US3877468A - Chewable tobacco substitute composition - Google Patents
Chewable tobacco substitute composition Download PDFInfo
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- US3877468A US3877468A US437031A US43703174A US3877468A US 3877468 A US3877468 A US 3877468A US 437031 A US437031 A US 437031A US 43703174 A US43703174 A US 43703174A US 3877468 A US3877468 A US 3877468A
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- nicotine
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- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B13/00—Tobacco for pipes, for cigars, e.g. cigar inserts, or for cigarettes; Chewing tobacco; Snuff
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
- A61K9/0058—Chewing gums
Definitions
- ABSTRACT Chewable smoking substitute composition comprises at least about 40 percent by weight of a gum base and a tobacco alkaloid dispersed in said gum base in an amount sufficent to provide smoking satisfaction.
- This invention relates to smoking substitutes that are chewed and that are of particular value for facilitating a persons withdrawal from smoking and/or decreasing a persons desire to smoke.
- the administration of nicotine can give satisfaction and the usual method is by smoking, either cigarette smoking, cigar smoking, or pipe smoking.
- smoking may have health hazards and so it would be desirable to formulate an alternative manner of administering nicotine in a pleasurable manner that can be used to facilitate withdrawal from smoking and/or as a replacement for smoking.
- compositions containing nicotine or alkaloids having a similar effect and which can be chewed or sniffed are known but generally are not very satisfactory. Examples of such compositions are found in US. Pat. Nos. 875,026 and 904,521.
- tobacco alkaloid as used herein and in the claims is taken to 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.
- Plant alkaloids of this type are obtainable from species of Nicotiana which is a source for nicotine and nor-nicotine, as well as species of Lobelia and Lobeliaceae (Indian tobacco) which are a source for lobeline.
- 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 alkaloid released 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 much ofa sensation in the mouth, this may lead one to excessive use of the substitute with less smoking satisfaction and thus lead to return to ordinary smoking.
- the procedure of incorporating the alkaloid into the chewing gum should be easy to perform and also assure substantially uniform distribution of alkaloid into the chewing gum.
- an alkaloid-regenerative adsorbent complex comprising the alkaloid or an acid addition salt thereof bound to or sorbed on a regenerative adsorbent such as finely divided silicic acid, amorphous silica, magnesium silicate, calcium silicate, kaolin, clays, crystalline aluminosilicates, macaloid bentonite, activated carbon, alumina, hydroxylapatite, and the like, is incorporated into the chewable gum base compositions having a relatively high gum base concentration.
- the alkaloid can be bound to the adsorbent either by absorption, adsorption, or both. thus the term sorbed as used herein is taken to mean either or both of the binding mechanisms.
- the smoking substitute composition preferably is acidic.
- the amount of tobacco alkaloid, such as nicotine, nor-nicotine, lobeline or mixtures thereof, present per chewable gum unit can vary over a wide range and can be present in an amount in the range of about 0.05 percent by weight to about 2 percent by weight, based on the weight of the gum base and calculated as the free base.
- a chewable gum unit contains about 1 milligram to about 10 milligrams of an alkaloid.
- each gum unit contains from about 1 to about 5 milligrams of an alkaloid.
- the total weight of a chewable gum unit can vary from about 0.5 to about 4 grams.
- the weight of each chewable gum unit is not critical for the purposes of the present invention but is chosen merely on the basis of convenience of manufacture, ease of dispensing, and, of course. ease of oral administration.
- the chewable gum unit can be in any desired form such as a stick, ball, or the like. Usually the weight of each gum unit is in the range from about 1 to about 3 grams.
- Release rate of the alkaloid from the composition can be varied by varying the amount of alkaloid that is incorporated into a given quantity of gum, either separately or bound to a given quantity of the adsorbent. A relatively higher amount of 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 minutes. Most preferably, the release time is at least minutes.
- lf 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 estimates in a positive way.
- 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-, Malaya-, and 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 cotton seed oil, hydrogenated coconut oil, mineral oil, olive oil, Vaseline, Carnauba wax, Candelilla wax, paraffin, beeswax, stearic acid, glyceryl monostearate, glycerine, honey, propylene glycol, hexylene glycol, and sorbitol. These softeners also act as moisture-retaining agents at the same time.
- Miscellaneous other optional additives in a chewing gum composition are: cerelose, mannitol, diastatic malt, starch, calcium carbonate, talcum, defatted cocoa, flavors and food colors.
- Sugar in the form of sucrose and commercial glucose (corn syrup) comprises the bulk ofa chewing gum formula, but completely sugar and/or glucosefree chewing gum compositions work equivalently in 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 of natural or synthetic origin, preferably the latter, and can be present in the chewing gum formulation in an amount in the range from about 40 to about 80 weight percent, preferably from about to about 80 weight percent, and most preferably from about to about weight percent.
- Powdered sugar preferably powdered sorbitol
- Corn syrup usually of about 41 to 46 Baume, preferably an about 70 percent aqueous solution of sorbitol, can be present in an amount in the range from about 4 to about 15 weight percent, preferably from about 4 to about 10 weight percent, and most preferably from about 5 to about 8 weight percent.
- 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 present invention can be-formed simply by mixing the chewing gum with the alkaloid or alkaloid salt, preferably together with an excess of a suitable acidifying agent. Before adding any solid component, except for the gum base, it is desirable to grind and size the solid component first, to ensure a good distribution.
- the mixing is preferably conducted at a suitable elevated temperature depending upon the viscosity of chewing gum employed, since the increased temperature decreases the viscosity of the gum and thereby enables the alkaloid or alkaloid salt, together with an excess of acid, if desired, to be evenly and intimately distributed into the chewing gum.
- the content of nicotine or other alkaloid in the complex can range from about 2 to about 60 percent and preferably about 5 to about 35 percent by weight.
- the exact amount of the alkaloid or alkaloid mixtures bound to the adsorbent is determined principally by the conditions employed in formulating the compositions and, of course, by the type of adsorbent used.
- the complex containing an alkaloid bound to the adsorbent is preferably prepared in a special unit.
- the solid complex thus prepared is easy to handle and minimizes personnel risks involved in the manufacture of the final chewing gum product.
- the complex also acts as a lubricant, thereby facilitating the mixture of the different ingredients into the gum mass. A homogeneous product is easily obtained in this manner.
- the complex in the form of a relatively small particle size adsorbent in the first place, the complex can be mixed directly with the gum. If, however, the complex is in the form of a relatively coarse adsorbent, then it is desirable to grind and size the complex first.
- the complex particle size in the gum should be small enough not to cause damage to teeth during chewing, however.
