US3901248A - Chewable smoking substitute composition - Google Patents

Chewable smoking substitute composition Download PDF

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US3901248A
US3901248A US497557A US49755774A US3901248A US 3901248 A US3901248 A US 3901248A US 497557 A US497557 A US 497557A US 49755774 A US49755774 A US 49755774A US 3901248 A US3901248 A US 3901248A
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nicotine
chewing
amount
composition
chewing gum
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US497557A
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Stefan Lichtneckert
Claes Lundgren
Ove Ferno
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Leo AB
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Leo AB
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23GCOCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00Chewing gum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A61K47/585Ion exchange resins, e.g. polystyrene sulfonic acid resin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056Mouth 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

Definitions

  • This invention relates to smoking substitutes that are chewed and that are of particular value for facilitating a person's withdrawal from smoking and/or for de-- 7 known but generally are not verysatisfactoryExamples of such compositions are found in U.S. Pat-Nos. 865,026 and 904,521.
  • the procedure of incorporating the alkaloid into the chewing gum should be easy to perform and also assure the substantially uniform distribution of alkaloid into the chewing gum.
  • a tobacco alkaloid is bound to a cation exchanger and in this form is incorporated into chewable gum compositions in an amount effective to provide smoking satisfaction.
  • the present invention contemplates a smoking substitute composition comprising agum base and a tobacco alkaloid held by a cation exchanger dispersed therein. The amount of tobacco alkaloid such as nicotine. nor-nicotine. lobeline.
  • present per chewable gum unit can finely ground tobacco, forinstance snuff. into chewing gum, but the use of a tobacco extract of unidentified composition is also mentioned.
  • tobacco extract of unidentified composition is also mentioned.
  • tobacco alkaloid as used herein and in the claims istakenjto mean nicotine or nicotine-like alkaloid such as nor-nicotine, lobeline, and the like, in the free base or pharmacologically acceptable acid addition salt form.
  • Source. for alkaloids of this type are species of Nicotiana (for nicotine and nor-nicotine: of Lobeliaceae-(Indian tobacco) and Lobelia (for lobeline); and the like,'as is well known in the art.
  • An ideal smoking substitute in the form of a chewing gum should have the following properties:
  • the release of the tobacco alkaloid should take place rather uniformly during not too short a period of time.
  • the released alkaloid should produce a feeling of smoking" not only after absorption into the blood stream but also in the mouth. This is very important because if the alkaloid is absorbed without producing vary over a wide range and can be present in'an amount in the range 'of about 0.05. weight percent to about 2 weight percent, based on the weight of gum base and calculated as the freebase.
  • a chewable gum unit contains about I to 10 milligrams of an alkaloid. preferably, about i to about 5 milligrams.
  • the smoking substitute composition is rendered acidic by the addition ofa pharmacologically acceptable acidifying agent.
  • Release rate of the alkaloid from the composition can bevaried 'by varying the amount .of alkaloid'that is bound to a given quantity of cation exchanger. A relatively higher amount of the alkaloid present in the composition gives a quicker release and vice versa.
  • slow release as used herein is meant that the major portion of the alkaloid is released from the smoking substitute composition substantially uniformly over. a period of several minutes and preferably over a period of at least 10 minutes. Most preferably the release time is at least 20 minutes.
  • nicotine is liberated as the nicotine cation, the absorption does not take place so quickly, thus allowing some of the nicotine to reach other parts of the buccal cavity including the throat, whereby some of the sensations of smoking are obtained, including a light burning sensation, which the smoker generally esti mates in a positive way.
  • the complex containing an alkaloid bound to the cation exchanger is preferably prepared in a special unit.
  • the solid complex thus prepared is easy to handle and minimizes personnel risksinvolved in the manufacture of the final chewing gum product. It has also been shown that the complex acts as a lubricant thereby facilitating the mixture of the different ingredients into the gum mass. A homogenous product is easily obtained in this manner.
  • the ion exchanger must have cation exchanging groups in order to form the alkaloid-ion exchanger complex. Preferably, before formation of the complex. these groups are in the hydrogen ionic form.
  • the exchanger can also contain anionic groups, in which event it is known as a polyampholyte.
  • the cation exchanging groups that are present may be strongly acidic. weakly acidic or of intermediate acidity. synthetic cationic exchangers containing these groups accordingly being called strongly acidic. weakly .acidic or intermediate acidic cation exchangers, de-
  • suitable acidic groups that may be present are carboxylic. sulphonic acid. phosphonous acid. phosphonic acid, phosphoric acid. iminodiacetic acid. or phenolic groups.
  • the acidic groups of the ion exchanger which may be termed an ion exchange resin, may be bound to a cross-linked polymer such as addition polymers of styrene and divinylbenzene. divinylbenzcne and methacrylic acid. divinylbenzene and acrylic acid, phenolic resins. or cellulose. dextran or pectin cross-linked with. e.g.. epichlorhydrine.
  • the acidic groups can be bound to insoluble linear polymers. e.g.. cellulose with nitrous gases. whereby mainly uronic acid groups are formed.
  • insoluble linear polymers e.g.. cellulose with nitrous gases. whereby mainly uronic acid groups are formed.
  • Such compounds are disclosed by Ott. E. and Spurlin. H.M.. Cellulose and Cellulose Derivatives. Part I. lnterscience. New York (1954). Carboxymethyl cellulose. sulphoethyl cellulose. cellulose sulphate. etc.. can also be used.
  • Such compounds are disclosed by Ott, E. and Spurlin, H.M., Cellulose and Cellulose Derivatives. Part II. Interscience. New York (1954). Representative
  • the amount of the alkaloid, e.g.. nicotine, nor-' nicotine, lobeline, acid addition salts thereof, or mixtures thereof bound to the tort exchanger may be varied cominued depending on the conditions employed and the type of ion exchanger used.
  • alkaloid-ion -xchan com l-x
  • alkaloid-ion exchange L pi Percent alkaloid by weight in complex complexes in which the content of nicotine or other alkaloid amounts to about 2 to 60 percent. and preferably about 5 to percent of the alkaloid to the ion exchange complex. are suitable for incorporation into the compositions of the invention.
  • carboxylic acid group containing ion exchangers the preferred range is about 5 to 35 percent, whereas for phosphonic acid group containing ion exchangers the preferred range is about 5 to 30 percent, and the preferred range for sulphonic acid group containing ion exchangers is about 5 to 25 percent.
  • Part of the nicotine, nor-nicotine, lobeline or mixtures thereof may occur bound to the ion exchanger through surface adsorption as opposed to real ion exchange reaction. 7
  • BlO-REX 40 nicotine complex Percent alkaloid by weight in complex BIO-REX 70 nicotine complex Duolite ES-62 nicotine complex Duolitc ES- nicotine complex Amberlite lRP 64M nicotine complex E2 60 preferably 5 35 Amberlite lRP 64M nor-nicotine complex 2 6 preferably 5 35 Amberlite lRP 64M lobeline complex 7 Chelex nicotine complex preferably 5 35 Ambcrlite lR l 18 nicotine complex 2 CM Scphadcx C-25 nicotine complex preferably 5 20 BIO-REX 63 nicotine complex (2 40 SE Sephadcx C-25 nicotine complex preferably 5 30 prelerably 5 30 preferably 5 25 2 35'.
  • the chewing gum component of the compositions of the invention may be of any convenient nature and preferably is of a generally available commercial type.
  • it can comprise a gum base of natural or synthetic origin.
  • Natural gum bases include. e.g., Chicle-, Jelutong-. Lechi di Caspi-. Soh-, Siak-, Katiau-. Sorwa-. Balata-. Pendare. Perillo-, Malayaand Percha gums, natural caoutchouc such as Crepe. Latex and Sheets. and natural resins such as Dammar and Mastix.
  • Synthetic gum bases are polyvinylacetate (Vinnapas).
  • Dreyco" commercial gum base polyvinyl esters, polyisobutylene and non-toxic butadienestyrene lattices among others.
  • Softeners plasticizers are. as is conventional in the art, incorporated into the commercially available chewing gum base to help reduce the viscosity of the rubber blend to a desirable consistency and to improve the texture.
  • Some of the common softeners or plasticizers are: lecithin, lanolin. hydrogenated coconut oil. hydrogenated cotton seed oil. mineral oil.
  • the chewing gum component can be formulated with the following constituents which are present in varying amounts.
  • the gum base can be natural or synthetic origin, preferably the latter, and can be present in the chewing gum formulation in an amount in the range from about to about 80 weight percent. preferably from about 50 to about 80 percent and most preferably from about 60 to about 75 weight percent.
  • Powdered sugar preferably powdered sorbitol. can be present in an amount in the range from about 15 to about 80 weight percent. preferably from about 16 to about 40 weight percent, and most preferably from about 20 to about 32 weight percent.
  • Corn syrup usually of about 41 to 46 Baume, pref- V erably an about 70 percent aqueous solution of sorbitol, can be present in an amount in the range from about 4 to about weight percent. preferably from about 4 to about 10 weight percent, and most preferably from about 5 to about 8 weight percent.
  • Special formulas for chewing gums exist, such as sugar-free compositions with a concentration of as much as 80 percent chewing gum base. preferably of synthetic origin (Preparation 13, below).
  • Variations of the consistency on the one hand the preliminary consistency at the very beginning of the chewing, and on the other hand the secondary consistency after some chewing, is achieved simply by varying amounts and proportions of the above formula.
  • the consistency and the stickiness of the chewing gum can be influenced by the addition of various substances. as previously mentioned.
  • compositions according to the invention can be formed simply by mixing the chewing gum mass with the alkaloid-ion exchanger complex. preferably together with an excess of a suitable acidifying agent. If the complex is in the form of a small particle size ion exchanger in the first place. then this can be mixed with the gum. If, however. the complex is in the form of a coarser ion exchanger then it is desirable to grind and size this first.
  • the mixing is preferably conducted at a suitable elevated temperature depending upon the viscosity of chewing gum mass employed, since the increased temperature decreases the viscosity of the gum and thereby enables the alkaloid-ion exchanger complex to be evenly and intimately distributed into the chewing gum.
  • the complex particle size in the gum should be small enough not to cause damage to teeth during chewing, however.
  • compositions of the present invention are made simultaneously with the incorporation of any additives such as corn syrup, sugar, sorbitol. and flavors into the chewing gum base.
  • the composition can be made in a suitable kettle. for example. a steam jacketed mixer, which is warmed and the gum base added and mixed until sufficiently free from lumps. Next, sorbitol or corn syrup and sugar are incorporated into the base.
  • the pharmacologically acceptable acid that may be incorporated as an additional ingredient according to this invention, it will be convenient to add this acid, as in the case of. for instance, sulphuric acid, with the liquid part of sorbitol or with the corn syrup. in the case of, for instance, malic acid. it will be convenient to add this particular acid with the solid, powdered part of sorbitol or sugar.
  • flavors, softeners and other additives are poured in and well distributed. The mass is cooled, rolled. scored. and hardened sufficiently. then coated if desired. before final wrapping and analyzing. Controlled humidity rooms assure consistent moisture content and prevent "sweating" of the gum.
  • the weight of one chewing gum unit e.g., stick. ball, or the like, according to the present invention, can be varied between 0.5 and 4.0 grams and preferably between l.0 and 3.0 grams, as is generally conventional in the chewing gum art.
  • compositions. wherein the percent by weight of the alkaloid ion exchange complex to the total weight of the gum is about 0.1 to l0 percent. preferably about 0.2 to 5 percent. and most preferably about 0.5 to 2 percent. are suitable.
  • Preparation 1 demonstrates the preparation of a suitable ion exchange complex while preparations 2 to 13
  • Preparation 12 (Sugarand glucose-free formula Percent Natural gum base 29.2 Powdered sorbitol 45.8 Calcium carbonate 8.5 Sorbitol. percent water solution 16.5
  • Preparation 13 Sugarand glucose-free formula with high chewing gum base concentration. Synthetic gum base 73.7 Powdered sorhitol 19.8 Sorbitol. 70 per cent water solution 3.8
  • Glycerin 0.7 Flavouring oil I The following Examples demonstrate the compositions according tothe invention. Each of these is made by warming the gum base in a kettle and then adding the variousadditives, in the general method described above;
  • EXAMPLE 7 Chewing gum containing a percent complex. obtained from 5 mg. of nor-nicotine bound to Amberlite lRP 64M. Chewing gum mass according to Preparation 2. 1000 pieces of gum per 450 grams of the mass. Amberlite lRP 64M 10 percent nor-nicotine complex 50.0
  • I I Phynn (aha) 05 g are usually so strongly bound thereto that they can be fi g a 5 geluted from such ion exchange complexes only with difa g. KSCN 0.1 g. 40 flculty' Water ad [000 ml. Saliva 2 NaCl 0.45 g. Chewmg Tests CaCl-'6H- ,O 0.12 cacc 1.0 5. The results of the analys1s w1th reference to n1cot1ne u d-[ 1 (dried) is shown below refer to chewing tests. Two persons iffi 5: 5: chewed the gum at different times, the analytical re- Cholesterine 0.06 g. sults were tabulated, and the mean value determlned. Water ad [000 ml.
  • Chewing time minutes Mean value nicotine released mg.
  • Chewing time minutes Mean value nicotine released mg.
  • Chewing time minutes Mean value HILOIII'IL released mg. Spending to 5 mg. nicotine and transfer to the distilla- 2 g 1 tion flask. Place 50 ml hydrochloric acid l+4) in a 500 5 ml volumetric flask. used as receiver, placed so that the l condenser tube dips into the solution. Add 50 ml alkali- '3 2:; 65 salt solution to the sample in the distillation flask and 30 4.8 steam distil as rapid as steam can be condensed efficiently. Effluent condensate should not be above room temperaturefApply heat to distillation flask to keep the If. X 500 X 1000 V 388 X 100 X (sample weight. g) mg'mumnc/g Sumplc' Determination of Nicotine in Chewing Gum Apparatus. Spectrophotometer Beckman DU.
  • EXAMPLE 19 A nicotine ion exchange complex with Amberlite lRP 64M was prepared by the method described in Preparation 1. the resultant complex containing 10% nicotine.
  • 434 Grammes natural gum base is put into a hot jacketed mixer fitted with stirrers.
  • the mixer is heated by steam at about lbs. per sq. inch.
  • the stirrers are run at intervals to turn the base over.
  • a low steam pressure A further 420 grammes of powdered sugar and 30 grammes of the nicotine ion exchange complex. both 300 mesh sieve. are mixed together and are then added as a powder mixture to the molten mixture in the kettle.
  • the melt is mixed for a further five minutes, so that the total mixing time is about 15 minutes.
  • the temperature in the kettle will at the end of this time have dropped to between 40 to 60C. It is desirable that the mix should be as cool as possible before mixing stops. but viscosity increases as the temperature drops and mixing must stop before the mixture becomes too stiff for the mixing machine. in practice the operator judges when to stop mixing not so much by the actual thermometer reading as by the consistency of the mix.
  • the batch of gum is cut into pieces of a size suitable for feeding to whatever type of extruder is available.
  • the extruder jacket is usually heated by means of warm water at 45 to 50C. This gives a more even extrusion than when the extruder is heated by steam and it permits better temperature control.
  • the extruded stick of gum should be well dusted with starch or a mixture of icing sugar and starch to prevent it from sticking to sizing rollers and cutters.
  • the rollers serve to roll it down to the desired size.
  • the cutters are preferably maintained at about 25C.
  • each piece generally weighs between t and 3 grammes. In this Example. 1000 pieces, each weighing two grammes. were provided by the conventional extruding and cutting procedure. Likewise, the pieces are packed and stored under fairly conventional conditions. For example the wrapping room is preferably maintained at 20C and a relative humidity of 45 to 50% and the pieces are preferably stored at a temperature of 18 to 20C and a relative humidity of 45 to 50%.
  • the smoking substitute compositons of this invention are acidic. This is desirable in order to enhance the feeling of smoking upon use of the present compositions, because in an acidic environment the nicotine cationnicotine base equilibrium. i.e.,
  • the cation exchanger initially in its ionic hydrogen form, is only partly loaded with nicotine or similar alkaloid when incorporated into a smoking substitute composition of this invention.
  • hydrogen ions are liberated from the cation exchanger and pH of saliva at the chewing site is decreased, which decrease in pH influences, in turn, the acid-base equilibrium.
  • the amount of pharmacologically acceptable acid present in the foregoing instances can be in the range of about 1.5 to about equivalents of acid per mole of the alkaloid base, preferably about 1.5 to about 6 equivalents of acid per mole of the alkaloid base, and most preferably about 2 to about 4 equivalents of acid per mole of the alkaloid base.
  • the amount of acid present can be in the range of about 0.5 to about 9 equivalents of acid per mole of the neutral alkaloid salt, preferably about 0.5 to about 5 equivalents of acid per mole of the neutral alkaloid salt, and most preferably about l to about 3 equivalents of acid per mole of the neutral alkaloid salt.
  • suitable acids are inorganic acids such as hydrochloric acid, sulphonic acid, phosphoric acid, and the like, as well as organic acids such as succinic acid, fumaric acid, glutaric acid, adipic acid, malic acid, tartaric acid, ascorbic acid, citric acid, mixtures of the aforesaid acids, the like.
  • organic acids are preferred.
  • the acid or acids may be incorporated directly into the gum composition at any convenient compounding stage thereof, or admixed beforehand with a watersoluble part of the composition, e.g., sorbitol, and then incorporated into the gum composition.
  • a watersoluble part of the composition e.g., sorbitol
  • a chewable substitute for smoking gum composition comprising 1. a chewing gum base and 2. nicotine, held by a saliva-insoluble cation exchanger, wherein the cation exchanger is selected from the group consisting of a) methacrylic type, weakly acidic, containing carboxylic functional groups; b) polystyrene type, strongly acidic, containing sulfonic functional groups; and c) polystyrene type, having intermediate acidity, containing phosphonic functional groups;
  • composition is in the form of a chewable gum unit weighing in the range of about 05 to about 4 grams;
  • the chewing gum base is present in said gum composition in an amount in the range of about l5 to about weight percent of said gum composition:
  • the nicotine is present in said composition in an amount in the range of about 0.05 weight percent to about 2 weight percent based on the weight of the chewing gum base and calculated as the free base;
  • the amount of nicotine held by the cation exchanger and distributed in said chewing gum base is in the range of about I to about 10 milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product;
  • said nicotine-cation exchange complex constitutes up to about 10 percent by weight of said chewing gum composition
  • the nicotine is present in said nicotine-cation exchange complex in an amount in the range of about 2 to about 60 percent by weight;
  • the nicotine held by said saliva-insoluble cation exchanger being present in said gum composition as a nicotine-cation exchanger complex which upon chewing liberates the nicotine cation, and
  • a chewable substitute for smoking gum composition comprising 1. a chewing gum base and 2. nicotine, held by a saliva-insoluble cation exchanger, substantially uniformly distributed in said chewing gum base,
  • composition is in the form of a chewable gum unit weighing in the range of about 0.5 to about 4 grams;
  • the chewing gum base is present in said gum composition in an amount in the range of about 15 to about 80 weight percent of said gum composition;
  • the nicotine is present in said composition in an amount in the range of about 0.05 weight percent to about 2 weight percent based on the weight of the chewing gum base and calculated as the free base;
  • the amount of nicotine held by the cation exchanger and distributed in said chewing gum base is in the range of about 1 to about l0 milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product;
  • said nicotine-cation exchange complex constitutes I up to about percent by weight of said chewing gum composition
  • the nicotine is present in said nicotine-cation exchange complex in an amount in the range of about 2 to about 60 percent by weight;
  • the nicotine held by said salivainsoluble cation exchanger being present in said gum composition as a nicotine-cation exchange complex which upon chewing liberates the nicotine cation, and

