RU2108099C1 - Saliva-soluble preparation for giving up tobacco smoking - Google Patents

Abstract

FIELD: medicine; toxicology; narcology. SUBSTANCE: preparation comprises active principle, namely, nicotin or alkaloid dispersed in gel-like pharmaceutically acceptable water-binding agent. EFFECT: higher efficiency. 15 cl, 1 dwg, 2 tbl

Description

 The invention relates to a saliva-soluble, nicotine-containing stimulant.

 It is a well-known fact that both active smoking and passive smoking of tobacco products such as pipe tobacco, cigars and cigarettes pose a serious danger to human health, as well as to the social environment.

 It is also a well-known fact that quitting the smoking habit is a serious problem for the smoker.

 These problems are mainly associated with the habit of nicotine. Indeed, it has been established that heavy smokers have an acute need for tobacco stimulation when the concentration of nicotine in the blood of such individuals drops to about 15 mg / ml.

 Furthermore, it is known that various nicotine-containing, smokeless stimulants (i.e., not taken through the respiratory tract) can be used to alleviate a high need for tobacco, and thereby help the smoker to quit smoking addiction without any noticeable worries .

 Nicotine stimulants, not consumed through the respiratory tract, have been known for a long time in the form of smokeless tobacco products, such as chewing tobacco and snuff, and developments have been constantly conducted to improve their quality.

 US Patent No. 1376586 describes a product comprising thinly sliced or chewed tobacco in the form of tablets or separate "chewing gum", the entire surface of which is covered with chewing gum, which makes it impervious to both air and moisture, and is very effective in preventing tobacco vaporization juice.

 U.S. Patent 4,545,392 discloses a smokeless tobacco product comprising chopped or otherwise minced tobacco and, as a basis, 1 to 35 wt.% Non-sugar, water-insoluble mastic resin, which is calculated based on the dry weight of the tobacco, in addition, the composition of the drug includes water-soluble resins, such as, for example, gum arabic to stabilize the resin composition; the preparation is formed in the form of pieces of chopped or otherwise crushed tobacco, and the mastic resin that forms the basis of its composition covers its surface in the form of a continuous shell. As prescribed, the individual particles of tobacco must therefore remain dispersed in the mouth.

 PCT International Application No. 81/02090 describes a product in the form of chewing tobacco in separate batches in which the chewing tobacco is either coated or distributed in the form of fine particles in a solid or semi-solid carrier material. A gum rubber is preferably used as the carrier material. However, it is further indicated that starch hydrolysates, for example non-sticky products used in the manufacture of "rubber candy", can be used as a carrier material, although this application is not illustrated by the corresponding examples. The carrier material may also contain additional substances, such as, for example, flavoring and flavoring additives, and dry, water-soluble extracts of natural products, such as coffee and tea extracts.

 Nicotine containing nebulizers or aerosols for oral use are described in DE-OS 3241437 and GB-PS 1528391. However, the administration of nicotine by spray or aerosol provides only a short-term effect.

 A nicotine-containing preparation for nasal use is known from DE-OS 3401763. However, nasal use is not entirely pleasant, since the nasal mucosa is more sensitive than the oral mucosa. And in addition, this use of the drug also provides only a short-term effect. In this regard, the nasal introduction should be considered as less suitable.

 DE-OS 3438284 proposes the application of a patch from which nicotine is supplied, however, the absorption of nicotine is very slow and uncontrolled. In addition, the desired sudden increase in the concentration of nicotine in the blood of the studied subjects and the accompanying physiological state corresponding to the state during the first cigarette inhalation are not achieved when using the patch applied.

 US Pat. No. 3,901,248 teaches a preparation based on the substitution of chewing smoking and which is in the form of a nicotine-containing chewing gum. The preparation comprises from about 15 to 80% resinous substrate and a complex of nicotine and a cation exchange resin dispersed in the substrate. The complex with a cation exchange resin consists of about 10% chewing gum, which ensures the release of the same amount of nicotine during chewing as with regular cigarettes.

 US Pat. No. 3,845,217 teaches other optimized formulations that are based on the replacement of smoking with chewing and which do not have an irritating effect on the larynx. The composition of these improved preparations includes from about 15 to 80% of a resinous substrate, nicotine, and at least one physiologically acceptable, water-soluble buffer substance, due to which, when chewing, the pH of saliva is maintained at a level exceeding normal, physiological, etc. e. about 7.4.

 Nicotine can be selected from the group comprising a nicotine-free base, a water-soluble, physiologically acceptable salt thereof, nicotine adsorbed on a physiologically acceptable adsorbent, and also nicotine in combination with an insoluble, cation exchange substance.

 The amount of nicotine calculated on the free base is from 1 to 10, preferably from 1 to 3 mg per chewing gum.

 In order to ensure a controlled, not too fast release of nicotine, it is recommended to use nicotine in combination with an insoluble, cation exchange substance.

 In French Patent Application, N publ. 2608156, other chewing gum preparations are presented, which are based on the replacement of smoking with chewing. These preparations contain nicotine incorporated in particles whose surface is coated with a layer of water-soluble material, which, according to the authors, provides a controlled, not too fast release of nicotine.

 EP 0135264, 1985 describes a preparation in the form of lozenges containing nicotine as an active principle. Pellets containing nicotine are prepared by compressing a mixture of an inert filler material, a binder, and either pure nicotine or a substance containing nicotine. Pressed cakes cannot be considered a gel according to the present invention. Pressed cakes usually have a percentage of deformation that provides the highest release of 2 to 3%, which is significantly lower than in the present invention, and the surface area of such pressed tablets can suddenly increase when it breaks, which leads to uncontrolled release of nicotine and additional ingredients.

 The closest in technical essence is the British patent GB 1388786, 1973, which describes a solid dosage form containing, as an active principle, smoking cessation gels included in various water-soluble gels, including those based on polysaccharides such as pectin, agar , algins and others. In said UK patent nothing is said regarding the controlled release of the active ingredient, and it is not indicated that nicotine may be the active ingredient.

 Typically, tobacco products that are avoided by smoking and which contain chopped tobacco and substrate material, such as chewing tobacco, shag, distributed in a water-soluble, resinous basis (chewing gum) or in starch hydrolysates (“rubber candies”) , in accordance with the available data, are characterized by the fact that after their use there are tobacco and / or substrates that are difficult or completely insoluble in saliva.

 In addition to the fact that the presence of these by-products can cause discomfort and be socially unacceptable, the high concentration of ingredients from chopped tobacco, which is necessary to obtain the stimulating effect of nicotine, causes pain in the stomach.

 Undesirable sudden release of ingredients, for example, nicotine and various flavoring components, can be observed with the use of tobacco products intended for use, bypassing smoking, and having a brittle or crystalline structure, if these products are bursting. Thus, large new surfaces of the product can be exposed, and the smoker receives large concentrations of ingredients, as a result of which he experiences undesirable changes in the expected physiological effects of stimulation.

 A similar uncontrolled release of nicotine is also observed with the use of nicotine-containing chewing gums when rubbed during chewing.

 The primary objective of this invention was to obtain a supplementing or replacing tobacco product in the form of a nicotine-containing stimulant for oral administration, which would provide a controlled release of nicotine and additional ingredients, for example, flavoring and aromatic additives.

 The purpose of the invention is to provide a nicotine-containing, saliva-soluble, stimulant preparation that provides nicotine stimulation that is higher or at least equal to the degree of stimulation caused by known tobacco products such as cigarettes, cigars, pipe tobacco and the aforementioned tobacco substitute products; at the same time, eliminating tobacco residues and / or substrate, undesirable changes in physiological effects, unpleasant presence of known tobacco products and tobacco substitutes.

 The purpose of the invention is also to obtain a saliva-soluble, stimulating drug, which provides its oral use in various conditions, including the simultaneous use of drinks, such as coffee, wine, beer; and in such a form that the dose of nicotine in it corresponds to the dose causing nicotine stimulation when smoking a cigar, a filled pipe of tobacco or, more preferably, a cigarette.

 According to the invention, the controlled release of nicotine and additional ingredients, such as flavoring and aromatic additives, as a result of nicotine stimulation without smoking, can be obtained by using a saliva-soluble stimulant, which includes a gel prepared using a water-binding agent to form a gel; nicotine or other alkaloids with a similar type of activity; additional ingredients, such as flavoring and aromatic additives; having a well-defined structure profile described below, including a set of mechanical properties, namely, strength, hardness, brittleness, adhesive ability, cohesive ability, elasticity; and having a certain concentration of nicotine or said alkaloids.