- the weight ratio of the complex to the total weight of the gum is not critical so long as the desired amount of the alkaloid is present, but varies between an upper and a lower most suitable range specific to the formulation used.
- compositions of the present invention are compounded simultaneously with the incorporation of any additives such as corn syrup, sugar, sorbitol and flavors into the chewing gum base.
- the composition can be compounded in a suitable kettle, such as a steam jacketed mixer, which is warmed and the gum base added and mixed until sufficiently free from lumps.
- sorbitol or corn syrup and sugar are incorporated into the base.
- the acidifying agent such as a 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.
- flavours, softeners and other additives are poured in and well distributed.
- the mass is cooled, rolled, scored, and hardened sufficiently, then coated if desired, before flnal 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 sufficient for mixing.
- sugar and syrup tends to lower the temperature, and the various alkaloids or alkaloid salts together with the flavouring agent if desired, are added only when the mixture has cooled sufficiently. This minimizes uncontrollable losses in alkaloid and/or flavour content to a marked degree.
- the smoking substitute compositions 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 adsorbent when utilizing an alkaloid-adsorbent complex, is only partly loaded with nicotine or similar alkaloid when incorporated into a smoking substitute composition of this invention and is also loaded with a releasable or desorbable acid which serves as the acidifying agent.
- the acid Upon chewing such a composition, the acid is also liberated from the adsorbent and pH of saliva at the chewing site is decreased. This decrease in pH influences, in turn, the acid-base equilibrium as set forth above.
- a cation exchanger in its ionic hydrogen form is introduced in the alkaloid-bearing gum composition to provide the desired acidity.
- 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 alkaloid-bearing gum composition is admixed with a pharmacologically acceptable organic or inorganic acid, or with a combination of a cation exchange resin in its acid form with a pharmacologically acceptable organic or inorganic salt.
- Type Functional Groups 1. Weakly acidic, metha- Carhoxylic crylic Type R.COO H 2. Weakly acidic, metha- Carhoxylic crylic Type R.COOH" 3. Strongly acidic. poly- Sulfonic styrene Type R.SO;,,," 4. intermediate acidic. Phosphonic polystyrene Type R.PO.1'( H) Chloride Solution About 6.0
- the amount of pharmacologically acceptable acid present in any of the foregoing instances can be in the range of about 1.5 to about 10 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 equivalents of acid per mole of the neutral alkaloid salt, and most preferably of about 1 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, and 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
- EXAMPLE 1 1000 Pieces of chewing gum each containing 2 mg of nicotine as acid nicotine d-tartrate (C H N 2 c.,H,,o 2 H 0).
- Chewing gum mass according to Preparation 1 991 grams Nicotine. 100 "/1 (C H N 4.0 grams Hydrochloric acid. 38 4.73 grams EXAMPLE 3
- Chewing gum mass according to Preparation 1 983 grams Nicotine. 100 "/1- 4.0 grams Sulfuric acid, 95 71 1.28 grams Amberlite lRP 64M. 9.0 meq/gram 12.0 grams
- EXAMPLE 4 1000 Pieces of chewing gum each containing 3 mg of nicotine as neutral nicotine sulfate (C H NQ H and an excess of acid (4.8 equivalents mole of alkaloid salt), present as adipic acid.
- Chewing gum mass 1490 grams Nicotine, 100% 3.0 grams, Sulfuric acid, 7p 0.96 grams Adipic acid 6.5 grams
- EXAMPLE 5 1000 Pieces of chewing gum each containing 2 mg of nicotine as base and an excess ,of acid (5.8 equivalents mole of alkaloid), present as the cation exchanger Amberlite IRP 69M converted to hydrogen ionic form.
- Chewing gum mass according to Preparation 1 983 grams Nicotine. 2.0 grams Amberlite lRP 60M, 4.8 meq/gram 14.9 grams EXAMPLE 6 1000 Pieces of chewing gum each containing 2 mg of nicotine as base together with 1 mg of nor-nicotine as EXAMPLE 1 l 1000 Pieces of chewing gum each containing 2 mg of nicotine as base and an excess of acid (3 equivalents base and an excess of acid (6 equivalents mole of al- 5 mole of alkaloid), present as monosodium phosphate. kaloid). present as succinic acid.
- Chewing gum mass according to Preparation 2 490 grams l Chewing gum mass according to Preparation I 19960 grams Nicotine. I00 7( 2.0 grams Nicotine. 100 2.0 grams Nor-n w t 100 (C, N2) g u Monosodium phosphate 2.22 grams EXAMPLE 7 EXAMPLE 12 1000 Piece of chewing gum each con aining 1 mg of 1000 Pieces of chewing gum each containing 3 mg of nicotine as base and an excess of acid equivalents gr-nicotine as b d an excess f id 4 i mole of alkaloid). pre en as f maric a i lents mole of alkaloid), present as malic acid.
- Chewing gum mass according to Preparation 2 990 grams Nicotine, I00 71 5.0 grams Hydrochloric acid 38 4A4 grams Chew ng gum mass according to Preparation l 993.0 grams Nicotine. i009: 2.0 grams Malic acid 2.48 grams Adipic acid 2.71 grams 40 EXAMPLE 9 1000 Pieces ofchewing gum each containing 1 mg of EXAMPLE nicotine as base together with 1 mg of lobeline as base and an excess of acid (8 equivalents mole of alkaloid), 1000 Pieces of chewing gum each containing 2mg of present as adipic acid. lobeline as base and an excess of acid (8equivalents mole of alkaloid), resent as monosodium fumarate.
- Chewing gum containing a 10 percent complex is ob- Chcwing gum mass according to Preparation 1 989.0 grams mined from 3 mg of nicotine bound to Silicic acid Nicotine. 100 Z grams O00 Mumsodiumcmme 793 grams Chewing gum mass according to Preparation 1,
- EXAMPLE 16 Chewing gum containing a 10 percent complex, obtained from 2.5 mg. of nicotine bound to silicic acid, and likewise a 20 percent complex, obtained from 2.5 mg. of nicotine bound to silicic acid.
- Chewing gum mass according to Preparation 2 1000 pieces of gum per 1835 grams of the mass.
- EXAMPLE 17 Chewing gum containing a 30 percent complex, obtained from 1 mg. of nicotine bound to silicic acid.
- Chewing gum mass according to Preparation 3 1000 pieces of gum per 3325 grams of the mass.
- EXAMPLE 18 Chewing gum containing a 30 percent complex, obtained from 2 mg of lobeline bound to silicic acid.