Abstract

A chewable smoking substitute composition is disclosed which comprises about 15 to about 80 percent gum base and a nicotine cation exchange resin complex dispersed in the base. The cation exchange resin complex constitutes up to about 10% of the chewing gum composition and affords a nicotine release, when chewed, of approximately that available when smoking a conventional cigarette.

Description

United States Patent 1191 Lichtneckert et a1.
[4 1 Aug. 26, 1975 CHEWABLE SMOKING SUBSTITUTE COMPOSITION Inventors: Stefan Lichtneckert; Claes Lundgren, both of Lund; Ove Ferno, Halsingborg, all of Sweden Aktiebolaget Leo, Helsingborg, Sweden Filed: Aug. 15, 1974 Appl. No.: 497,557
Related US. Application Data Continuation of Ser. No. 164,098, June 19, 1971, abandoned.
Assignee:
Foreign Application Priority Data July 22, 1970 United Kingdom 35607/ US. Cl. 131/2; 424/48; 131/262 Int. Cl A241) 15/00 Field of Search 131/2, 1, 5, 17, -144;
References Cited UNITED STATES PATENTS 11/1908 Ellis 131/2 2,341,986 2/1944 Hale et a1 131/5 UX 2,600,700 6/1952 Smith...L... 424/263 2,990,332 6/1961 Keating 424/79 3,003 ,920 10/1961 Dominick 424/48 3,109,43 ll/l963 Bavley et al. 131 262 A 3,368,567 2/1968 Speer 131/143 OTHER PUBLICATIONS The Chemical Composition of Tobacco and Tobacco smoke, (pub) by R. L. Stedman, from The Chemical Review, Vol. 8, No. 2, April 1968, pp. and 176.
Primary Examiner-Melvin D. Rein Attorney, Agent, or Firm-Gordon W. Hueschen [57] ABSTRACT ing a conventional cigarette.
4 Claims, No Drawings CI-IEWABLE SMOKING SUBSTITUTE COMPOSITION This is a Continuation of application Ser. No. 164,098, filed 1.9, July 1971, now abandoned.
BACKGROUND OF THE INVENTION This invention relates to smoking substitutes that are chewed and that are of particular value for facilitating a person's withdrawal from smoking and/or for de-- 7 known but generally are not verysatisfactoryExamples of such compositions are found in U.S. Pat-Nos. 865,026 and 904,521.
These patents are mostly concerned with mixing much of a sensation in the mouth. this may lead to an excessive use of the substitute with less smoking satisfaction. and. thus. lead to return to ordinary smoking.
e. The procedure of incorporating the alkaloid into the chewing gum should be easy to perform and also assure the substantially uniform distribution of alkaloid into the chewing gum.
SUMMARY OF THE INVENTION It hasnow surprisingly been found that all these ad-. vantages are obtained if a tobacco alkaloid is bound to a cation exchanger and in this form is incorporated into chewable gum compositions in an amount effective to provide smoking satisfaction. The present invention contemplates a smoking substitute composition comprising agum base and a tobacco alkaloid held by a cation exchanger dispersed therein. The amount of tobacco alkaloid such as nicotine. nor-nicotine. lobeline.
' or mixtures thereof. present per chewable gum unit can finely ground tobacco, forinstance snuff. into chewing gum, but the use of a tobacco extract of unidentified composition is also mentioned. However, we have found that when nicotine or other tobacco alkaloid is incorporated into an ordinary gum composition of the type that is most used and accepted today. the release of the alkaloid takes place very quickly. This is disadvantageous for two'reasons: firstly, if the alkaloid is released too quickly, higher blood concentrations of the alkaloid are produced than with ordinary smoking, and secondly, the substitute has too short an effect.
It has been our object to devise a chewable composi-' tion in which a'tobacco alkaloid such as nicotineor a related alkaloid is released slowly, the composition thereby imitating satisfactorily the effect of the administration ,of nicotine by smoking.
The term'ftobacco alkaloid as used herein and in the claims istakenjto mean nicotine or nicotine-like alkaloid such as nor-nicotine, lobeline, and the like, in the free base or pharmacologically acceptable acid addition salt form. Source. for alkaloids of this type are species of Nicotiana (for nicotine and nor-nicotine: of Lobeliaceae-(Indian tobacco) and Lobelia (for lobeline); and the like,'as is well known in the art.
An ideal smoking substitute in the form of a chewing gum should have the following properties:
a. The release of the tobacco alkaloid should take place rather uniformly during not too short a period of time.
b. The release of the tobacco alkaloid should take place rather uniformly when using different gum compositions.
c. It should be possible without changing the gum composition to change the release rate of the tobacco alkaloid, for instance when employing smaller quantities of the alkaloid it may be desirable to increase somewhat the release rate in order to give a better satisfaction to the person who is using the substitute in question.
d. The released alkaloid should produce a feeling of smoking" not only after absorption into the blood stream but also in the mouth. This is very important because if the alkaloid is absorbed without producing vary over a wide range and can be present in'an amount in the range 'of about 0.05. weight percent to about 2 weight percent, based on the weight of gum base and calculated as the freebase. Usually a chewable gum unit contains about I to 10 milligrams of an alkaloid. preferably, about i to about 5 milligrams. Preferably the smoking substitute composition is rendered acidic by the addition ofa pharmacologically acceptable acidifying agent. f
DESCRIPTION OF THE PREFERRED r v EMBODIMENTS When the alkaloid bound is cation exchangers is incorporated into the chewing gum mass it is possible to use a wide variety of chewing gum compositions. A manufacturer 'of chewing gums can thus incorporate the solidcornplex of alkaloid bound to a'cation exchanger into his own composition without having to change the same and it is also possible to satisfy different taste preferences. I I
Release rate of the alkaloid from the composition can bevaried 'by varying the amount .of alkaloid'that is bound to a given quantity of cation exchanger. A relatively higher amount of the alkaloid present in the composition gives a quicker release and vice versa. By the term slow release" as used herein is meant that the major portion of the alkaloid is released from the smoking substitute composition substantially uniformly over. a period of several minutes and preferably over a period of at least 10 minutes. Most preferably the release time is at least 20 minutes.
It is generally known that nicotine is absorbed from mucous membranes in the form of nicotine base. It has now been found that the feeling of smoking" is weaker, if the alkaloid is released from the gum as the base. This is presumably due to the fact that the alkaloid is absorbed very readily at the chewing site, that is, the part of the mouth that is in direct contact with the chewing gum. Thus only-a relatively small amount of the alkaloid is transported to other parts of the mouth including the throat. The throat seems to be very sensitive to nicotine. If, as is the case with the present composition, nicotine is liberated as the nicotine cation, the absorption does not take place so quickly, thus allowing some of the nicotine to reach other parts of the buccal cavity including the throat, whereby some of the sensations of smoking are obtained, including a light burning sensation, which the smoker generally esti mates in a positive way.
The complex containing an alkaloid bound to the cation exchanger is preferably prepared in a special unit. The solid complex thus prepared is easy to handle and minimizes personnel risksinvolved in the manufacture of the final chewing gum product. It has also been shown that the complex acts as a lubricant thereby facilitating the mixture of the different ingredients into the gum mass. A homogenous product is easily obtained in this manner.
The ion exchanger must have cation exchanging groups in order to form the alkaloid-ion exchanger complex. Preferably, before formation of the complex. these groups are in the hydrogen ionic form.
The exchanger can also contain anionic groups, in which event it is known as a polyampholyte.
The cation exchanging groups that are present may be strongly acidic. weakly acidic or of intermediate acidity. synthetic cationic exchangers containing these groups accordingly being called strongly acidic. weakly .acidic or intermediate acidic cation exchangers, de-
pending on the strength of the acid from which these functional groups are derived. Examples of suitable acidic groups that may be present are carboxylic. sulphonic acid. phosphonous acid. phosphonic acid, phosphoric acid. iminodiacetic acid. or phenolic groups.
which is generally synthetic. should be non-toxic in the amounts used and it should not be such as to give an undesirable taste to the compositions. However these requirements do not present any serious problem since the amount of ion exchanger required for binding a sufficient amount of nicotine or other alkaloid in suitable compositions according to the invention is small.
The acidic groups of the ion exchanger. which may be termed an ion exchange resin, may be bound to a cross-linked polymer such as addition polymers of styrene and divinylbenzene. divinylbenzcne and methacrylic acid. divinylbenzene and acrylic acid, phenolic resins. or cellulose. dextran or pectin cross-linked with. e.g.. epichlorhydrine.
The acidic groups can be bound to insoluble linear polymers. e.g.. cellulose with nitrous gases. whereby mainly uronic acid groups are formed. Such compounds are disclosed by Ott. E. and Spurlin. H.M.. Cellulose and Cellulose Derivatives. Part I. lnterscience. New York (1954). Carboxymethyl cellulose. sulphoethyl cellulose. cellulose sulphate. etc.. can also be used. ln order to ensure that cellulose polymers containing the acidic groups are insoluble in the saliva, it is necessary that the number of acidic groups be relatively low. e.g.. a maximum of l per 3 glucose units. Such compounds are disclosed by Ott, E. and Spurlin, H.M., Cellulose and Cellulose Derivatives. Part II. Interscience. New York (1954). Representative cation exchangers suitable for use according to the invention are given in'Table I.
TABLE 1 Representative Cation Exchangers in Accord with the Foregoing Name Type Cross Linked Polymer Functional Groups Manufacturer Antherlite lRC 50 Divinylbenzene-methacrylic acid Carboxylic Rohm and Haas Co. Amberlite lRP 64 do. do. do.
I Amherlitc lRP 64M do. do. do. BIO-REX 7O Divinylhenzene-acrylic acid do. BIO-RAD Lab. Amherlite IR 1 l8 Styrcne-divinylhenzcne Sulfonic Rohm and Haas Cov Amherlite [RP 69 do. do. do. Amherlitc lRP 69M do. do. do. BIO-REX 40 Phenolic do. BIO-RAD Labv Antberlitc lR lZO Styrcne-divinylbcnzene do. Rohm and Haas Co. Dowex 50 do. do. Dow Chemical Co. Dowex 50W do. do. do. Duolite C 25 do. do. Chemical Process Co. Lewatit S I00 do. do. Farbcnfahrikcn Bayer lonac C 240 do. do. lonac Chemical Co. Wolatit KPS 200 do. do. I. G. Farben Wolfen Amhcrlyst l5 do. do. Rohm and Haas Co. Duolite (-3 Phenolic do. Chemical Process Co.
Duolite C-lt) Phenolic do. do. Lewatit KS Phenolic Sulfonic Farhenlabriken Bayer Zcrolit 215 Phenolic do. The Permutit Co. Duolite ES-62 St \'rcne-divinylbcnzene Phosphonous Chemical Process Co. BIO-REX 63 do. Phosphonic BIO-RAD Lab Duolite ES-63 do. do. Chemical Process Co. Duolite ES-oS Phenolic Phosphoric do. Chelex lOO Styrene-divinylhenzcne lminodiacctic BIO-RAD Lab Dow Chelating Resin do. do. Dow Chemical Co. A-l CM Sephadex C-25 Dextran Carhoxy methyl Pharmacia Fine Chemicals SE Scphadex C-25 Dcxtran Sulphocthyl do.
ply by using a suitable mixture of counter-ions in the same ion-exchanger or a suitable mixture of different We set out below the properties and characteristics of four ion exchange resins that we have found to be of ion-exchangers. the real compound ion-exchangers. 60 particular suitability in the invention and which are dispolyampholytes included. It is also possible to vary the pattern of release by altering the amount of alkaloid which is bound to a given amount of ion exchanger.
cussed frequently elsewhere in the specification.
LAN-
Name
Ainberlite lRP 64 Ambcrlite lRP 64M do Ambcrlite lRP 69M for the formation of the ion exchange resin complexes Alkaloid-ion exchange complex -continued No. Name Manufacturer 4. BIO-REX 63 BlO RAD Lab. Richmond.
California No. Type Functional groups l. Weakly acidic. methacrylic Carboxylic Type R.COO H 2. do. do, 3. Strongly acidic. poly- Sulfonie styrene Type R.SO H' 4. Intermediate acidic. Phosphonic polystyrene Type R.PO;, H): No, lonic Form Cross-linkage. "/1 divinylbcnzene 1. Hydrogen Not published. but according to the manufacturer this resin "While a gel resin" reacts as a relatively high porosity" resin. 2. do. do. 3. Sodium converted Not published. but according to the to hydrogen manufacturer this resin reacts as a conventional gel porosity" resin. 4. do. Not published. but according to the manufacturer this resin reacts as a "large porosity" resin. No. Apparent pK Value in Exchange Capacity One Molar Potassium meq/gm Chloride Solution of Oven Dried Resin l. About 6.0 10.3 2. do. do. 3. About 1.3 5.2 4. Not published 6. I No. Particle size u. Percent External Water 1. 150-40 Maximum 50 2. 9571 40 do. 3. 95'/( 40 Maximum 100 4. 150-75 Maximum 4.0
The amount of the alkaloid, e.g.. nicotine, nor-' nicotine, lobeline, acid addition salts thereof, or mixtures thereof bound to the tort exchanger may be varied cominued depending on the conditions employed and the type of ion exchanger used.
Alkaloid-ion -xchan" com l-x Thus it has been found that alkaloid-ion exchange L pi Percent alkaloid by weight in complex complexes in which the content of nicotine or other alkaloid amounts to about 2 to 60 percent. and preferably about 5 to percent of the alkaloid to the ion exchange complex. are suitable for incorporation into the compositions of the invention. For carboxylic acid group containing ion exchangers. the preferred range is about 5 to 35 percent, whereas for phosphonic acid group containing ion exchangers the preferred range is about 5 to 30 percent, and the preferred range for sulphonic acid group containing ion exchangers is about 5 to 25 percent.
Part of the nicotine, nor-nicotine, lobeline or mixtures thereof may occur bound to the ion exchanger through surface adsorption as opposed to real ion exchange reaction. 7
Suitable and preferred amounts of various alkaloids BlO-REX 63 nor-nicotine complex BlO-REX 63 lobeline eotnplex Amberlite lRP 69M nicotine complex Amberlite lRP 69M nor-nicotine complex Amberlitc lRP 69M lobeline complex Amberlitc lRP 64 nicotine complex Amberlitc [RC 50 nicotine complex Amberlite [RP 69 nicotine complex for use in the invention are set out below.
BlO-REX 40 nicotine complex Percent alkaloid by weight in complex BIO-REX 70 nicotine complex Duolite ES-62 nicotine complex Duolitc ES- nicotine complex Amberlite lRP 64M nicotine complex E2 60 preferably 5 35 Amberlite lRP 64M nor-nicotine complex 2 6 preferably 5 35 Amberlite lRP 64M lobeline complex 7 Chelex nicotine complex preferably 5 35 Ambcrlite lR l 18 nicotine complex 2 CM Scphadcx C-25 nicotine complex preferably 5 20 BIO-REX 63 nicotine complex (2 40 SE Sephadcx C-25 nicotine complex preferably 5 30 prelerably 5 30 preferably 5 25 2 35'.
