CANNABINOID CHEWING GUM WITH SUGAR ALCOHOLS

Abstract

The present invention relates to a chewing gum for delivering cannabinoids to mucous membranes, the chewing gum being characterized in that it comprises water-soluble chewing gum ingredients and a water-insoluble chewing gum base, the chewing gum base comprising one or more natural resins in an amount of 10-40% by weight of the gum base, one or more elastomers in an amount of 3-30% by weight of the gum base, and one or more polyvinyl acetate elastomeric plasticizers in an amount of 8-50% by weight of the chewing gum base, wherein the water-soluble chewing gum ingredients comprise one or more sugar alcohols in an amount of 35-80% by weight of the chewing gum, and wherein the chewing gum comprises one or more cannabinoids in an amount of 0.1 to 200 mg per piece of chewing gum.

Description

DETAILED DESCRIPTION OF THE INVENTION The invention will now be described in more detail with respect to certain aspects and embodiments of the invention. It is intended that these aspects and embodiments be understood in relation to the rest of the description, including the brief description of the invention and the examples of the invention. The verb understand as used in this description and in the claims and its conjugations is used in its non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. / uuoa jo Furthermore, the reference to an item by the indefinite article "un" or "una" does not preclude the possibility of more than one item being present, unless the context clearly requires that there be one and only one item. Therefore, the indefinite article "un" or "una" normally means "at least one." In addition, the words "un" and "una," when used herein in conjunction with the word comprising or containing, denote one or more. The terms gum base and gum base matrix refer to the primarily water-insoluble ingredients and the hydrophobic gum base ingredients that are blended together, typically before the bulk of the chewing gum is added. The gum base may contain gum-based polymers and plasticizers, waxes, emulsifiers, fats, and / or fillers. Therefore, gum base can designate the typical water-insoluble components of chewing gum, which may be manufactured in a first step and subsequently blended with the primarily water-soluble portion in a second step. The term gum base can also, of course, refer to the relevant gum base components that can be fed into an extruder and that become part of the final chewing gum when blended with the chewing gum components in the extruder. The term bulk portion or water-soluble ingredients is intended to mean the primarily hydrophilic and water-soluble chewing gum ingredients that can be blended into the gum base matrix, either in a separate process or in a one-step process by means of an extruder. The term "weight of chewing gum" or similar wording meaning the same thing is defined in the present context as the weight of the chewing gum, excluding the weight of an outer coating, such as a hard coating, a soft coating, and the like. The term "texture" refers to a qualitative measure of the viscoelastic properties of chewing gum and the overall sensation experienced by the user in the mouth during chewing. Therefore, the term "texture" encompasses measurable quantities such as hardness and elasticity, as well as more subjective parameters related to the chewing sensation experienced by the user. The term in vivo mastication is intended to mean that the chewing gum system is chewed by a human subject in an experimental setting of trained test subjects according to statistical principles and that the human subject's saliva is subject to measurements or the chewed chewing gum is subject to measurements, the experimental setting is carried out at a chewing frequency of 60 chews per minute. The term in vivo release or in vivo release test or similar wording is intended to mean that the chewing gum is tested in accordance with Example 24. The term in vitro release or in vitro release test or similar wording is intended to mean that the chewing gum is tested according to Example 25, in particular according to the dissolution test for chewing gum, General Monograph 2.9.25. In the European Pharmacopoeia, 5th ed. The term "release" in this context is intended to mean under in vivo or in vitro conditions. In particular, the release rate over a certain period of time is intended to mean the percentage of cannabinoids released during that period at a chewing frequency of 60 chews per minute. The term sustained release or prolonged release is intended herein to mean a prolonged release over time. The term rapid release or quick release or high release is intended herein to mean a higher content released over a specified period of time. The term controlled release is intended to mean the release of a substance from chewing gum by means of actively