- Chewing gum mass according to Preparation 3 1000 pieces of gum per 3325 grams of the mass.
- EXAMPLE 19 Chewing gum containing a 20 percent complex, ob tained from 1 mg of lobeline bound to silicic acid, and likewise a 35 percent complex obtained from 1 mg. of nicotine bound to silicic acid.
- Chewing gum mass according to Preparation 1 1000 pieces of gum per 1565 grams of the mass.
- Chewing gum mass according to Preparation 2 1000 pieces of gum per 450 grams of the mass.
- EXAMPLE 21 Chewing gum containing a percent complex, obtained from 2 mg of nicotine bound to silicic acid, and likewise a 10 percent complex obtained from 1 mg. of nor-nicotine bound to silicic acid.
- Chewing gum mass according to Preparation 1 1000 pieces of gum per 2975 grams of the mass.
- Chewing time minutes Mean value nicotine released mg EXAMPLE 23 Chewing gum containing 4 mg of nicotine as nicotine dihydrochloride, i.e. 2 equivalents of acid mole of alkaloid.
- Chewing time minutes Mean value nicotine released mg
- Table 1 is a compilation of experimental results showing the amount of nicotine released as a function of time.
- Chewing gum containing 4 milligrams of nicotine as neutral nicotine sulfate and an excess of acid (4.8 equivalents of cation exchanger Amberlite lRP 64M in ionic hydrogen form per mole of the alkaloid salt) and 1 gram chewing gum mass having a high gum base concentration, prepared in accordance with Preparation 1. Release brought about by chewing. Very pronounced feeling of smoking was observed.
- EXAMPLE 24 About 400 grammes natural gum base is put into a hot jacketed mixer fitted with stirrers. The mixer is heated by steam at about 15 lbs. per sq. inch. The stirrers are run at intervals to turn the base over. A low steam pressure is selected to prevent overheating of the base. After the base is completely melted the steam is turned off in the mixer and cold water is run through the jacket to reduce the temperature of the contents to about 85C. 460 Grammes of powdered sugar (300 mesh sieve), grammes Corn syrup 45 Baume, 5 grammes of glycerine, l0 grammes of flavouring oil, 5.3 grammes of nicotine sulfate and 12 grammes Amberlite [RP 64M (9.9 meq. acid/gram) are then added to the melted base in the mixer and the mass is mixed for about fifteen minutes. The mixture will now have a temperature of between 60 to 75C, or lower.
- 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 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.
- each piece generally weighs between 1 and 3 grammes. In this Example, 1000 pieces, each weighing about one gram, 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 percent and the pieces are preferably stored at a temperature of 18 to 20C and a relative humidity of 45 to 50 percent.
- the nicotine-adsorbent complex thus obtained is then analyzed with reference to the nicotine content after careful blending and sieving through a 300 mesh sieve.
- Table II is a compilation of experimental results showing the amount of nicotine released as a function of time.
- EXAMPLE 18 A nicotine-silicic acid complex with Aerosil T.M. was prepared by the method described in Preparation 5, the resultant complex containing 10 percent 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 square inch.
- the stirrers are run at intervals to turn the base over.
- a low steam pressure is selected to prevent overheating of the base.
- the steam is turned off in the mixer and cold water is run through the jacket to'reduce the temperature of the contents to about 85C.
- 840 Grammes of powdered sugar (300 mesh sieve) and 276 grammes corn syrup 45 Baume are then added to the melted base in the mixer and the mass is mixed for about fifteen minutes. The mixture will now have a temperature of between 60 to 75C.
- a further 420 grammes of powdered sugar and 30 grammes of the nicotine-silicic acid 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 fifteen 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.
- rollers serve to roll it down to the desired size.
- the cutters are preferably maintained at about 25C.
- a chewable substitute for smoking gum composition having a high percentage of gum base, as said high percentage is hereinafter defined, comprising:
- 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 a relatively high percentage, that is, an amount constituting at least about 40 percent by weight 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 distributed in said chewing gum base is in the range of about 1 to about milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product;
- the nicotine being present in said gum composition as a nicotine compound selected from the group consisting of a. a nicotine free base,
- a nicotine-regenerative adsorbent complex comprising a compound selected from the group consisting of nicotine and a pharmacologicallyacceptable salt of nicotine sorbed on a regenerative adsorbent;
- G especially within the first ten minutes of chewing releasing the nicotine at a rate less than if the nicotine were present in an ordinary chewing gum composition, having a relatively low percentage of chewing gum base, that is, an amount constituting less than about 40 percent by weight of the gum composition.
- the chewing gum composition of claim 1 wherein the amount of nicotine 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.
- composition of claim 1 wherein the nicotine is present as a nicotine-regenerative adsorbent complex.
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Abstract
Chewable smoking substitute composition comprises at least about 40 percent by weight of a gum base and a tobacco alkaloid dispersed in said gum base in an amount sufficent to provide smoking satisfaction.
Description
United States Patent [191 Lichtneckert et a1.
1 1 CHEWABLE TOBACCO SUBSTITUTE COMPOSITION [75] Inventors: Stefan Lichtneckert; Claes Lundgren, both of Lund; Ove Ferno, Halsingborg, all of Sweden [73] Assignee: Aktiebolaget Leo, Halsingborg,
Sweden 22 Filed: Jan. 28, 1974 [21] Appl. No.: 437,031
Related US. Application Data [63] Continuation of Scr. No. 164,105, July 19, 1971,
abandoned.
[30] Foreign Application Priority Data July 22, 1970 United Kingdom 35605/70 July 22, 1970 United Kingdom.... 35606/70 [52] US. Cl 131/2; 131/1 Apr. 15, 1975 [51] Int. Cl A24b 15/00 [58] Field of Search 131/2, 15, 5, 17, 140-144, 131/16; 424/267, 266, 48, 79, 254, 48
Primary ExaminerMelvin D. Rein Attorney, Agent, or Firm-Gordon W. l-luescher [57] ABSTRACT Chewable smoking substitute composition comprises at least about 40 percent by weight of a gum base and a tobacco alkaloid dispersed in said gum base in an amount sufficent to provide smoking satisfaction.
3 Claims, No Drawings CHEWABLE TOBACCO SUBSTITUTE COMPOSITION This is a continuation of application Ser. No. 164,105, filed July 19, 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 persons withdrawal from smoking and/or decreasing a persons desire to smoke.
The administration of nicotine can give satisfaction and the usual method is by smoking, either cigarette smoking, cigar smoking, or pipe smoking. However, smoking may have health hazards and so it would be desirable to formulate an alternative manner of administering nicotine in a pleasurable manner that can be used to facilitate withdrawal from smoking and/or as a replacement for smoking.