(preferably 5 25 preferably 5 25 2 60;
preferably 5 35 2 60: l t l l l l l l l l preferably 5 35 preferably 5 2s preferably 5 l5 2 60;
preferably 5 35 2 35'.
preferably 5 25 2 25;
prefcrably S l5 2 25:
preferably 5 l5 2 301' preferably 5 20 2 15'.
preferably 5 l0 The chewing gum component of the compositions of the invention may be of any convenient nature and preferably is of a generally available commercial type. For example it can comprise a gum base of natural or synthetic origin. Natural gum bases include. e.g., Chicle-, Jelutong-. Lechi di Caspi-. Soh-, Siak-, Katiau-. Sorwa-. Balata-. Pendare. Perillo-, Malayaand Percha gums, natural caoutchouc such as Crepe. Latex and Sheets. and natural resins such as Dammar and Mastix. Synthetic gum bases are polyvinylacetate (Vinnapas). Dreyco" commercial gum base, polyvinyl esters, polyisobutylene and non-toxic butadienestyrene lattices among others. Softeners (plasticizers) are. as is conventional in the art, incorporated into the commercially available chewing gum base to help reduce the viscosity of the rubber blend to a desirable consistency and to improve the texture. Some of the common softeners or plasticizers are: lecithin, lanolin. hydrogenated coconut oil. hydrogenated cotton seed oil. mineral oil.
For the purposes of the present invention the chewing gum component can be formulated with the following constituents which are present in varying amounts. The gum base can be natural or synthetic origin, preferably the latter, and can be present in the chewing gum formulation in an amount in the range from about to about 80 weight percent. preferably from about 50 to about 80 percent and most preferably from about 60 to about 75 weight percent.
Powdered sugar, preferably powdered sorbitol. can be present in an amount in the range from about 15 to about 80 weight percent. preferably from about 16 to about 40 weight percent, and most preferably from about 20 to about 32 weight percent.
Corn syrup usually of about 41 to 46 Baume, pref- V erably an about 70 percent aqueous solution of sorbitol, can be present in an amount in the range from about 4 to about weight percent. preferably from about 4 to about 10 weight percent, and most preferably from about 5 to about 8 weight percent.
Special formulas for chewing gums exist, such as sugar-free compositions with a concentration of as much as 80 percent chewing gum base. preferably of synthetic origin (Preparation 13, below).
Variations of the consistency, on the one hand the preliminary consistency at the very beginning of the chewing, and on the other hand the secondary consistency after some chewing, is achieved simply by varying amounts and proportions of the above formula. The consistency and the stickiness of the chewing gum can be influenced by the addition of various substances. as previously mentioned.
Compositions according to the invention can be formed simply by mixing the chewing gum mass with the alkaloid-ion exchanger complex. preferably together with an excess of a suitable acidifying agent. If the complex is in the form of a small particle size ion exchanger in the first place. then this can be mixed with the gum. If, however. the complex is in the form of a coarser ion exchanger then it is desirable to grind and size this first. The mixing is preferably conducted at a suitable elevated temperature depending upon the viscosity of chewing gum mass employed, since the increased temperature decreases the viscosity of the gum and thereby enables the alkaloid-ion exchanger complex to be evenly and intimately distributed into the chewing gum. The complex particle size in the gum should be small enough not to cause damage to teeth during chewing, however.
Conveniently compositions of the present invention are made simultaneously with the incorporation of any additives such as corn syrup, sugar, sorbitol. and flavors into the chewing gum base. Thus. for example. the composition can be made in a suitable kettle. for example. a steam jacketed mixer, which is warmed and the gum base added and mixed until sufficiently free from lumps. Next, sorbitol or corn syrup and sugar are incorporated into the base.
Depending on the physical properties of the pharmacologically acceptable acid that may be incorporated as an additional ingredient according to this invention, it will be convenient to add this acid, as in the case of. for instance, sulphuric acid, with the liquid part of sorbitol or with the corn syrup. in the case of, for instance, malic acid. it will be convenient to add this particular acid with the solid, powdered part of sorbitol or sugar. Finally. flavors, softeners and other additives are poured in and well distributed. The mass is cooled, rolled. scored. and hardened sufficiently. then coated if desired. before final wrapping and analyzing. Controlled humidity rooms assure consistent moisture content and prevent "sweating" of the gum. It is preferred to use just enough heat to soften the gum base sufficiently for mixing. The addition of sugar and syrup lends to lower the temperature, and the various alkaloid-ion exchange complexes together with flavor. if desired. are added only when the mixture has cooled sufficiently. This minimizes uncontrollable losses in alkaloid and/0r flavor content to a marked degree.
The weight of one chewing gum unit. e.g., stick. ball, or the like, according to the present invention, can be varied between 0.5 and 4.0 grams and preferably between l.0 and 3.0 grams, as is generally conventional in the chewing gum art.
The percent by weight of the various alkaloid ion exchange complexes. either each or mixtures thereof, to the total weight of the gum, is not critical but varies between an upper and a lower most suitable range, specific to the formula used. Thus it has been found that compositions. wherein the percent by weight of the alkaloid ion exchange complex to the total weight of the gum is about 0.1 to l0 percent. preferably about 0.2 to 5 percent. and most preferably about 0.5 to 2 percent. are suitable.
Some Preparations and Examples are now given. Preparation 1 demonstrates the preparation of a suitable ion exchange complex while preparations 2 to 13 Preparation 1-: A nicotine ion exchange complex containing 200 mg. of nicotine in 800 mg. of the ion-exchanger Amberlite lRP 64M in the dry state. i.e.. a percent compound (complex) The moisture content of the ion exchanger is determined by drying in an oven at 105C. to a constant weight. t I
100.0 grams of the ion exchanger, calculated as dry. are added to a beaker containing 25.0 grams nicotine. calculated as 100 percent. dilutedtoa total volume of 500 ml. by an addition of distilled water. The mixture is stirred for at least 1 hourwith a magnetical stirrer. or the like. The loaded ion exchanger is then separated by filtration or centrifugation. The filtercake is then broken into pieces and dried at about 20 C. in a drying cabinet provided with a fan. The nicotine ionexchange complex thus obtained is then analyzed with reference to the nicotine content after careful blending and sieving through a 300 mesh sieve.
Preparation of the other various alkaloid ion ex change complexes mentioned below in accordance with the present invention is in accord with the foregoing example. or with only minor variations as are well known to one skilled in the art of handling ionexchangers. Allpercentages indicated are by weight.
Preparation 5 Natural gum base l 22.0 Diastatic malt Corn syrup 44 Baume Powdered sugar Calcium carbonate Natural gum base Diastatic malt lnvert sugar Corn syrup 44 Baume Powdered sugar Cerelose Preparation 7 (Summer Formula) Natural gum base Powdered sugar Corn syrup 45 Baume Calcium carbonate Powdered starch Preparation 8 (Winter formula) Natural gum base Powdered sugar Corn syrup 44 Baumc Calcium carbonate Powdered starch Preparation 9 (Stick gum formula) Stick gum base Powdered sugar tel/Ito Mutter '41- q; IQN- b ld teluhcte \p-wtn ore C 00000 OOQCO The gums are coated with white or colored sugar in rotating-pans in the usual manner for the coating of dragees.
Preparation 12 (Sugarand glucose-free formula Percent Natural gum base 29.2 Powdered sorbitol 45.8 Calcium carbonate 8.5 Sorbitol. percent water solution 16.5 Preparation 13: Sugarand glucose-free formula with high chewing gum base concentration. Synthetic gum base 73.7 Powdered sorhitol 19.8 Sorbitol. 70 per cent water solution 3.8
Glycerin 0.7 Flavouring oil I The following Examples demonstrate the compositions according tothe invention. Each of these is made by warming the gum base in a kettle and then adding the variousadditives, in the general method described above;
EXAMPLE 1 Chewing gum containing a 10 percent complex obtained from 3 mg. of nicotine bound to' Amberlite [RP 64M. Chewing gum mass according to Preparation 4. 1000 pieces of gum per 1970 grams of the mass. Amberlite IRP 64M 10 percent nicotine complex 30.0 grams 1 EXAMPLE 2 Chewing gum containing a 10 percent complex, obtained from 2.5 mg. of nicotine bound to Amberlite IRP 64M, and likewise a 20 percent complex. obtained from 2.5 mg. of nicotine bound to Amberlite lRP 64M. Chewing gum mass according to Preparation 4, 1000 pieces of gum per 1835 grams of the mass. Amberlite lRP 64M 10 percent nicotine complex 25.0 grams Amberlite IRP 64M 20 percent nicotine complex 12.5
grams EXAMPLE 3 Chewing gurn containing a 30 percent complex, ob-
tained from 1 mg. of nicotine bound to Amberlite IRP 64M. Chewing gum mass according to Preparation 6, 1000 pieces of gum per 3325 grams of the mass. Am-
ll berlite lRP 64M 30 percent nicotine complex 3.33
grams.
EXAMPLE 4 Chewing gum containing a 20 percent complex, obtained from 3 mg. of nicotine bound to Amberlite lRP 69M. Chewing gum mass according to Preparation 4. 1000 pieces of gum per 1485 grams of the mass. Am berlite lRP 69M 20 percent nicotine complex 15.0
grams EXAMPLE 5 Chewing gum containing a 15 percent complex. obtained from 4 mg. of nicotine bound to BIO-REX 63, converted to the hydrogen ionic form. Chewing gum mass according to Preparation 4. 1000 pieces of gum per 2025 grams of the mass. BIO-REX 63 i5 percent nicotine complex 26.7 grams EXAMPLE 6 Chewing gum containing a 30 percent complex. obtained from 2 mg. of lobeline bound to Amberlite lRP 64M. Chewing gum mass according to Preparation 3. 1000 pieces of gum per 3325 grams of the mass. Amberlite lRP 64M 30 percent lobeline complex 6.67
grams EXAMPLE 7 EXAMPLE 8 Chewing gum containing a percent complex. obtained from 5 mg. of nor-nicotine bound to Amberlite lRP 64M. Chewing gum mass according to Preparation 2. 1000 pieces of gum per 450 grams of the mass. Amberlite lRP 64M 10 percent nor-nicotine complex 50.0
grams EXAMPLE 9 Chewing gum containing a per cent complex, obtained from 2 mg. of nicotine bound to Amberlite lRP 69M. Chewing gum mass according to Preparation 13. 1000 pieces of gum per 987 grams of the mass. Amberlite lRP 69M l5 percent nicotine complex 13.33 grams EXAMPLE l0 Chewing gum containing a 15 percent complex, obtained from 2 mg. of nicotine bound to Amberlite lRP 64M. and likewise a 10 percent complex, obtained from 1 mg. of nor-nicotine bound to Amberlite lRP 64M. Chewing gum mass according to Preparation 4.
12 1000 pieces of gum per 2975 grams of the mass. Amberlite lRP 64M 15 percent nicotine complex l3.33 grams Amberlite lRP 64M 10 percent nor-nicotine complex 10.0 grams Preparation of chewing gums containing the other various alkaloid-ion exchange complexes mentioned in the present application. either separately or mixtures thereof. is carried out in the manner of the foregoing examples, with only such minor variations as are well known to every person skilled in the art of manufacturing chewing gums.
It is particularly surprising that slow and controlled release of the alkaloid is obtained in the compositions of the invention when one considers the results that we have obtained in prior experiments. Thus we have found previously that one does not obtain a satisfactory release rate for the alkaloid from alkaloid-ion exchange complexes in the absence of chewing gum. Table l below is a compilation of experimental results showing the amount of nicotine released as a function of time.
TABLE I RELEASED NICOTINE lN PERCENT BY WEIGHT AS A FUNCTION OF TIME Al Chewing gum containing 20 milligrams Amberlite lRP 64M resin complexed with nicotine base (20 weight percent nicotine) and l gram chewing gum mass having a high gum base concentration. prepared in accordance with Preparation l3. Release brought about by chewing. Very pronounced feeling of smoking was observed.
A2 Chewing gum containing 20 milligrams Amberlite lRP 64M complexed with nicotine base (20 weight percent nicotine) and 3 grams chewing gum mass having a low gum base concentration. prepared in accordance with Preparation 4. Release brought about by chewing. Very pronounced feeling of smoking was observed. l) Amberlite lRP 64M resin complexed with nicotine base l 10 weight percent nicotine). Release brought about with it) milliliters of synthetic saliva No. 2. infra. contacting 50 milligrams of the complex at 37 C.
F. Same complex as in D but release brought about with It) milliliters of physiological saline solution contacting 50 milligrams of the complex at 37 C.
Detailed desorption and chewing tests have been conducted.
Desorption Tests Desorption tests in vitro of alkaloid cation exchange complexes without incorporation into chewing gum mass have been made. In one series of experiments a quantity of 25 mg. of the cation exchange complex in question including 5 mg. of nicotine was shaken for different times with 10 ml. of water, physiological sodium chloride solution, 20 percent (w/v) sugar solution. and saliva. The shaking was carried out in a thermostat at 20: 01C and at 37-: O.lC. Samples of the filtered solution were analysed with reference to nicotine by UV- determination. The ion exchange resins Amberlite lRP 64M and [RP 69M were tested with the following re sults. However. the use of other ion exchangers in accordance with this invention produces similar results.
Results:
Total released quantity of nicotine in mg/lO ml.
Medium Water NaCl lon Ex changer Temperature Time. Minutes '-continued Medium Sugar Saliva l [on EX- changcr [RP 64M [RP 69M [RP 64M [RP 69M Temperature 20 37 20 20 37 20 37 Time. Minutes Medium Saliva 2 [on Exchanger [RP 64M [RP 69M Tempera- 20 37 20 37 ture Time. Minutes 2 3.24 5 r 1.51 10 3.45 4.57 4.05 15 20 30 3.46 4.60 1.57 4.23
of the mucin, the desorption could take place too Media slowly for any practical effect, especially from the Water: twice ion exchanged. distilled water Physiological sodium chloride solution: 0.9 percent in standgomt creatlon of A proper and deslrdble distilled water taste sensation Sugar: sflccamsc 20 P m This phenomenon seems to be particularly unobvious Saliva 1; Gelatine 2 g, in the case of strongly acidic cation exchangers, e.g., Glycm? l Amberlite [RP 69M, in view of the fact that alkaloids Asparne acid I g. I I Phynn (aha) 05 g are usually so strongly bound thereto that they can be fi g a 5 geluted from such ion exchange complexes only with difa g. KSCN 0.1 g. 40 flculty' Water ad [000 ml. Saliva 2 NaCl 0.45 g. Chewmg Tests CaCl-'6H- ,O 0.12 cacc 1.0 5. The results of the analys1s w1th reference to n1cot1ne u d-[ 1 (dried) is shown below refer to chewing tests. Two persons iffi 5: 5: chewed the gum at different times, the analytical re- Cholesterine 0.06 g. sults were tabulated, and the mean value determlned. Water ad [000 ml.