chewing the gum in the subject's oral cavity, whereby active chewing controls the amount of substance released. The term "supply to the oral mucosa" or similar wording is intended to mean that the chewing gum is tested in accordance with Example 27. A self-emulsifying agent is an agent that will form an emulsion when presented with an alternating phase with minimal energy requirements. Conversely, an emulsifying agent, unlike a self-emulsifying agent, requires additional energy to form an emulsion. The term natural resin, as used in this document, means resinous compounds that are polyterpenes derived from naturally occurring terpenes or resinous compounds derived from gum rosin, wood rosin, or tall oil rosin. The gum base is the chewing substance of chewing gum, which imparts its chewing characteristics to the final product. The gum base typically defines the release profile and plays a significant role in the gum product. The base portion of the chewing gum is retained in the mouth throughout the chewing process. The water-soluble portion is dissolved over time during chewing. According to the embodiments of the invention, a preferred amount of rubber base matrix in the final chewing gum is 30-75% by weight of the chewing gum before any optionally applied coating, such as 35-70% by weight of the chewing gum or 40-65% by weight of the chewing gum or 45-60% by weight of the chewing gum. Elastomers impart the rubbery, elastic, and rebound properties to the rubber, which vary depending on the chemical structure of this ingredient and how it is combined with other ingredients. Elastomers suitable for use in the base rubber and rubber of the present invention may include natural or synthetic types. Polyvinyl acetate elastomeric plasticizers are not considered elastomers according to the invention. The elastomers can be selected from the group consisting of styrene-butadiene copolymers, polyisobutylene, isobutylene-isoprene copolymers, polyethylene, polyurethane, or any combination thereof. The preferred elastomers are styrene-butadiene copolymers (SBR), polyisobutylene, and isobutylene-isoprene copolymers (BR). Butadiene-styrene elastomers, or SBRs as they are sometimes called, are typically copolymers of approximately 20:80 to 60:40 styrene:butadiene monomers. The ratio of these monomers affects the elasticity of the SBR as assessed by its Mooney viscosity. As the styrene:butadiene ratio decreases, the Mooney viscosity decreases. The structure of SBR typically consists of linear-chain 1,3-butadiene copolymerized with phenylethylene (styrene). The average molecular weight of SBR is <600,000 g / mol. Isobutylene-isoprene, or butyl, elastomers have molar percentage levels of isoprene ranging from 0.2 to 4.0. Similar to SBR, as the isoprene:isobutylene ratio decreases, so does the elasticity, as measured by Mooney viscosity. The structure of butyl rubber typically consists of branched 2-methyl-1,3-butadiene (isoprene) copolymerized with branched 2-methylpropene (isobutylene). The average molecular weight of SBR is in the range of 150,000 g / mol to 1,000,000 g / mol. Polyisobutylene-type elastomers, or PIB as they are sometimes called, are polymers of 2-methylpropene. Low molecular weight elastomers provide soft chewing characteristics to the rubber base while still offering the elastic qualities of other elastomers. Average molecular weights can range from approximately 30,000 to 120,000 g / mol, and penetration can range from approximately 4 mm to 20 mm. The greater the penetration, the softer the PIB. Like SBR and butyl, high molecular weight elastomers provide elasticity to the rubber. Average molecular weight can range from 120,000 to 1,000,000 g / mol. Polybutene varies in average molecular weight from approximately 5,000 g / mol to approximately 30,000 g / mol. Useful natural elastomers include natural rubber such as smoked or liquid latex and guayule, and natural gums such as jelutong, lechi caspi, perillo, sorva, massaranduba balata, massaranduba chocolate, níspero, rosidinha, chicle, gutta-percha, gutta kataiu, niger gutta, tunu, chilte, chiquibul, and gutta hang kang. Natural elastomers may also be applied in aspects of the present invention. Elastomer plasticizers vary the firmness of the rubber base. Their specificity in breaking the intermolecular chain of the elastomer (plasticization), along with their different softening points, result in varying degrees of firmness and compatibility of the finished rubber when used as a base. Polyvinyl acetate elastomer plasticizers are examples of elastomer plasticizers of the present invention. In some embodiments of the invention, the weight average molecular weight (Mw) of one or more polyvinyl acetate elastomeric plasticizers is from 5,000 to 40,000. In some embodiments of the invention, the weight average molecular weight (Mw) of one or more polyvinyl acetate