Compositions containing nicotine or alkaloids having a similar effect and which can be chewed or sniffed are known but generally are not very satisfactory. Examples of such compositions are found in US. Pat. Nos. 875,026 and 904,521.
These patents are mostly concerned with mixing finely ground tobacco, for instance 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 mostly used and accepted today. the release of the alkaloid takes place very quickly. This is disadvantageous for two reasons: firstly, the alkaloid is released too quickly, higher blood concentrations of the alkaloid are produced than with ordinary smoking, and secondly, the substitute in question has too short an effeet.
It has been our object to devise a chewable composition in which a tobacco alkaloid such as nicotine or a related alkaloid is released slowly, the composition thereby imitating satisfactorily the effect of the admin istration of nicotine by smoking.
The term tobacco alkaloid as used herein and in the claims is taken to 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. Plant alkaloids of this type are obtainable from species of Nicotiana which is a source for nicotine and nor-nicotine, as well as species of Lobelia and Lobeliaceae (Indian tobacco) which are a source for lobeline.
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 also 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 using the substitute in question.
(I. The alkaloid released 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 much ofa sensation in the mouth, this may lead one to excessive use of the substitute with less smoking satisfaction and thus lead to return to ordinary smoking.
3. The procedure of incorporating the alkaloid into the chewing gum should be easy to perform and also assure substantially uniform distribution of alkaloid into the chewing gum.
SUMMARY OF THE INVENTION It has now been found that all of the foregoing advantages are realized if an amount effective to provide smoking satisfaction of a tobacco alkaloid, either as a base or in the form of a salt, is incorporated into chewable gum compositions having a relatively high gum base concentration. That is, contemplated are gum compositions having a gum base concentration of at least about 40 percent by weight or higher and containing the alkaloid dispersed therein. Preferably the smoking substitute composition of this invention is rendered acidic by the addition of a pharmacologically acceptable acidifying agent. In an alternate embodiment an alkaloid-regenerative adsorbent complex comprising the alkaloid or an acid addition salt thereof bound to or sorbed on a regenerative adsorbent such as finely divided silicic acid, amorphous silica, magnesium silicate, calcium silicate, kaolin, clays, crystalline aluminosilicates, macaloid bentonite, activated carbon, alumina, hydroxylapatite, and the like, is incorporated into the chewable gum base compositions having a relatively high gum base concentration. The alkaloid can be bound to the adsorbent either by absorption, adsorption, or both. thus the term sorbed as used herein is taken to mean either or both of the binding mechanisms. Also in this embodiment the smoking substitute composition preferably is acidic.
The amount of tobacco alkaloid, such as nicotine, nor-nicotine, lobeline or mixtures thereof, present per chewable gum unit can vary over a wide range and can be present in an amount in the range of about 0.05 percent by weight to about 2 percent by weight, based on the weight of the gum base and calculated as the free base. Usually a chewable gum unit contains about 1 milligram to about 10 milligrams of an alkaloid. Preferably each gum unit contains from about 1 to about 5 milligrams of an alkaloid.
The total weight of a chewable gum unit can vary from about 0.5 to about 4 grams. The weight of each chewable gum unit is not critical for the purposes of the present invention but is chosen merely on the basis of convenience of manufacture, ease of dispensing, and, of course. ease of oral administration. The chewable gum unit can be in any desired form such as a stick, ball, or the like. Usually the weight of each gum unit is in the range from about 1 to about 3 grams.
DESCRIPTION OF THE PREFERRED EMBODIMENTS When the alkaloid is incorporated into the chewing gum mass in accordance with this invention it is possible to use a wide variety of chewing gum compositions as long as a relatively high gum base concentration is present.
Release rate of the alkaloid from the composition can be varied by varying the amount of alkaloid that is incorporated into a given quantity of gum, either separately or bound to a given quantity of the adsorbent. A relatively higher amount of 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 minutes. Most preferably, the release time is at least 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 sensi tive to nicotine. lf 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 estimates in a positive way.
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-, Malaya-, and 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 cotton seed oil, hydrogenated coconut oil, mineral oil, olive oil, Vaseline, Carnauba wax, Candelilla wax, paraffin, beeswax, stearic acid, glyceryl monostearate, glycerine, honey, propylene glycol, hexylene glycol, and sorbitol. These softeners also act as moisture-retaining agents at the same time. Miscellaneous other optional additives in a chewing gum composition are: cerelose, mannitol, diastatic malt, starch, calcium carbonate, talcum, defatted cocoa, flavors and food colors. Sugar in the form of sucrose and commercial glucose (corn syrup) comprises the bulk ofa chewing gum formula, but completely sugar and/or glucosefree chewing gum compositions work equivalently in the present invention.
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 of natural or synthetic origin, preferably the latter, and can be present in the chewing gum formulation in an amount in the range from about 40 to about 80 weight percent, preferably from about to about 80 weight percent, and most preferably from about to about weight percent.
Powdered sugar, preferably powdered sorbitol, can be present in an amount in the range from about 15 to about 50 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, preferably an about 70 percent aqueous solution of sorbitol, can be present in an amount in the range from about 4 to about 15 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 percent chewing gum base, preferably of synthetic origin (Preparation 1, 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 present invention can be-formed simply by mixing the chewing gum with the alkaloid or alkaloid salt, preferably together with an excess of a suitable acidifying agent. Before adding any solid component, except for the gum base, it is desirable to grind and size the solid component first, to ensure a good distribution. The mixing is preferably conducted at a suitable elevated temperature depending upon the viscosity of chewing gum employed, since the increased temperature decreases the viscosity of the gum and thereby enables the alkaloid or alkaloid salt, together with an excess of acid, if desired, to be evenly and intimately distributed into the chewing gum.
As to the alkaloid-adsorbent complexes hereinabove mentioned, the content of nicotine or other alkaloid in the complex can range from about 2 to about 60 percent and preferably about 5 to about 35 percent by weight. The exact amount of the alkaloid or alkaloid mixtures bound to the adsorbent is determined principally by the conditions employed in formulating the compositions and, of course, by the type of adsorbent used.
The complex containing an alkaloid bound to the adsorbent is preferably prepared in a special unit. The solid complex thus prepared is easy to handle and minimizes personnel risks involved in the manufacture of the final chewing gum product. The complex also acts as a lubricant, thereby facilitating the mixture of the different ingredients into the gum mass. A homogeneous product is easily obtained in this manner.
