DE2136119C3 - Chewing gum as a substitute for tobacco products - Google Patents

Description

The invention relates to a chewing gum product which is suitable as a substitute for tobacco products, containing a Chewing gum base, tobacco alkaloids and possibly other common chewing gum ingredients that thereby is characterized as being dispersed in the gum base, nicotine or a pharmacologically contains compatible nicotine salt bound to a cation exchanger, the Msnge der Chewing gum base 15 to 80% by weight and the amount of nicotine, calculated as the free base and based on the weight of the chewing gum base, is 0.05 to 2% by weight.

The chewing gum product according to the invention is a substitute product for smoking products that is chewed and is particularly valuable to facilitate the transition to non-smokers and / or to reduce the number of people the need to smoke.

Ingestion of nicotine, usually from smoking cigarettes, cigars, or pipes, can stimulate. However, smoking can be detrimental to health, so it is desirable Find another mode of nicotine administration that will help facilitate smoking cessation and / or can be used as a substitute for smoking.

Nicotine-containing products that can be chewed or snorted are known, but they are not very satisfactory. Examples of such products include: described in US-PS 8 65 026 and 9 04 521, after which finely ground tobacco, e.g. B. snuff, is mixed into chewing gum.

The GB-PS 7 11 187 describes a chewing gum product in which a tobacco powder, pepsin and a filler were kneaded. The tobacco powder was made by drying tobacco at relatively high temperatures obtained from about 150 ° C and subsequent grinding. It was known at the time that chewing tobacco and snuff were already around earlier and that the rates of release for the tobacco alkaloids in the mouth when they come into contact with saliva are very different. Chewing tobacco, for example, has a very slow release rate of tobacco alkaloids when not chewed will. The rate of release for the tobacco alkaloids of snuff in contact with saliva in the mouth is higher than that of chewing tobacco and requires no chewing. But if a dried tobacco powder, as it is used according to GB-PS 7 11 187, with

If saliva is brought into contact, the release of tobacco alkaloids is undoubtedly faster than with snuff. On the other hand, there is a very large difference in the rate of release of tobacco alkaloids from any type of tobacco product compared to pure nicotine or nicotine salt, which is immediately released when it comes into contact with saliva in the mouth. In GB-PS 7 11 187 the proposal was made for the first time to incorporate a tobacco preparation, namely dried tobacco powder, into a chewing gum composition in order to obtain a product which should be suitable as a tobacco product substitute. The problem arose that the release of the alkaloids from the chewing gum product containing the tobacco powder, even after drying and grinding the tobacco during chewing, was far too low to be accepted by a smoker. For this reason, the pepsin was added in order to accelerate the release of the tobacco alkaloids through an enzymatic reaction with the tobacco powder. The drying temperature of about! 5O ⁰ C made the tobacco powder permeable to the pepsin and the saliva and thus supported the release.

In contrast to this, the invention relates to a chewing gum product which is suitable as a tobacco product substitute and which does not contain dried tobacco powder but rather nicotine in the form of the free base or a nicotine salt. In this case, a useful release rate that would give an acceptable tobacco substitute for a smoker had to be achieved in some other way, since the difficulty was not in accelerating the release of the alkaloids from the tobacco powder, but in accelerating the release of the nicotine base or nicotine salt to be adjusted or delayed in such a way that a "feeling of smoking" is produced in the smoker's mouth when used. According to GB-PS 7 11 187 it was by no means to be expected that the composition of the chewing gum product according to the invention would be suitable as a tobacco product substitute.
From GB-PS 9 24 052 a shaped product is known which, in contrast to a chewing gum product, is elastic and regains its shape even after chewing and z. B. can be prepared by first absorbing an aqueous tobacco extract on an ion exchange resin, then mixing the resin granules with tobacco extract with a water-soluble powder such as gelatin powder, adding the mixture to a rubber latex emulsion and spreading it out and allowing it to dry on a plate. Part of the plate obtained in this way is finally surrounded by a rubber sheet with small holes in it. When such a shaped product is put into the mouth, saliva passes through the holes in the casing into the inside of the casing and dissolves the gelatin powder there.

Then the saliva can also get to the ion exchange resin and from this components of the to release absorbed tobacco extract. A chewing gum should be used for the molded, elastic product

cannot be used.

The chewing gum according to the invention is in contrast to the elastic, molded product of GB-PS 9 24 052 is a plastic product that just does not retain its shape when chewed or Regained When chewing gum are known to be by squeezing and stretching the plastic chewing gum base is constantly forming new surfaces. Constantly chewing on them The nicotine dispersed in the chewing gum base is then released from newly formed surfaces

The chewing gum product according to the invention is much safer than the molded product of GB-PS 9 24 052. In fact, when this shaped product is swallowed, all of it is released in the stomach Alkaloids. But when the chewing gum of the invention is swallowed, it travels through the body, without nicotine being released, since the nicotine is released from the chewing gum product according to the invention a chewing process is absolutely necessary, in which new surfaces are constantly being formed. In contrast is through the holes in the shell of the product of GB-PS 9 24 052 and the water solubility of the incorporated gelatin powder ensures that aqueous liquids adhere to the ion exchange resin can release absorbed components of the tobacco extract.