elastomeric plasticizers is from 6,000 to 35,000. In some embodiments of the invention, the weight average molecular weight (Mw) of one or more polyvinyl acetate elastomeric plasticizers is from 7,000 to 30,000. In some embodiments of the invention, the weight average molecular weight (Mw) of one or more polyvinyl acetate elastomeric plasticizers is from 8,000 to 25,000. In some embodiments of the invention, the weight average molecular weight (Mw) of one or more polyvinyl acetate elastomeric plasticizers is from 10,000 to 20,000. In some embodiments of the invention, the viscosity of one or more polyvinyl acetate elastomeric plasticizers is from 1.0 to 3.0 mPa*s as measured according to ASTM D445-06 (10% by weight in ethyl acetate), such as from 1.0 to 2.5 mPa*s. In some embodiments of the invention, the K value of one or more polyvinyl acetate elastomeric plasticizers is from 15 to 33 measured according to DIN 53726 (1% by weight in acetone), such as from 18 to 30. Generally, the term polyvinyl acetate elastomeric plasticizer is intended to mean polyvinyl acetate having a weight average molecular weight (Mw) of less than approximately 40,000. Generally, the term polyvinyl acetate elastomer is intended to mean polyvinyl acetate having a weight average molecular weight (Mw) of more than approximately 40,000. In certain embodiments of the invention, the rubber base comprises less than 10% by weight of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base comprises less than 5% by weight of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base comprises from 2% to 6% by weight of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base comprises from 3% to 5% by weight of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base is substantially free of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base comprises 15 to 35% by weight of one or more polyvinyl acetate elastomeric plasticizers and less than 10% by weight of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base comprises 15 to 35% by weight of one or more polyvinyl acetate elastomeric plasticizers and less than 5% by weight of polyvinyl acetate elastomer. In certain embodiments of the invention, the rubber base comprises 15 to 35% by weight of one or more polyvinyl acetate elastomeric plasticizers and 2 to 6% by weight of polyvinyl acetate elastomer. Natural resins can be selected from ester gums that include, for example, partially hydrogenated rosin glycerol esters, polymerized rosin glycerol esters, partially dimerized rosin glycerol esters, tall oil rosin glycerol esters, partially hydrogenated rosin pentaerythritol esters, rosin methyl esters, partially hydrogenated rosin methyl esters, pentaerythritol rosin esters, synthetic resins such as terpene resins derived from alpha-pinene, beta-pinene and / or d-limonene, and natural terpene resins. In one embodiment of the invention, the chewing gum comprises other chewing gum ingredients selected from the group consisting of flavorings, dry binders, tablet-forming aids, anti-caking agents, emulsifiers, antioxidants, enhancers, absorption enhancers, high-intensity sweeteners, color softeners, active ingredients, water-soluble non-digestible polysaccharides, water-insoluble polysaccharides, or any combination thereof. According to embodiments of the invention, the emulsifiers can be selected from the group consisting of sucrose esters of fatty acids (such as sucrose monostearate), polyethylene glycol (PEG) esters or ethers (such as caprylocaproyl macrogol-8 and lauroyl macrogol-32-glycerides), mono- and diglycerides of fatty acids (such as glycerol monostearate, glycerol monolaurate, glyceryl behenate ester), acetic acid esters of mono- and diglycerides of fatty acids (Acetem), polyoxyethylene alkyl ethers, diacetyl tartaric acid ester of monoglycerides, lactylated monoglycerides, glycerophospholipids (such as lecithin), poloxamer (nonionic block copolymer of ethylene oxide and propylene oxide), cyclodextrins, fatty acid esters of sorbitol (such as monolaurate of sorbitan, sorbitan monostearate, sorbitan tristearate, polysorbates).Self-emulsifying emulsifiers can be phospholipids (lecithin), polysorbates (polysorbate 80). SEDDS (self-emulsifying drug delivery systems) may consist of hard or soft capsules filled with a liquid or gel comprising self-emulsifiers, one or more cannabinoids, oil (to dissolve the cannabinoids), and a surfactant. SEDDS may comprise a combination or mixture of self-emulsifiers, one or more cannabinoids, oil (to dissolve the cannabinoids), and a surfactant. SEDDS may comprise granules comprising self-emulsifiers, one or more cannabinoids, oil (to dissolve the cannabinoids), and a surfactant. Upon contact with gastric fluid, SEDDS spontaneously emulsify due to the presence of surfactants. However, many surfactants are lipid-based and interact with lipases in the