In compounding the present compositions with an alkaloid-adsorbent complex, if the complex is in the form of a relatively small particle size adsorbent in the first place, the complex can be mixed directly with the gum. If, however, the complex is in the form of a relatively coarse adsorbent, then it is desirable to grind and size the complex first. The complex particle size in the gum should be small enough not to cause damage to teeth during chewing, however.
ln compounding the compositions with the various alkaloid-adsorbent complexes, singly or as admixtures of several alkaloids, the weight ratio of the complex to the total weight of the gum is not critical so long as the desired amount of the alkaloid is present, but varies between an upper and a lower most suitable range specific to the formulation used. Compositions wherein the alkaloid-adsorbent complex is present in an amount of about 0.1 to percent by weight of the total weight of the gum, preferably about 0.2 to 5 percent, and most preferably about 0.5 to 2 percent, are suitable.
Conveniently compositions of the present invention are compounded 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 compounded in a suitable kettle, such as 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 acidifying agent such as a 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 acid with the solid, powdered part of sorbitol or sugar. Finally, flavours, softeners and other additives are poured in and well distributed. The mass is cooled, rolled, scored, and hardened sufficiently, then coated if desired, before flnal 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 sufficient for mixing. The addition of sugar and syrup tends to lower the temperature, and the various alkaloids or alkaloid salts together with the flavouring agent if desired, are added only when the mixture has cooled sufficiently. This minimizes uncontrollable losses in alkaloid and/or flavour content to a marked degree.
As mentioned hereinabove, it is preferred that the smoking substitute compositions 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, thereby 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 upon chewing at a pH of less than about 7, and preferably in the range of about 5 to about 4, by incorporating a pharmacologically acceptable acidifying agent into the composition.
In one preferred embodiment of this invention when utilizing an alkaloid-adsorbent complex, the adsorbent is only partly loaded with nicotine or similar alkaloid when incorporated into a smoking substitute composition of this invention and is also loaded with a releasable or desorbable acid which serves as the acidifying agent. Upon chewing such a composition, the acid is also liberated from the adsorbent and pH of saliva at the chewing site is decreased. This decrease in pH influences, in turn, the acid-base equilibrium as set forth above. Similarly, it is possible to admix a fully nicotineloaded adsorbent with a cation exchange resin in its acid form which releases hydrogen ions upon chewing to bring about the desired acidity at the chewing site, or to admix a fully nicotine-loaded adsorbent with a pharmacologically acceptable organic or inorganic acid, or to admix a fully nicotine-loaded adsorbent with a combination of a cation exchange resin in its acid form with a pharmacologically acceptable organic or inorganic salt.
In another preferred embodiment of this invention a cation exchanger in its ionic hydrogen form is introduced in the alkaloid-bearing gum composition to provide the desired acidity. 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. In still another preferred embodiment, the alkaloid-bearing gum composition is admixed with a pharmacologically acceptable organic or inorganic acid, or with a combination of a cation exchange resin in its acid form with a pharmacologically acceptable organic or inorganic salt.
The properties and characteristics of four cation exchange resins that we have found to be particularly suitable for use with the present invention are:
No. Name Manufacturer 1. Amherlite lRP 64 Rohm & Haas Co., Philadelphia 2. Amberlite lRP 64M Rohm & Haas Co.. Philadelphia 3. Amberlite lRP 69M Rohm & Haas Co.. Philadelphia 4. BIOREX 63 BIO-RAD Lab. Richmond. Cal.
No. Type Functional Groups 1. Weakly acidic, metha- Carhoxylic crylic Type R.COO H 2. Weakly acidic, metha- Carhoxylic crylic Type R.COOH" 3. Strongly acidic. poly- Sulfonic styrene Type R.SO;,,," 4. intermediate acidic. Phosphonic polystyrene Type R.PO.1'( H) Chloride Solution About 6.0
-Continued Apparent pK Value in Exchange Capacity meq/gm of The amount of pharmacologically acceptable acid present in any of the foregoing instances, can be in the range of about 1.5 to about 10 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 equivalents of acid per mole of the neutral alkaloid salt, and most preferably of about 1 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, and 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.
Some Preparations and Examples are now given which are illustrative of the present invention.
PREPARATIONS OF THE INVENTION 73.7 weight-percent 19.8 weight-percent 3.8 weight-percent 0.7 weight-percent 2.0 weight-percent 55.0 weight-percent 34.0 weight-percent 8.9 weight percent 0.6 weight-percent 1.5 weight-percent 40.0 weight-percent 46.7 weight-percent 1 1.7 weight-percent 0.5 weight-percent 1.1 weight-percent Preparation NOT According to the Invention Preparation 4 Natural gum base Powdered sugar Corn syrup 45 Baume 22.0 weight-percent 64.0 weight-percent 14.0 weight-percent The following Examples demonstrate the compositions according to the invention. Each of these is made by warming the gum base in a kettle and then adding the various additives, in the general method described above.
EXAMPLE 1 1000 Pieces of chewing gum each containing 2 mg of nicotine as acid nicotine d-tartrate (C H N 2 c.,H,,o 2 H 0).
1994 grams 6.16 grams Chewing gum mass according to Preparation 1 Acid nicotine d-tartrate EXAMPLE 2 1000 Pieces of chewing gum each containing 4 mg of nicotine as nicotine dihydrochloride (C H N 2 HCl).
Chewing gum mass according to Preparation 1 991 grams Nicotine. 100 "/1 (C H N 4.0 grams Hydrochloric acid. 38 4.73 grams EXAMPLE 3 Chewing gum mass according to Preparation 1 983 grams Nicotine. 100 "/1- 4.0 grams Sulfuric acid, 95 71 1.28 grams Amberlite lRP 64M. 9.0 meq/gram 12.0 grams EXAMPLE 4 1000 Pieces of chewing gum each containing 3 mg of nicotine as neutral nicotine sulfate (C H NQ H and an excess of acid (4.8 equivalents mole of alkaloid salt), present as adipic acid.
Chewing gum mass according to Preparation 1 1490 grams Nicotine, 100% 3.0 grams, Sulfuric acid, 7p 0.96 grams Adipic acid 6.5 grams EXAMPLE 5 1000 Pieces of chewing gum each containing 2 mg of nicotine as base and an excess ,of acid (5.8 equivalents mole of alkaloid), present as the cation exchanger Amberlite IRP 69M converted to hydrogen ionic form.
