.
  • Nicotine supplementation has proven to be an effective therapy as an adjunct to smoking cessation in helping to reduce the craving for smoking and provide relief from smoking withdrawal symptoms. However, there are many smokers for whom nicotine supplementation alone is inadequate.
  • a composition can be formulated which provides the combination of nicotine and caffeine or caffeine equivalent in a single therapy. It has also been discovered that such a combination 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 individuals who stop smoking.
  • the present invention relates to an oral composition for the treatment of nicotine craving or smoking withdrawal symptoms comprising nicotine and caffeine or caffeine equivalent, wherein the composition delivers from about 0.05mg to about lOmg of nicotine, and from about 0. lmg to about 250mg of caffeine or caffeine equivalent.
  • the present invention further 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 an oral 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 oral 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, diluents, binders, lubricants, glidants, disintegrants, gum bases, elastomer solvents, liquid oral carriers, emollients, emulsifiers, buffering agents, solvents, preservatives, agents for regulating isotonicity, fillers, wetting agents, thickening agents, suspending agents, solubilizing agents, humectants, sweeteners, flavorings, plasticizers, bioadhesive compounds, surfactants, aromatic compounds, agents for aiding the film-forming properties and substantivity of the formulations, antimicrobials for maintaining the antimicrobial integrity of the compositions, antioxidants, 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 oral administration refers to any formulation that is suitable for the convenient administration of the composition whereby the composition is taken into the mouth and swallowed, placed in contact with mucous membranes of the mouth, and/or throat and/or pharynx and dissolved slowly over a period of time, or taken into the mouth but not necessarily swallowed, e.g., chewing gum.
  • 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 0.05mg to about lOmg, preferably from about 0.25mg to about 7.5mg, and most preferably from about 0.5mg to about 3mg. 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 0.1 mg to about 250mg, preferably from about lOmg to about 180mg, and most preferably from about 50mg to about 125mg.
  • Pharmaceuticallv-Acceptable Carrier
  • compositions preferably also contain one or more pharmaceutically-acceptable carriers suitable for oral administration.
  • Such compositions include (but are not limited to) lozenges, chewing gums, sublingual delivery systems, capsules, gelcaps, caplets, syrups, aqueous solutions, suspensions, or other formulations suitable for administering the present compositions orally.
  • the present compositions also include formulations which deliver the nicotine and/or caffeine or caffeine equivalent in a sustained release system or at varying intervals or levels throughout the oral administration of the composition.
  • 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 1-4 hours of administration.
  • the desired blood level of caffeine or caffeine equivalent is from about O.Olug/ml to about 20ug ml, preferably from about 0. lug/ml to about 15ug/ml, and most preferably from about 0.5ug/ml to about lOug/ml, preferably within 1-4 hours of administration.
  • 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 oral compositions herein deliver to a human or lower animal from about 0.05mg to about lOmg, preferably from about 0.25mg to about 7.5mg, and most preferably from about 0.5mg to about 3mg of nicotine; and from about 0.1 mg to about 250mg, preferably from about lOmg to about 180mg, and most preferably from about 50mg to about 125mg, of caffeine or caffeine equivalent.
  • the present invention may be an oral composition 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 oral administration, wherein the composition delivers from about 0.05mg to about lOmg of nicotine, and from about 0. lmg to about 250mg 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 12 times per day, preferably from about 3 to about 9 times per day, and most preferably from about 4 to about 8 times per day.
  • compositions of the present invention may be in lozenge form.
  • Lozenges are flavored solid dosage forms intended to be held in the mouth and sucked for slow dissolution and absorption by the oral mucosa. They may occur in various shapes and are generally formed either as compressed tablets or hard candies. Lozenges and their preparation are further described in Remington's Pharmaceutical Sciences, 18th Edition, 1990, pp. 1664-5, which is incorporated herein by reference. Lozenges prepared by compression are prepared similarly to any compressed tablet. This process provides a hard tablet which is desirable for slow dissolution in the mouth.
  • These lozenges may include: fillers such as dicalcium phosphate, spray dried lactose, microcrystalline cellulose; disintegrating agents, lubricants, and glidants.
  • Hard candy lozenges typically contain a base of sugar, flavored syrups such as high fructose corn syrups, and/or other carbohydrates.
  • a base contains up to 92% corn syrup, up to 55% sugar, and from 0.1% to about 5% water. Additional ingredients may also be included such as flavorings, sweeteners, colorants, an adhesive substance such as mucilage or gum, acidulents, and the like.
  • the base is heated and the lozenges are formed by molding and drying.
  • Lozenges may also be formulated with soft confectionery materials such as those contained in nougat. These materials generally contain a high boiling syrup such as corn syrup or the like, and a relatively light textured frappe. Typically the frappe is prepared from gelatin, egg albumen, milk proteins such as casein, and vegetable proteins such as soy protein, and the like. Flavorings oils, additional sugar, and sweeteners may also be added.