gastrointestinal tract (GIT).This can lead to a reduced ability of lipid-based surfactants to emulsify one or more cannabinoids, as well as the oil carrier, reducing both bioavailability. According to embodiments of the invention, the aromas can be selected from the group consisting of coconut, coffee, chocolate, vanilla, grapefruit, orange, lime, menthol, licorice, caramel, honey, peanut, walnut, cashew, hazelnut, almond, pineapple, strawberry, raspberry, tropical fruits, cherries, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, and mint; fruit essences such as apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, and plum essences. Essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay leaf oil, anise, thyme, cedarwood oil, nutmeg, and the oils of the aforementioned fruits. Petroleum waxes aid in the curing of the finished rubber made from the rubber base and improve shelf life and texture. The size of the wax crystals influences flavor release. Waxes with a high isoalkane content have smaller crystal sizes than waxes with a high content of normal alkanes, especially those with normal alkanes having fewer than 30 carbon atoms. The smaller crystal size allows for a slower release of flavor, as there are more obstacles for the flavor to escape from this wax compared to a wax with larger crystal sizes. Petroleum wax (refined paraffin and microcrystalline wax) and paraffin wax are composed primarily of straight-chain normal alkanes and branched isoalkanes. The ratio of normal alkanes to isoalkanes varies. Antioxidants extend the shelf life and storage of base gum, finished gum, or their respective components, including fats and flavoring oils. Suitable antioxidants for use in gum base include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), beta-carotenes, tocopherols, acidulants such as vitamin C (ascorbic acid or corresponding salts (ascorbates)), propyl gallate, catechins, other synthetic and natural types or mixtures thereof. Other ingredients of chewing gum, which may be included in the chewing gum according to the present invention, include surfactants and / or solubilizers. For examples of types of surfactants to be used as solubilizers in a chewing gum composition according to the invention, reference is made to HP Fiedler, Lexikon der Hilfstoffe für Pharmacie, Kosmetik und Angrenzende Gebiete, pages 63-64 (1981) and the lists of approved food emulsifiers for each country. Anionic, cationic, amphoteric, or non-ionic solubilizers may be used. Suitable solubilizers include lecithin, polyoxyethylene stearate, polyoxyethylsorbitan fatty acid esters, fatty acid salts, mono- and diacetyl tartaric acid esters of mono- and diglycerides of edible fatty acids, citric acid esters of mono- and diglycerides of edible fatty acids, sucrose esters of fatty acids, polyglycerol esters of fatty acids, polyglycerol esters of interesterified castor oil (E476), sodium stearoyltylate, sodium lauryl sulfate and sorbitan esters of fatty acids and polyoxyethylated hydrogenated castor oil (e.g., the product sold under the trade name CREMOPHOR), ethylene oxide and propylene oxide block copolymers (e.g.,products sold under the trade names PLURONIC and POLOXAMER), polyoxyethylene ethers of fatty alcohols, polyoxyethylene sorbitan esters of fatty acids, sorbitan esters of fatty acids and polyoxyethylene stearic esters. Particularly suitable solubilizers include polyoxyethylene stearates, such as polyoxyethylene stearate (8) and polyoxyethylene stearate (40); polyoxyethylsorbitan fatty acid esters sold under the trade name TWEEN, such as TWEEN 20 (monolaurate), TWEEN 80 (monooleate), TWEEN 40 (monopalmitate), TWEEN 60 (monostearate), or TWEEN 65 (triestearate); mono- and diacetyl tartaric acid esters of edible mono- and diglycerides of edible fatty acids; citric acid esters of edible mono- and diglycerides of edible fatty acids; sodium stearoyltylate; sodium lauryl sulfate; polyoxyethylated hydrogenated castor oil; ethylene oxide-propylene oxide block copolymers; and polyoxyethylene fatty alcohol ether. The solubilizer may be a single compound or a combination of several compounds.In the presence of an active ingredient, such as one or more cannabinoids, the chewing gum may also preferably comprise a vehicle known in the chewing gum art and active ingredients. Poloxamer F68 is another very suitable solubilizer. High-intensity artificial sweeteners may also be used according to preferred embodiments of the invention. Preferred high-intensity sweeteners include, but are not limited to, sucralose, aspartame, acesulfame salts, alitame, neotame, saccharin and its salts, adamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, monk fruit extract, advantame, stevioside, and the like, alone or in combination. To provide a longer-lasting perception of sweetness and flavor, it may be desirable to encapsulate or otherwise