Chewing gum mass according to Preparation 1 983 grams Nicotine. 2.0 grams Amberlite lRP 60M, 4.8 meq/gram 14.9 grams EXAMPLE 6 1000 Pieces of chewing gum each containing 2 mg of nicotine as base together with 1 mg of nor-nicotine as EXAMPLE 1 l 1000 Pieces of chewing gum each containing 2 mg of nicotine as base and an excess of acid (3 equivalents base and an excess of acid (6 equivalents mole of al- 5 mole of alkaloid), present as monosodium phosphate. kaloid). present as succinic acid.
Chewing gum mass according to Preparation 2 490 grams l Chewing gum mass according to Preparation I 19960 grams Nicotine. I00 7( 2.0 grams Nicotine. 100 2.0 grams Nor-n w t 100 (C, N2) g u Monosodium phosphate 2.22 grams EXAMPLE 7 EXAMPLE 12 1000 Piece of chewing gum each con aining 1 mg of 1000 Pieces of chewing gum each containing 3 mg of nicotine as base and an excess of acid equivalents gr-nicotine as b d an excess f id 4 i mole of alkaloid). pre en as f maric a i lents mole of alkaloid), present as malic acid.
h i gum WWW-ling to preparation 2 995 gram Chewing gum mass according to Preparation 1 1492.0 grams Nlwllne. "107! U) grams Nor-nicotine. [00 "/1 3.0 grams Fumaric acid 3.58 grams Malic acid 5.43 grams EXAMPLE 8 EXAMPLE 13 1000 Pieces of Chewing gum each Containing 5 mg of 1000 Pieces of chewing gum each containing 2 mg of nicotine as base and an excess of acid 1.5 equivalents i i as base and-an excess f id 6 equivalents mole of alkalmd), P as hydrochlorlc ac|dmole of alkaloid), present as a mixture of malic acid and adipic acid.
Chewing gum mass according to Preparation 2 990 grams Nicotine, I00 71 5.0 grams Hydrochloric acid 38 4A4 grams Chew ng gum mass according to Preparation l 993.0 grams Nicotine. i009: 2.0 grams Malic acid 2.48 grams Adipic acid 2.71 grams 40 EXAMPLE 9 1000 Pieces ofchewing gum each containing 1 mg of EXAMPLE nicotine as base together with 1 mg of lobeline as base and an excess of acid (8 equivalents mole of alkaloid), 1000 Pieces of chewing gum each containing 2mg of present as adipic acid. lobeline as base and an excess of acid (8equivalents mole of alkaloid), resent as monosodium fumarate. EXAMPLE 9, CONTINUED p Chewing gum mass according to Preparation 2 l49l.0 grams Chewing gum mass according to Preparation 3 2993.0 grams Labeling 100 r 10 grams Nicfilimi. 100 H) gram Monosodium fumaratc 6.54 grams Loheline, 100 71 (CZZH-HNOZ) L0 gram Adipic acid 5.34 grams 5 5 CHEWING TESTS EX M 10 The chewing gums in the following examples refer to 1000 Pieces of chewing gum each containing 3 mg of a formulanmf Prepamd 'f l 9 Preparatmn nicotine as base and an excess of acid (4 equivalents Each chwmg gum 0r Plece 1S composed of mole of alkaloid). present as monosodium-citrate. gram of thls mass EXAMPLE l5 Chewing gum containing a 10 percent complex is ob- Chcwing gum mass according to Preparation 1 989.0 grams mined from 3 mg of nicotine bound to Silicic acid Nicotine. 100 Z grams O00 Mumsodiumcmme 793 grams Chewing gum mass according to Preparation 1,
pieces of gum per 1970 grams of the mass. Silicic acid 10 percent nicotine complex 30.0 grams.
EXAMPLE 16 Chewing gum containing a 10 percent complex, obtained from 2.5 mg. of nicotine bound to silicic acid, and likewise a 20 percent complex, obtained from 2.5 mg. of nicotine bound to silicic acid.
Chewing gum mass according to Preparation 2, 1000 pieces of gum per 1835 grams of the mass.
Silicic acid 10 percent nicotine complex 25.0
grams.
Silicic acid 20 percent nicotine complex 12.5
grams.
EXAMPLE 17 Chewing gum containing a 30 percent complex, obtained from 1 mg. of nicotine bound to silicic acid.
Chewing gum mass according to Preparation 3, 1000 pieces of gum per 3325 grams of the mass.
Silicic acid 30 percent nicotine complex 3.33
grams.
EXAMPLE 18 Chewing gum containing a 30 percent complex, obtained from 2 mg of lobeline bound to silicic acid.
Chewing gum mass according to Preparation 3, 1000 pieces of gum per 3325 grams of the mass.
Silicic acid 30 percent lobeline complex 6.67 grams.
EXAMPLE 19 Chewing gum containing a 20 percent complex, ob tained from 1 mg of lobeline bound to silicic acid, and likewise a 35 percent complex obtained from 1 mg. of nicotine bound to silicic acid.
Chewing gum mass according to Preparation 1, 1000 pieces of gum per 1565 grams of the mass.
Silicic acid 20 percent lobeline complex 5.0 grams.
Silicic acid 35 percent nicotine complex 2.86
grams.
EXAMPLE 20 Chewing gum containing a 10 percent complex, ob-
tained from mg of nor-nicotine bound to silicic acid.
Chewing gum mass according to Preparation 2, 1000 pieces of gum per 450 grams of the mass.
Silicic acid percent nor-nicotine complex 50.0
grams.
EXAMPLE 21 Chewing gum containing a percent complex, obtained from 2 mg of nicotine bound to silicic acid, and likewise a 10 percent complex obtained from 1 mg. of nor-nicotine bound to silicic acid.
Chewing gum mass according to Preparation 1, 1000 pieces of gum per 2975 grams of the mass.
Silicic acid 15 percent nicotine complex 13.33
grams.
Silicic acid 10 percent nor-nicotine complex 10.0
grams.
Preparation of chewing gums containing the other various alkaloid -absorbent 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.
EXAMPLE 22 Chewing gum containing 4 mg of nicotine as neutral nicotine sulfate and an excess of acid (4.8 equivalents mole of alkaloid salt), present as the cation exchanger Amberlite [RP 64M in hydrogen ionic form.
Chewing time minutes Mean value nicotine released mg EXAMPLE 23 Chewing gum containing 4 mg of nicotine as nicotine dihydrochloride, i.e. 2 equivalents of acid mole of alkaloid.
Chewing time minutes Mean value nicotine released mg We have found that it is possible to get a rather uniform extended release from a chewing gum upon chewing provided the alkaloid as such or as alkaloid salt is incorporated in a chewing gum formula containing a sufficiently high percentage of gum base. Among such chewing compositions those containing an excess of acid are more satisfactory as smoking substitutes, because they give a more pronounced feeling of smoking.