  • Solid oral dosage forms may be tablets, chewable tablets, caplets, capsules, gelcaps and other solid oral dosage forms known in the art. These forms include a buccal or sublingual tablet. Such a tablet is typically flat and oval and intended to be dissolved in the buccal pouch or beneath the tongue for absorption through the oral mucosa.
  • the tablets may be compressed, titurated, freeze dried, sugar or film coated, or multiply compressed.
  • the tablets may also contain suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, preservatives and flow-inducing agents.
  • carrier materials suitable for preparation of unit dosage forms for oral administration are well-known in the art.
  • compositions may also be in the form of a chewing gum.
  • Such formulations typically comprise a gum base, elastomer solvents, plasticizers or softeners, fillers, flavorings, colorants, emulsifiers, and sweeteners.
  • the gum base may be any water-insoluble gum base which includes (but is not limited to): natural elastomers including substances of vegetable origin such as chicle, jelutong, gutta percha, and crown gum; rubbers; and synthetic elastomers such as butadiene-styrene polymers, polyethylene, polyisobutylene, polyvinylacetate, and mixtures thereof.
  • the gum base may be present at a level of from about 5% to about 45%, and preferably from about 15% to about 25%, by weight of the composition.
  • suitable elastomer solvents may comprise methyl, glycerol or pentaerythritol esters of rosins or modified rosins, such as hydrogenated, dimerized or polymerized rosins or mixtures thereof.
  • the elastomer solvents may be present at a level of from about 5% to about 75%, and preferably from about 35% to about 70%, by weight of the composition.
  • Plasticizers or softeners may also be included to achieve a variety of textures and consistency properties.
  • Such ingredients include without limitation: lanolin, stearic acid, sodium stearate, potassium stearate, glyceryl triacetate, glycerin, natural waxes, petroleum waxes, microcrystalline waxes, and mixtures thereof.
  • Plasticizers or softeners may be present at a level of up to about 30%, and preferably from about 3% to about 20%, by weight of the composition.
  • Fillers such as aluminum hydroxide, alumina, aluminum silicates, calcium carbonate, talc and mixtures thereof, may also be included at a level of from about 4% to about 30%, by weight of the composition.
  • 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.
  • the present invention may also be in a liquid oral dosage form. Liquid oral dosage forms include aqueous and nonaqueous solutions, emulsions, pseudo emulsions, suspensions, and solutions and/or suspensions reconstituted from non- effervescent granules. These dosage forms also contain suitable solvents, emulsifying agents, buffering agents, suspending agents, diluents, natural and artificial sweeteners, coloring agents, and flavoring agents.
  • Antioxidants such as butylated hydroxy anisole or butylated hydroxy toluene, and preservatives such as methyl or propyl paraben or sodium benzoate may also be included.
  • Specific examples of carriers and excipients that may be used to formulate oral dosage forms, are described by Roberts in U.S. Patent 3,903,297, issued September 2, 1975, which is incorporated herein by reference.
  • Water-insoluble or poorly soluble ingredients may also be incorporated into aqueous-based orally acceptable carriers such as dispersions, suspensions, oil-in-water emulsions and the like by means of suitable dispersing, suspending or emulsifying agents, respectively, which are readily apparent to those skilled in the art of formulations.
  • aqueous-based orally acceptable carriers such as dispersions, suspensions, oil-in-water emulsions and the like by means of suitable dispersing, suspending or emulsifying agents, respectively, which are readily apparent to those skilled in the art of formulations.
  • aqueous-based orally acceptable carrier is one wherein the entire or predominant solvent content is water.
  • Typical carriers include simple aqueous solutions, syrups, dispersions and suspensions, and aqueous based emulsions such as the oil-in-water type.
  • the most preferred carrier is a suspension or solution of the phosphate derivative and active in an aqueous vehicle containing a suitable suspending or solubilizing agent.
  • suitable suspending agents include celluloses, carboxymethyl cellulose and its salts, guar gum and the like.
  • Suitable solubilizing agents include sucrose solutions, ethanol, and surfactants such as polyoxyethylene derivatives of fatty acid partial esters of sorbitol anhydrides (e.g., Polysorbate 80).
  • Suspension systems, suspension and solubilizing agents, and methods for their use are described in M. Pernarowski, "Solutions, Emulsions and Suspensions” Remington's Pharmaceutical Sciences (A. Osol, editor, 15th Edition, 1975), which is incorporated herein by reference.
  • typical oral formulations also contain a co-solvent including but not limited to alcohol, propylene glycol, glycerin, sorbitol solution, and the like, to assist solubilization and incorporation of water-insoluble ingredients, flavoring oils and the like into the composition.
  • a co-solvent including but not limited to alcohol, propylene glycol, glycerin, sorbitol solution, and the like, to assist solubilization and incorporation of water-insoluble ingredients, flavoring oils and the like into the composition.
  • the compositions may contain from about 5 to about 25 volume/volume percent of the co-solvent, most preferably from about 10 to about 20 volume/volume percent of the co-solvent.
  • Non-aqueous carriers may also be used in the present compositions.
  • Non ⁇ aqueous carriers include, without limitation, oil of animal, mineral or vegetable origin such as almond oil, olive oil, safflower oil, sunflower oil, and sucrose polyester (sold under the brand name Olestra).