Accordingly, in a broader aspect, the invention provides a saliva-soluble, stimulant preparation comprising the active ingredient and additional components, which include flavoring and aromatic additives enclosed in a gel, prepared using a water-binding agent to form a gel, the active the ingredient includes nicotine or other alkaloids with a similar type of activity; the specified drug has the following properties:
I / Analysis of the structure profile allowed us to determine the following limits of parameter values:
a / strength, i.e. module, above 100 N (newton) / cm ² ;
b / hardness, i.e. maximum force impact during the first compression period, more than 5 N / cm ² ;
in / fragility, i.e. deformation, expressed as a percentage, necessary for the destruction of the gel, approximately 30%;
g / adhesive ability, i.e. the ratio of the region of the negative peak between the two stages of compression to the region of the first peak, from 0 to 70%.

d / elasticity, i.e. ratio 100 • (D - d) / D,
where: D is the usual height (in cm) before the first compression period, and d is the permanent deformation of the sample (in cm) before the second compression period in the range from 25 to 100%.

 e / cohesive ability, i.e. the total working ratio between the first and second compression periods ranging from 25 to 100%.

II / Disintegration time determined at 37 ^° C. using a disintegration testing apparatus according to the second edition of Ph. Eur., Ranging from 5 to 60 minutes;
III / Nicotine content from 0.5 to 10 mg or the corresponding content of these alkaloids.

The disintegration time is determined at 37 ^° C. using a disintegration testing apparatus according to the second edition of Ph. Eur., V. 5.1.1 under the conditions described below. It is noted that the disintegration time, determined in other cases, is approximately one third of the above disintegration time.

 Definitions of the terms “structure profile” and “structure profile analysis” are described by J. Sanderson et al. in Resins and Stabilizers for the Food Industry, Proceedings of the 4th Jnternational Conference, Wrexham, Clwyd, Wales, July 1987, JRL Press Ltd (1988), and Szczesniar et al. J. Food Science 28 (1963) 385) 403 listed.

 In the version of the structure profile analysis used here, a force-strain curve is obtained by sequentially double compressing the sample to 70% of its initial height using the selected compression rate. According to the curve, the force impact - deformation is obtained by objectively measured values of physical parameters, closely related to the sensitive, structural characteristics of strength, hardness, brittleness, adhesion, cohesive ability and elasticity.

In this way:
a. Strength is measured using the initial angle of inclination of the curve force impact - deformation, which is expressed in force per unit area;
b. Hardness is measured through the maximum force per unit area, carried out at any time during the first compression period;
in. Fragility is measured by the first significant drop in the force impact – deformation curve during the first compression period, i.e. the point of the first break, expressed as the percentage of deformation necessary for fracture of the sample;
g. Adhesive ability is measured (in this description) as the ratio of the region of the negative peak between two compression periods to the region of the first peak;
e. Elasticity is measured as a ratio of 100 • (D - d) / D,
where D is the height of the sample (in cm) before the first compression period,
d - residual deformation of the sample (in cm) before the second compression period;
e. Cohesive ability is measured through the ratio of the peak areas of the second and first compression periods, expressed in%.

It was found that by selecting the structure in accordance with the invention provides a controlled release of nicotine
- since the surface area of the stimulant exposed to the drug remains basically constant throughout the meal, i.e. during the gradual dissolution of the surface layers of the stimulating drug;
- since during chewing there is no significant deformation of the stimulating drug;
- since the ingredient contained in a given unit volume of a stimulating drug is released only when this part of the drug is on the surface and its matrix dissolves under the influence of saliva.

Selected Limits:
- hardness and brittleness ensure that the exposed surface area does not undergo a sudden increase as a result of the destruction of the stimulating drug;
- strength, elasticity and cohesiveness guarantee that the stimulant is not subjected to grinding during chewing;
- adhesive ability ensures that the stimulant does not have a noticeable tack, therefore, does not get stuck in the teeth.

 It is desirable and particularly preferred that the values of the parameters of the structure profile and disintegration time satisfy paragraphs 2 and 3 of the claims.

Buffer substance or agent
The absorption of nicotine from saliva into blood plasma depends on the pH of saliva, the pH of the plasma, and PKa (= 8.02) of nicotine.

Taking plasma pH 7.4 and saliva pH 7.0, only about 30% of nicotine will be present in free base form. Thus, in order to improve the absorption of nicotine, it is necessary to increase the pH of saliva. At pH 8.5, about 80% of nicotine is in its free base form, and the total plasma nicotine concentration is about 3.8 times higher than the total concentration in saliva according to the formula:
[1 + 10 ^{- (pHp - pKa)} ] / [1 + 10 ^{- (pHs - pKa} )]
described by Martin et al. Clin. Pharmacol Ther. 16, 1052-1058, (1974).

 Thus, in the most desirable cases, the composition of the stimulating preparation includes physiologically acceptable buffering agents or agents in the form of additives, and their concentrations are selected in order to guarantee the maintenance of saliva pH 8-10 during the disintegration of the preparation. In general, the content of the buffering agent or agent in the stimulant preparation is from 5 to 50 mg per preparation.

 Doses of nicotine.

 Stimulating drugs are prepared in such a way as to provide a dose of nicotine, the effect of which would correspond to stimulation of nicotine due to smoking, for example, cigarettes.

 Thus, in the most preferred cases, the nicotine content in the stimulating drug is brought to a concentration that would provide a dose of nicotine in the range from 0.5 to 5.0 mg of nicotine per drug. The amount of nicotine in the stimulant preparation can be selected to provide, under certain conditions, stimulation of nicotine, which is sensitive, for example, to light, medium, concentration, etc. The most desirable concentrations are in the range: 1.0 to 1.5 mg of nicotine, from 1.5 to 2.5 mg of nicotine, and from 2.5 to 3.0 mg of nicotine per drug.

 Nicotine release profiles.

 Stimulating drugs are prepared in a form that provides the desired nicotine release profiles.

 "Continuous release."

 So, in accordance with the desire, the continuous release of nicotine, i.e. prolonged, mostly constant, release is ensured as a result of the homogeneous distribution of nicotine throughout the drug.

 Typically, the nicotine release profile depends on the area of the effective surface of the drug during disintegration. So, at a first approximation, ignoring the edge effects, it is clear that the drug is destroyed with a constant rate of nicotine release, which decreases gradually as the weight of the drug decreases.

 The initial, primary, and sustained release of nicotine.

Further, in accordance with other needs, a two-stage release of nicotine, including initial and sustained release of nicotine, is ensured by the uneven distribution of nicotine in the multilayer stimulating drug:
I / the outer layer is formed in such a way as to provide a short disintegration time and the amount of nicotine that is needed so that as a result of the initial release of nicotine, its concentration in the smoker's blood plasma exceeds the lowest effective concentration in the blood plasma; and
II / inner layer is formed in such a way as to provide a longer disintegration time and corresponding amounts of nicotine, maintaining its plasma concentration above the lowest effective concentration for a desired period of time.

 Forms of stimulant drugs.

 Nicotine released from nicotine-containing stimulant preparations in accordance with the invention is predominantly absorbed in the oral cavity if the drug is placed under the tongue, near the cheek or against the palate. Thus, the nicotine-containing stimulant preparation may take any form convenient for holding it in the indicated places.

 Further, in the appropriate form, the stimulating drug is fixed and can be used with the simultaneous consumption of drinks.

 It is desirable that the stimulant preparation be in a form that fully or partially matches the shape of the sky.

 Application procedure.

 Nicotine-containing stimulant preparations can be used, according to the invention, to obtain nicotine stimulation similar to stimulation due to smoking or using tobacco products, bypassing smoking, the corresponding stimulant drug is administered orally, placing it in a specific, if desired, place of the oral cavity using the tongue, slightly sucking or licking the drug in the place of the oral cavity, selected depending on the individual sensations and the stimulating effect of nicotine.

(a) Analysis of the structure profile
As used herein, the term “material structure” is used to indicate the consistency characteristics of a material. The structure of the material can be represented objectively in the form of a set of values for six physical parameters, and the structure profile "is determined by analyzing the structure profile described by Sanderson et al., As described above.

The following explains the procedure for calculating the values of these parameters, i.e. the profile of the structure, based on the curve "force-strain" (at 20 ^o C), presented in the drawing and constructed according to the data of a cylindrical test sample of a stimulating drug having a diameter of 15.4 mm, a height of 12.3 mm and subjected to sequential, two-stage compression to 70% of the initial sample height at a compression rate of 50 mm / min.

The structure profile includes the first compression period 10 and the second compression period 20. From the first compression stage 10, the strength (modulus) 169 N / cm ² is defined as the initial angle of inclination 11 of the curve at its beginning 12, when the deformation process multiplied by the height of the sample begins before compression and divided by the area of the final surface of the sample.

Further, the hardness of 58 N / cm ² is defined as the maximum force 13 (the height of the first face), carried out at any time during the first stage of compression 10, i.e. at strain level 14 divided by the area of the final surface of the sample.