When nicotine is incorporated into chewing gum products of the type commonly used today, the is released Nicotine very quickly. This is disadvantageous for two reasons: If the nicotine is released too quickly, then higher levels of nicotine are produced in the blood than when smoking habitually; further is the Effect of the replacement product too short.

The invention is based on the object of providing a chewing gum product that releases nicotine so slowly gives that the product mimics the effect of nicotine intake by smoking satisfactorily will.

Even if from W. A. Ritschel, »Die Tablette«, page 45, the slow release of ion exchange resins bound alkaloids or from J. Chem. Soc. 1952, 2111 quantitative information on the absorption of nicotine on carboxylic acid ion exchangers or from US Pat. No. 3,109,436 various ion exchange resins were known for binding nicotine, it must be regarded as surprising that the Invention underlying task to find a substitute for tobacco products, the nicotine with a "Feeling of smoking" inducing speed in the mouth of the smoker, and is also accepted by smokers, is dissolved with a piece of chewing gum can be incorporated into the nicotine bound to a cation exchanger. The characteristics of the invention cause the release of nicotine from the chewing gum according to the invention in is controlled in two ways, namely on the one hand by the fact that the chewing process surfaces be released, with which the saliva comes into contact, and on the other hand by that then the saliva has to dissolve the nicotine from the complex with the ion exchanger.

An ideal substitute for tobacco products in the form of chewing gum should have the following properties:

(a) The release of nicotine should be steady over a not too short period of time;

(b) the release of nicotine should be almost even

65 Big, even if different gum bases are used;

(c) Without changing the gum base, the rate of release of nicotine should be can be changed as it is desirable, for example, when using lower amounts of nicotine can be to increase the release speed somewhat to satisfy the consumer;

(d) The nicotine released should not only be absorbed by the bloodstream but also in the Produce a "feeling of smoking" in the mouth. This is very important because when the Nicotine without a taste sensation, excessive use of the substitute product without the The satisfaction obtained from smoking may occur, resulting in a relapse to habitual smoking can result;

(e) Incorporation of the nicotine into the chewing gum ware should be easy to do while ensuring an essentially even distribution.

Surprisingly, it has now been found that all of these advantages are achieved by giving nicotine to one Cation exchanger binds and in this form in the generation of the caused by smoking Satisfying sufficient amount incorporated into a chewing gum product. The invention thus becomes a Tobacco substitute provided that contains a gum base and nicotine that is produced by a Cation exchanger is kept in dispersion. The amount of nicotine in a chewing gum unit can fluctuate within wide limits. So can from 0.05 to 2 wt .-% nicotine, based on the weight of the Chewing gum base and calculated as the free base. Usually chewing gum units contain 1 to 10 mg, preferably 1 to 5 mg of nicotine.

When the nicotine is bound to a cation exchanger, it is incorporated into the gum base a variety of gum compositions can be used. The chewing gum manufacturer can thus the solid complex of nicotine and cation exchanger in its existing chewing gum mass incorporate without this having to be changed. It is also possible to have different flavors to satisfy.

The rate of release of nicotine from the chewing gum can be changed by the amount of nicotine bound to a given amount of the cation exchanger varies relatively larger Nicotine levels result in faster delivery and vice versa. The phrase "slow release" is supposed to mean that the majority of the nicotine from the chewing gum product is essentially uniform over the course of several minutes and preferably in the course of at least 10 minutes. The release time is particularly preferably at least 20 minutes.

The complex containing nicotine bound to the cation exchanger is preferably in a special unit made. The complex so produced is easy to handle, and thus be Sources of error in the production of the finished chewing gum are kept to a minimum. It could also be shown be that the complex acts as a lubricant, so that the mixing of the individual components to form the chewing gum product is facilitated. A homogeneous product is easily obtained in this way.

The cation exchanger used must have cation-exchanging groups so that a Forms complex with nicotine. These groups are preferably located in the prior to complex formation Hydrogen ion form.

The cation exchanger used can also contain anionic groups, in which case a Polyampholyte is present

The! '. Ationic exchange groups can be strong be acidic, slightly acidic or moderately acidic. Synthetic cation exchangers containing such groups are therefore referred to as strongly acidic, weakly acidic or medium acidic cation exchangers, depending on the the strength of the acid from which the functional groups are derived. Examples of suitable acidic groups are the carboxylic acid groups, sulfonic acid groups, phosphonous acid groups, phosphonic acid groups, Phosphoric acid groups, iminodiewigsäuregruppen or phenolic groups. If as cationic Exchanger groups phenolic groups are used, these groups should preferably be such arranged or used in such an amount that the acid strength is relatively high. Such Ion exchangers containing phenolic groups have been described by B. A. Adams and E. L Holmes in J. Soc. Chem. Ind. 54, IT (1935). It is possible to simply use any sharing scheme a suitable mixture of counter-ions in the same ion exchanger or a suitable one Mixture of different ion exchangers, including the exchanger for real compound ions and polyampholytes. It is also possible the release scheme by changing the amount of nicotine attached to a given amount of the cation exchanger is bound to change.

The usually synthetic cation exchanger must be non-toxic in the amounts used and should not add any undesirable taste to the finished products. These demands result however, no problem as the amount required to bind a sufficient amount of nicotine of cation exchanger is low.