  • 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.
  • Diluents, binders, lubricants, glidants, and disintegrants may also be included at al level of from about 0% to about 25%, and preferably from about 2% to about 20%, by weight of the composition.
  • Suitable diluents include microcrystalline cellulose, mannitol, dicalcium phosphate, and celluloses.
  • Binders useful include starch; gelatin; sugars such as sucrose, glucose and dextrose; natural and synthetic gums such as acacia, sodium alginate, ghatti gum, carboxymethylcellulose, and polyvinylpyrrolidine; polyethylene glycol, water, and alcohol.
  • Lubricants include talc, magnesium stearate, stearic acid, polyethylene glycol, and hydrogenated vegetable oils.
  • Glidants include colloidal silicon dioxide and disintegrants include starches, clays, celluloses, algins, gums, and cross-linked polymers.
  • the present invention may also comprise one or more bioadhesive compounds which adhere to moist area of biological membranes. Such 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.
  • 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, sodium benzoate, ascorbic acid, thimerosal, chlorobutanol, phenylmercuric acetate or benzalkonium chloride may also be employed.
  • parabens, 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.
  • 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.
  • the nicotine and/or caffeine may also be protectively coated using techniques known in the art, such as an enteric coating, to protect the compounds in the gastrointestinal tract.
  • 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.
  • the present compositions may also contain one or more flavorings.
  • Suitable flavorings include both natural and artificial flavors, spearmint, peppermint, wintergreen, cinnamon, anise, vanilla, fruit essences including apple, peach, pear, strawberry, raspberry, cherry, pineapple, and the like, or any other flavorings that will effectively mask the taste of the nicotine and caffeine or caffeine equivalent.
  • Preferred are peppermint, spearmint, anise, and fruit essences.
  • Flavorings may be present at levels of from about 0% to about 5%, and preferably from about 0.5% to about 3%, by weight of the compositions.
  • Sweetening agents suitable for use herein include any sweetener commercially available and suitable for human consumption such as sugars such as sucrose, glucose, dextrose, fructose, saccharin and its various salts, cyclamic acid and its salts, dipeptide sweeteners such as aspartame, and mixtures thereof.
  • sugars such as sucrose, glucose, dextrose, fructose, saccharin and its various salts, cyclamic acid and its salts, dipeptide sweeteners such as aspartame, and mixtures thereof.
  • dipeptide sweeteners such as aspartame, and mixtures thereof.
  • 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
  • humectants such as urea, glycerol, sorbitols and glycerin
  • thickeners such as methylcellulose, xanthan gum, and carbomer
  • surfactants such as Tween 80 and Polyoxyl 40 Stearate
  • 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 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 as disclosed herein comprises the administration of a safe and effective amount of an oral composition comprising nicotine, and caffeine or caffeine equivalent.
  • Such compositions preferably further comprise one or more pharmaceutically-acceptable carriers suitable for oral administration.
  • the nicotine and caffeine or caffeine equivalent are administered in an oral carrier composition comprising both nicotine and caffeine (or caffeine equivalent)
  • the desired blood levels of nicotine and caffeine be achieved through concurrent administration of nicotine and caffeine (or caffeine equivalent) but not necessarily by a carrier which comprises both compounds.
  • caffeine be administered in a tablet formulation and that nicotine be administered concurrently by a transdermal delivery system.
  • Another example is the administration of nicotine by an aqueous nasal spray and concurrent administration of caffeine by chewing gum.
  • the present invention also encompasses 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 administering a safe and effective amount of nicotine and concurrently administering a safe and effective amount of caffeine or caffeine equivalent.
  • a method for providing treatment and/or relief of nicotine craving and/or smoking withdrawal symptoms comprising administering a safe and effective amount of nicotine and concurrently administering a safe and effective amount of caffeine or caffeine equivalent.
  • concurrently mean that the safe and effective amounts of nicotine and caffeine or caffeine equivalent are administered simultaneously or within 6 hours of each other.
  • nicotine and/or caffeine or caffeine equivalent may be concurrently administered through a variety of embodiments or carriers as long as the desired blood levels taught in the present invention are achieved.
  • embodiments or carriers include without limitation: intranasal delivery systems such as nasal drops, nasal sprays, nasal gels, ointments applied in the nasal cavity and systems which allow for the inhalation of vapors produced by nicotine or caffeine (or caffeine equivalent); transdermal and transmucosal delivery systems; and oral delivery systems or carriers such as those disclosed herein.
  • EXAMPLE ⁇ The following is a chewing gum composition of the present invention. Ingredient Weight %
  • liquid oral dosage form composition according to the present invention is prepared having the following components:
  • Alcohol 10.00 Mix together sucrose and about 1/3 the amount of water and heat to about
  • sucrose 60°C until sucrose is dissolved.
  • Add flavor. Mix together sucrose solution with propylene glycol solution. Mix together this solution and potassium sorbate solution. Lastly, add flavor solution. Adjust water level for proper batch size. Adjust pH to about 6.5- 8.5. Mix for 30-35 minutes.