From the results it will be apparent that the equilibrium is reached very quickly. After 2 minutes, no further release occurs. The addition of sugar does not influence the release. The ion exchange resin Amberlite [RP 69M appears to bind the nicotine stronger than the ion exchanger [RP 69M. The strength of the binding is of the same order in saliva and physiological sodium chloride solution, but considerably lower than in water and sugar solution.
No particular difference between the release at 20 C and 37 was found except in one case. The test with the artificial saliva 2 gave a more rapid release at the higher temperature. Said saliva solution 2 includes mucin, which is also present in human saliva. It therefore seems probable that the presence of mucin in human saliva gives a reasonable basis for explaining the unobvious effect of the initially rather rapid release of nicotine, nor-nicotine, lobeline, etc., which is noticed when smoking substitutes in accordance with the present invention are being chewed. Thus. without the presence The chewing gums in these refer to the following formula:
Natural gum base Powdered sugar Corn syrup 45 Baume 22.0 percent 640 [4.0
EXAMPLE ll mg. of nicotine per g. of Amberlite [RP 64M nicotine complex.
Chewing time minutes Mean value nicotine released mg.
ln the following Examples the chewing gum was pre- -continued pared according to Preparation 13. Each piece of gum Chewing time minutes Mean value nicotine released mg. Contains gram f hi composition.
s 2. .2 5 EXAMPLE l6 l; l70 mg of nicotine per g. of Amberlite lRP 64M nic- 30 4.4 otine complex. l.5 mg. nicotine per chewing gum.
l0 Chewing time minutes Mean value nicotine released mg. EXAMPLE l2 0 0 105 mg. ofnicotine per g. of Amberlite IRP 64M nic otine complex. i 020 0.98 15 1.14 1.32 Chewing time minutes Mean value nicotine released mg.
0 0 2 0.6 5 1.2 10 23 20 EXAMPLE 17 53 175 mg. of nicotine per g. of Amberlite [RP 64M nic- 30 otine complex. 4 mg. nicotine per chewing gum.
75 Chewing time minutes Mean value nicotine released mg. EXAMPLE l3 0 0 3 179 mg. of nicotine per g. of Amberlite IRP 64 mcog $1 tine complex. 10 2.44 20 3.64 30 Chewing time minutes Mean value nicotine released mg.
0 0 EXAMPLE l8 2 2.0 5 88 mg. of nicotine per g. of BIO-REX 63 nicotine complex. 2 mg. nicotine per chewing gum. 20 4.0 30 4.2
Chewing time minutes Mean value nicotine released mg.
0 0 2 0.13 EXAMPLE 14 5 (m 10 0.50 210 mg. of nicotine per g. of Amberllte lRP 69M mc- 20 L35 otine complex. 30
u u I Chewing time minutes Mean value nicotine released mg. T0 determine lllCOtll'lfi, IllCOtll'lC has been quantita- 0 0 tively determined by titration with perchloric acid. 2 2.3 As identification test an lR-spectrum has been used. 5 2.6 Determination of Nicotine Bonded to lon Exchangers 20 -3 Method taken from Off. Meth. Anal. of the A.O.A.C. 30 47 9th ed. 1960 pp. 9495.
Reagents. Alkali-salt solution. Dissolve 300 g NaOH in 700 ml water and saturate with NaCl. Hydro- EXAMPLE 15 chloric acid. Dilute conc. HCl l+4 (one part conc.
HCl diluted with 4 parts distilled water) Apparatus. Steam distillation assembly (i.e.. of the type used for nitrogen determination according to Kjeldahl). Spectrophotometer Beckman DU. Determination. Weigh accurately sample corre- 333 mg. of nicotine per g. of Amberlite lRP 64M nicotine complex.
Chewing time minutes Mean value HILOIII'IL released mg. Spending to 5 mg. nicotine and transfer to the distilla- 2 g 1 tion flask. Place 50 ml hydrochloric acid l+4) in a 500 5 ml volumetric flask. used as receiver, placed so that the l condenser tube dips into the solution. Add 50 ml alkali- '3 2:; 65 salt solution to the sample in the distillation flask and 30 4.8 steam distil as rapid as steam can be condensed efficiently. Effluent condensate should not be above room temperaturefApply heat to distillation flask to keep the If. X 500 X 1000 V 388 X 100 X (sample weight. g) mg'mumnc/g Sumplc' Determination of Nicotine in Chewing Gum Apparatus. Spectrophotometer Beckman DU.
Determination. Homogenize one chewing gum with a 20 g seasand in a mortar under ether. Transfer the homogenous mixture to a glass column with a glass wool plug at the bottom. Elute the column with ca. 100 ml ether and collect the eluate in a separation funnel. Make the column as free from ether as possible. Extract the ether in the separation funnel with 3 X 15 ml 0.1 N hydrochloric acid and combine the extracts in a 250 ml volumetric flask. The ether phase is then discarded. Elute the now nearly dry column with 0.1 N hydrochloric acid into the flask containing the combined extracts until the total volume is 250 ml.
Read absorbance in the spectrophotometer at 259 (max), 236 (min) and 282 mu.
Calculate r'orr mum min E282) E (corr) has been determined to be 338 1000 250 g W= mg nlcotrnc/chewmg gum The method is applicable also to chewed gums for determination of remaining nicotine.
Many ion exchangers according to given examples are suitable for use in the preparation of the smoking substitutes, and we have also given many examples of smoking substitute compositions according to the invention. We now give a detailed example of the preparation of one of the smoking substitutes.
EXAMPLE 19 A nicotine ion exchange complex with Amberlite lRP 64M was prepared by the method described in Preparation 1. the resultant complex containing 10% nicotine.
434 Grammes natural gum base is put into a hot jacketed mixer fitted with stirrers. The mixer is heated by steam at about lbs. per sq. inch. The stirrers are run at intervals to turn the base over. A low steam pressure A further 420 grammes of powdered sugar and 30 grammes of the nicotine ion exchange complex. both 300 mesh sieve. are mixed together and are then added as a powder mixture to the molten mixture in the kettle. The melt is mixed for a further five minutes, so that the total mixing time is about 15 minutes.
The temperature in the kettle will at the end of this time have dropped to between 40 to 60C. It is desirable that the mix should be as cool as possible before mixing stops. but viscosity increases as the temperature drops and mixing must stop before the mixture becomes too stiff for the mixing machine. in practice the operator judges when to stop mixing not so much by the actual thermometer reading as by the consistency of the mix.
After mixing, the batch of gum is cut into pieces of a size suitable for feeding to whatever type of extruder is available. The extruder jacket is usually heated by means of warm water at 45 to 50C. This gives a more even extrusion than when the extruder is heated by steam and it permits better temperature control. The extruded stick of gum should be well dusted with starch or a mixture of icing sugar and starch to prevent it from sticking to sizing rollers and cutters. The rollers serve to roll it down to the desired size. The cutters are preferably maintained at about 25C.
The precise manner of shaping the gum in the extruder and afterwards is however fairly conventional and will be selected according to the desired shape and size ofthe resultant pieces. Each piece generally weighs between t and 3 grammes. In this Example. 1000 pieces, each weighing two grammes. were provided by the conventional extruding and cutting procedure. Likewise, the pieces are packed and stored under fairly conventional conditions. For example the wrapping room is preferably maintained at 20C and a relative humidity of 45 to 50% and the pieces are preferably stored at a temperature of 18 to 20C and a relative humidity of 45 to 50%.
It will be appreciated that combinations of alkaloid ion exchange complexes with gum other than those demonstrated in the foregoing Examples can be used and that combinations with other flavouring agents, sweetening agents, binders and such additives can also be used.
As mentioned hereinabove. it is preferred that the smoking substitute compositons of this invention are acidic. This is desirable in order to enhance the feeling of smoking upon use of the present compositions, because in an acidic environment the nicotine cationnicotine base equilibrium. i.e.,
is shifted to the left, further decreasing the nicotine absorption rate at the chewing site and allowing some of the released nicotine to reach other parts of the buccal cavity including the throat. It has been found that it is desirable, for the purposes of this invention, to maintain the pH at the chewing site at a pH of less than about 7. and preferably in the range from about 5 to about 4. by incorporating a pharmacologically acceptable acidifying agent into the composition.
In one preferred embodiment of this invention. the cation exchanger, initially in its ionic hydrogen form, is only partly loaded with nicotine or similar alkaloid when incorporated into a smoking substitute composition of this invention. Upon chewing such a composition, hydrogen ions are liberated from the cation exchanger and pH of saliva at the chewing site is decreased, which decrease in pH influences, in turn, the acid-base equilibrium. Similarly, it is possible to admix a fully nicotine-loaded cation exchange resin with a cation exchange resin in its acid form to bring about the desired acidity at the chewing site, or to admix a fully nicotine-loaded cation exchange resin with a pharmacologically acceptable organic or inorganic acid, or to admix a fully nicotine-loaded cation exchange resin with a combination of a cation exchange resin in its acid form with a pharmacologically acceptable organic or inorganic salt.
The amount of pharmacologically acceptable acid present in the foregoing instances can be in the range of about 1.5 to about equivalents of acid per mole of the alkaloid base, preferably about 1.5 to about 6 equivalents of acid per mole of the alkaloid base, and most preferably about 2 to about 4 equivalents of acid per mole of the alkaloid base. Expressed in terms of the alkaloid present as a neutral salt, the amount of acid present can be in the range of about 0.5 to about 9 equivalents of acid per mole of the neutral alkaloid salt, preferably about 0.5 to about 5 equivalents of acid per mole of the neutral alkaloid salt, and most preferably about l to about 3 equivalents of acid per mole of the neutral alkaloid salt.
For the purposes of the present invention suitable acids are inorganic acids such as hydrochloric acid, sulphonic acid, phosphoric acid, and the like, as well as organic acids such as succinic acid, fumaric acid, glutaric acid, adipic acid, malic acid, tartaric acid, ascorbic acid, citric acid, mixtures of the aforesaid acids, the the like. The organic acids are preferred.
The acid or acids may be incorporated directly into the gum composition at any convenient compounding stage thereof, or admixed beforehand with a watersoluble part of the composition, e.g., sorbitol, and then incorporated into the gum composition.
Tests, where substitutes according to the present invention have been given to habit smokers, have produced very good results. In several cases it has been possible for a known subject, by using 6 to pieces of gum per day, to give up smoking completely and in other cases for the subject to reduce smoking considerably.
We claim:
I. A chewable substitute for smoking gum composition comprising 1. a chewing gum base and 2. nicotine, held by a saliva-insoluble cation exchanger, wherein the cation exchanger is selected from the group consisting of a) methacrylic type, weakly acidic, containing carboxylic functional groups; b) polystyrene type, strongly acidic, containing sulfonic functional groups; and c) polystyrene type, having intermediate acidity, containing phosphonic functional groups;
substantially uniformly distributed in said chewing gum base,
wherein:
A. the composition is in the form of a chewable gum unit weighing in the range of about 05 to about 4 grams;
B. the chewing gum base is present in said gum composition in an amount in the range of about l5 to about weight percent of said gum composition:
C. the nicotine is present in said composition in an amount in the range of about 0.05 weight percent to about 2 weight percent based on the weight of the chewing gum base and calculated as the free base;
D. the amount of nicotine held by the cation exchanger and distributed in said chewing gum base is in the range of about I to about 10 milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product;
E. said nicotine-cation exchange complex constitutes up to about 10 percent by weight of said chewing gum composition;
F. the nicotine is present in said nicotine-cation exchange complex in an amount in the range of about 2 to about 60 percent by weight;
G. the nicotine held by said saliva-insoluble cation exchanger being present in said gum composition as a nicotine-cation exchanger complex which upon chewing liberates the nicotine cation, and
H. said chewing gum composition when chewed releasing nicotine in small and reduced amounts within a period of the first few minutes of chewing, and
I. especially within the first ten minutes of chewing releasing the nicotine at a rate less than if the nicotine were present by itself in an ordinary gum composition and less than if the nicotine-cation exchanger complex were used by itself absent the gum.
2. The chewing gum composition of claim 1 wherein the amount of nicotine held by said cation exchanger and distributed in said chewing gum base is in the range of about 1 to about 5 milligrams, such amount of nicotine approximating that available upon smoking a cigarette.
3. A chewable substitute for smoking gum composition comprising 1. a chewing gum base and 2. nicotine, held by a saliva-insoluble cation exchanger, substantially uniformly distributed in said chewing gum base,
wherein:
A. the composition is in the form of a chewable gum unit weighing in the range of about 0.5 to about 4 grams;
B. the chewing gum base is present in said gum composition in an amount in the range of about 15 to about 80 weight percent of said gum composition;
C. the nicotine is present in said composition in an amount in the range of about 0.05 weight percent to about 2 weight percent based on the weight of the chewing gum base and calculated as the free base;
D. the amount of nicotine held by the cation exchanger and distributed in said chewing gum base is in the range of about 1 to about l0 milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product;
E. said nicotine-cation exchange complex constitutes I up to about percent by weight of said chewing gum composition;
F. the nicotine is present in said nicotine-cation exchange complex in an amount in the range of about 2 to about 60 percent by weight;
G. the nicotine held by said salivainsoluble cation exchanger being present in said gum composition as a nicotine-cation exchange complex which upon chewing liberates the nicotine cation, and
H. said chewing gum composition when chewed releasing nicotine in small and reduced amounts within a period of the first few minutes of chewing. and