The acidic groups of the cation exchanger, which can be referred to as cation exchange resin, can be attached to a crosslinked polymer, e.g. B. an addition polymer of styrene and divinylbenzene, from Divinylbenzul and methacrylic acid or from divinylbenzene and acrylic acid, or a phenolic resin, or on z. B. cellulose, dextran or pectin linked by epichlorohydrin.

The acidic groups can be converted to insoluble linear polymers, e.g. B. cellulose bound whereby mainly uronic acid groups are formed. Also carboxymethyl cellulose, sulfoethyl cellulose and cellulose sulfate can be used. To make sure that the the acidic groups containing cellulose polymers are insoluble in saliva, the number of acidic groups must be relatively low be, for example, maxim, *! an acidic group amount to 3 glucose units each. Connections of this kind are by Ott and Spurlin in Cellulose and Cellulose Derivatives, Parts I and II, Interscience, New York (1954). Typical cation exchangers that are used to produce the chewing gum product according to the invention are suitable are crosslinked polymers containing carboxyl groups of divinylbenzene and methacrylic acid or acrylic acid, crosslinked polymers of styrene and divinylbenzene containing sulfonic acid groups, Phenolic polymers containing sulfonic acid groups, phosphonous acid groups crosslinked polymers of styrene and divinylbenzene, crosslinked containing phosphonic acid groups Polymers of styrene and divinylbenzene, phenolic polymers containing phosphonic acid groups, Crosslinked polymers of styrene and divinylbenzene containing iminodiacetic acid groups, carboxymethyl groups containing dextran polymers and sulfoethyl group-containing dextran polymers.

The 4 cation exchange resins described in more detail below with regard to characteristics and properties have been found to be particularly suitable for use in the chewing gum products of the invention and will later be used as ion exchange resins No. 1, 2, 3 and 4 are often mentioned again

The ion exchange resin No. 1 is a weakly acidic, crosslinked polymer containing carboxyl groups from divinylbenzene and methacrylic acid, whose cation-exchanging groups are in the hydrogen ion form are present. Although this resin is a gel resin, it reacts like a relatively highly porous resin. It has a pK value in 1 molar potassium chloride solution of about 6.0, an exchange capacity after drying in the Drying cabinet of 10.3 meq / g, a particle size of 40 to 150 μm and a content of external water of a maximum of 5.0% (Amberlite IRP 64®).

The ion exchange resin No. 2 is also a weakly acidic, carboxyl group-containing crosslinked one Polymer of divinylbenzene and methacrylic acid, whose cation-exchanging groups are in the Hydrogen ion form. This resin also reacts like a relatively highly porous resin, although it is a Gel resin is. The pK value in i-molar potassium chloride solution is also about 6.0, the exchange capacity after drying in the drying cabinet 10.3 meq / g and the content of external water a maximum of 5.0%. the Particle size is smaller, however, since 95% of the particles have a size below 40 μm (Amberlite IRP 64 M®).

The ion exchange resin No. 3 is a strongly acidic, Crosslinked polymer of styrene and divinylbenzene containing sulfonic acid groups, its cations exchanging groups are present in a hydrogen ion form converted from sodium ions. That Resin reacts like a resin with normal gel porosity. It has a pK value in 1 molar potassium chloride solution of about 1.3, an exchange capacity after drying in a drying cabinet of 5.2 meq / g, a particle size, in which 95% of the particles are smaller than 40 μπι, and a content of external water of a maximum of 10.0% (Amberlite IRP 69 M®).

The ion exchange resin No. 4 is a moderately acidic, phosphonic acid group-containing crosslinked resin Polymer made of styrene and divinylbenzene, the cation-exchanging groups in one of sodium ions converted hydrogen ion form are present. The resin reacts like a resin with a relatively large Porosity. It has an exchange capacity after drying in the drying cabinet of 6.6 meq / g, one Particle size from 75 to 150 μm and a content of external water of a maximum of 4.0 (BIO-REX 63®).

The amount of nicotine bound to a cation exchange, of water-soluble, physiologically compatible Nicotine salts or mixtures thereof, depending on the conditions used and the type of the ion exchanger used can be varied. Complexes of nicotine and ion exchangers with one

Nicotine content of about 2 to 60% by weight nicotine, preferably 5 to 35% by weight nicotine, based on the Weight of the ion exchange complex, are for use in the chewing gum product according to the invention particularly suitable, the preferred range is for ion exchangers which contain carboxyl groups about 5 to 35%, while the preferred range for ion exchangers containing phosphonic acid groups is about 5 to 30%, and furthermore the preferred range for ion exchangers containing sulfonic acid groups is about 5 to 25%, again the

to

Percentages refer to percent nicotine, calculated on the complex of exchanger and nicotine. Eir Part of the nicotine can get to the ion exchanger by surface adsorption and not by actual be bound before ion exchange reaction.