 Fragility of more than 30% is defined as the point of the first break (which could not be achieved in this test), i.e. the brittleness for this sample is more than 30%, since the sample was compressed to 30% level of deformation 14 without kink (a large number shows that the structure is small brittleness).

 The adhesion capacity of about 4% is defined as the ratio of the region of the negative peak 17 after the first compression stage 10 to the peak region of the first compression stage. If the material has adhesive properties, then it adheres to the compression plates and stretches the plates in the opposite direction to their movement between the two stages of compression.

 The elasticity of 85% is determined using the ratio of the height D (12.3 mm) of the sample before the first compression stage 10 minus strain d (1.8 mm), i.e. distance 22 - 18, to the height of the sample to the first stage of compression. The initial number 18 of the second stage of compression is found as the doubled distance of 30% strain 14-12.

 The cohesive capacity of 57% is defined as the ratio between the peak areas of the second and first stages of compression. In a first approximation, this peak ratio is calculated by multiplying the ratio between the peak heights, i.e., 23 and 13, by the ratio between the peak bases, i.e. distances 26-22 and 16-12. Alternatively, peak areas can be calculated in numbers using a computer, graphically using a planometer, or by weighing replicas of peak areas.

 (b) Active ingredient.

In accordance with the invention, any compound from the following group can be selected as the active ingredient:
nicotine (3- (1-methyl-2-pyrrolidinyl) pyridine), including synthetic nicotine and extracts of nicotine from tobacco plants, such as from the genus Nicotiana; and
other alkaloids with a similar type of activity, including nornicotin and lobelin, for example, from the species Lobeliaceae and Lobelia; methylanabazine and anabazine;
One compound may be used or in combination; and in the form of a free base or attached acid salts.

 Further, the active ingredient may include various oxidation products, such as nicotine-1'-N-oxide.

 (c) Water-binding gelling agent.

 An important factor in obtaining the desired structure of the stimulant preparation according to the invention is the selection of a suitable water binding, gelling agent.

 In accordance with the invention, a water-binding, gelling agent can be selected from the group of the following substances: organic gelling agents, including gelatin, modified and unmodified starch; and resins, which include: agar, alginate, gum arabic, carob resin, karagen, gatti resin, gar resin, karaya resin, pectin, tragacanth resin, resin from the barrel of false acacia (locust), xanthine resin.

 The most preferred gelling agents include gum arabic, starch, gelatin, agar and pectin. The most preferred of the solid resins is gum arabic, comprising 50 to 70% of the total solids. However, for gentler stimulants, another gelling agent, such as gelatin, is recommended, while more than one gelling agent can be used at the same time.

 (d) Optional (additional) ingredients.

 Optional, additional ingredients include additives for sweetening, imparting a certain taste, smell, color, as well as for stabilization, vitamins, mineral salts, buffering agents or agents that provide the necessary pH of saliva, which promotes the flow of nicotine into the blood plasma.

 Sweetening.

 For sweetening, one or more synthetic or natural sugars can be used, that is, any of the carbohydrates suitable in the manufacture of confectionery products for sweetening them.

According to the invention for sweetening, you can choose any of the substances presented in the following group:
individual sugars, which include: sugars extracted from sugarcane and sugar beets (sucrose), dextrose (also called glucose), fructose (also called (levulose), and lactose (also called milk sugar); sorbitol, mannitol, glycerin, xylitol, sodium saccharin; and
sugar mixtures, including glucose syrup, for example starch hydrolysates, containing a mixture of dextrose, maltose and a number of complex sugars, invert sugar syrup, for example, invertase invert sucrose (also called sucrose invertase), containing a mixture of dextrose and fructose, higher sugar syrups, such as molasses and honey, containing mainly a mixture of levulose, dextrose, maltose, sucrose, spring, dextrin and more complex sugars; and malt extracts.

 Flavoring and aromatic additives.

 Flavoring and aromatic additives may include one or more synthetic or natural flavors and aromatics.

According to the invention, flavoring and aromatic substances can be selected from:
essential oils, including distillation, solvent extraction, squeezing in the cold masses of chopped flowers, leaves, peels or porridge-like masses of whole fruits, including mixtures of alcohols, esters, aldehydes and lactones;
essences, including either dilute solutions of essential oils, or mixtures of synthetic substances that are mixed to match the natural taste of the fruit, such as strawberries, raspberries, black currants; artificial and natural flavors of jams and drinks, such as cognac, whiskey, rum, gin, sherry, port, wine; tobacco, coffee, tea, cocoa, mint; fruit juices from washed, peeled fruits such as lemon, orange and lime;
licorice root, menthol, eucalyptus, anise, nuts (for example, peanut, coconut, hazelnut, chestnut, walnut, stake seeds), almonds, raisins; and
powder, flour or shredded, vegetative parts of plants, including parts of tobacco plants, for example of the genus Nicotiana, in quantities that do not change the level of nicotine, and ginger.

 Especially preferred flavoring and aromatic substances of natural origin are obtained from essential oils, essences, powder, flour or ground parts of tobacco plants in an amount that does not significantly affect the nicotine content.

 Particularly preferred aromatic and flavoring additives can be selected from the group of substances including essential oils and extracts of tobacco, coffee, tea, cocoa, and also mint.

 Coloring additives.

 In accordance with the invention, coloring additives can be obtained from paints containing chemical groups that absorb light, including paints that are resistant to the presence of reducing sugars and confectionery acids; paints that are resistant to heat and light, paints that do not break up into individual primary colors; Paints, which are mixtures of tartracin and indigo carmine, forming a pea-green color, are of particular advantage; mixtures of erythrosine and indigo carmine giving a purple color; and mixtures of tartracin, amaranth and indigo carmine, giving a chocolate brown color; caramel containing burnt sugar in the form of a powder or liquid to obtain a brown color; black coal, giving a black color; and titania, giving a white color.

 Stabilizing additives.

According to the invention, stabilizing additives can be selected from the following group of compounds:
antioxidants including vitamin E, ascorbic acid, sodium pyrosulfite, butyloxytoluene, and preservatives including citric acid, tartaric acid, lactic acid, acetic acid, benzoic acid, sorbic acid.

 Vitamins and minerals.

 It is shown that due to smoking, the body of smokers is significantly depleted in minerals and vitamins, especially vitamin C. These losses can be compensated by stimulant preparations containing vitamin and mineral supplements.

 Therefore, according to the invention, the additional ingredients may contain one or more vitamins and minerals as additives.

The most preferred vitamins are selected from the group consisting of A, B ₁ , B ₂ , B ₆ , C, D ₂ , D ₃ , E, F, K and P - vitamins, especially C - vitamins.

 The most preferred minerals are selected from the group consisting of magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, cobalt, vanadium, nickel, tin, fluorine, silicon. However, according to the invention, in addition to adding vitamins and minerals to the preparations, it is necessary to create conditions in which these substances are not destroyed, as, for example, is observed with vitamins A, B, C and E when they are in contact with air, and especially all vitamins in high temperature conditions. Further, vitamins and minerals can have a very strong flavor, which is difficult to eliminate, just as they can have an adverse effect on other ingredients, in particular acids. In addition, vitamins are very sensitive to light and are destroyed, albeit slowly, during storage.

 Buffer substances or agents.

 In accordance with the invention, buffering agents or agents can be selected from the group consisting of physiologically acceptable buffering agents or agents which are capable of stabilizing the pH in the range of 6.5 to 9, including alkali metal carbonates and bicarbonates or phosphate systems, especially sodium carbonate and sodium bicarbonate; potassium carbonate and potassium bicarbonate; trisodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphoric acid, potassium hydrogen phosphate, potassium dihydrogen phosphate; and a mixture of these compounds.

 (e) Preparation of stimulant preparations.

 The main parameters that determine the structure of the stimulating drug include prescriptions of substances, pH and temperature of the initial mixture or solution, as well as the conditions of the individual stages of the process during which the initial mixture / solution turns / thickens into "green preparations" (semi-finished products), of which then, by thickening and preservation, stimulant preparations are obtained. In the event that products such as rubber, jelly or pastilles are obtained by thickening in molds using starch or resins, it is necessary to pay attention to the fact that the final moisture content corresponds to the required value, usually it does not exceed 20% and, basically, depends on the selected gelling agent.

 According to the invention, stimulant preparations can be obtained using a number of methods known in practice (see "Sugar, Confectionary and Chocolade Manufacture" R. Lees and EB Jackson, Leonard Hill Books 1973), which include methods for producing gum arabic rubber, agar jellies, gelatin jelly, starch-rubber jelly and pastille; starch jellies, such as orange slices, marmalade and jelly beans; fruit pastille, such as wine gum, chewing gum, tablet jelly, tablets, lozenges, licorice paste and pectin jellies.