Claims (8)

1. A CHEWABLE ''''SUBSTITUTE FOR SMOKING'''' GEM COMPOSITION COMPRISING
1. A CHEWING GUM BASE AND
2. NICOTINE, HELD BY A SALIVA-INSOLUBLE CATION EXCHANGER, WHEREIN THE CATION EXCHANGER IS SELECTED FROM THE GROUP CONSISTING OF A) METHACRYLIC TYPE, WEAKLY ACIDIC, CONTAINING CARBOXYLIC FUNCTIONAL GROUPS: B) POLYSTYRENE TYPE, STRONGLY ACIDIC, CONTAINING SULFONIC FUNCTIONAL GROUPS: AND C) POLYSTYRENE TYPE, HAVING INTERMEDIATE ACIDITY, CONTAINING PHOSPHONIC FUNCTIONAL GROUPS: SUBSTANTIALLY UNIFORMALY DISTRIBUTED IN SAID CHEWING GUM BASE, WHEREIN: A. THE COMPOSITION IS IN THE FORM OF A CHEWABLE GUM UNIT WEIGHING IN THE RANGE OF ABOUT 0.5 TO ABOUT 4 GRAMS: B. THE CHEWING GUM BASE IS PRESENT IN SAID GUM COMPOSITION IN AMOUNT IN THE RANGE OF ABOUT 15 TO ABOUT 80 WEIGHT PERCENT OF SAID GUM COMPOSITION: C. THE NICOTINE IS PRESENT IN SAID COMPOSITION IN AN AMOUNT IN THE RANGE OF ABOUT 0.05 WEIGHT PERCENT TO ABOUT 2 WEIGHT PERCENT BASED ON THE WEIGHT OF THE CHEWING GUM BASE AND CALCULATED AS THE FREE BASE: D. THE AMOUNT OF NICOTINE HELD BY THE CATION EXCHANGER AND DISTRIBUTED IN SAID CHEWING GUM BASE IS IN THE RANGE OF ABOUT 1 TO ABOUT 10 MILLIGRAMS, SUCH AMOUNT OF NICOTINE APPROXIMATING THE AMOUNT AVAILABLE UPON SMOKING A SMOKING TOBACCO PRODUCT, E. SAID NICOTINE-CATION EXCHANGE COMPLEX CONSTITUTFES UP TO ABOUT 10 PERCENT BY WEIGHT OF SAID CHEWING GUM COMPOSITION, F. THE NICOTINE IS PRESENT IN SAID NICOTINE-CATION EXCHANGE COMPLEX IN AN AMOUNT IN THE RANGE OF ABOUT 2 TO 60 PERCENT BY WEIGHT G. THE NICOTINE HELD BY SAID SILIVA-INSOLUBLE CATION EXCHANGER BEING PERCENT IN SAID GUM COMPOSITION AS A NICOTINE-CATION EXCHANGE COMPLEX WHICH UPON CHEWING LIBERATES THE NICOTINE CATION, AND H. SAID CHEWING GUM COMPOSITION WHEN CHEWING RELEASING NICOTINE IN SMALL AND REDUCED AMOUNT WITHIN A PERIOD OF THE FIRST FEW MINUTES OF CHEWING, AND I. ESPECIALLY WITHIN THE FIRST TEN MINUTES OF CHEWING RELEAAASIN THE NICOTINE AT A RATE LESS THAN IF THE NICOTINE WERE PRESENT BY ITSELF IN AN ORDINARY GUM COMPOSITION AND LESS THAN IF THE NICOTINE-CATION EXCHANGER COMPLEX WERE USED BY ITSELF ABSENT THE GUM.
2. The chewing gum composition of claim 1 wherein the amount of nicotine held by said cation exchanger and distributed in said chewing gum base is in the range of about 1 to about 5 milligrams, such amount of nicotine approximating that available upon smoking a cigarette.
2. nicotine, held by a saliva-insoluble cation exchanger, substantially uniformly distributed in said chewing gum base, wherein: A. the composition is in the form of a chewable gum unit weighing in the range of about 0.5 to about 4 grams; B. the chewing gum base is present in said gum composition in an amount in the range of about 15 to about 80 weight percent of said gum composition; C. the nicotine is present in said composition in an amount in the range of about 0.05 weight percent to about 2 weight percent based on the weight of the chewing gum base and calculated as the free base; D. the amount of nicotine held by the cation exchanger and distributed in said chewing gum base is in the range of about 1 to about 10 milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product; E. said nicotine-cation exchange complex constitutes up to about 10 percent by weight of said chewing gum composition; F. the nicotine is present in said nicotine-cation exchange complex in an amount in the range of about 2 to about 60 percent by weight; G. the nicotine held by said saliva-insoluble cation exchanger being present in said gum composition as a nicotine-cation exchange complex which upon chewing liberates the nicotine cation, and H. said chewing gum composition when chewed releasing nicotine in small and reduced amounts within a period of the first few minutes of chewing, and I. especially within the first ten minutes of chewing releasing the nicotine at a rate less than if the nicotine were present by itself in an ordinary gum composition and less than if the nicotine-cation exchanger complex were used by itself absent the gum.
2. nicotine, held by a saliva-insoluble cation exchanger, wherein the cation exchanger is selected from the group consisting of a) methacrylic type, weakly acidic, containing carboxylic functional groups; b) polystyrene type, strongly acidic, containing sulfonic functional groups; and c) polystyrene type, having intermediate acidity, containing phosphonic functional groups; substantially uniformly distributed in said chewing gum base, wherein: A. the composition is in the form of a chewable gum unit weighing in the range of about 0.5 to about 4 grams; B. the chewing gum base is present in said gum composition in an amount in the range of about 15 to about 80 weight percent of said gum composition; C. the nicotine is present in said composition in an amount in the range of about 0.05 weight percent to about 2 weight percent based on the weight of the chewing gum base and calculated as the free base; D. the amount of nicotine held by the cation exchanger and distributed in said chewing gum base is in the range of about 1 to about 10 milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product; E. said nicotine-cation exchange complex constitutes up to about 10 percent by wEight of said chewing gum composition; F. the nicotine is present in said nicotine-cation exchange complex in an amount in the range of about 2 to about 60 percent by weight; G. the nicotine held by said saliva-insoluble cation exchanger being present in said gum composition as a nicotine-cation exchanger complex which upon chewing liberates the nicotine cation, and H. said chewing gum composition when chewed releasing nicotine in small and reduced amounts within a period of the first few minutes of chewing, and I. especially within the first ten minutes of chewing releasing the nicotine at a rate less than if the nicotine were present by itself in an ordinary gum composition and less than if the nicotine-cation exchanger complex were used by itself absent the gum.
3. A chewable ''''substitute for smoking'''' gum composition comprising
4. The chewing gum composition of claim 3 wherein the amount of nicotine held by said cation exchanger and distributed in said chewing gum base is in the range of about 1 to about 5 milligrams, such amount of nicotine approximating that available upon smoking a cigarette.
US497557A 1970-07-22 1974-08-15 Chewable smoking substitute composition Expired - Lifetime US3901248A (en)