The following list shows suitable and preferred amounts of nicotine for manufacture ment of complexes with the ion exchangers listed in the chewing gum according to the invention goods can be used:

Complex of nicotine and ion exchanger

% Nicotine by weight based on the weight of the complex

Complex of ion exchange resin No. 1 or No. 2 or other crosslinked polymers containing carboxyl groups Divinylbenzene and methacrylic acid or acrylic acid with nicotine complex of ion exchange resin No. 3 or other sulfonic acid groups containing crosslinked polymers of styrene and divinylbenzene with nicotine

Complex of ion exchange resin No. 4 with nicotine complex of groups containing phosphonic acid crosslinked polymers of styrene and divinylbenzene with nicotine complexes containing sulfonic acid or phosphonic acid groups phenolic polymers with nicotine

Complex of crosslinked polymers of styrene and divinylbenzene containing iminodiacetic acid groups with nicotine Complex of dextran polymers containing carboxymethyl groups with nicotine

Complex of dextran polymers containing sulfoethyl groups with nicotine

2-60, preferably 5-35

2-35,

preferably 5-25 or 5-20

2-40, preferably 5-30
2-35, preferably 5-25

2-25, preferably 5-15
2-25, preferably 5-15
2-30, preferably 5-20
2-15, preferably 5-10

The chewing gum base of the chewing gum product according to the invention can be a conventional chewing gum base and consist of a natural product or a synthetic product. Natural rubbery Basic masses are for example Chicle-, Jelutong-, Lechi di Caspi-, Soh-, Siak-, Katiau-, Sorwa-, Balata-, Pendare, Perillo, Malaya and Percha types of rubber as well as natural rubber or natural resins, such as for example dammar and mastic.

Examples of synthetic chewing gum bases

oiiiu ι vMjr "iiijia> _v-i.cm 1,111 ι iMjrio" jjji cn ^ vjuiia-rviMiicu hydrogen-containing commercial product, polyvinyl ester, polyisobutylene and non-toxic butadiene-styrene latices. 5Plasticizers and various plasticizers are generally contained in the commercially available chewing gum bases or are incorporated into them. These plasticizers help to reduce the viscosity of the gum mixture to the desired consistency and to improve the bonding of the base composition. Some common emollients or emollients are: lecithin, lanolin, hydrogenated coconut oil, hydrogenated cottonseed oil, mineral oil, olive oil, vasilin, carnauba wax, candellila wax, paraffin, beeswax, stearic acid, glycerin monostearate, glycerin, honey, propylene glycol, and hexylene glycol Sorbitol These plasticizers also act as humectants at the same time. Furthermore, the following additional ingredients can optionally be incorporated into the chewing gum base: cerelose, mannitol, diastatic malt, starch, calcium carbonate, talc, defatted cocoa flavorings and food colors. If sugar in the form of sucrose or glucose, for example corn syrup, usually represents the main part of a chewing gum mass, completely sugar-free and / or glucose-free chewing gum mass can also be used to produce the chewing gum products according to the invention, with equally good results! will.

For the production of chewing gum products according to the invention The chewing gum component can be formulated from the following ingredients: The synthetic or natural chewing gum base, which is preferably of synthetic origin, can be present in the chewing gum would be 15 to 80% by weight, preferably 50 to 80% by weight and in particular 60 to 75% by weight Icing sugar, preferably powdered sorbitol, can be ir an amount of 15 to 80% by weight, preferably 16 to 40% by weight and in particular 20 to 32% by weight to be available. Corn syrup, usually at 41 to 46 ° Baume, preferably about 70% aqueous Solution of sorbitol, can in an amount of 4 to 3C wt .-%, preferably 4 to 10 wt .-% and in particular 5 to 8 wt .-% be present. Special formulations for chewing gum, for example sugar-free Chewing gum mixtures can comprise up to 80% of the preferably synthetic chewing gum base (see preparation 13 below).

Changes in consistency, on the one hand the initial consistency at the beginning of chewing and on the other hand the secondary consistency after some chewing can be achieved simply by changing the proportions achieved in the above formulation. The consistency and adhesion of the chewing gum product can be improved by adding various substances of the above kind are affected.

Chewing gum products according to the invention can be made by simply adding the chewing gum base mixes with the complex of nicotine and cation exchanger. The complex lies in the form of a finely divided cation exchanger, then it can be mixed directly with the chewing gum base. However, if the complex has the form of coarser ion exchange particles, then it is advisable to to marry them first. Mixing is preferably carried out at suitable elevated temperatures, which depend on the viscosity of the chewing gum mass, since higher temperatures increase the viscosity of the Gums is lowered so that you get the nicotine-cation exchange complex evenly and intimately with the Can combine gum mass. The particle size of the complex in the rubber should be so small that one Damage to the teeth when chewing is avoided.

The chewing gum product according to the invention is expedient directly with the incorporation of other additives such as Corn syrup, sugar, sorbitol and flavorings are made into the gum base. The chewing gum can for example in a suitable boiler, e.g. B. a mixer provided with a steam jacket will. This is heated, the gum base is added and mixed until practically none Lumps are more present. Then sorbitol or. Corn syrup and sugar added. The crowd will cooled, rolled out, cut up and hardened sufficiently, if necessary coated, before finally is wrapped or analyzed. Controlled humidity storage rooms provide a suitable one Safe moisture content and prevent the gum from »exuding«. Preferably will be straight sufficient heat is applied to the gum base to the extent necessary for mixing soften. The addition of sugar and syrup lowers the temperature and the nicotine-cation-exchange complexes and, if applicable, flavors are only added when the mixture has cooled down sufficiently. This will make it uncontrollable Loss of nicotine and / or aroma is significantly reduced. so

The weight of a chewing gum unit, e.g. B. a rod or a ball can, as usual, be 0.5 to 4.0 g and is preferably 1.0 to 3.0 g.