control the release of at least some of the artificial sweeteners. Techniques such as wet granulation, wax granulation, spray drying, spray cooling, fluidized bed coating, preservation, encapsulation in yeast cells, and fiber extrusion can be used to achieve the desired release characteristics. Encapsulation of sweetening agents can also be provided using another component of chewing gum, such as a resinous compound. The usage level of high-intensity sweetener will vary considerably and will depend on factors such as the sweetener's potency, release rate, desired product sweetness, the level and type of flavoring used, and cost considerations. Therefore, the active level of artificial sweetener may range from approximately 0.001 to approximately 8% by weight (preferably from approximately 0.02 to approximately 8% by weight). When the carriers used for encapsulation are included, the usage level of the encapsulated high-intensity sweetener will be proportionally higher. A chewing gum and / or gum base may, if desired, include one or more fillers / texturizers, including, for example, magnesium and calcium carbonate, sodium sulfate, ground limestone, silicate compounds such as magnesium and aluminum silicate, kaolin and clay, aluminum oxide, silicon oxide, talc, titanium oxide, mono-, di-, and tricalcium phosphates, cellulose polymers such as wood, and combinations thereof. According to one embodiment of the invention, a preferred reylene / texturizer is calcium carbonate. Several well-known chewing gum components may be applied within the scope of the present invention. Such components include, but are not limited to, waxes, fats, softeners, fillers, bulk sweeteners, flavorings, antioxidants, emulsifiers, coloring agents, binders, and acidulants. In one embodiment of the invention, the water-soluble ingredients comprise at least one sugar alcohol. The at least one sugar alcohol may be selected from the group consisting of xylitol, sorbitol, mannitol, maltitol, isomaltitol, isomalt, erythritol, lactitol, maltodextrin, hydrogenated starch hydrolysates, and combinations thereof. A specific example of a category of polyol sweeteners includes sugars, in particular a sugar selected from the group consisting of dextrose, sucrose, maltose, fructose, lactose and combinations thereof. One method for manufacturing extruded chewing gum may be the following: Rubber bases are typically prepared by adding a quantity of elastomer, elastomeric plasticizer, and filler to a heated (100°C-120°C) sigma blade mixer with a forward-to-reverse speed ratio of approximately 1.2:1 to approximately 2:1, the higher ratio typically used for rubber bases that require a more rigorous composition of their elastomers. The initial quantities of ingredients comprising the initial mass can be determined by the mixing kettle's capacity to achieve a suitable consistency and by the desired degree of blending to break down the elastomer and increase chain branching. The higher the initial filler level or the selection of a filler with a specific particle size distribution, the greater the degree of blending and, consequently, the more the elastomeric chain crosslinking will be broken, resulting in more elastomer branching, lower viscosity rubber bases, and therefore a softer final rubber base and rubber manufactured from that base. Conversely, the longer the blending time, the use of lower molecular weight or softening point rubber base ingredients, the lower the viscosity and firmness of the final rubber base. The mixture typically begins to take effect once the ingredients have combined. The mixing time can range from 15 to 90 minutes. Ideally, the preparation time is 20 to approximately 60 minutes. The amount of elastomeric plasticizer added depends on the level of elastomer and filler present. If too much elastomeric plasticizer is added, the initial mass becomes overly plasticized and non-homogeneous. After the initial ingredients have been thoroughly kneaded and combined for the desired time, the remaining rubber base ingredients are added sequentially until a completely homogeneous melt is achieved. Typically, any remaining elastomer, elastomeric plasticizer, and filler are added within 60 minutes of the initial preparation time. The filler and elastomeric plasticizer are usually weighed individually and added in portions during this time. Optional waxes, softeners, and antioxidants are typically added after the elastomers and elastomeric plasticizers and during the following 60 minutes. The mass is then allowed to become homogeneous before pouring. Typical processing times for the rubber base can vary from approximately one to approximately three hours, preferably from approximately 1.5 to 2.5 hours, depending on the formulation. The final temperature of the mass when poured can be between 70°C and 130°C and preferably between 100°C and 