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Cited By (203)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3332429T1 (en) * 1982-02-22 1984-01-26 Belorusskij naučno-issledovatel'skij sanitarno-gigieničeskij institut, 220012 Minsk MEDICINAL PRODUCT WITH ANTINICOTINE EFFECT AND METHOD FOR THE PRODUCTION THEREOF
US4975270A (en) * 1987-04-21 1990-12-04 Nabisco Brands, Inc. Elastomer encased active ingredients
US5004610A (en) * 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5147654A (en) * 1990-07-23 1992-09-15 Alza Corporation Oral osmotic device for delivering nicotine
US5298257A (en) * 1987-05-01 1994-03-29 Elan Transdermal Limited Method for the treatment of withdrawal symptoms associated with smoking cessation and preparations for use in said method
WO1994008572A1 (en) * 1992-10-15 1994-04-28 Alza Corporation Delayed onset transdermal delivery device
US5387416A (en) * 1993-07-23 1995-02-07 R. J. Reynolds Tobacco Company Tobacco composition
LT3670B (en) 1989-11-07 1996-01-25 Anders Dam Stimulating preparation with nicotine
LT3722B (en) 1990-06-08 1996-02-26 Kabi Pharmacia Ab Nicotine - impermeable container and method of fabricating the same
EP0707478A1 (en) 1993-07-26 1996-04-24 Pharmacia & Upjohn Aktiebolag Improved nicotine lozenge and therapeutic method for smoking cessation
US5512306A (en) * 1992-06-19 1996-04-30 Pharmica Ab Smoking substitute
US5760049A (en) * 1997-02-21 1998-06-02 Synapse Pharmaceuticals International, Inc. Method for controlling tobacco use and alleviating withdrawal symptoms due to cessation of tobacco use
US5830904A (en) * 1997-02-05 1998-11-03 University Of Kentucky Research Foundation Lobeline compounds as a treatment for psychostimulant abuse and withdrawal, and for eating disorders
US5845647A (en) * 1996-06-28 1998-12-08 Regent Court Technologies Tobacco and related products
US5889028A (en) * 1996-02-09 1999-03-30 Mayo Foundation For Medical Education And Research Colonic delivery of nicotine to treat inflammatory bowel disease
US5939100A (en) * 1993-11-01 1999-08-17 Pharmacia And Upjohn Ab Composition for drug delivery comprising nicotine or a derivative thereof and starch microspheres and method for the manufacturing thereof
ES2141024A1 (en) * 1997-10-03 2000-03-01 Manzanares Jesus Mari Gonzalez Preparation with antinicotinic action.
WO2000013662A2 (en) 1998-09-03 2000-03-16 Jsr Llc Medicated chewing gum delivery system for nicotine
US6087376A (en) * 1997-02-05 2000-07-11 University Of Kentucky Research Foundation Use of lobeline compounds in the treatment of central nervous system diseases and pathologies
US6135121A (en) * 1996-06-28 2000-10-24 Regent Court Technologies Tobacco products having reduced nitrosamine content
US6166032A (en) * 1997-02-07 2000-12-26 Synapse Pharmaceuticals International, Inc. Method for controlling tobacco use and alleviating withdrawal symptoms due to cessation of tobacco use
US6202649B1 (en) 1996-12-02 2001-03-20 Regent Court Technologies Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US20010000386A1 (en) * 1999-04-26 2001-04-26 Peele David Mccray Tobacco processing
US6248760B1 (en) * 1999-04-14 2001-06-19 Paul C Wilhelmsen Tablet giving rapid release of nicotine for transmucosal administration
US6290985B2 (en) 1999-04-06 2001-09-18 Wm. Wrigley, Jr. Company Over-coated chewing gum formulations including tableted center
US6311695B1 (en) 1996-06-28 2001-11-06 Regent Court Technologies Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US6344222B1 (en) 1998-09-03 2002-02-05 Jsr Llc Medicated chewing gum delivery system for nicotine
US6355265B1 (en) 1999-04-06 2002-03-12 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6358060B2 (en) 1998-09-03 2002-03-19 Jsr Llc Two-stage transmucosal medicine delivery system for symptom relief
JP2002114682A (en) * 2000-07-27 2002-04-16 Rohm & Haas Co Method for loading nicotine into ion exchange resin under anhydrous condition
US6409991B1 (en) * 1999-12-15 2002-06-25 Mark Reynolds Treatment and system for nicotine withdrawal
US6444241B1 (en) 2000-08-30 2002-09-03 Wm. Wrigley Jr. Company Caffeine coated chewing gum product and process of making
WO2002102357A1 (en) 2001-06-20 2002-12-27 Pharmacia Ab A coated nicotine-containing chewing gum, manufacture and use thereof
US20030022912A1 (en) * 2001-02-08 2003-01-30 Martino Alice C. Rapid-onset medicament for treatment of sexual dysfunction
US20030031630A1 (en) * 2001-06-26 2003-02-13 Reznick Abraham Z. Methods, pharmaceutical compositions, oral compositions,filters and tobacco products for preventing or reducing tobacco smoke-associated injury in the aerodigestive tract of a subject
US6531114B1 (en) 1999-04-06 2003-03-11 Wm. Wrigley Jr. Company Sildenafil citrate chewing gum formulations and methods of using the same
US6541048B2 (en) 1999-09-02 2003-04-01 Wm. Wrigley Jr. Company Coated chewing gum products containing an acid blocker and process of preparing
US20030087937A1 (en) * 2001-10-15 2003-05-08 Nils-Olof Lindberg Nicotine and cocoa powder compositions
USRE38123E1 (en) 1996-06-28 2003-05-27 Regent Court Technologies, Llc. Tobacco products having reduced nitrosamine content
US6569472B1 (en) 2000-09-01 2003-05-27 Wm. Wrigley Jr. Company Coated chewing gum products containing antacid and method of making
US6572900B1 (en) 2000-06-09 2003-06-03 Wm. Wrigley, Jr. Company Method for making coated chewing gum products including a high-intensity sweetener
US6579545B2 (en) 2000-12-22 2003-06-17 Wm. Wrigley Jr. Company Coated chewing gum products containing an antigas agent
US6586023B1 (en) 1998-12-15 2003-07-01 Wm. Wrigley Jr. Company Process for controlling release of active agents from a chewing gum coating and product thereof
US6586449B1 (en) * 2002-05-28 2003-07-01 Cambrex Charles City, Inc. Nicotine-containing, controlled release composition and method
US6627234B1 (en) 1998-12-15 2003-09-30 Wm. Wrigley Jr. Company Method of producing active agent coated chewing gum products
US6645535B2 (en) 1999-09-02 2003-11-11 Wm. Wrigley Jr. Company Method of making coated chewing gum products containing various antacids
US6663849B1 (en) 2000-09-01 2003-12-16 Wm. Wrigley Jr. Company Antacid chewing gum products coated with high viscosity materials
US20040020503A1 (en) * 2001-05-01 2004-02-05 Williams Jonnie R. Smokeless tobacco product
US20040034068A1 (en) * 2002-06-03 2004-02-19 Woodcock Washburn Llp New formulation and use thereof
GB2393392A (en) * 2002-09-17 2004-03-31 Abhijit De Betel nut and nicotine chewing gum
US6749882B2 (en) 2000-05-17 2004-06-15 Stephen Fortune, Jr. Coffee having a nicotine composition dissolved therein
US6773716B2 (en) 1999-04-06 2004-08-10 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US20040158747A1 (en) * 2003-02-08 2004-08-12 Kim Han-Jong Processor having high-speed control circuit and low-speed and low-power control circuit and method of using the same
US20040248946A1 (en) * 2001-12-10 2004-12-09 Knight Joseph R Beverage treated with nicotine
WO2005053691A2 (en) * 2003-12-02 2005-06-16 Fertin Pharma A/S Nicotine delivery product and method for producing it
US6949264B1 (en) 1996-11-27 2005-09-27 Wm. Wrigley Jr. Company Nutraceuticals or nutritional supplements and method of making
US20060073189A1 (en) * 2000-05-19 2006-04-06 Npd, Llc Chewing gums, lozenges, candies, tablets, liquids, and sprays for efficient delivery of medications and dietary supplements
US20060105023A1 (en) * 2001-12-10 2006-05-18 Knight Joseph R Treatment of neurological disorders with nicotine
US20060130857A1 (en) * 2004-09-30 2006-06-22 Roth Brett J Device, method, and composition for reducing the incidence of tobacco smoking
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
WO2006128468A1 (en) * 2005-06-01 2006-12-07 Fertin Pharma A/S A method of manufacturing a nicotine delivery product
US20060275344A1 (en) * 2005-05-18 2006-12-07 Seema Mody Flavoring of drug-containing chewing gums
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
USRE39588E1 (en) 1987-11-09 2007-04-24 Alza Corporation Transdermal drug delivery device
US20070144544A1 (en) * 2005-09-30 2007-06-28 Cai David J Oral composition and method for stress reduction associated with smoking cessation
US20070163610A1 (en) * 2002-01-21 2007-07-19 Pharmacia Ab Formulation and Use and Manufacture Thereof
US20070269386A1 (en) * 2006-05-16 2007-11-22 Per Steen New product and use and manufacture thereof
US20070269492A1 (en) * 2006-05-16 2007-11-22 Per Steen New product and use and manufacture thereof
US20080020050A1 (en) * 2006-07-21 2008-01-24 Chau Tommy L Medicinal delivery system, and related methods
US20080124283A1 (en) * 2004-11-30 2008-05-29 Carsten Andersen Method of Providing Fast Relief to a User of a Nicotine Chewing Gum
US20080226579A1 (en) * 2005-09-21 2008-09-18 Chong Kun Dang Pharmaceutical Corp. Novel Resinate Complex of S-Clopidogrel and Production Method Thereof
US20080286341A1 (en) * 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered coated nicotine containing products
US20080286340A1 (en) * 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered nicotine containing products
US20090130189A1 (en) * 2004-03-19 2009-05-21 Pfizer Health Ab Means for transdermal administration of nicotine
US20100124560A1 (en) * 2008-11-14 2010-05-20 Mcneil Ab Multi portion intra-oral dosage form and use thereof
US20100130562A1 (en) * 2008-11-25 2010-05-27 Watson Laboratories, Inc. Stabilized Nicotine Chewing Gum
EP2198865A1 (en) 2008-12-19 2010-06-23 Siegfried Ltd. Nicotine-containing product
US20100154810A1 (en) * 2008-12-23 2010-06-24 Williams Jonnie R Tobacco Curing Method
EP2233134A1 (en) 2009-03-27 2010-09-29 McNeil AB Multi-portion intra-oral dosage form with organoleptic properties
US20100247586A1 (en) * 2009-03-27 2010-09-30 Andreas Hugerth Multi-Portion Intra-Oral Dosage Form With Organoleptic Properties
US20100260690A1 (en) * 2007-09-18 2010-10-14 Arne Kristensen Stable chewing gum compositions comprising maltitol and providing rapid release of nicotine
US7935362B2 (en) 1999-04-06 2011-05-03 Wm. Wrigley Jr. Company Over-coated product including consumable center and medicament
US20110214681A1 (en) * 2008-09-17 2011-09-08 Niconovum Ab Process for preparing snuff composition
WO2011119722A2 (en) 2010-03-23 2011-09-29 Rock Creek Pharmaceuticals, Inc. Use of anatabine to treat inflammation and methods of synthesizing anatabine
WO2011139684A2 (en) 2010-04-28 2011-11-10 Niconovum Usa, Inc. Nicotine-containing pharmaceutical compositions
WO2011139811A1 (en) 2010-05-07 2011-11-10 Niconovum Usa, Inc. Nicotine-containing pharmaceutical compositions
WO2012083947A1 (en) 2010-12-21 2012-06-28 Fertin Pharma A/S Chewing gum composition comprising cross-linked polyacrylic acid
US8241680B2 (en) 2010-06-30 2012-08-14 Rock Creek Pharmaceuticals, Inc. Nutraceutical product containing anatabine and yerba maté
WO2013043866A1 (en) 2011-09-22 2013-03-28 Niconovum Usa, Inc. Nicotine-containing pharmaceutical composition
WO2013059592A1 (en) 2011-10-21 2013-04-25 Niconovum Usa, Inc. Excipients for nicotine-containing therapeutic compositions
WO2013119760A1 (en) 2012-02-10 2013-08-15 Niconovum Usa, Inc. Multi-layer nicotine-containing pharmaceutical composition
US8529875B2 (en) 2004-06-29 2013-09-10 Fertin Pharma A/S Tobacco alkaloid releasing chewing gum
WO2013158643A2 (en) 2012-04-17 2013-10-24 R. J. Reynolds Tobacco Company Remelted ingestible products
US8679522B2 (en) 1999-09-20 2014-03-25 Jack Barreca Chewing gum
US8728444B2 (en) 2010-05-31 2014-05-20 Fertin Pharma A/S Formulation comprising nicotine and a cation exchange resin
US8728443B2 (en) 2010-05-31 2014-05-20 Fertin Pharma A/S Formulation comprising nicotine and a cation exchange resin
WO2014164509A1 (en) 2013-03-11 2014-10-09 Niconovum Usa, Inc. Method and apparatus for differentiating oral pouch products
US9084439B2 (en) 2011-09-22 2015-07-21 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
WO2015179388A1 (en) 2014-05-20 2015-11-26 R. J. Reynolds Tobacco Company Electrically-powered aerosol delivery system
US9253991B2 (en) 1999-09-20 2016-02-09 Jack Barreca Chewing gum with B vitamins
WO2016040754A1 (en) 2014-09-12 2016-03-17 R. J. Reynolds Tobacco Company Nonwoven pouch comprising heat sealable binder fiber
WO2016090075A1 (en) 2014-12-05 2016-06-09 R. J. Reynolds Tobacco Company Smokeless tobacco pouch
US9387201B2 (en) 2011-08-29 2016-07-12 Rcp Development, Inc. Methods of providing anti-inflammation support
US9387168B2 (en) 1999-09-20 2016-07-12 Jack Barreca Chewing gum with tomatidine
US9402809B2 (en) 2006-03-16 2016-08-02 Niconovum Usa, Inc. Snuff composition
US9474303B2 (en) 2011-09-22 2016-10-25 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
WO2017004185A2 (en) 2015-06-30 2017-01-05 R. J. Reynolds Tobacco Company Heat generation segment for an aerosol-generation system of a smoking article
US9629832B2 (en) 2002-12-20 2017-04-25 Niconovum Usa, Inc. Physically and chemically stable nicotine-containing particulate material
US9629392B2 (en) 2011-09-22 2017-04-25 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
WO2017093941A1 (en) 2015-12-03 2017-06-08 Niconovum Usa, Inc. Multi-phase delivery compositions and products incorporating such compositions
WO2017098443A1 (en) 2015-12-10 2017-06-15 Niconovum Usa, Inc. Protein-enriched therapeutic composition of a nicotinic compound
WO2017182084A1 (en) 2016-04-21 2017-10-26 Fertin Pharma A/S Nicotine delivery product, related uses and oral dosage forms, and methods of production
WO2017200740A1 (en) 2016-05-16 2017-11-23 Cv Sciences, Inc. Pharmaceutical formulations containing cannabidiol and nicotine for treating smokeless tobacco addiction
WO2018015910A2 (en) 2016-07-21 2018-01-25 Rai Strategic Holdings, Inc. Aerosol delivery device with a liquid transport element comprising a porous monolith and related method
WO2018015889A1 (en) 2016-07-21 2018-01-25 Rai Strategic Holdings, Inc. Aerosol delivery device with a unitary reservoir and liquid transport element comprising a porous monolith and related method
WO2018055558A1 (en) 2016-09-23 2018-03-29 Rai Strategic Holdings, Inc. An aerosol delivery device with replaceable wick and heater assembly
WO2018211390A1 (en) 2017-05-17 2018-11-22 Rai Strategic Holdings, Inc. Aerosol delivery device
WO2018219650A1 (en) 2017-05-30 2018-12-06 Enorama Pharma Ab Nicotine-containing chewing gum compositions
US10213438B2 (en) 2014-11-18 2019-02-26 Mymd Pharmaceuticals, Inc. Alkaloid compounds for treating depression, substance addictions, and indications associated with chronic inflammation
DE102018221520A1 (en) 2017-12-13 2019-06-13 Mymd Pharmaceuticals, Inc. Genetically modified tobacco
WO2019116276A1 (en) 2017-12-15 2019-06-20 Rai Strategic Holdings, Inc. Aerosol delivery device with multiple aerosol delivery pathways
US10368576B2 (en) 2014-03-28 2019-08-06 British American Tobacco (Investments) Limited Additive carrying composition
WO2019239356A1 (en) 2018-06-15 2019-12-19 R. J. Reynolds Tobacco Company Purification of nicotine
US10555558B2 (en) 2017-12-29 2020-02-11 Rai Strategic Holdings, Inc. Aerosol delivery device providing flavor control
WO2020053766A1 (en) 2018-09-11 2020-03-19 Rai Strategic Holdings, Inc. Wicking element for aerosol delivery device
WO2021048792A1 (en) 2019-09-11 2021-03-18 R. J. Reynolds Tobacco Company Oral product with cellulosic flavor stabilizer
WO2021048791A1 (en) 2019-09-11 2021-03-18 R. J. Reynolds Tobacco Company Pouched products with enhanced flavor stability
WO2021069044A1 (en) 2019-10-11 2021-04-15 Fertin Pharma A/S An ion-exchange composition with water-soluble mucoadhesive polymers
WO2021086367A1 (en) 2019-10-31 2021-05-06 Nicoventures Trading Limited Oral product and method of manufacture
WO2021116884A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Layered fleece for pouched product
WO2021116895A2 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Stimulus-responsive pouch
WO2021116917A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with nanocrystalline cellulose
WO2021116822A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with reduced irritation
WO2021116868A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with controlled release
WO2021116890A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Liquid composition for oral use or for use in an aerosol delivery device
WO2021116865A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Agents for oral composition
WO2021116853A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Fibrous fleece material
WO2021116834A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Nanoemulsion for oral use
WO2021116887A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Lipid-containing oral composition
WO2021116825A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product
WO2021116894A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Pouched products with heat sealable binder
WO2021116862A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions with reduced water content
WO2021116878A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with improved binding of active ingredients
WO2021116879A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with beet material
WO2021116854A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with active ingredient combinations
WO2021116841A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Moist oral compositions
WO2021116866A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Pouched products with enhanced flavor stability
WO2021116876A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with salt inclusion
WO2021116881A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product in a pourous pouch comprising a fleece material
WO2021116893A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product and method of manufacture
WO2021116824A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product comprising a cannabinoid
WO2021116892A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions with reduced water activity
WO2021116856A2 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products
WO2021116842A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with controlled release
WO2021116919A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Fleece for oral product with releasable component
WO2021116827A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Process
WO2021116916A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product with multiple flavors having different release profiles
WO2021116914A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with polymeric component
WO2021116867A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Buffered oral compositions
WO2021116855A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions and methods of manufacture
WO2021116891A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral foam composition
WO2021116918A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions including gels
WO2021116823A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product
WO2021116852A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product with dissolvable component
WO2021116837A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Pouched products
WO2021171185A1 (en) 2020-02-24 2021-09-02 Nicoventures Trading Limited Beaded tobacco material and related method of manufacture
WO2021250516A1 (en) 2020-06-08 2021-12-16 Nicoventures Trading Limited Effervescent oral composition comprising an active ingredient
WO2022043700A1 (en) 2020-08-27 2022-03-03 Nicoventures Trading Limited Oral product
WO2022043919A1 (en) 2020-08-27 2022-03-03 Rai Strategic Holdings, Inc. Aerosol delivery device
WO2022043666A1 (en) 2020-08-27 2022-03-03 Nicoventures Trading Limited Consumable
WO2022053982A1 (en) 2020-09-11 2022-03-17 Nicoventures Trading Limited Alginate-based substrates
WO2022074566A1 (en) 2020-10-07 2022-04-14 Nicoventures Trading Limited Methods of making tobacco-free substrates for aerosol delivery devices
WO2022107031A1 (en) 2020-11-19 2022-05-27 Nicoventures Trading Limited Oral products
WO2022112949A1 (en) 2020-11-25 2022-06-02 Nicoventures Trading Limited Oral cannabinoid product with lipid component
WO2022162558A1 (en) 2021-01-28 2022-08-04 Nicoventures Trading Limited Method for sealing pouches
WO2022189977A1 (en) 2021-03-09 2022-09-15 Nicoventures Trading Limited Oral products and methods of manufacture
EP4059365A1 (en) 2015-11-24 2022-09-21 R. J. Reynolds Tobacco Company Electrically-powered aerosol delivery system
RU2782018C1 (en) * 2021-11-26 2022-10-21 Леонид Борисович Потёмкин Remedy for those quitting smoking
WO2022224198A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Oral lozenge products
WO2022224197A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Effervescent oral composition
WO2022224196A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Orally dissolving films
WO2022224200A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Oral compositions and methods of manufacture
WO2022229926A1 (en) 2021-04-30 2022-11-03 Nicoventures Trading Limited Multi-compartment oral pouched product
WO2022229929A1 (en) 2021-04-30 2022-11-03 Nicoventures Trading Limited Oral products with high-density load
WO2022264066A1 (en) 2021-06-16 2022-12-22 Nicoventures Trading Limited Pouched product comprising dissolvable composition
WO2022269556A1 (en) 2021-06-25 2022-12-29 Nicoventures Trading Limited Oral products and method of manufacture
WO2022269475A1 (en) 2021-06-21 2022-12-29 Nicoventures Trading Limited Oral product tablet and method of manufacture
WO2023281469A1 (en) 2021-07-09 2023-01-12 Nicoventures Trading Limited Extruded structures
WO2023002199A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Composition comprising a constituent, derivative or extract of cannabis
WO2023002201A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising constituents, derivatives or extracts of cannabis
WO2023002198A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising a constituent, derivative or extract of cannabis
WO2023002196A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Constituent, derivative or extract of cannabis in a water soluble matrix
WO2023002200A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Constituent, derivative or extract of cannabis in amorphous form
WO2023002194A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising constituents, derivatives or extracts of cannabis
WO2023002195A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Methods of preparing compositions comprising a constituent, derivative or extract of cannabis
WO2023002197A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising a constituent, derivative or extract of cannabis
WO2023053060A1 (en) 2021-09-30 2023-04-06 Nicoventures Trading Limited Oral gum composition
WO2023084498A1 (en) 2021-11-15 2023-05-19 Nicoventures Trading Limited Oral products with nicotine-polymer complex
WO2023084499A1 (en) 2021-11-15 2023-05-19 Nicoventures Trading Limited Products with enhanced sensory characteristics
WO2023106407A1 (en) * 2021-12-09 2023-06-15 日本たばこ産業株式会社 Composition for oral cavity and pouch product for oral cavity
WO2023119134A1 (en) 2021-12-20 2023-06-29 Nicoventures Trading Limited Substrate material comprising beads for aerosol delivery devices
WO2023187675A1 (en) 2022-03-31 2023-10-05 R. J. Reynolds Tobacco Company Agglomerated botanical material for oral products
WO2023194959A1 (en) 2022-04-06 2023-10-12 Nicoventures Trading Limited Pouched products with heat sealable binder

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US904521A (en) * 1908-04-20 1908-11-24 Carleton Ellis Masticable tobacco substitute.
US2341986A (en) * 1941-03-27 1944-02-15 Nat Agrol Company Therapeutic confection
US2600700A (en) * 1949-03-08 1952-06-17 Colburn J Smith Composition for alleviation of the tobacco habit
US2990332A (en) * 1958-04-02 1961-06-27 Wallace & Tiernan Inc Pharmaceutical preparations comprising cation exchange resin adsorption compounds and treatment therewith
US3003920A (en) * 1956-08-02 1961-10-10 William E Dominick Chewing gum preparation
US3109436A (en) * 1961-11-02 1963-11-05 Bavley Abraham Tobacco products
US3368567A (en) * 1965-03-23 1968-02-13 Morton Pharmaceuticals Inc Method of producing a tablet containing a tobacco concentrate

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US904521A (en) * 1908-04-20 1908-11-24 Carleton Ellis Masticable tobacco substitute.
US2341986A (en) * 1941-03-27 1944-02-15 Nat Agrol Company Therapeutic confection
US2600700A (en) * 1949-03-08 1952-06-17 Colburn J Smith Composition for alleviation of the tobacco habit
US3003920A (en) * 1956-08-02 1961-10-10 William E Dominick Chewing gum preparation
US2990332A (en) * 1958-04-02 1961-06-27 Wallace & Tiernan Inc Pharmaceutical preparations comprising cation exchange resin adsorption compounds and treatment therewith
US3109436A (en) * 1961-11-02 1963-11-05 Bavley Abraham Tobacco products
US3368567A (en) * 1965-03-23 1968-02-13 Morton Pharmaceuticals Inc Method of producing a tablet containing a tobacco concentrate