The weight fraction of the nicotine-cation exchanger complexes, based on the total weight of the chewing gum product, is not critical, but ranges between an upper and lower limit specific to the formulation in question. Chewing gum products which have about 0.1 to 10, preferably 0.2 to 5 and particularly preferably 0.5 to 2% by weight of nicotine-cation exchanger complex, based on the total weight of the chewing gum product, have proven to be suitable.

Some preparations are given below by way of illustration. Preparation 1 explains the production of a cation exchanger complex which can be used according to the invention, while preparations 2 to 13 explain suitable chewing gum compositions. For the purposes of the invention, however, such masses do not have to be preformed, but can be produced simultaneously with the incorporation of the complex.

Preparation 1

Nicotine cation exchange complex

with a content of 200 mg nicotine in 800 mg ion exchange resin No. 2

Ion exchange resin # 2 was dried in an oven at 105 ° C to constant weight.

100.0 g of the ion exchange resin was placed in a beaker containing 25.0 g of nicotine (as 100% calculated), and made up to a total volume of 500 ml with distilled watercourse. The mixture was stirred with a magnetic stirrer for at least 1 hour. The loaded ion exchanger was then filtered off or centrifuged. The filter cake was broken into pieces and stored in one with a at about 20 ° C Fan-equipped drying chamber dried. The nicotine cation exchange complex was then after careful mixing and sieving through a sieve with a mesh size of 0.059 mm analyzed for its nicotine content.

The preparation of further nicotine-cation exchange complexes for the following examples was carried out carried out according to the procedure of the above preparation. Refer to the following preparations all percentages are based on weight.

Preparation 2 14.5% Granulated sugar Condensed sugared milk 4.5% (low fat content) 30.0% Glucose powder 20.0% Chicle gum 30.0% powdered sugar 1.0% Tolu balm Preparation 3 Containing polyisoprene 16.9% Commercial product ¹ y 22.5% Glucose powder 60.0% powdered sugar 0.3% water 0.3% Glycerin

') »Dreyco« ⁸ (a commercially available chewing gum base, consisting of 5 to 8% gutta hydrocarbons, 30 to 40% resins, 18 to 25% plasticizers and 30 to 40% water-insoluble additives, whereby all components comply with the food law regulations of V. St A . correspond)

Preparation 4

Natural chewing gum base 22.0% Icing sugar 64.0%

Corn syrup 45 ° Baume 14.0%

Preparation 5

Natural chewing gum base 22.0% Diastatic malt 1.0% Corn syrup 44 ° Baum6 15.0% Powdered sugar 60.0% Calcium carbonate 2.0%

Preparation 6

Natural gum base Diastatic malt

Invert sugar

Corn syrup 44 ° Baume

powdered sugar

Cerelose

Preparation 7 (summer formulation) Natural chewing gum bulk powdered sugar

Corn syrup 45 ° Baume

Calcium carbonate

Starch powder

Preparations (winter formulation) Natural chewing gum base powdered sugar

Corn syrup 44 ° Baume

Calcium carbonate

Starch powder

Preparation 9 (adhesive rubber)

Adhesive rubber base
powdered sugar
Glucose powder
Corn syrup 45 ° Baume
Glycerin
flavoring oil

Preparation 10 (bubble gum) Bubble gum base
powdered sugar
Glucose powder
Corn syrup 45 ° Baume
Glycerin
flavoring oil

22.0%

2.0%

5.0%

13.0%

51.0%

7.0%

22.0%

50.0%

24.0%

2.0%

2.0%

22.0%

53.0%

21.0%

2.0%

2.0%

19.9% 54.5%

9.9% 14.9%

0.2-0.5%

0.6%

18.0% 55.9%

9.0% 16.2%

0.2-0.7%

0.6% The following examples show the chewing gum products of the invention. Any of these chewing gum products was made by heating the gum base in a kettle and adding the various additives prepared according to the above general procedure.

example 1

1000 pieces of chewing gum were made, each containing 3 mg of nicotine in the form of a 10% complex bound to ion exchange resin No. 2 and the chewing gum composition according to preparation 4 contained, for which 1970 g of the mass and 30.0 g of the nicotine complex were used.

Preparation 11 (sugar-coated chewing gum) Chewing gum base for

Sugar coating 22.0%

Icing sugar 55.1% Glucose powder 5.5%

Corn syrup 45 ° Baume 16.5% Glycerin 0.2-0.5%

flavoring oil 0.7%

The chewing gums are coated with white or colored sugar in conventional coating drums.

Preparation 12

(Sugar and glucose free formulation)

Natural chewing gum base 29.2%

Sorbitol powder 45.8%

Calcium carbonate 8.5%

Sorbitol, 70% aqueous solution 16.5%

Preparation 13

(Sugar and glucose free

High chewing gum base formulation)

Synthetic gum base 73.7% Sorbitol powder 19.8%

Sorbitol, 70% aqueous solution 3.8%

Glycerine 0.7%

flavoring oil 2.0%

Example 2

1000 pieces of chewing gum were made, each containing 2.5 mg of nicotine in the form of a 10% or 20% complex bound to ion exchange resin # 2 and the chewing gum mass according to preparation 4, including 1835 g of the mass and 25.0 g of the 10% and 12.5 g of the 20% Nicotine complexes were used.