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Abstract

L'invention concerne une composition administrée par voie orale, 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/US1995/007381 1994-06-23 1995-06-09 Traitement du besoin de nicotine et/ou des symptomes de manque du fumeur au moyen d'une composition contenant de la nicotine et de la cafeine ou de la xanthine pour administration par voie orale WO1996000070A1 (fr)

Priority Applications (1)

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AU27708/95A AU2770895A (en) 1994-06-23 1995-06-09 Treatment of nicotine craving and/or smoking withdrawal symptoms with an oral composition containing nicotine and caffeine or xanthine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26455494A 1994-06-23 1994-06-23
US08/264,554 1994-06-23

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WO1996000070A1 true WO1996000070A1 (fr) 1996-01-04

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AU (1) AU2770895A (fr)
IL (1) IL114128A0 (fr)
MA (1) MA23587A1 (fr)
PE (1) PE41096A1 (fr)
WO (1) WO1996000070A1 (fr)
ZA (1) ZA955031B (fr)

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997034605A1 (fr) * 1996-03-21 1997-09-25 Mayo Foundation For Medical Education And Research Utilisation de nicotine pour traiter une hepatopathie
WO1997042941A3 (fr) * 1996-05-13 1997-12-24 Novartis Consumer Health Sa Systeme de liberation gingivo-jugal
WO1998003175A1 (fr) * 1996-07-18 1998-01-29 International Diabetes Institute Traitement de l'obesite
EP0828489A1 (fr) * 1996-03-13 1998-03-18 Yale University Traitements pour cesser de fumer impliquant l'utilisation de naltrexone et de composes associes
US6165516A (en) * 1996-11-27 2000-12-26 Wm. Wrigley Jr. Company Method of controlling release of caffeine in chewing gum
DE20018196U1 (de) 2000-10-25 2001-01-11 Peter, Michael N., 22297 Hamburg Erzeugnis aus Zuckerware für Raucherentwöhnung
US6949264B1 (en) 1996-11-27 2005-09-27 Wm. Wrigley Jr. Company Nutraceuticals or nutritional supplements and method of making
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
US7090830B2 (en) 2001-05-24 2006-08-15 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
US7115288B2 (en) 2000-06-09 2006-10-03 Wm. Wrigley Jr. Company Method for making coated chewing gum products with a coating including an aldehyde flavor and a dipeptide sweetener
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
EP1938806A1 (fr) 2003-09-05 2008-07-02 Arrow No. 7 Ltd. Administration de médicaments par voie orale
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
WO2012083947A1 (fr) * 2010-12-21 2012-06-28 Fertin Pharma A/S Composition de chewing-gum comprenant du poly(acide acrylique) réticulé
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
EP3033951A1 (fr) * 2005-05-25 2016-06-22 U.S. Smokeless Tobacco Company LLC Compositions de tabac
US10098376B2 (en) 2003-11-07 2018-10-16 U.S. Smokeless Tobacco Company Llc Tobacco compositions
WO2022049256A1 (fr) * 2020-09-03 2022-03-10 Nicoventures Trading Limited Compositions et procédés
CN115590855A (zh) * 2022-10-26 2023-01-13 江南大学（Cn） 一种降低尼古丁制品中尼古丁含量的方法
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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EP0828489A1 (fr) * 1996-03-13 1998-03-18 Yale University Traitements pour cesser de fumer impliquant l'utilisation de naltrexone et de composes associes
EP0828489A4 (fr) * 1996-03-13 2001-04-04 Univ Yale Traitements pour cesser de fumer impliquant l'utilisation de naltrexone et de composes associes