Cited By (284)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4971079A (en) * 1982-02-22 1990-11-20 Talapin Vitaly I Pharmaceutical preparation possessing antinicotine effect and method of producing same in a gum carrier
DE3332429T1 (en) * 1982-02-22 1984-01-26 Belorusskij naučno-issledovatel'skij sanitarno-gigieničeskij institut, 220012 Minsk MEDICINAL PRODUCT WITH ANTINICOTINE EFFECT AND METHOD FOR THE PRODUCTION THEREOF
US4975270A (en) * 1987-04-21 1990-12-04 Nabisco Brands, Inc. Elastomer encased active ingredients
US5298257A (en) * 1987-05-01 1994-03-29 Elan Transdermal Limited Method for the treatment of withdrawal symptoms associated with smoking cessation and preparations for use in said method
USRE39588E1 (en) 1987-11-09 2007-04-24 Alza Corporation Transdermal drug delivery device
US5633008A (en) * 1988-06-14 1997-05-27 Osborne; James L. Method of administering nicotine transdermally
US5004610A (en) * 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US6165497A (en) * 1988-06-14 2000-12-26 Alza Corporation Subsaturated nicotine transdermal therapeutic system
LT3670B (en) 1989-11-07 1996-01-25 Anders Dam Stimulating preparation with nicotine
US5543424A (en) * 1989-12-21 1996-08-06 Pharmacia Ab Smoking substitute
LT3722B (en) 1990-06-08 1996-02-26 Kabi Pharmacia Ab Nicotine - impermeable container and method of fabricating the same
US5147654A (en) * 1990-07-23 1992-09-15 Alza Corporation Oral osmotic device for delivering nicotine
US5512306A (en) * 1992-06-19 1996-04-30 Pharmica Ab Smoking substitute
WO1994008572A1 (en) * 1992-10-15 1994-04-28 Alza Corporation Delayed onset transdermal delivery device
US5387416A (en) * 1993-07-23 1995-02-07 R. J. Reynolds Tobacco Company Tobacco composition
EP0707478A1 (en) 1993-07-26 1996-04-24 Pharmacia & Upjohn Aktiebolag Improved nicotine lozenge and therapeutic method for smoking cessation
US5939100A (en) * 1993-11-01 1999-08-17 Pharmacia And Upjohn Ab Composition for drug delivery comprising nicotine or a derivative thereof and starch microspheres and method for the manufacturing thereof
US5889028A (en) * 1996-02-09 1999-03-30 Mayo Foundation For Medical Education And Research Colonic delivery of nicotine to treat inflammatory bowel disease
US6166044A (en) * 1996-02-09 2000-12-26 Mayo Foundation For Medical Education And Research Colonic delivery of nicotine to treat inflammatory bowel disease
US6338348B1 (en) 1996-06-28 2002-01-15 Regent Court Technologies Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US5845647A (en) * 1996-06-28 1998-12-08 Regent Court Technologies Tobacco and related products
USRE38123E1 (en) 1996-06-28 2003-05-27 Regent Court Technologies, Llc. Tobacco products having reduced nitrosamine content
US6135121A (en) * 1996-06-28 2000-10-24 Regent Court Technologies Tobacco products having reduced nitrosamine content
US6311695B1 (en) 1996-06-28 2001-11-06 Regent Court Technologies Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US6949264B1 (en) 1996-11-27 2005-09-27 Wm. Wrigley Jr. Company Nutraceuticals or nutritional supplements and method of making
US20020174874A1 (en) * 1996-12-02 2002-11-28 Regent Court Technologies Llc Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US6425401B1 (en) 1996-12-02 2002-07-30 Regent Court Technologies Llc Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US6202649B1 (en) 1996-12-02 2001-03-20 Regent Court Technologies Method of treating tobacco to reduce nitrosamine content, and products produced thereby
US5830904A (en) * 1997-02-05 1998-11-03 University Of Kentucky Research Foundation Lobeline compounds as a treatment for psychostimulant abuse and withdrawal, and for eating disorders
US6087376A (en) * 1997-02-05 2000-07-11 University Of Kentucky Research Foundation Use of lobeline compounds in the treatment of central nervous system diseases and pathologies
US6166032A (en) * 1997-02-07 2000-12-26 Synapse Pharmaceuticals International, Inc. Method for controlling tobacco use and alleviating withdrawal symptoms due to cessation of tobacco use
US5760049A (en) * 1997-02-21 1998-06-02 Synapse Pharmaceuticals International, Inc. Method for controlling tobacco use and alleviating withdrawal symptoms due to cessation of tobacco use
ES2141024A1 (en) * 1997-10-03 2000-03-01 Manzanares Jesus Mari Gonzalez Preparation with antinicotinic action.
WO2000013662A2 (en) 1998-09-03 2000-03-16 Jsr Llc Medicated chewing gum delivery system for nicotine
US20050214229A1 (en) * 1998-09-03 2005-09-29 Jsr, Llc Two-stage transmucosal medicine delivery system for symptom relief
US6358060B2 (en) 1998-09-03 2002-03-19 Jsr Llc Two-stage transmucosal medicine delivery system for symptom relief
US6344222B1 (en) 1998-09-03 2002-02-05 Jsr Llc Medicated chewing gum delivery system for nicotine
US6627234B1 (en) 1998-12-15 2003-09-30 Wm. Wrigley Jr. Company Method of producing active agent coated chewing gum products
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
US6592850B2 (en) 1998-12-15 2003-07-15 Wm. Wrigley Jr. Company Sildenafil citrate chewing gum formulations and methods of using the same
US6586023B1 (en) 1998-12-15 2003-07-01 Wm. Wrigley Jr. Company Process for controlling release of active agents from a chewing gum coating and product thereof
US6290985B2 (en) 1999-04-06 2001-09-18 Wm. Wrigley, Jr. Company Over-coated chewing gum formulations including tableted center
US6465003B2 (en) 1999-04-06 2002-10-15 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6322806B1 (en) 1999-04-06 2001-11-27 Wm. Wrigley Jr. Company Over-coated chewing gum formulations including tableted center
US7935362B2 (en) 1999-04-06 2011-05-03 Wm. Wrigley Jr. Company Over-coated product including consumable center and medicament
US6773716B2 (en) 1999-04-06 2004-08-10 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6531114B1 (en) 1999-04-06 2003-03-11 Wm. Wrigley Jr. Company Sildenafil citrate chewing gum formulations and methods of using the same
US6355265B1 (en) 1999-04-06 2002-03-12 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6558692B2 (en) 1999-04-06 2003-05-06 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6248760B1 (en) * 1999-04-14 2001-06-19 Paul C Wilhelmsen Tablet giving rapid release of nicotine for transmucosal administration
US6895974B2 (en) 1999-04-26 2005-05-24 R. J. Reynolds Tobacco Company Tobacco processing
US20030047190A1 (en) * 1999-04-26 2003-03-13 Peele David Mccray Tobacco processing
US6805134B2 (en) 1999-04-26 2004-10-19 R. J. Reynolds Tobacco Company Tobacco processing
US20050022832A1 (en) * 1999-04-26 2005-02-03 Peele David Mccray Tobacco processing
US7404406B2 (en) 1999-04-26 2008-07-29 R. J. Reynolds Tobacco Company Tobacco processing
US20010000386A1 (en) * 1999-04-26 2001-04-26 Peele David Mccray Tobacco processing
US6541048B2 (en) 1999-09-02 2003-04-01 Wm. Wrigley Jr. Company Coated chewing gum products containing an acid blocker and process of preparing
US6645535B2 (en) 1999-09-02 2003-11-11 Wm. Wrigley Jr. Company Method of making coated chewing gum products containing various antacids
US8679522B2 (en) 1999-09-20 2014-03-25 Jack Barreca Chewing gum
US9253991B2 (en) 1999-09-20 2016-02-09 Jack Barreca Chewing gum with B vitamins
US9387168B2 (en) 1999-09-20 2016-07-12 Jack Barreca Chewing gum with tomatidine
US6409991B1 (en) * 1999-12-15 2002-06-25 Mark Reynolds Treatment and system for nicotine withdrawal
US6749882B2 (en) 2000-05-17 2004-06-15 Stephen Fortune, Jr. Coffee having a nicotine composition dissolved therein
US20060073189A1 (en) * 2000-05-19 2006-04-06 Npd, Llc Chewing gums, lozenges, candies, tablets, liquids, and sprays for efficient delivery of medications and dietary supplements
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
US6572900B1 (en) 2000-06-09 2003-06-03 Wm. Wrigley, Jr. Company Method for making coated chewing gum products including a high-intensity sweetener
JP2002114682A (en) * 2000-07-27 2002-04-16 Rohm & Haas Co Method for loading nicotine into ion exchange resin under anhydrous condition
US6607752B2 (en) * 2000-07-27 2003-08-19 Rohm And Haas Company Method for the anhydrous loading of nicotine onto ion exchange resins
US6444241B1 (en) 2000-08-30 2002-09-03 Wm. Wrigley Jr. Company Caffeine coated chewing gum product and process of making
US6569472B1 (en) 2000-09-01 2003-05-27 Wm. Wrigley Jr. Company Coated chewing gum products containing antacid and method of making
US6663849B1 (en) 2000-09-01 2003-12-16 Wm. Wrigley Jr. Company Antacid chewing gum products coated with high viscosity materials
US6579545B2 (en) 2000-12-22 2003-06-17 Wm. Wrigley Jr. Company Coated chewing gum products containing an antigas agent
US20030022912A1 (en) * 2001-02-08 2003-01-30 Martino Alice C. Rapid-onset medicament for treatment of sexual dysfunction
US20040020503A1 (en) * 2001-05-01 2004-02-05 Williams Jonnie R. Smokeless tobacco product
US20040194793A1 (en) * 2001-06-20 2004-10-07 Lindell Katarina E.A. Coated nicotine-containing chewing gum, manufacture and use thereof
WO2002102357A1 (en) 2001-06-20 2002-12-27 Pharmacia Ab A coated nicotine-containing chewing gum, manufacture and use thereof
US20030031630A1 (en) * 2001-06-26 2003-02-13 Reznick Abraham Z. Methods, pharmaceutical compositions, oral compositions,filters and tobacco products for preventing or reducing tobacco smoke-associated injury in the aerodigestive tract of a subject
US20050084459A1 (en) * 2001-06-26 2005-04-21 Reznick Abraham Z. Filters for preventing or reducing tobacco smoke-associated injury in the aerodigestive tract of a subject
US6789546B2 (en) 2001-06-26 2004-09-14 Technion Research & Development Foundation Ltd. Filters for preventing or reducing tobacco smoke-associated injury in the aerodigestive tract of a subject
US20030087937A1 (en) * 2001-10-15 2003-05-08 Nils-Olof Lindberg Nicotine and cocoa powder compositions
US20040248946A1 (en) * 2001-12-10 2004-12-09 Knight Joseph R Beverage treated with nicotine
US7435749B2 (en) 2001-12-10 2008-10-14 Knight Joseph R Beverage treated with nicotine
US20060105023A1 (en) * 2001-12-10 2006-05-18 Knight Joseph R Treatment of neurological disorders with nicotine
US20100063111A1 (en) * 2002-01-21 2010-03-11 Lindell Katarina E A Formulation and use and manufacture thereof
US20070163610A1 (en) * 2002-01-21 2007-07-19 Pharmacia Ab Formulation and Use and Manufacture Thereof
EP1549633A1 (en) * 2002-05-28 2005-07-06 Cambrex Charles City, Inc. Nicotine-containing, controlled release composition and method
US20030224048A1 (en) * 2002-05-28 2003-12-04 Walling John A. Nicotine-containing, controlled release composition and method
EP1549633A4 (en) * 2002-05-28 2007-04-04 Cambrex Charles City Inc Nicotine-containing, controlled release composition and method
US6828336B2 (en) * 2002-05-28 2004-12-07 Cambrex Charles City, Inc. Nicotine-containing, controlled release composition and method
US6586449B1 (en) * 2002-05-28 2003-07-01 Cambrex Charles City, Inc. Nicotine-containing, controlled release composition and method
WO2003101982A1 (en) * 2002-05-28 2003-12-11 Cambrex Charles City, Inc. Nicotine-containing, controlled release composition and method
US7767698B2 (en) 2002-06-03 2010-08-03 Mcneil Ab Formulation and use thereof
US20100260688A1 (en) * 2002-06-03 2010-10-14 Warchol Mark P New Formulation and Use Thereof
US20040034068A1 (en) * 2002-06-03 2004-02-19 Woodcock Washburn Llp New formulation and use thereof
US8642627B2 (en) 2002-06-03 2014-02-04 Mcneil Ab Formulation and use thereof
GB2393392A (en) * 2002-09-17 2004-03-31 Abhijit De Betel nut and nicotine chewing gum
US9629832B2 (en) 2002-12-20 2017-04-25 Niconovum Usa, Inc. Physically and chemically stable nicotine-containing particulate material
US20040158747A1 (en) * 2003-02-08 2004-08-12 Kim Han-Jong Processor having high-speed control circuit and low-speed and low-power control circuit and method of using the same
WO2005053691A2 (en) * 2003-12-02 2005-06-16 Fertin Pharma A/S Nicotine delivery product and method for producing it
US8741935B2 (en) 2003-12-02 2014-06-03 Fertin Pharma A/S Nicotine delivery product and method for producing it
WO2005053691A3 (en) * 2003-12-02 2005-07-14 Fertin Pharma As Nicotine delivery product and method for producing it
US9801408B2 (en) 2003-12-02 2017-10-31 Fertin Pharma A/S Nicotine delivery product and method for producing it
US20090130189A1 (en) * 2004-03-19 2009-05-21 Pfizer Health Ab Means for transdermal administration of nicotine
US8828361B2 (en) 2004-06-29 2014-09-09 Fertin Pharma A/S Tobacco alkaloid releasing chewing gum
US8529875B2 (en) 2004-06-29 2013-09-10 Fertin Pharma A/S Tobacco alkaloid releasing chewing gum
US8733368B2 (en) 2004-09-30 2014-05-27 Smoke-Break, Inc. Device, method and compositions for reducing the incidence of tobacco smoking
US8662087B2 (en) 2004-09-30 2014-03-04 Smoke-Break, Inc. Device, method, and composition for reducing the incidence of tobacco smoking
US20060130857A1 (en) * 2004-09-30 2006-06-22 Roth Brett J Device, method, and composition for reducing the incidence of tobacco smoking
US7766018B2 (en) 2004-09-30 2010-08-03 Smoke-Break, Inc. Device and composition for reducing the incidence of tobacco smoking
US20100275938A1 (en) * 2004-09-30 2010-11-04 Roth Brett J Device, Method and Compositions For Reducing the Incidence of Tobacco Smoking
US8858919B2 (en) 2004-11-30 2014-10-14 Fertin Pharma A/S Method of providing fast relief to a user of a nicotine chewing gum
US8524196B2 (en) 2004-11-30 2013-09-03 Fertin Pharma A/S Method of providing fast relief to a user of a nicotine chewing gum
US20080124283A1 (en) * 2004-11-30 2008-05-29 Carsten Andersen Method of Providing Fast Relief to a User of a Nicotine Chewing Gum
US8658200B2 (en) 2005-05-18 2014-02-25 Mcneil-Ppc, Inc. Flavoring of drug-containing chewing gums
US8323683B2 (en) 2005-05-18 2012-12-04 Mcneil-Ppc, Inc. Flavoring of drug-containing chewing gums
US20060275344A1 (en) * 2005-05-18 2006-12-07 Seema Mody Flavoring of drug-containing chewing gums
WO2006128468A1 (en) * 2005-06-01 2006-12-07 Fertin Pharma A/S A method of manufacturing a nicotine delivery product
US8986668B2 (en) 2005-06-01 2015-03-24 Fertin Pharma A/S Method of manufacturing a nicotine delivery product
US20080226579A1 (en) * 2005-09-21 2008-09-18 Chong Kun Dang Pharmaceutical Corp. Novel Resinate Complex of S-Clopidogrel and Production Method Thereof
US20070144544A1 (en) * 2005-09-30 2007-06-28 Cai David J Oral composition and method for stress reduction associated with smoking cessation
US9402809B2 (en) 2006-03-16 2016-08-02 Niconovum Usa, Inc. Snuff composition
US11547660B2 (en) 2006-03-16 2023-01-10 Niconovum Usa, Inc. Snuff composition
US11129792B2 (en) 2006-03-16 2021-09-28 Modoral Brands Inc. Snuff composition
US10219999B2 (en) 2006-03-16 2019-03-05 Niconovum Usa, Inc. Snuff composition
US20070269492A1 (en) * 2006-05-16 2007-11-22 Per Steen New product and use and manufacture thereof
US20070269386A1 (en) * 2006-05-16 2007-11-22 Per Steen New product and use and manufacture thereof
US20080020050A1 (en) * 2006-07-21 2008-01-24 Chau Tommy L Medicinal delivery system, and related methods
US8642016B2 (en) 2006-07-21 2014-02-04 Jsrnti, Llc Medicinal delivery system, and related methods
US10799449B2 (en) 2006-07-21 2020-10-13 Jsrnti, Llc Medicinal delivery system and related methods
US20080286340A1 (en) * 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered nicotine containing products
US20080286341A1 (en) * 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered coated nicotine containing products
US20100260690A1 (en) * 2007-09-18 2010-10-14 Arne Kristensen Stable chewing gum compositions comprising maltitol and providing rapid release of nicotine
US20110214681A1 (en) * 2008-09-17 2011-09-08 Niconovum Ab Process for preparing snuff composition
US8833378B2 (en) 2008-09-17 2014-09-16 Niconovum Ab Process for preparing snuff composition
US20100124560A1 (en) * 2008-11-14 2010-05-20 Mcneil Ab Multi portion intra-oral dosage form and use thereof
US20100130562A1 (en) * 2008-11-25 2010-05-27 Watson Laboratories, Inc. Stabilized Nicotine Chewing Gum
EP2392331A1 (en) 2008-12-19 2011-12-07 Siegfried Ltd. Nicotine-containing product
US20110207782A1 (en) * 2008-12-19 2011-08-25 Siegfried Ltd. Nicotine-containing product
US9585967B2 (en) 2008-12-19 2017-03-07 Siegfried Ltd. Nicotine-containing product
EP2198865A1 (en) 2008-12-19 2010-06-23 Siegfried Ltd. Nicotine-containing product