Preparation of chewing gums containing other formulation variants mentioned in the present application can be 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.
Table 1 below is a compilation of experimental results showing the amount of nicotine released as a function of time.
TABLE 1 RELEASED NlCOTlNE 1N PERCENT BY WEIGHT AS A FUNCTION OF TIME Al Chewing gum containing 4 milligrams of nicotine base and 1 gram chewing gum mass having a high gum base concentration, prepared in accordance with Preparation 1. Release brought about by chewing. Moderate feeling of smoking was b served.
A2 Chewing gum containing 4 milligrams of nicotine base and 3 grams chewing gum mass having a low gum base concentration, prepared in accordance with Preparation 4. Release brought about by chewing. The observed initial nicotine release rate is too rapid for this composition to be suitable as a smoking substitute.
Bl Chewing gum containing 4 milligrams of nicotine as neutral nicotine sulfate and 1 gram chewing gum mass having a high gum base concentration, prepared in accordance with Preparation 1. Release brought about by chewing. Moderate feeling of smoking was observed.
B2 Chewing gum containing 4 milligrams of nicotine as neutral nicotine sulfate and 3 grams of chewing gum mass having a low gum base concentration, prepared in accordance with Preparation 4. Release brought about by chewing. The observed initial release rate is too rapid for this composition to be suitable as a smoking substitute.
Cl Chewing gum containing 4 milligrams of nicotine as neutral nicotine sulfate and an excess of acid (4.8 equivalents of cation exchanger Amberlite lRP 64M in ionic hydrogen form per mole of the alkaloid salt) and 1 gram chewing gum mass having a high gum base concentration, prepared in accordance with Preparation 1. Release brought about by chewing. Very pronounced feeling of smoking was observed.
C2 Chewing gum containing 4 milligrams of nicotine as neutral nicotine sulfate and an excess of acid (4.8 equivalents of cation exchanger Amberlite [RP 64M in ionic hydrogen form per mole of the alkaloid salt) and 3 grams chewing gum mass with low gum base concentration, prepared in accordance with Preparation 4. Release brought about by chewing. The observed initial release rate is too high for this composition to be suitable as a smoking substitute.
D Chewing gum containing 4 milligrams of nicotine as nicotine dihydrochloride (i.e., containing 2 equivalents of acid per mole of alkaloid) and 1 gram chewing gum mass having a high gum base concentration, prepared in accordance with Preparation l. Release brought about by chewing. Very pronounced feeling of smoking was observed.
From the data in the foregoing Table it is readily apparent that the presence of a high gum base concentration is essential for a satisfactory smoking composition which provides a substantially uniform, extended release of the alkaloid either in the form of a base or as a salt. Moreover, in compositions C1 and D the presence of an excess of an acid provided a more pronounced feeling of smoking.
DETERMINATION OF NICOTINE lN CHEWING GUM Apparatus. Spectrophotometer Beckman DU.
Determination. Homogenize one chewing gum with a 20 g seasand in a mortar under ether. Transfer the ho mogenous mixture to a glass column with a glass wool plug at the bottom. Elute the column with ca. 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 my" Calculate corr mu.r min E282) E (corr) has been determined to be 338 lcm E X 1000 X 250 W mg nicotine/chewing gum The method is applicable also to chewed gums for determination of remaining nicotine.
A detailed example of the preparation of a smoking substitute composition is given below.
EXAMPLE 24 About 400 grammes natural gum base is put into a hot jacketed mixer fitted with stirrers. The mixer is heated by steam at about 15 lbs. per sq. inch. The stirrers are run at intervals to turn the base over. A low steam pressure is selected to prevent overheating of the base. After the base is completely melted the steam is turned off in the mixer and cold water is run through the jacket to reduce the temperature of the contents to about 85C. 460 Grammes of powdered sugar (300 mesh sieve), grammes Corn syrup 45 Baume, 5 grammes of glycerine, l0 grammes of flavouring oil, 5.3 grammes of nicotine sulfate and 12 grammes Amberlite [RP 64M (9.9 meq. acid/gram) are then added to the melted base in the mixer and the mass is mixed for about fifteen minutes. The mixture will now have a temperature of between 60 to 75C, or lower.
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 of the resultant pieces. Each piece generally weighs between 1 and 3 grammes. In this Example, 1000 pieces, each weighing about one gram, 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 percent and the pieces are preferably stored at a temperature of 18 to 20C and a relative humidity of 45 to 50 percent.
It will be appreciated that combinations of alkaloid with gum other than those demonstrated in the foregoing Examples can be used and that combination with other flavouring agents, sweetening agents, binders and such additives can also be used.
Some Preparations and Examples are now given exemplifying the use of an alkaloid-regenerative adsorbent complex. It should be realized from what has been said before that these compositions may not be preformed but may in fact be formed simultaneously with the incorporation of the complex into the compositions. All precentages indicated are by weight. Preparation A nicotine-adsorbent complex containing 200 mg. of nicotine in 800 mg. of absorbent in the dry state, i.e., a 20 percent compound (complex) The moisture content of the adsorbent is determined by drying in an oven at 105C. to a constant weight.
100.0 Grammes of silicic acid (Aerosil T.M.), calculated as dry, are added to a beaker containing 25.0 grams nicotine, calculated as 100 percent, diluted to a total volume of 500 ml. by an addition of distilled water. The mixture is fully homogenized by stirring and afterwards dried to a weight of 125 grams at about 40C in a drying cabinet provided with fan.
The nicotine-adsorbent complex thus obtained is then analyzed with reference to the nicotine content after careful blending and sieving through a 300 mesh sieve.
Preparation of other various alkaloid-adsorbent 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 adsorbents.
Table II below is a compilation of experimental results showing the amount of nicotine released as a function of time.
TABLE 1] RELEASED NlCOTlNE lN PERCENT BY WEIGHT AS A FUNCTION OF TlME Composition El E2 Time. min.
tion, prepared in accordance with Preparation 4. Release brought about by chewing. The observed initial nicotine release rate is too rapid for this composition to be suitable as a smoking substitute. 5 Many regenerative adsorbents such as amorphous silica, silicic acid, clays, and the like are suitable for use in the preparation of the smoking substitutes. A detailed example of the preparation of one of the smoking substitutes is presented below.