120°C. The complete melt is emptied from the mixing kettle into lined or coated containers, extruded or poured into any desired shape, and allowed to cool and solidify. Those skilled in the art will recognize that many variations of the procedure described above may be followed. The water-soluble portion of chewing gum may comprise softeners, sweeteners, high-intensity sweeteners, flavoring agents, acidulants, fillers, antioxidants, and other components that provide the desired attributes. Softeners typically constitute approximately 0.5% to approximately 25.0% by weight of the chewing gum. Bulking agents generally comprise approximately 5% to approximately 90%, preferably approximately 20% to approximately 80% of the chewing gum. High-intensity sweeteners in chewing gum typically range from approximately 0.01% to 0.50% by weight. A flavoring agent may be present in the chewing gum in an amount ranging from approximately 0.1% to approximately 15.0% by weight of the gum. In general, chewing gum can be manufactured by sequentially adding the various chewing gum ingredients to a commercially available mixer, a known product of the art, where the finished gum base is already present. Once the initial ingredients are thoroughly mixed, the gum mass is discharged from the mixer and shaped as desired, for example, by rolling it into sheets and cutting it into sticks, extruding it into lumps, or melting it into granules. Generally, the ingredients can be mixed by first melting the gum base and adding it to the running mixer. Colorants, active ingredients, and / or emulsifiers can also be added at this time. A softener such as glycerin can also be added at this point, along with syrup and a portion of the bulking agent / sweetener. Additional portions of the bulking agent / sweetener can then be added to the mixer. A flavoring agent is typically added with the final portion of the bulking agent / sweetener. Preferably, a high-intensity sweetener is added after the final portion of bulking agent and flavoring. The complete mixing procedure typically takes thirty to forty minutes, but longer mixing times may sometimes be necessary. Those skilled in the technique will recognize that many variations of the procedure described above can be followed. According to the invention, the chewing gum may comprise from approximately 0.1 to approximately 75% by weight of an outer coating applied over the center of the chewing gum. Therefore, suitable coating types include hard coatings, film coatings, and soft coatings of any composition, including those currently used in chewing gum coating. A currently preferred type of outer coating is a hard coating, a term used in its conventional sense, which includes sugar coatings, sugar-free (or sugar-free) coatings, and combinations thereof. The purpose of a hard coating is to obtain a sweet, crisp layer that is appealing to the consumer and can also protect the gum cores for various reasons. In a typical process for coating chewing gum cores with a protective sugar layer, the gum cores are successively treated in suitable coating equipment with aqueous solutions of crystallizable sugar such as sucrose or dextrose, which, depending on the coating stage achieved, may contain other functional ingredients, such as fillers, binders, colorants, etc.In the present context, the sugar coating may contain other functional or active compounds including flavoring compounds and / or active compounds. In a typical hard coating process, as described in detail below, a suspension containing crystallizable sugar and / or polyol is applied to the gum cores, and the water it contains is evaporated by blowing air over them. This cycle must be repeated several times, typically from 3 to 80 times, to achieve the required swelling. The term swelling refers to the increase in weight or thickness of the products, considered at the end of the coating operation compared to the beginning, and in relation to the final weight or thickness of the coated products. According to the present invention, the coating layer constitutes approximately 0.1 to approximately 75% by weight of the finished chewing gum element, such as approximately 10 to approximately 60% by weight, including approximately 15 to approximately 50% by weight. In further useful embodiments, the outer coating of the chewing gum element of the invention is an element that undergoes a film-coating process and therefore comprises one or more film-forming polymeric agents and optionally one or more auxiliary compounds, for example, plasticizers, pigments, and opacifiers. A film coating is a thin, polymer-based coating applied to a chewing gum core in any of the above forms. The thickness of such a coating is typically between 20 and 100 µm. Generally, film coating is achieved by passing chewing gum centers through a spray zone containing atomized droplets of the