 Specific prescriptions and methods for preparing gelling, water-binding agents (known in the art).

 (a) Gum arabic gum.

Prescription - Weight parts
Gum Arabic - 100
Cold water - 120
Sugar - 90
Glucose Syrup - 14
Water - 15
Dyes, aromatic and flavoring agents and acid are added in the amount necessary to obtain the desired taste and shade.

Cooking method
1. Slowly dissolve pieces of gum arabic in water.

 2. Carefully pass the solution through a thin sieve or cloth in order to remove impurities and foreign materials.

3. Dissolve sugar in water, add glucose syrup and heat to 124 ^o C (256 ^o F).

 4. Add the heated solution to the gum arabic solution and mix thoroughly.

 5. Stir and let stand for at least one hour. (During this period, the mixture begins to clear and a foam appears on its surface, which must be removed before the next stage of the procedure).

 6. Add dye, aromatic and flavoring agents, acid solution.

 7. Stir.

 8. Place in starch molds.

 9. Transfer the pressed fingerprint to the drying oven and keep in it until the desired hardness is obtained.

 10. Thoroughly clean the product and cover with glaze.

 (b) Agar jelly.

Prescription - Weight parts
Agar - 2.0
Water - 70.0
Sodium Citrate - 0.7
Sugar - 60
Glucose Syrup - 40
Aromatic and flavoring, coloring and acid - To taste
Cooking method
1. Agar, depending on the source, must first be soaked in cold water for 3-12 hours.

 2. The mixture is slowly heated in an open steam boiler until a solution is obtained.

 3. Add sodium citrate.

 4. Pass through a fine sieve.

5. Sugar and glucose syrup are added to the agar solution, and then heated to a temperature of 107 ^° C (225 ^° F).

6. Cool to a temperature not exceeding 76 ^o C (170 ^o F), and add a solution of any acid.

 7. Add dye and aromatic and flavoring agents.

 8. Place in warm, dry, starchy molds.

 9. Jelly is kept in starch molds for 12-24 hours.

 10. Check that the total soluble solids content of the final jelly is greater than 76% before starch removal.

Forming starch should have a moisture content of 5-8% and be maintained at a temperature of 26-43 ^o C (79-110 ^o F).

 (c) Gelatin jelly.

Prescription - Weight parts
180 Bloom Gelatin Powder - 25
Hot water - 50
Sugar - 80
Glucose Syrup - 80
Water - 40
Cooking method.

 1. Prepare a gelatin solution in advance by slowly adding the powdered gelatin to the right amount of warm water. Stir in order to obtain a solution and leave to stand until enlightened.

2. Dissolve sugar in water and add glucose syrup. Heat to 116 ^o C (241 ^o F).

3. At this stage, it is recommended to cool this solution to about 70 ^° C (158 ^° F) before adding the gelatin solution.

 4. Add the heated solution to the gelatin solution and mix.

 5. Add dissolved dye and acid solution and mix. Add the required amount of aromatic and flavoring substances and mix.

 6. Place in starch molds.

 7. Transfer the pressed fingerprint to the drying oven and keep it there until it acquires the required hardness.

 In the case of using sheet or granular gelatin, it must be soaked for at least three hours in an amount of water equal to the weight of gelatin. In most factories, soaking is carried out, usually during the night.

 (g). Dextrin jelly and pastille (table. 1).

 The main way of cooking.

 1. Heat sugar and glucose syrup with two-thirds of the water in a steam jacketed boiler.

 2. In the remaining water, prepare a suspension of starch.

 3. Slowly add the starch suspension to the boiling sugar mixture at a rate at which the mixture would not stop boiling. Strong mixing is recommended at this stage.

 4. Continue cooking until the desired consistency is reached.

 5. Add dye, aromatic and flavoring agents, acid solution.

 6. Place in starch form and dry in a hot room for 24 hours.

 Jam can be prepared by boiling 50% sugar with 50% fruit pulp. The types of diluted boiled starch that are recommended to be acidified are characterized by a fluidity of 20, 30, 40 and 50.

 (e) Starch jelly (continuous production).

Copy
Jelly with starch as a base - Weight parts
Sugar - 25
Glucose Syrup 42 DE - 25
Water - 19
Diluted boiled starch with a fluidity of 75 - 10
Dyes, Aromas, Acids - How Much Required
Cooking method.

 1. Add water to the tank with mixer / cooling /.

 2. Add sugar and mix / cooling /.

 3. Add starch and mix / cooling /.

 4. Add glucose syrup and mix.

5. Raise the temperature to 80 - 90 ^o C / 176-194 ^o F /.

6. Check the total solids in the premixed mixture at 20 ^° C / 68 ^° F / using a refractometer. Jelly should have this value in the range of 76-82%.

 7. Transfer to a cooking oven.

 8. Check the total solids after cooking; it should not change by more than 2% water.

 9. Place in starch molds in a hot room for 24 hours.

Orange slices (as the basis of starch) weight.h .:
Glucose Syrup - 200.0
Glucose - 104.0
Sugar - 200.0
Starch / Fluidity 85 / - 60.0
Water - 100.0
The total solids content is 76 - 80%. Cooking temperature 278-283 ^o F.

 Structure: fragile / delicate.

Marmalade, parts by weight:
Glucose Syrup - 200.0
Sugar - 160.0
Starch / Flowability 75 / - 64.0
Glucose - 80.0
Water - 80.0
The total solids content is 78%. Cooking temperature 275-285 ^o F.

 Structure: brittle / harder.

Jelly Beans - Weight Parts
Water - 132.0
Starch / Flowability 70 / - 60.0
Glucose Syrup - 330.0
Sugar - 130.0
The total solids content is 68-70%. Cooking temperature 285-295 ^o F.

Structure: Durable / Gum Type
/ e / Fruit candy.

Copy
A: Pastille (starch as a base), parts by weight:
Sugar - 90.0
36 DE glucose syrup - 90.0
Water - 35.0
Diluted Boiled Starch / Flowability 60 / - 20.0
Gelatin / Bloom Medium / - 12.0
Fruit Pulp - 16.0
Tartaric acid - 3.5
Dyes and Aromas - To taste.

 Cooking method.

 1. Add sugar to water, bring to a boil.

 2. Add boiled glucose syrup.

 3. Slowly add a suspension of starch in 50 parts of cold water, boil for 10 minutes.

4. Add the pulp of the fruit, heat to 110 ^o C / 230 ^o F /.

5. Cool to 93 ^o C (200 ^o F).

 6. Add gelatin dissolved in 24 hours of hot water.

 7. Add dye, aromatic substances, acid dissolved in 5 parts water.

 8. Place in warm, dry starch.

9. Place in oven at 54 ^° C (130 ^° F) for 48 hours.

 10. Free from starch and cover with crystalline sugar or wet sugared.

B: Pastille with resin as a basis, parts by weight:
Sugar - 100
Glucose Syrup - 75
Water - 30
The prepared solution of gum arabic - 100
Gelatin - 10
Water - 20
Dye, Aromatics, Acid - To taste
Cooking method
1. Solvent sugar in water, add glucose syrup, heat to 127 ^o C (260 ^o F).

 2. Stir the prepared gum arabic solution.

 3. Dissolve gelatin in the double volume of its weight of hot water.

4. Add to the total batch at 82 ^o C (180 ^o F).

 5. Add dye, flavors and acid dissolved in an equal weight of water.

 6. Place in warm, dry starch.

7. Dry in an oven at 54 ^o C (130 ^o F) to the desired structure.

 (g) Tiled jelly.

Prescription - Weight parts
Cane and Beet Sugar - 280
Invert Sugar Syrup (70%) - 245
Water - 70
Party exit - 595
Cooking method.

 1. Pour the required amount of hot water into the large heated boiler.

2. Bring the temperature to 90 ^o C (194 ^o F).

 3. Add a certain weight of cane or beet sugar and dissolve.

 4. Add a certain weight of invert sugar syrup, mix.

 5. Pass through the filter under pressure.

6. Withstand, as required, at a temperature of 60 ^o C (140 ^o F).

 Boiling.

 7. Suck out 590 hours of syrup.

8. Quickly heat to 123 ^o C (252 ^o F). Alternatively, pass through a hot exchanger in order to concentrate the syrup until the total content of solid, soluble substances in it is 90%.

 Cooling.

9. Stop cooling the material and bring the temperature of the syrup to below 100 ^o C (212 ^o F).

 Cooking other ingredients.

Gelatin
10. Slowly add 80 parts of gelatin to 145 parts of hot water at 90 ^° C (194 ^° F) in a mixing tank.

 11. The mixing blades should rotate at a slow speed until all the syrup has been poured into the vat.

Acid
12. A solvent of 12 parts of citric acid in 12 parts of water.