US8151804B2 (en) 2008-12-23 2012-04-10 Williams Jonnie R Tobacco curing method
US20100154810A1 (en) * 2008-12-23 2010-06-24 Williams Jonnie R Tobacco Curing Method
US20100247586A1 (en) * 2009-03-27 2010-09-30 Andreas Hugerth Multi-Portion Intra-Oral Dosage Form With Organoleptic Properties
EP2233134A1 (en) 2009-03-27 2010-09-29 McNeil AB Multi-portion intra-oral dosage form with organoleptic properties
WO2011119722A2 (en) 2010-03-23 2011-09-29 Rock Creek Pharmaceuticals, Inc. Use of anatabine to treat inflammation and methods of synthesizing anatabine
EP3524245A1 (en) 2010-03-23 2019-08-14 Philip Morris Products S.A. Use of anatabine to treat inflammation and methods of synthesizing anatabine
EP3871674A1 (en) 2010-03-23 2021-09-01 Philip Morris Products S.A. Use of anatabine for reducing blood serum levels of c-reactive protein in an individual
EP3524246A1 (en) 2010-03-23 2019-08-14 Philip Morris Products S.A. Use of anatabine to treat inflammation and methods of synthesizing anatabine
WO2011139684A2 (en) 2010-04-28 2011-11-10 Niconovum Usa, Inc. Nicotine-containing pharmaceutical compositions
EP3284467A1 (en) 2010-05-07 2018-02-21 Niconovum USA, Inc. Nicotine-containing pharmaceutical compositions
WO2011139811A1 (en) 2010-05-07 2011-11-10 Niconovum Usa, Inc. Nicotine-containing pharmaceutical compositions
US8728443B2 (en) 2010-05-31 2014-05-20 Fertin Pharma A/S Formulation comprising nicotine and a cation exchange resin
US8728444B2 (en) 2010-05-31 2014-05-20 Fertin Pharma A/S Formulation comprising nicotine and a cation exchange resin
US8241680B2 (en) 2010-06-30 2012-08-14 Rock Creek Pharmaceuticals, Inc. Nutraceutical product containing anatabine and yerba maté
US9707175B2 (en) * 2010-12-21 2017-07-18 Fertin Pharma A/S Chewing gum composition comprising cross-linked polyacrylic acid
WO2012083947A1 (en) 2010-12-21 2012-06-28 Fertin Pharma A/S Chewing gum composition comprising cross-linked polyacrylic acid
US20130280179A1 (en) * 2010-12-21 2013-10-24 Fertin Pharma A/S Chewing Gum Composition Comprising Cross-Linked Polyacrylic Acid
US9387201B2 (en) 2011-08-29 2016-07-12 Rcp Development, Inc. Methods of providing anti-inflammation support
US9084439B2 (en) 2011-09-22 2015-07-21 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US9629392B2 (en) 2011-09-22 2017-04-25 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US9474303B2 (en) 2011-09-22 2016-10-25 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US10952461B2 (en) 2011-09-22 2021-03-23 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US9901113B2 (en) 2011-09-22 2018-02-27 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
WO2013043866A1 (en) 2011-09-22 2013-03-28 Niconovum Usa, Inc. Nicotine-containing pharmaceutical composition
DE202012013755U1 (en) 2011-09-22 2021-06-24 Modoral Brands Inc. Pharmaceutical composition containing nicotine
US11129898B2 (en) 2011-09-22 2021-09-28 Modoral Brands Inc. Nicotine-containing pharmaceutical composition
US10617143B2 (en) 2011-09-22 2020-04-14 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US11533944B2 (en) 2011-09-22 2022-12-27 R.J. Reynolds Tobacco Company Translucent smokeless tobacco product
US9907748B2 (en) 2011-10-21 2018-03-06 Niconovum Usa, Inc. Excipients for nicotine-containing therapeutic compositions
WO2013059592A1 (en) 2011-10-21 2013-04-25 Niconovum Usa, Inc. Excipients for nicotine-containing therapeutic compositions
EP3744313A1 (en) 2011-10-21 2020-12-02 Modoral Brands Inc. Excipients for nicotine-containing therapeutic compositions
WO2013119760A1 (en) 2012-02-10 2013-08-15 Niconovum Usa, Inc. Multi-layer nicotine-containing pharmaceutical composition
EP3735972A1 (en) 2012-02-10 2020-11-11 Modoral Brands Inc. Multi-layer nicotine-containing pharmaceutical composition
WO2013158643A2 (en) 2012-04-17 2013-10-24 R. J. Reynolds Tobacco Company Remelted ingestible products
WO2014164509A1 (en) 2013-03-11 2014-10-09 Niconovum Usa, Inc. Method and apparatus for differentiating oral pouch products
US10368576B2 (en) 2014-03-28 2019-08-06 British American Tobacco (Investments) Limited Additive carrying composition
EP3741239A1 (en) 2014-05-20 2020-11-25 RAI Strategic Holdings, Inc. Electrically-powered aerosol delivery system
WO2015179388A1 (en) 2014-05-20 2015-11-26 R. J. Reynolds Tobacco Company Electrically-powered aerosol delivery system
EP3527088A1 (en) 2014-05-20 2019-08-21 RAI Strategic Holdings, Inc. Electrically-powered aerosol delivery system
WO2016040754A1 (en) 2014-09-12 2016-03-17 R. J. Reynolds Tobacco Company Nonwoven pouch comprising heat sealable binder fiber
US10213438B2 (en) 2014-11-18 2019-02-26 Mymd Pharmaceuticals, Inc. Alkaloid compounds for treating depression, substance addictions, and indications associated with chronic inflammation
WO2016090075A1 (en) 2014-12-05 2016-06-09 R. J. Reynolds Tobacco Company Smokeless tobacco pouch
EP3815551A2 (en) 2015-06-30 2021-05-05 R. J. Reynolds Tobacco Company Heat generation segment for an aerosol-generation system of a smoking article
WO2017004185A2 (en) 2015-06-30 2017-01-05 R. J. Reynolds Tobacco Company Heat generation segment for an aerosol-generation system of a smoking article
EP4292454A2 (en) 2015-11-24 2023-12-20 R.J. Reynolds Tobacco Company Electrically-powered aerosol delivery system
EP4059365A1 (en) 2015-11-24 2022-09-21 R. J. Reynolds Tobacco Company Electrically-powered aerosol delivery system
WO2017093941A1 (en) 2015-12-03 2017-06-08 Niconovum Usa, Inc. Multi-phase delivery compositions and products incorporating such compositions
WO2017098443A1 (en) 2015-12-10 2017-06-15 Niconovum Usa, Inc. Protein-enriched therapeutic composition of a nicotinic compound
EP3445344B1 (en) 2016-04-21 2020-08-19 Fertin Pharma A/S Nicotine delivery product, related uses and oral dosage forms, and methods of production
WO2017182084A1 (en) 2016-04-21 2017-10-26 Fertin Pharma A/S Nicotine delivery product, related uses and oral dosage forms, and methods of production
US11311623B2 (en) 2016-04-21 2022-04-26 Fertin Pharma A/S Nicotine delivery product, related uses and oral dosage forms, and methods of production
EP3936129A1 (en) 2016-05-16 2022-01-12 CV Sciences, Inc. Pharmaceutical formulations containing cannabidiol and nicotine for treating smokeless tobacco addiction
WO2017200740A1 (en) 2016-05-16 2017-11-23 Cv Sciences, Inc. Pharmaceutical formulations containing cannabidiol and nicotine for treating smokeless tobacco addiction
WO2018015889A1 (en) 2016-07-21 2018-01-25 Rai Strategic Holdings, Inc. Aerosol delivery device with a unitary reservoir and liquid transport element comprising a porous monolith and related method
WO2018015910A2 (en) 2016-07-21 2018-01-25 Rai Strategic Holdings, Inc. Aerosol delivery device with a liquid transport element comprising a porous monolith and related method
EP4169400A1 (en) 2016-07-21 2023-04-26 RAI Strategic Holdings, Inc. Aerosol delivery device with a liquid transport element comprising a porous monolith
WO2018055558A1 (en) 2016-09-23 2018-03-29 Rai Strategic Holdings, Inc. An aerosol delivery device with replaceable wick and heater assembly
EP4197369A1 (en) 2017-05-17 2023-06-21 RAI Strategic Holdings, Inc. Aerosol delivery device
WO2018211390A1 (en) 2017-05-17 2018-11-22 Rai Strategic Holdings, Inc. Aerosol delivery device
WO2018219650A1 (en) 2017-05-30 2018-12-06 Enorama Pharma Ab Nicotine-containing chewing gum compositions
EP4074309A1 (en) 2017-05-30 2022-10-19 Enorama Pharma AB Nicotine-containing chewing gum compositions
DE102018221520A1 (en) 2017-12-13 2019-06-13 Mymd Pharmaceuticals, Inc. Genetically modified tobacco
WO2019116276A1 (en) 2017-12-15 2019-06-20 Rai Strategic Holdings, Inc. Aerosol delivery device with multiple aerosol delivery pathways
US10791769B2 (en) 2017-12-29 2020-10-06 Rai Strategic Holdings, Inc. Aerosol delivery device providing flavor control
US10555558B2 (en) 2017-12-29 2020-02-11 Rai Strategic Holdings, Inc. Aerosol delivery device providing flavor control
WO2019239356A1 (en) 2018-06-15 2019-12-19 R. J. Reynolds Tobacco Company Purification of nicotine
WO2020053766A1 (en) 2018-09-11 2020-03-19 Rai Strategic Holdings, Inc. Wicking element for aerosol delivery device
WO2021048791A1 (en) 2019-09-11 2021-03-18 R. J. Reynolds Tobacco Company Pouched products with enhanced flavor stability
WO2021048792A1 (en) 2019-09-11 2021-03-18 R. J. Reynolds Tobacco Company Oral product with cellulosic flavor stabilizer
WO2021069044A1 (en) 2019-10-11 2021-04-15 Fertin Pharma A/S An ion-exchange composition with water-soluble mucoadhesive polymers
WO2021086367A1 (en) 2019-10-31 2021-05-06 Nicoventures Trading Limited Oral product and method of manufacture
WO2021116866A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Pouched products with enhanced flavor stability
WO2021116852A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product with dissolvable component
WO2021116854A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with active ingredient combinations
WO2021116841A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Moist oral compositions
WO2021116878A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with improved binding of active ingredients
WO2021116876A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with salt inclusion
WO2021116881A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product in a pourous pouch comprising a fleece material
WO2021116893A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product and method of manufacture
WO2021116824A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product comprising a cannabinoid
WO2021116892A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions with reduced water activity
WO2021116856A2 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products
WO2021116842A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with controlled release
WO2021116919A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Fleece for oral product with releasable component
WO2021116827A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Process
WO2021116916A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product with multiple flavors having different release profiles
WO2021116914A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with polymeric component
WO2021116867A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Buffered oral compositions
WO2021116855A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions and methods of manufacture
WO2021116891A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral foam composition
WO2021116918A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions including gels
WO2021116823A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product
WO2021116868A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with controlled release
WO2021116837A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Pouched products
WO2021116862A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral compositions with reduced water content
WO2021116894A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Pouched products with heat sealable binder
WO2021116822A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with reduced irritation
WO2021116825A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral product
WO2021116887A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Lipid-containing oral composition
WO2021116917A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with nanocrystalline cellulose
WO2021116834A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Nanoemulsion for oral use
WO2021116890A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Liquid composition for oral use or for use in an aerosol delivery device
WO2021116865A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Agents for oral composition
WO2021116895A2 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Stimulus-responsive pouch
WO2021116884A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Layered fleece for pouched product
WO2021116879A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral composition with beet material
WO2021116853A1 (en) 2019-12-09 2021-06-17 Nicoventures Trading Limited Fibrous fleece material
WO2021171185A1 (en) 2020-02-24 2021-09-02 Nicoventures Trading Limited Beaded tobacco material and related method of manufacture
WO2021250516A1 (en) 2020-06-08 2021-12-16 Nicoventures Trading Limited Effervescent oral composition comprising an active ingredient
WO2022043666A1 (en) 2020-08-27 2022-03-03 Nicoventures Trading Limited Consumable
WO2022043919A1 (en) 2020-08-27 2022-03-03 Rai Strategic Holdings, Inc. Aerosol delivery device
WO2022043700A1 (en) 2020-08-27 2022-03-03 Nicoventures Trading Limited Oral product
WO2022053982A1 (en) 2020-09-11 2022-03-17 Nicoventures Trading Limited Alginate-based substrates
WO2022074566A1 (en) 2020-10-07 2022-04-14 Nicoventures Trading Limited Methods of making tobacco-free substrates for aerosol delivery devices
WO2022107031A1 (en) 2020-11-19 2022-05-27 Nicoventures Trading Limited Oral products
WO2022112949A1 (en) 2020-11-25 2022-06-02 Nicoventures Trading Limited Oral cannabinoid product with lipid component
WO2022162558A1 (en) 2021-01-28 2022-08-04 Nicoventures Trading Limited Method for sealing pouches
WO2022189977A1 (en) 2021-03-09 2022-09-15 Nicoventures Trading Limited Oral products and methods of manufacture
WO2022224196A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Orally dissolving films
WO2022224200A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Oral compositions and methods of manufacture
WO2022224197A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Effervescent oral composition
WO2022224198A1 (en) 2021-04-22 2022-10-27 Nicoventures Trading Limited Oral lozenge products
WO2022229926A1 (en) 2021-04-30 2022-11-03 Nicoventures Trading Limited Multi-compartment oral pouched product
WO2022229929A1 (en) 2021-04-30 2022-11-03 Nicoventures Trading Limited Oral products with high-density load
WO2022264066A1 (en) 2021-06-16 2022-12-22 Nicoventures Trading Limited Pouched product comprising dissolvable composition
WO2022269475A1 (en) 2021-06-21 2022-12-29 Nicoventures Trading Limited Oral product tablet and method of manufacture
WO2022269556A1 (en) 2021-06-25 2022-12-29 Nicoventures Trading Limited Oral products and method of manufacture
WO2023281469A1 (en) 2021-07-09 2023-01-12 Nicoventures Trading Limited Extruded structures
WO2023002200A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Constituent, derivative or extract of cannabis in amorphous form
WO2023002201A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising constituents, derivatives or extracts of cannabis
WO2023002198A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising a constituent, derivative or extract of cannabis
WO2023002194A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising constituents, derivatives or extracts of cannabis
WO2023002195A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Methods of preparing compositions comprising a constituent, derivative or extract of cannabis
WO2023002197A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Compositions comprising a constituent, derivative or extract of cannabis
WO2023002196A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Constituent, derivative or extract of cannabis in a water soluble matrix
WO2023002199A1 (en) 2021-07-22 2023-01-26 Nicoventures Trading Limited Composition comprising a constituent, derivative or extract of cannabis
WO2023053060A1 (en) 2021-09-30 2023-04-06 Nicoventures Trading Limited Oral gum composition
WO2023084498A1 (en) 2021-11-15 2023-05-19 Nicoventures Trading Limited Oral products with nicotine-polymer complex
WO2023084499A1 (en) 2021-11-15 2023-05-19 Nicoventures Trading Limited Products with enhanced sensory characteristics
RU2782018C1 (en) * 2021-11-26 2022-10-21 Леонид Борисович Потёмкин Remedy for those quitting smoking
WO2023106407A1 (en) * 2021-12-09 2023-06-15 日本たばこ産業株式会社 Composition for oral cavity and pouch product for oral cavity
WO2023119134A1 (en) 2021-12-20 2023-06-29 Nicoventures Trading Limited Substrate material comprising beads for aerosol delivery devices
WO2023187675A1 (en) 2022-03-31 2023-10-05 R. J. Reynolds Tobacco Company Agglomerated botanical material for oral products
WO2023194959A1 (en) 2022-04-06 2023-10-12 Nicoventures Trading Limited Pouched products with heat sealable binder

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