WO1997034605A1 (fr) * 1996-03-21 1997-09-25 Mayo Foundation For Medical Education And Research Utilisation de nicotine pour traiter une hepatopathie
CZ298212B6 (cs) * 1996-05-13 2007-07-25 Novartis Consumer Health S. A. Pomalu se rozpadající pastilka
WO1997042941A3 (fr) * 1996-05-13 1997-12-24 Novartis Consumer Health Sa Systeme de liberation gingivo-jugal
US6183775B1 (en) 1996-05-13 2001-02-06 Novartis Consumer Health S.A. Buccal delivery system
WO1998003175A1 (fr) * 1996-07-18 1998-01-29 International Diabetes Institute Traitement de l'obesite
US6165516A (en) * 1996-11-27 2000-12-26 Wm. Wrigley Jr. Company Method of controlling release of caffeine in chewing gum
US6949264B1 (en) 1996-11-27 2005-09-27 Wm. Wrigley Jr. Company Nutraceuticals or nutritional supplements and method of making
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
US7115288B2 (en) 2000-06-09 2006-10-03 Wm. Wrigley Jr. Company Method for making coated chewing gum products with a coating including an aldehyde flavor and a dipeptide sweetener
DE20018196U1 (de) 2000-10-25 2001-01-11 Peter, Michael N., 22297 Hamburg Erzeugnis aus Zuckerware für Raucherentwöhnung
US7585493B2 (en) 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
US9211382B2 (en) 2001-05-24 2015-12-15 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
US10350157B2 (en) 2001-05-24 2019-07-16 Alexza Pharmaceuticals, Inc. Drug condensation aerosols and kits
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
US7537009B2 (en) 2001-06-05 2009-05-26 Alexza Pharmaceuticals, Inc. Method of forming an aerosol for inhalation delivery
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
US9308208B2 (en) 2001-06-05 2016-04-12 Alexza Pharmaceuticals, Inc. Aerosol generating method and device
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
US8603517B2 (en) 2003-09-05 2013-12-10 Gelmedic Holdings APS Buccal drug delivery
EP1938806A1 (fr) 2003-09-05 2008-07-02 Arrow No. 7 Ltd. Administration de médicaments par voie orale
US8343532B2 (en) 2003-09-05 2013-01-01 Arrow No. 7 Limited Buccal drug delivery
US8603516B2 (en) 2003-09-05 2013-12-10 Gelmedic Holding Aps Buccal drug delivery
US10945454B2 (en) 2003-11-07 2021-03-16 U.S. Smokeless Tobacco Company Llc Tobacco compositions
US10765140B2 (en) 2003-11-07 2020-09-08 U.S. Smokeless Tobacco Company Llc Tobacco compositions
US10098376B2 (en) 2003-11-07 2018-10-16 U.S. Smokeless Tobacco Company Llc Tobacco compositions
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
EP3033951A1 (fr) * 2005-05-25 2016-06-22 U.S. Smokeless Tobacco Company LLC Compositions de tabac
US11642473B2 (en) 2007-03-09 2023-05-09 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US12138383B2 (en) 2007-03-09 2024-11-12 Alexza Pharmaceuticals, Inc. Heating unit for use in a drug delivery device
US9707175B2 (en) 2010-12-21 2017-07-18 Fertin Pharma A/S Chewing gum composition comprising cross-linked polyacrylic acid
WO2012083947A1 (fr) * 2010-12-21 2012-06-28 Fertin Pharma A/S Composition de chewing-gum comprenant du poly(acide acrylique) réticulé
US12214118B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device
US12214119B2 (en) 2018-02-02 2025-02-04 Alexza Pharmaceuticals, Inc. Electrical condensation aerosol device
WO2022049256A1 (fr) * 2020-09-03 2022-03-10 Nicoventures Trading Limited Compositions et procédés
CN115590855A (zh) * 2022-10-26 2023-01-13 江南大学（Cn） 一种降低尼古丁制品中尼古丁含量的方法

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MA23587A1 (fr) 1995-12-31
IL114128A0 (en) 1995-10-31

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