Buffer
13. A solvent of 2.5 parts of sodium citrate in 2.5 parts of water.

 Flavoring and aromatic additives (optional).

 14. Measure out 45 hours of aromatic additives and add to party.

 15. Dissolve 0.025 parts of dye in 0.25 parts of water and add to the batch.

Mix
16. After the end of stage 8, the syrup is fed by gravity or by pump into the gelatin mixture of stage II.

 17. Stirring for 3 to 5 minutes

 18. Up to 5% jelly waste can be included at this stage.

 19. Add a buffer solution, aromatic additives, dyes and, finally, acid.

 20. At the end of mixing, stop the blades and transfer the mixture to the feed funnel to pass it through a sieve with large holes.

Upholding
21. Allow foam to form.

 22. Verify that the support plates or molds are well coated with the release agent.

 23. Settle at a relatively low speed to avoid the formation and inclusion of air bubbles.

(h) Tablets
Prescription - Weight parts
Sugar Glaze - 100
Stearic acid - 0.75
Isopropanol - 1.25
Gelatin - 0.75
Glucose Syrup - 0.5
Water - 4.0
Aromatic additives - 0,125
Cooking method. Wet granulation
1. Dissolve stearic acid in isopropanol.

 2. Dissolve gelatin in the required amount of warm water and mix with glucose syrup.

 3. Place sugar icing in the mixer vessel.

 4. Add liquid components and form a batch.

 5. Check that the mixture forms a ball if held in hand.

 6. If the mixture has a satisfactory consistency, it is subjected to granulation and passed through appropriate sieves (normal N 6) to obtain a mixture of fine granules.

 7. Distribute the crushed mass on the tray and transfer to a drying oven.

8. Dry at 60 ^o C (140 ^o F) for 10 hours

 9. Transfer to a mixer with a tumbler and add lubricant and aromatic additives. Mix.

 10. Transfer to a tabletting machine and compress to an appropriate shape.

(i) Tortillas - Weight parts
Sugar Glaze - 300
Resin A Solution
Gum Arabic - 4
Water - 6
Gelatin solution
Gelatin (100 Bloom) - 5
Water - 3
Resin Solution B
Tragacanth - 0.03
Water - 0.5
Aromatic additives - 2
Cooking method
1. Put sugar icing in the mixer.

2. Prepare a mixture of gelatin with water, the temperature of which should not exceed 80 ^o C (176 ^o F).

 3. Add resin solutions (prepared the previous day) to the gelatin mixture. Filter the resin / gelatin solution and mix before use.

 4. Mix flavorings with part of the icing and add to the rest of the batch.

 5. Add gelatin / resin / mixture to sugar icing.

 6. Stir the mixture slowly and thoroughly for the time required for this mixer model.

 7. Pour into containers and transfer to the loading funnels of punching devices.

 Size: large flat cakes - 200/1 pkg. (440 / kg): Cajons - 1000/1 pack. (2200 / kg), small cakes - 500/1 pack. (1100 / kg).

Options
Centers with indoor boilers
Add 10 hours of rice flour in stage I - this will lead to the production of pellets, characterized by greater hardness and lower ability to destruction in rotating boilers. Painted and fragrant cakes (Cajons).

 To obtain the desired pastel shade, it is recommended to use 0.05 parts of dye, and to give the desired smell, add 0.02 parts of violet, peach, rose or lily.

 (j) Licorice paste (Table 2).

 Red licorice can be prepared by removing liquid caramel and replacing it with golden syrup from molasses. To obtain a bright red shade that replaces black dyeing, it is necessary to add 1 part red dye.

 Method A. Continuous Process.

 1. Place glucose syrup and water in a vessel with a steam jacket of a disintegrator or mixer and add brown sugar.

 Mix.

2. Raise the temperature to 40 ^o C / 104 ^o F /.

 3. Break the juice block and add up to 1 gallon with hot water: heat to dissolve and add to the previous mixture.

 4. Add the remaining ingredients and, using a 20-minute recirculation, prepare a homogeneous suspension.

5. Raise the temperature to 60 ^o C / 140 ^o F / and subject the mixture to recirculation for two minutes.

 6. Submit by means of a pump to the voting device at a constant speed / the installation of the mechanism is determined by the structure that it is desirable to obtain /.

 Model B - Batch Process.

 1. Place the aqueous suspension in a mixer vessel and add wheat flour; mix.

 2. Pour the aqueous mixture into a cooking vessel, heat to a boil and add hydrol, brown sugar, salt and a block of juice previously dissolved in boiling water.

 3. In the case of licorice, add molasses, glucose syrup and black molasses.

 4. Continue heating and, upon boiling, pour into a starch suspension.

 5. After adding the entire volume of starch suspension, bring to a boil and cook for a specified period.

 6. In the case of licorice novelties and corks, it is necessary to add the required amount of glucose syrup and black molasses 30 minutes before the end of cooking.

 7. At the end of the cooking period, release heat and add liquid caramel, flavoring anise seeds, black color and the prepared gelatin solution.

 8. Stir until a consistent color is achieved.

 9. Unload the welded mass and transport to the forming apparatus.

Method C. Plant with BCH "NK" production line
1. Mix the liquid ingredients of the unmodified batch impregnation and transfer to a device with a pre-mixed suspension.

 2. Turn on the mixer and add the remaining "solid" materials; recycle to prepare a homogeneous mixture.

3. Enable
/ a / steam in the fm cooker
(b) an extractor fan to remove evaporating water, and
/ in / water flow in a condenser device located at the steam outlet.

 4. Feed the mixture into the cooker using a pump and start cooking.

 5. Observe the level of condensed water collected in the measuring vessel and current readings. / It should be noted: the amount of condensed water is an indicator of an increase in the solids content, while an increase in energy consumption indicates an increase in the degree of gelation.

 6. Once the amount of condensed water reaches a level that provides the desired moisture content in the licorice paste at the end of cooking, you must turn off the steam, fan and cooling water.

7. Ship the cooked paste to the conveyor and transport to the forming apparatus. Forming at 70 - 82 ^o C (158 - 180 ^o F).

 8. Pass the squeezed sheet through a 40-foot cooling tunnel for 1.5 - 5 minutes (depending on the shape) and gelatin or cut into certain sections using a rotary cutting machine.

(l) Pectin jelly
Copy
(A) Buffer, slowly hardening pectins, parts by weight:
Pectin - 1.25
Citric Acid Monohydrate - 0.4
Sugar - 51
Glucose Syrup 42 DE - 29
Water - 40
Dye and Flavors - As Required
Exit - 100
(B) Buffer, slowly hardening pectins (using 63 DE glucose syrup), parts by weight:
Pectin - 1.25
Citric Acid Monohydrate - 0.4
Sugar - 38
Glucose Syrup 63 DE - 42
Water - 37
Dye and Flavors - As Required
Exit - 100
Formula (A) produces a moderately hard jelly, while formula (B) provides the formation of a slightly softer product.

(B) Non-buffered, slowly hardening pectins, parts by weight:
Pectin - 0.82
Citric Acid Monohydrate 0.28
Potassium Citrate - 0.25
Sugar - 51
Glucose Syrup - 29
Water - 40
Dye and Flavors - As Required
Exit - 100
The amount of citric acid monohydrate used depends on the type of pectin. For some types of non-buffered, slowly hardening apple pectins, 0.28 hours are required, while for non-buffered, slowly hardening, citrus pectins, 0.4 parts of citric acid is required.

(D) Non-buffered, slowly hardening pectins (using 63 DE glucose syrup), parts by weight:
Pectin - 0.82
Citric Acid Monohydrate - 0.28
Potassium Citrate - 0.25
Sugar - 38
Glucose Syrup - 42
Water - 37
Dye and Flavors - As Required
Exit - 100
Methods for continuous production.

 For continuous production, it is necessary first of all to prepare a stable pectin solution. The most suitable are slowly hardening, buffering and low methoxyl (buffering) pectins. It is very important to be sure of complete dissolution before use. In the opposite case, the formation of a weak gel and insufficient utilization of the full gel-forming ability may be noted. It is recommended that solutions be prepared by adjusting their concentration by weight, and instructions should be obtained from the pectin manufacturer in accordance with the type and solubility of the buffer salt used.

Pectin Solution - Parts by Weight
Pectin - 2
Sugar - 10
Water - 88
Cooking method
1. Mix pectin and sugar in a dry state.

2. Pour water into the mixing vessel and heat to 70-77 ^o C (158-170 ^o F).

 3. Turn on the stirrer and add the mixture of pectin and sugar to the water.

 4. Heat to boiling point and stir for one minute.

5. Cool the solution to 50-60 ^o C (122-140 ^o F).

 Cooling is necessary to prevent the breakdown of pectin. It can be neglected if the solution should be used immediately.