Example 3

1000 pieces of chewing gum were made, each containing 1 mg of nicotine in the form of a 30% complex bound to ion exchange resin No. 2 and the chewing gum composition according to preparation 6 contained, for which 3325 g of the mass and 3.33 g of the nicotine complex were used.

Example 4

1000 pieces of chewing gum were made, each containing 3 mg of nicotine in the form of a 20% complex bound to ion exchange resin No. 3 and the chewing gum composition according to preparation 4 contained, for which 1485 g of the mass and 15.0 g of the nicotine complex were used.

Example 5

1000 pieces of chewing gum were made, each containing 4 mg of nicotine in the form of a 15% complex bound to ion exchange resin No. 4 and the chewing gum mass according to preparation 4 contained, for which 2025 g of the mass and 26.7 g of the nicotine complex were used.

Example 6

JO 1000 pieces of chewing gum were made, each containing 1 mg of nicotine in the form of a 35% complex bound to ion exchange resin No. 2 and the chewing gum composition according to preparation 12 contained, for which 1565 g of the mass and 2.86 g of the nicotine complex were used.

Example 7

1000 pieces of chewing gum were made, each containing 2 mg of nicotine in the form of a 15% complex bound to ion exchange resin No. 3 and the chewing gum mass according to preparation 13 contained, for which 987 g of the mass and 1333 g of the nicotine complex were used.

Example 8

1000 pieces of chewing gum were made, each containing 2 mg of nicotine in the form of a 15% complex bound to ion exchange

Resin No. 2 and the chewing gum composition according to preparation 4, including 2975 g of the composition and 13.33 g of the Nicotine complexes were used.

The manufacture of chewing gum with the other nicotine-cation exchange complexes above individually or as a mixture was carried out according to the procedure of the preceding examples.

In comparative tests it was found that the slow and controlled release of nicotine from the chewing gum products according to the invention was surprisingly a satisfactory rate of release of the Nicotine from nicotine-cation exchange complexes did not occur in the absence of chewing gum. the following table I! shows the results of experiments on the amount of nicotine released as a function of time.

Table 11 Al in% by weight in dependence of E. [ Released nicotine 18% A2 D. 64% currently 36% 66% Time 61% 18% 54% 66% (Min.) 91% 39% 70% 66% 2 65% 70% 5 92% 70% 10 20th

10

15th

20th

Al: chewing gum containing 20 mg of ion exchange resin per piece No. 2 to which the nicotine base (20% by weight nicotine) was complexed, and 1 g of high concentration chewing gum Chewing gum base, prepared according to Preparation 13. Release occurred while chewing. A pronounced feeling of smoking was observed.

A2: chewing gum containing 20 mg of ion exchange resin no.2 per piece, to which the nicotine base (20 % By weight nicotine) was bound in a complex, and 3 g of chewing gum composition with a low concentration Chewing gum base, prepared according to preparation 4. The release occurred while chewing. It was observed a distinct feeling of smoking.

D: Ion exchange resin No. 2 complexed with nicotine base (10% by weight nicotine). Releases With approximately 10 ml of No. 1 synthetic saliva below), in contact with 50 mg of the complex at 37 ° C.

E: The same complex as for D, released with 10 ml of physiological saline solution, which is mixed with 50 ml of des Complex came into contact at 37 ° C.

The following desorption and chewing tests were performed to determine release:

Desorption tests were carried out in vitro with the nicotine-cation exchanger complexes, without any training in chewing gum paste. In a series of experiments, 25 mg of the respective complex, which contained 5 mg of nicotine, for different times with 10 ml of water, physiological sodium chloride solution, 20% (weight / volume) sugar solution and saliva shaken. It was in a thermostat shaken at 20 ± 0.1 ° C and at 37 ± 0.1 ° C. Samples of the filtered solutions were analyzed for nicotine by UV examination. The ion exchange resins No. 2 and No. 3 gave the results shown below. With other ion exchangers were similar results achieved:

Total amount of nicotine released in mg / 10 ml

medium 37 C No. 3 37 C No. 3 NaCl solution 37C No. 3 37 ° C water 20 C No. 2 20 C Ion exchanger No. 2 20 C temperature 20 ° C 0.21 4.01 1.90 2.00 Time, minutes 3.68 1.93 2 0.22 3.88 1.95 5 0.23 3.96 1.96 10 0.23 0.25 0.01 3.98 4.11 1.97 2.01 15th 0.25 0.01 3.98 1.97 20th 0.25 4.08 Saliva 2 30th 0.27 No. 3 Saliva 1 No. 2 medium No. 2 No. 3 Sugar solution Ion exchanger No. 2

Temperature 20 ⁰ C 37 ° C 20 ⁰ C 20 ⁰ C 37 ° C 20 ° C 37 ^r C 20 ° C 37 ° C 2OC 37 ° C

Time, minutes

2 0.39 3.24

5 0.46 0.43 2.94 3.40 2.24 2.21 1.51

10 0.47 3.21 2.26 3.45 4.57 4.05

15 0.50

20 0.50 2.30

30 0.59 0.44 0.02 3.28 3.46 2.30 2.70 3.46 4.60 1.57 4.23

16

Media:
Water:

Physiological
NaCI solution:
Sugar solution:
Saliva 1:

2 χ distilled water passed through an ion exchanger;

0.9% in distilled water.
Sucrose, 20% in water

Saliva 2:

gelatin

Glycine

Aspartic acid

Phytin

NaHCO ₃

NaCl

KSCN

water

NaCl

CaCl ₂ · _{6H 2} O

CaCO ₃

Na ₂ HPO ₄ (dry)

Taka diastasis

cholesterol

water

2g
Ig
Ig
0.5 g

Ig
0.5 g
0.1g

ad 1000 ml
0.45 g
0.12 g
1.0 g
0.07 g
16.0 g
0.06 g

adlOOOml The quantity ratio between nicotine and ion exchanger was used with the various raw materials used in the following samples, varies:

Example 9

mg of nicotine per gram of the ion exchange resin complex No. 2 and nicotine.

10 chewing time.

2 5

15 20 30

15th

Mean Nicotine Released (mg) 1.9 2.6 3.2 3.3 4.2 4.4

20th

Example 10

mg nicotine per g of the complex of ion exchange resin No. 2 and nicotine.

It can be seen from the above results that equilibrium is reached very quickly. After 2 minutes there is no further approval. The addition of sugar does not affect the release. The ion exchange resin No. 3 apparently binds nicotine more strongly than ion exchange resin No. 2. The strength of the bond is of the same order of magnitude in saliva and physiological sodium chloride solution, but considerable less than in water and sugar solution.

With the exception of one case, there was no significant difference with regard to the release at 20 or 37 ° C observed. The test with artificial saliva # 2 showed a faster release at a higher temperature achieved. This saliva solution # 2 contains mucin, the

is also present in natural saliva. Therefore

The presence of mucin in human saliva probably explains the surprising effect of the

Initially quite rapid release of nicotine

Chewing of the chewing gum product according to the invention is observed. Without mucin, the desorption could mean for any practical use be too slow, especially 45 of the free with regard to the generation of the desired laws taste sensation. Nicotine

The phenomenon is particularly surprising in the case of the (mg) strongly acidic cation exchangers, e.g. B. No. 3, due to the fact that nicotine is usually so tightly bound that it is difficult to get out of it can be eluted.

The analytical data for nicotine given in the examples below were used in the following chewing test obtain:

2 people chewed the chewing gum for different lengths of time, the analysis results were recorded and the Mean values determined. The chewing gum masses used in the tests had the following composition:

Natural chewing gum base 22.0%
Powdered sugar 64.0%

Corn syrup 45 ° Baume 14.0%

Chewing time (minutes)
2 5 10

15 20 30

0.6 1.2 2.3 2.7 3.3 4.1

Mean value ₃₀ of nicotine released (mg) Example 11

mg nicotine per g of the complex of ion exchange resin No. 2 and nicotine.

Chewing time (minutes)

2 5 10 15 20 30

2.0 2.2 3.3 3.6 4.0 4.2

Example 12

mg nicotine per g of the complex of ion exchange resin No. 3 and nicotine.

Chewing time (minutes)
2 5 10

15 20

Mean value 60 of nicotine released (mg) 2.3 2.6 3.5 4.1 4.3 4.7

Each individual piece of chewing gum consisted of 3.0 g <, 5 this mass and a certain amount of a nicotine ion exchange complex with each 5.0 mg nicotine.

Example 13

mg nicotine per g of the complex of ion exchange resin No. 2 and nicotine.

030 225/96

Chewing time (minutes)

O 2 5 10 15 20

30th

0 3.1 3.8 4.4 4.5 4.6 4.8

Average
of the released
Nicotine
(mg)

In the following examples, a chewing gum mean value of 0

mass according to preparation 13 used each piece of the released contained 1.0 g of this mass. Nicotine (mg)

Example 16

88 mg nicotine per g of the complex of ion exchange resin No. 4 and nicotine; 2 mg nicotine per Chewing gum.

Chewing time (minutes) 0 2 5

10

20th

0.13 0.17 0.50 1.25 1.68

Example 14 _{| 5}

170 mg of nicotine per g of the complex of ion exchange resin No. 2 and nicotine; 1.5 mg nicotine per Chewing gum.

Chewing time (minutes)
0 2 5 10

20th

15 20 30

0 0.02 0.26 0.70 0.98 1.14 1.32

Average
of the released
Nicotine
(mg)

Example 15

175 mg nicotine per g of the complex of ion exchange resin No. 2 and nicotine; 4 mg of nicotine per chewing gum.

25th

30th

Chewing time (minutes) 0 2 5

35

10

20th

Mean value 0

of the released
Nicotine (mg)

0.72 1.44 2.44 3.64

40 The quantitative determination of nicotine was carried out by titration with perchloric acid. The IR spectrum was used for identification

The determination of nicotine bound to ion exchangers was after an in Off. Meth. Anal of the A. O. A. C 9th Edition, 1960, pp. 94-95 Method carried out. For the determination, a sample corresponding to 5 mg of nicotine was weighed and placed in transferred to a distillation flask (for nitrogen determination according to Kjedahl). 50 ml hydrochloric acid (1 part concentrated hydrochloric acid diluted with 4 parts of distilled water) were placed in a 500 ml flask, which served as a template and was arranged so that the cooling tube was immersed in the solution. The sample in The distillation flask was filled with 50 ml of a 30% strength (7 by weight) aqueous sodium hydroxide solution solution obtained with sodium chloride was added, and then steam distillation was carried out performed with the cooler at full capacity. The escaping condensate should not be more than Have room temperature. The distillation flask was warmed to its volume to keep constant. 480 ml of condensate were collected and appropriately made up with water. In the spectrophotometer the absorbance was read at 259 (max), 236 (min) and 282 nm.