EXAMPLE 18 A nicotine-silicic acid complex with Aerosil T.M. was prepared by the method described in Preparation 5, the resultant complex containing 10 percent 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 square inch. The stirrers are run at intervals to turn the base over. A low steam pressure is selected to prevent overheating of the base. After the base is completely melted, the steam is turned off in the mixer and cold water is run through the jacket to'reduce the temperature of the contents to about 85C. 840 Grammes of powdered sugar (300 mesh sieve) and 276 grammes corn syrup 45 Baume are then added to the melted base in the mixer and the mass is mixed for about fifteen minutes. The mixture will now have a temperature of between 60 to 75C.
A further 420 grammes of powdered sugar and 30 grammes of the nicotine-silicic acid 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 fifteen 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
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 afterward is however fairly conventional extruder stick of gum should be well-dusted with starch It will be appreciated that combinations of alkaloidsilicic acid complexes with gum other than those demonstrated in the foregoing Examples can be used and that combinations with other regenerative adsorbents, fiavouring agents, sweetening agents, binders and such additives can also be used.
The foregoing discussion and examples are intended as illustrative and are not to be construed as limiting. Still other variations within the spirit and scope of the present invention will readily present themselves to one skilled in the art.
We claim:
1. A chewable substitute for smoking gum composition, having a high percentage of gum base, as said high percentage is hereinafter defined, comprising:
1. a chewing gum base and 2. nicotine, 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 a relatively high percentage, that is, an amount constituting at least about 40 percent by weight 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 distributed in said chewing gum base is in the range of about 1 to about milligrams, such amount of nicotine approximating the amount available upon smoking a smoking tobacco product;
E. the nicotine being present in said gum composition as a nicotine compound selected from the group consisting of a. a nicotine free base,
b. a pharmacologically-acceptable salt of nicotine,
and
c. a nicotine-regenerative adsorbent complex comprising a compound selected from the group consisting of nicotine and a pharmacologicallyacceptable salt of nicotine sorbed on a regenerative adsorbent;
F. said chewing gum composition when chewed releasing nicotine in small and reduced amounts within a period of the first few minutes of chewing, and
G. especially within the first ten minutes of chewing releasing the nicotine at a rate less than if the nicotine were present in an ordinary chewing gum composition, having a relatively low percentage of chewing gum base, that is, an amount constituting less than about 40 percent by weight of the gum composition.
2. The chewing gum composition of claim 1 wherein the amount of nicotine 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. The composition of claim 1, wherein the nicotine is present as a nicotine-regenerative adsorbent complex.
Claims (6)
1. A CHEWABLE "SUBSTITUTE FOR SMOKING" GUM COMPOSITION, HAVING A "HIGH PERCENTAGE" OF GUM BASE, AS SAID "HIGH PERCENTAGE" IS HEREINAFTER DEFINED, COMPRISING:
1. A CHEWING GUM BASE AND
2. The chewing gum composition of claim 1 wherein the amount of nicotine 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, 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 a relatively high percentage, that is, an amount constituting at least about 40 percent by weight 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 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. the nicotine being present in said gum composition as a nicotine compound selected from the group consisting of a. a nicotine free base, b. a pharmacologically-acceptable salt of nicotine, and c. a nicotine-regenerative adsorbent complex comprising a compound selected from the group consisting of nicotine and a pharmacologically-acceptable salt of nicotine sorbed on a regenerative adsorbent; F. said chewing gum composition when chewed releasing nicotine in small and reduced amounts within a period of the first few minutes of chewing, and G. especially within the first ten minutes of chewing releasing the nicotine at a rate less than if the nicotine were present in an ordinary chewing gum composition, having a relatively low percentage of chewing gum base, that is, an amount constituting less than about 40 percent by weight of the gum composition.
2. NICOTINE, 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 A RELATIVELY HIGH PERCENTAGE, THAT IS, AN AMOUNT CONSTITUTING AT LEAST ABOUT 40 PERCENT BY WEIGHT OF SAID GUM COMPOSITION; C. THE NICOTINE IS PRESENT IN SAID COMPOSITION IN AN AMOUNT IN THE RANGE OF ABOUT 0.05 WEIGHT OF THE CHEWING GUM WEIGHT PERCENT BASED ON THE WEIGHT OF THE CHEWING GUM BASE AND CALCULATED AS THE FREE BASE; D. THE AMOUNT OF NICOTINE DISTRIBUTED IN SAID CHEWING GUM A. A NICOTINE FREE BASE, SUCH AMOUNT OF NICOTINE APPROXIMATING THE AMOUNT AVAILABLE UPON SMOKING TOBACCO PRODUCT; E. THE NICOTINE BEING PRESENT IN SAID GUM COMPSOTION AS A NICOTINE COMPOUND SELECTED FROM THE GROUP CONSISTING OF A. A NICOTINE FREE BASE, B. A PHARMACOLOGICALLY-ACCEPTABLE SALT OF NICOTINE, AND C. A NICOTINE-REGENERATIVE ADSORBENT COMPLEX COMPRISING A COMPOUND SELECTED FROM THE GROUP CONSITING OF NICOTINE AND A PHARMACOLOGICALLY-ACCEPTABLE SALT OF NICOTINE SORBED ON A REGENERATIVE ADSORBENT; F. SAID CHEWING GUM COMPOSITION WHEN CHEWED RELEASING NICOTINE IN SMALL AND REDUCED AMOUNTS WITHIN A PERIOD OF THE FIRST FEW MINUTES OF CHEWING, AND G. ESPECIALLY WITHIN THE FIRST TEN MINUTES OF CHEWING RELEASING THE NICOTINE AT A RATE LESS THAN IF THE NICOTINE WERE PRESENT IN AN ORDINARY CHEWING GUM COMPOSITION, HAVING A RELATIVELY LOW PERCENTAGE OF CHEWING GUM BASE, THAT IS, AN AMOUNT CONSTITUTING LESS THAN ABOUT 40 PERCENT BY WEIGHT OF THE GUM COMPOSITION.
3. The composition of claim 1, wherein the nicotine is present as a nicotine-regenerative adsorbent complex.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US437031A US3877468A (en) | 1970-07-22 | 1974-01-28 | Chewable tobacco substitute composition |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB3560570 | 1970-07-22 | ||
GB3560670 | 1970-07-22 | ||
US16410571A | 1971-07-19 | 1971-07-19 | |
US437031A US3877468A (en) | 1970-07-22 | 1974-01-28 | Chewable tobacco substitute composition |
Publications (1)
Publication Number | Publication Date |
---|---|
US3877468A true US3877468A (en) | 1975-04-15 |
Family
ID=27448864
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US437031A Expired - Lifetime US3877468A (en) | 1970-07-22 | 1974-01-28 | Chewable tobacco substitute composition |
Country Status (1)
Country | Link |
---|---|
US (1) | US3877468A (en) |
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