Other prescriptions for obtaining various types of rubber products, jelly, pastilles can be found in a series of articles "rubber-jelly-pastilles", part 1.-6, "Sweetmaher" in the Confectionery Industry, from June 1983 to November 1983, links to which are presented in the list of references. The invention is further illustrated by a number of examples:
4. Examples.

 The following examples present a number of formulations that can be used in the manufacture of stimulant drugs in accordance with this invention.

 The production of a stimulant preparation is based on the preparation of a homogeneous liquid composition, including sugar, water, saccharides or carbohydrates selected for each particular case, as well as, if desired, additional, untreated, poorly purified materials of animal origin, such as gelatin. Coloring and aromatic substances, preservatives, other additives are used in this composition, which is contained under conditions of such temperature and viscosity that it can be a sample for obtaining the desired preparations. According to the recommendations, the active ingredient, for example, nicotine, is added to the composition immediately before the molding process. This procedure is necessary to ensure strict control of the highly active chemical compound, nicotine, so that the total amount of active substance used in production during a certain period of the process should correspond to the content of the active ingredient in the final product plus the content of the active ingredient in any of the added materials. Each of these materials, in accordance with the wording and the procedure used, can be remelted for use in subsequent production; if, for any reason, this is not feasible, the material must be carefully collected and decomposed, for example, by calcination. The preparation of the stimulant preparations according to the invention can be accomplished using any suitable production method known to those skilled in the art. Such methods, in particular the preparation of appropriate solutions of polysaccharides and / or starches, as well as gelatin, and subsequent mixing of the resulting solutions with sugar solutions (including other carbohydrates, such as dextrose syrup) should be selected according to the choice of raw materials, which will determine obtaining final products of suitable structure with properties within the above parameters.

 The production method commonly used is to mold the liquid composition into the respective cavities formed in the starch material of a certain purity and humidity by depressing a suitable size and shape immediately before the molding procedure begins. If desired, other molding methods can be used, for example, using molds made from elastic materials, such as elastomers. In special cases, the stimulant preparations according to the invention can also be obtained by known methods such as extrusion followed by cutting, or by stamping tablets from a suitable mixture of ingredients in the form of powders or granules.

 After hardening for an appropriate period of time under conditions of controlled temperature and relative humidity in ambient air, stimulant preparations are removed from starch material using known methods, due to which the preparation is cleaned of excess starch, for example, using brushes or by blowing with a stream of air; after the above operations, it is recommended to subject the product to the so-called glazing or polishing using oils that can be applied directly or as a solution in volatile solvents, and which leave a thin film that causes an attractive surface gloss, eliminating stickiness and resistance to changes in water content in case of strong drying out, or, conversely, the ingress of moisture with its excess in the surrounding atmosphere.

 While the production method used in the examples is based on the receipt of preparations in batches and, more or less manually, controlled molding in trays with starchy material, a partially or fully automated production method can also be applied, such as the “Module” - installation, however, conversion of this type of high-speed technique will naturally require the introduction of certain adjustments to the composition of the material, ready for molding.

In the examples, the following materials were used:
Raw, unrefined materials:
Dextrose Syrup, Glycosum Liquidum (Lof no. 302 589) Mecobenson, Denmark;
Sugar (preferably shaped) Dannsukker Melis, DDS, Denmark;
Gum arabic (purified), Gummi Arabicum (chemical pure powder Lk (E414), (lot no. 233200), Notdisk Droge Handels A / s, Denmark,
Gelatin (preferably bloom 215), 215 g gelatin powder (lot no. 232883), Nordisk Droge Handels A / s, Denmark;
Tap water
Tobacco dust, half granulate and half pipe tobacco, American Branch;
Lemon acid;
Peppermint essence;
Anise;
Almond Essence; and
Cocoa.

Drying materials
Corn Starch, Maydis Amylum / lot no. 257329 /, Mecobengon, Denmark
Wheat starch Tritici Amylum / lot no. 257535 /, Mecobengon, Denmark
Before using the starch material, it is necessary to dry at 150-200 ^° C. for at least 2 hours until the moisture content exceeds 10%.

Gum arabic solutions
A solution of 1/50% gum arabic /.

3.5 kg of water heated to 30 ^o C, slowly poured with constant stirring to 3.5 kg of gum arabic, then shake vigorously and leave to stand for about 20 hours. Foam is removed from the surface of the solution and left to stand for 1 hour . Before use, the surface of the solution is again cleaned.

 A solution of 2/50% gum arabic /.

3.5 kg of gum arabic is slowly added with constant stirring to 3.5 kg of water heated to 30 ^° C., after which the solution is treated as described for solution 1.

 A solution of 3 / 33.3% gum arabic /.

2 kg of warm water / 30 ^o C / slowly poured with constant stirring to 1 kg of gum arabic, and then treated as described for solution 1.

 Solutions of pre-soaked gelatin.

Solution 4 / 33.3% gelatin /
900 g of gelatin is slowly added with constant stirring in water / 12 ^o C /, after which 900 g of warm water / 70 ^o C / is poured into this solution with stirring and left to stand for 20 hours.

 Take note: Solution 4 cannot be used without reheating and filtering.

 A solution of 5 / 33.3% gelatin /.

900 g of gelatin is slowly added with constant stirring to 1800 g of warm water / 70 ^o C /, then shaken vigorously and left to stand for 20 hours

 A solution of 6 (33.3% gelatin).

in 1800 g of warm water / 50 ^o C / slowly 900 g of gelatin are dissolved with constant stirring, shaken vigorously and left to stand for 20 hours

 A solution of 7 / 33.3% gelatin /.

150 g of gelatin and 300 g of water are placed in a vessel, slowly heated to 95 ^o C, and when all the material has dissolved, the solution is cooled to 50 ^o C and immediately used.

Solution 8/25% gelatin /
1800 g of warm water / 70 ^o C / are slowly poured with constant stirring to 600 g of gelatin, after which they are shaken vigorously and left to stand for 20 hours.

 Samples.

 The dry weight in% is shown in parentheses.

 Prescription A.

210 g sugar / 25% /
210 g dextrose / 25% /
50 g of water
420 g of gum arabic / 50% / / 1260 g of solution N 3 /
Water and sugar are mixed and heated until sugar is completely dissolved. Dextrose is added and the mixture is slowly heated to 125 ^o C / boiling time 23 min /. Gum arabic is added and the mixture is simmered for 80 minutes, after which it is left to stand for 3 hours at 35 ^° C. The final pH of the mixture is 4.0-5.0.

The surface of the mixture is thoroughly cleaned, then the mixture is poured into separate cells of the mold with corn starch and subjected to drying at 50 ^° C. until the moisture content is 5-10%.

 Prescription B.

210 g sugar / 19% /
365 g dextrose / 32% /
60 g of water
560 g of gum arabic / 49% / / solution N 1 /
Water and sugar are mixed and heated until sugar is completely dissolved. After adding dextrose, the mixture is heated to 125 ^o C / heating time 55 min /. Gum arabic is added to the mixture with constant stirring and heated to 75 ^° C. Then the mixture is left to stand for 1.5 hours at 35 ^° C. The final pH of the mixture is 5.0-5.5.

The surface of the mixture is thoroughly cleaned, after which the mixture is poured into molds with corn starch and dried at 50 ^° C. until the moisture content is 5-10%.

 Copy c.

210 g sugar / 24% /
350 g of dextrose / 41% /
55 g of water
300 g of gum arabic / 35 / / solution N 1 /
A mixture of sugar and the like, prepared as described in sections A and B, is heated to 117 ^o C / heating time 20 min /. Add gum arabic and heat to a boil. The mixture is allowed to stand for about 1 hour at 35 ^° C. The mixture has a final pH of 4.5-5.5.

The surface of the mixture is carefully cleaned of foam, after which the mixture is poured into the cells of starch molds and is dried at 50 ^o C to a state where the moisture content is 5-10%.

 Prescription E.

210 g sugar / 23% /
210 g dextrose / 23% /
60 g of water
480 g of gum arabic / 53% / / solution N 2 /
The sugar mixture is heated for 23 minutes to 118 ^° C. The gum arabic is added to the mixture with constant stirring, after which the mixture is left to stand for 1.5 hours at 35 ^° C. The final pH of the mixture is 3.5-5.0.

The surface of the mixture is thoroughly cleaned of foam, then the mixture is poured into the cells of the mold with corn starch and dried at 50 ^o C to a state in which the moisture content is 5-10%.

 Prescription F.

210 g sugar / 17% /
360 g dextrose / 30% /
60 g of water
640 g of gum arabic / 53% / / solution N 2 /
The sugar mixture is heated to 122 ^° C. / heating time 20 minutes /, and then the mixture is cooled to 115 ^° C. Gum arabic is added. The mixture was left to stand for 1.5 hours at 35 ^° C. The mixture had a final pH of 3.0-5.0.