The following formulas were used for the calculation:

tiiirr - Emax ~ lli ^ miii + £ 382)!

for Ej ^ _n , (fo / r) was found to be 338;

£, "". χ 500 χ 1000

338 χ 100 χ (sample weight, g) = mg nicotine / g sample.

To determine nicotine in chewing gum, chewing gum was homogenized with 20 g of sea sand in a mortar under ether. The homogeneous mixture was transferred to a glass tube which was provided with a plug of glass wool at the bottom. The filling of the tube was eluted with 100 ml of ether and the eluate was collected in a separatory funnel. Then the filling of the tube was freed of ether as much as possible. The ether in the separating funnel was _{extracted 3 times with 15 ml of O 1} in hydrochloric acid each time, and the extracts were combined in a 250 ml flask. Then the ether phase was discarded. The almost dry filling of the tube was then eluted with 0.1 η hydrochloric acid, the eluate was added to the combined extracts until the total volume was 250 ml.

The absorbances at 259 (max), 236 (min) and 282 nm were read off in the spectrophotometer.

Calculation:

338 was found for E \ "? _m (corr);

E _m " χ 1000 χ 250
~ x: TOO

.... ^Nlkolln / ^Kau 8 ^umml ·

The method could also be used on chewed gums to determine the remaining nicotine.

The following example explains the production of a chewing gum product according to the invention in great detail.

Example 17

A nicotine ion exchange complex with ion exchange resin No. 2 was made according to the method of

Preparation 1 prepared, the resulting complex contained 10% nicotine.

434 grams of natural chewing gum base was placed in a heated mantle and stirrer Given mixer. The mixer was heated with steam at about 1.03 bar. The stirrers were turned on periodically turned on to invert the gum base. In order to avoid overheating of the chewing gum base, a low vapor pressure was chosen After complete melting, the base became the Steam was turned off and cold water was passed through the jacket to maintain the temperature of the Reduce the contents of the flask to about 85 ° C. Then 840 g of powdered sugar (particle size 0.059 mm) and 276 g of corn syrup with 45 ° Baume were added, then the mass was mixed for about 15 minutes. The Gercisch then had a temperature between 60 and 75 ° C.

Another 420 g of powdered sugar and 30 g of the nicotine ion exchange complex, Particle size below 0.059 mm, were mixed and then added as a powder mixture to the molten mixture, then stirring was continued for 5 minutes so that the total mixing time was about 15 minutes.

The temperature in the boiler was dropped after the mixing process to 40 to 6O ⁰ C. The mass should be cooled as much as possible before mixing is complete, but the viscosity decreased with decreasing temperature and the mixing process had to be stopped before the mass became too stiff. In practice, the mixing process was terminated less for the thermometer reading than for the consistency of the mixture.

After mixing, the batch was cut into pieces which were fed to the existing extruder became. The exir oar was usually with warm water heated to 45 to 50 "C. This achieved a more uniform extrusion than with Heating with steam, also better temperature control. The extruded rubber was made with Starch or a mixture with granulated sugar and starch dusted to stick to forming rollers

ίο and avoid cutting devices. With the Rolling was achieved the desired thickness. The cutters were held at about 25 ° C.

The shaping in the extruder and the further treatment took place accordingly in the usual way the desired shape and size of the chewing gum sticks. 1000 pieces of 2 g each were passed through customary extrusion and cutting made. The bits were then also made in the customary manner packed and stored The wrapping room was kept at 20 ° C and a relative humidity of 45 to 50% and the bits were kept at 18 to 20 ° C and a relative humidity of 45 to 50%

When the chewing gum product according to the invention was administered to habitual smokers, the results were very good Results Achieved In numerous cases, using 6 to 20 pieces of chewing gum per day quit smoking completely in others Cases a considerable reduction was possible.

The exploitation of the invention can be made by statutory provisions, in particular by the Food Act or the chewing gum regulation.

Claims (3)

Patent claims: 1. Chewing gum that is suitable as a substitute for smoking products, containing a chewing gum base, Tobacco alkaloids and possibly other common chewing gum ingredients, thereby characterized in that it is dispersed in the chewing gum base nicotine or a pharmacologically contains compatible nicotine salt bound to a cation exchanger, the amount of Chewing gum base 15 to 80% by weight and the amount of nicotine, calculated as the free base and based on the weight of the chewing gum base, is 0.05 to 2% by weight 2. chewing gum ware according to claim 1, characterized in that it is the chewing gum base contains in an amount of 60 to 75 wt .-% 3. Chewing gum according to one of claims 1 to 3, characterized in that it is used as a cation exchanger, to which the nicotine is bound, a weakly acidic one containing carboxyl groups Methacrylic acid resin, a sulfonic acid group-containing strong acid polystyrene resin or a Contains medium-acid polystyrene resin containing phosphonic acid groups