The surface of the mixture is carefully cleaned of foam. Then the mixture is poured into the cells of the molds with corn starch and dried at 50 ^o C to a state in which the moisture content is 5-10%.

 G.

210 g sugar / 23% /
280 g of dextrose / 31% /
70 g of water
400 g of gum arabic / 44% / / solution N 2 /
25 g of gelatin / 3% / / solution N 8 /
The mixture of sugars is heated to 140 ^o C / heating time 25 minutes /. Gum arabic was added and the mixture was cooled to 80 ^° C. The gelatin was heated to 70 ^° C. and added to the mixture. The mixture is left to stand for 80 minutes at 35 ^° C. The mixture has a final pH of 4.0-5.0.

The surface of the mixture is thoroughly cleaned of foam. Then the mixture is poured into the cells of the mold with corn starch and are dried at 50 ^o C to a state in which the moisture content is 5-10%.

 Prescription H.

210 g sugar / 33% /
280 g of dextrose / 44% /
50 g of water
150 g of gelatin / 23% / / solution N 5 /
The mixture of sugars is heated to 120 ^o C / heating time 25 min /. The mixture was cooled to 90 ^° C. The gelatin was heated to 70 ^° C. and added to the mixture. The mixture is left to stand for 35 minutes. The final pH of the mixture is 4.0-5.0.

 The surface of the mixture is carefully cleaned of foam, after which the mixture is poured into the cells of the molds with corn starch and dried at room temperature to a state in which the moisture content is 5-10%.

Prescription I
210 g sugar / 32% /
350 g of dextrose / 53% /
50 g of water
100 g of gelatin / 15% / / solution N 6 /
The mixture of sugars is heated to 116 ^o C / heating time 15 min /. Then the mixture is cooled to 80 ^o C. The gelatin is heated to 60 ^o C and added to the mixture with constant stirring. The mixture is left to stand for 35 minutes at 35 ^° C. The mixture has a final pH of 3.0-6.0.

 The surface of the mixture is carefully cleaned of foam. Then the mixture is poured into the cells of the mold with corn starch and dried at room temperature to a state in which the moisture content is 5-10%.

Prescription J
210 g sugar / 23% /
290 g of dextrose / 31% /
50 g of water
350 g of gum arabic / 38% / / solution N 2 /
75 g of gelatin / 8% / / solution N 6 /
The mixture of sugars is heated to 120 ^o C / heating time 25 minutes /. Gum arabic is added to the mixture with stirring, the mixture is cooled to 90 ^o C. The gelatin is heated to 60 ^o C and added to the mixture with stirring. The mixture is left to stand for 80 minutes at 35 ^° C. The mixture has a final pH of 3.0-5.5.

 The surface of the mixture is carefully cleaned of foam, after which the mixture is poured into the cells of the starch mold and is dried at room temperature to a state where the humidity is 5-10%.

 Prescription K.

210 g sugar / 20% /
350 g of dextrose / 34% /
50 g of water
400 g of gum arabic / 39% / / solution N 2 /
75 g of gelatin / 7% / / solution N 7 |
The sugar mixture is heated to 120 ^o C / heating time 20 min /. Add gum arabic. Then the mixture is cooled to 100 ^o C and poured into it gelatin heated to 70 ^o C. The mixture is allowed to stand for 100 minutes at 35 ^° C. The final pH of the mixture is 4.5-5.0.

 The surface of the mixture is carefully cleaned of foam, after which the mixture is poured into the cells of starch molds and is dried at room temperature to a state in which the moisture content is 5-10%.

 Additional ingredients.

Samples marked I do not contain any additives. Citric acid is added to the samples designated II (pH is given in various prescriptions). Samples designated III-VII add citric acid and flavoring agents as follows:
I - No additives
II - Citric Acid
III - Peppermint Essence
IV - Anise / powder /
V - Almond Essence
VI - Cocoa
VII - Tobacco Powder
Gum arabic solutions.

 A solution of 9/50% gum arabic /.

2000 g of gum arabic is added to 2000 g of warm water / 50 ^o C /. The solution is shaken vigorously and left to stand for 24 hours, shaking vigorously from time to time. Mix two completely identical portions.

 Gelatin solutions.

 A solution of 10 (33.3% gelatin).

100 g of gelatin is mixed with 100 g of warm water / 70 ^o C / to obtain a homogeneous mixture. Additionally, 100 g of warm water / 70 ^° C. / is added to this mixture. The mixture is then left to stand for 5 hours.

 Prescription M.

400 g sugar / 33% /
70 g of water
100 g dextrose / 8% /
100 g of gelatin / 8% / / solution N 10 /
600 g of gum arabic / 50% / / solution N 9 /
Water and sugar are mixed when heated until sugar is completely dissolved. After adding dextrose, the mixture is heated to 120 ^o C / heating time 15 min /. The gelatin is then heated to 70 ^° C. and added to the mixture. Gum arabic is added here with constant stirring in order to distribute it evenly. One half of the mixture (M ') is drained and stored for 30 minutes at 35 ^° C. The other half is boiled for an additional 35 minutes and then left to stand for 50 minutes at 35 ^° C. The mixtures have a final pH of 3.5-5, 0.

The surfaces of both mixtures are carefully cleaned of foam. Then the mixture M 'is poured into the cells of the mold with corn starch and dried at 50 ^o C to a state in which the moisture content is 5-10%, after which the mixture M is poured into the cells of the mold with starch of wheat and dried at 50 ^o C to a state in which the moisture content is 5-10%.

 Prescription O.

400 g sugar / 29% /
70 g of water
100 g dextrose / 7% /
900 g of gum arabic / 64% / / solution N 9 /
Sugar and water are mixed when heated until sugar is completely dissolved. Dextrose is added and heated to 117 ^° C. / heating time 13 minutes /. Gum arabic is added and mixed until a homogeneous mixture is obtained. One half / O '/ is decanted and stored for 65 minutes at 35 ^° C. The other half is boiled for an additional 45 minutes and then left for 70 minutes at 35 ^° C. The mixtures have a final pH of 3.0-5.0.

The surfaces of both mixtures / O and O '/ are carefully cleaned of foam. Then both mixtures are placed in the cells of the molds with corn starch and dried at 50 ^o C to a state in which the moisture content is 5-10%.

 P.

400 g sugar / 27% /
70 g of water
100 g dextrose / 7% /
1000 g of gum arabic / 67% / / solution N 9 /
Sugar and water are mixed when heated until sugar is completely dissolved. Dextrose is added, after which the mixture is heated to 118 ^° C / heating time 12 min /. Gum arabic is added and mixed until a homogeneous mixture is obtained. One half / P '/ is drained and stored for 70 minutes at 35 ^o C. The second half of the mixture is boiled for an additional 50 minutes and then remains at 35 ^o C for 120 minutes The final pH of the mixtures is 4.0-5.0.

The surfaces of both mixtures P and P 'are carefully cleaned of foam. Then the mixture P 'is poured into the cells of the molds with corn starch and dried at 50 ^o C to a state where the moisture content is 5-10%, and the mixture P is poured into the cells of the molds with starch from wheat and dried at 50 ^o C to a state in which the moisture content is 5-10%.

 Additional ingredients used in M-P prescriptions.

 Samples designated I were prepared without adding any additional ingredients. Samples designated II, obtained with the addition of nicotine after the initial gelation / pH not changed /. Samples designated III are prepared with the addition of nicotine and citric acid.

 In the following examples, the Q prescription and the R prescription provide the formation of the foundations of various stimulant preparations to which certain amounts of the active ingredient are added, and also aromatize by adding tobacco. The basis of these stimulating drugs is a solution of gum arabic N 11.

 A solution of 11/50% gum arabic /.

1500 g of gum arabic are mixed with 1500 g of warm water / 50 ^o C /. The mixture is then left to stand for approximately 40 hours.

 Prescription Q.

200 g sugar / 25.6% /
30 g of water
80 g of dextrose / 10.3% /
500 g of gum arabic / 64.1% / / solution N 11 /
Ingredients Added:
I 4 ml of 10% nicotine base
II 1 ml of 50% tobacco as a flavoring agent, approximately 1 g
III 5 g Na ₂ CO ₃ + 5 g NaHCO ₃
Water and sugar are mixed by heating until sugar is completely dissolved. Dextrose is added and heated to 116 ^° C. / heating time 14 minutes /. Gum arabic is added with stirring until it is evenly distributed in the mixture. The mixture is refluxed for 26 minutes until it becomes clear. Then the mixture is left to stand for 155 minutes, at about 30 ^° C., after which the surface of the mixture is cleaned of foam.

Q ¹ and Q ²
Added I and II
Nicotine content: - 0.5-1.0 mg / g
Flavoring Tobacco Content: - 1.0-1.5 mg / g
pH is approximately 5.0
Q ³
Like Q ¹ and Q ² + III
Nicotine content: - 0.5-1.0 mg / g
Flavoring Tobacco Content: - 1.0-1.5 mg / g
Na ₂ CO ₃ : - approximately 1.3%
NaHCO ₃ : - approximately 1.3%
pH: - approximately 9.0
Copy R
200 g sugar / 25.8% /
30 g of water
76 g of dextrose / 9.8% /
500 g of gum arabic / 64.4% / / solution N 11 /
Ingredients Added:
I: 4 ml of 10% nicotine base
II: 1 ml of 50% flavor tobacco approximately 1 g
IV: 7.5 g of Na ₂ CO ₃ dissolved in 15 ml of water
V: 7.5 g of NaHCO ₃ dissolved in 15 ml of water
VI: 5.0 g of Na ₂ CO ₃ dissolved in 5 ml of water
VII: 5.0 g of NaHCO ₃ dissolved in 5 ml of water
The mixture is boiled, as described in the recipe Q, using the following parameters:
Boiling point - 120 ^o C
Boiling time - 12 min.
Slow boiling time - 28 min.
Settling time - 150 min
R ¹ and R ²
Added I + II + IV + V
Nicotine content: - 0.5-1.0 mg / g
Flavoring Tobacco Content: - 1.0-1.5 mg / g
Na ₂ CO ₃ content: - approximately 0.9%
Na ₂ HCO ₃ content: - approximately 0.9%
pH: - approximately 8.0
R ³
Equivalent to R ¹ + R ² + VI + VII
Nicotine content: - 0.5-1.0 mg / g
Flavoring Tobacco Content: - 1.0-1.5 mg / g
Na ₂ CO ₃ content: - approximately 2.3%
Na ₂ HCO ₃ content: - approximately 2.3%
pH: - approximately 9.0
R ³ + Q ³ mixture
Nicotine content: - 0.5-1.0 mg / g
Flavoring Tobacco Content: - 1.0-1.5 mg / g
Na ₂ CO ₃ content: - approximately 1.8%
Na ₂ HCO ₃ content: - approximately 1.8%
pH: - approximately 9.0
All samples designated Q and R are dried in starch molds at 50 ^o C.

Take note: in all cases, the contents of the various compounds presented in the general mixtures reflect the dry matter content. Similarly, after turning on the carbonate buffer and before drying in starch molds, the solutions cannot be reheated to prevent the formation of CO ₂ .

 Defining a structure profile.

Analysis of the structure profile by the above method of Sanderson et al., Ibid, is carried out in accordance with the following procedure:
/ a / Procedure:
A cylindrical sample was prepared 15 mm in diameter and 7-10 mm high and placed between two compression plates of the Product Testing Tool, JJ Jnstrument M30K, Lloyd Jnstrument, PLC. The plates are surrounded by a heating element to ensure that a constant, selected temperature is maintained.

 The sample is compressed twice at a speed of 50 mm / min to 70% of its original height, while the resistance due to the material is measured and recorded.

 After the first compression, the compression plates are brought to their initial position, and immediately begins the second stage of compression.

/ b / Sample preparation
Samples for structural analysis are prepared by placing one or more stimulants in a mold with an internal diameter of 15 mm and a compression piston. Then the mold and its contents are placed in the oven for 10-15 minutes at 80 ^o C. After removal from the oven, the compression piston is pressured at about 3 kg until the sample acquires a mold that is stable at room temperature. After that, the form and its contents are cooled using liquid N ₂ , after which a sample of a certain structure is removed from the form.

 / c / Test conditions.

Samples for structural analysis are placed in a waterproof plastic bag at the required temperature, for example, 35 ^o C, for 24 hours

Disintegration Time Measurement
Further, in some cases, the disintegration time was measured according to Ph.Eur.2. Ed., V. 5.1.1, in accordance with the following procedure:
/ a / Procedure.

Test samples with dimensions of 10 mm x 10 mm x 5 mm and weight from 0.5 to 1.5 g are placed in cylindrical, glass tubes, which are maintained in a special rack, and subjected to suspension in a grinder containing purified water at 37 ^o C in a disintegration apparatus type: Pharma Test PT 21.

 Disintegration time is expressed as the time needed to destroy the last test preparation.

 / b / pH measurement.

 pH is measured using a pH meter such as Metrom 691.

 Results.

 The results are presented in table. 3 and 4.

Take note: The structure parameters are measured at 35 ^o C.

Take note: the disintegration time is determined at 37 ^o C.

 Stimulating preparations prepared in accordance with the A - R formulas possessed structural parameters and disintegration time corresponding to the limits indicated in the claims, p. 1.

The buffering capacity of the stimulant preparations according to the invention is illustrated by measuring pH for 1.0773 g of a test sample of R prescription, which break down with a disintegration time of 25.26 minutes. The following pH values were obtained:
Time / minutes / - pH
5 - 8.66
10 - 8.84
15 - 8.95
20 - 9.01
25 - 8.89g

Claims (15)

1. A saliva-soluble drug for eliminating tobacco smoking, containing an active principle included in a gel of a pharmaceutically acceptable water binding agent, characterized in that it contains nicotine or a similar action alkaloid in an amount of 0.5-10 mg per dose, the preparation has the following physical and mechanical parameters: strength more than 100 N / cm ² , hardness more than 5 N / cm ² , brittleness not less than 30%, adhesive capacity 0 - 70%, elasticity 25 - 100%, cohesive ability 25 - 100 % and disintegration time at 37 ^o From 5 to 60 minutes 2. The drug according to claim 1, characterized in that it has the following physical and mechanical parameters: strength more than 200 N / cm ² , hardness more than 25 N / cm ² , brittleness of at least 30%, adhesive ability 0 - 40%, elasticity 50 - 100%, cohesive ability 40 - 100% and disintegration time 6 - 45 min. 3. The drug according to claim 1 or 2, characterized in that it has the following physical and mechanical parameters: strength more than 400 N / cm ² , hardness from 80 to 300 N / cm ² , brittleness of at least 30%, adhesive ability 0 - 20%, elasticity from 30 to 100%, cohesive ability from 40 to 100% and a disintegration time of 15 to 40 minutes.  4. The preparation according to claims 1 to 3, characterized in that the water-binding agent is gelatin or one or more synthesized or natural polysaccharides, preferably used in the confectionery industry.  5. The drug according to claims 1 to 3, characterized in that the water-binding agent is selected from the group consisting of agar, algin, carrageenan, gar resin, gum arabic, gatti resin, tragacanth resin, karaya resin, resin from the trunk of pseudoacacia (locust), pectin, xanthan gum, preferably gum arabic and carrageenan.  6. The drug according to claims 1 to 5, characterized in that it additionally contains flavoring and aromatic additives selected from the group including synthesized or natural aromatic compounds obtained from essential oils, essences, fruit juices and powdered in the form of flour or vegetative powder parts of plants, such as tobacco, coffee, tea, mint.  7. The drug according to claims 1 to 6, characterized in that it additionally contains one or more vitamins and minerals selected from the group comprising magnesium, iron, zinc, copper, iodine, manganese, chromium, selenium, molybdenum, cobalt, vanadium , nickel, tin, fluorine and silicon.  8. The drug according to claims 1 to 7, characterized in that it additionally contains physiologically acceptable buffer substances.  9. The drug according to claim 8, characterized in that it contains buffering substances in an amount that guarantees the maintenance of the pH value of saliva in the range of 8-10 during the period of disintegration of the drug.  10. The drug according to paragraphs. 8 and 9, characterized in that the amount of buffer substance is 5 to 50 mg per dose.  11. The drug according to claims 8 to 10, characterized in that the buffer substance is selected from the group comprising alkali metal carbonates, bicarbonates, phosphates and hydrophosphates.  12. The drug according to any one of paragraphs.1 to 11, characterized in that the preferred nicotine content per dose is in the range of 0.5 - 5.0, 1.0 - 1.5, 1.5 - 2.5 and 2 5 - 3.0 mg.  13. The drug according to any one of claims 1 to 12, characterized in that nicotine is evenly distributed over the weight of the drug.  14. The drug according to claims 1 to 12, characterized in that it has a multilayer structure, and the outer layer has a sufficient amount of active ingredient to quickly achieve effective concentration of the active ingredient in the blood plasma and the inner layer has an uneven distribution of the active ingredient to maintain the specified concentration for the desired amount of time.  15. The drug according to any one of paragraphs.1 to 14, characterized in that it is made in a form convenient for attachment to the sky.

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