coating materials in a suitable aqueous or organic solvent vehicle. The material adhering to the gum centers then dries before the next coating portion is applied. This cycle is repeated until the coating is complete. In the present context, suitable film-coating polymers include edible cellulose derivatives such as cellulose ethers, including methylcellulose (MC), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC). Other useful film-coating agents are acrylic polymers and copolymers, for example, methyl acrylate amino ester copolymer or mixtures of cellulose derivatives and acrylic polymers. A particular group of film-coating polymers, also called functional polymers, are those that, in addition to their film-forming characteristics, confer a modified release capability with respect to the active components of the chewing gum formulation. Such release-modifying polymers include methyl acrylate ester copolymers, ethylcellulose (EC), and enteric polymers designed to resist the acidic environment of the stomach.The last group of polymers includes: cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP), shellac, methacrylic acid copolymers, cellulose acetate trimellitate (CAT), and HPMC. It will be appreciated that the outer film coating according to the present invention may comprise any combination of the above film coating polymers. According to the invention, one or more cannabinoids can be selected from among several cannabinoids. Cannabinoids are a group of compounds that include endocannabinoids, phytocannabinoids, and those that are neither endocannabinoids nor phytocannabinoids, hereafter referred to as synthocannabinoids. Endocannabinoids are endogenous cannabinoids, which are high-affinity ligands of CB1 and CB2 receptors. Phytocannabinoids are cannabinoids that originate in nature and can be found in the cannabis plant. Phytocannabinoids can be present in an extract containing a botanical, isolated, or synthetically produced pharmacological substance. Syntocannabinoids are compounds that can interact with cannabinoid receptors (CB1 and / or CB2) but are not found endogenously or in the cannabis plant. Examples include WIN 55212 and rimonabant. An isolated phytocannabinoid is one that has been extracted from the cannabis plant and purified to such an extent that additional components, such as secondary and minor cannabinoids and the non-cannabinoid fraction, have been removed. A synthetic cannabinoid is one that has been produced by chemical synthesis. This term includes modifying an isolated phytocannabinoid, for example, by forming a pharmaceutically acceptable salt of it. A substantially pure cannabinoid is defined as a cannabinoid that is present at more than 95% (w / w) pure. More preferably more than 96% (w / w) up to 97% (w / w) up to 98% (w / w) up to 99% (w / w) and more. A highly purified cannabinoid is defined as a cannabinoid that has been extracted from the cannabis plant and purified to the extent that other cannabinoids and non-cannabinoid components that are extracted together with the cannabinoids have been substantially removed, so that the highly purified cannabinoid is greater than or equal to 95% (w / w) pure. Plant material is defined as a plant or part of a plant (e.g., bark, wood, leaves, stems, roots, flowers, fruits, seeds, berries, or parts thereof), as well as exudates, and includes material that falls within the definition of botanical raw material in the Draft Guide for Industry Botanical Pharmaceutical Products, August 2000, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research. In the context of this application, the terms cannabinoid extract or cannabinoid extract, used interchangeably, encompass botanical pharmaceutical substances derived from cannabis plant material. A botanical pharmaceutical substance is defined in the Guide for the Industry Draft Guide to Botanical Pharmaceutical Products, August 2000, U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research, as: A pharmaceutical substance derived from one or more macroscopic plants, algae, or fungi. It is prepared from botanical raw materials by one or more of the following processes: Pulverization, decoction, expression, aqueous extraction, ethanolic extraction, or other similar processes. A botanical pharmaceutical substance does not include a highly purified or chemically modified substance derived from natural sources. Therefore, in the case of cannabis, botanical pharmaceutical substances derived from cannabis plants do not include highly purified, pharmacopoeial-grade cannabinoids. The term cannabis plant(s) encompasses wild-type Cannabis sativa and its variants, including cannabis chemovars that naturally contain varying amounts of individual cannabinoids, Cannabis sativa subspecies indica, including the variants var. indica and var. kafiristanica, Cannabis indica, Cannabis ruderalis, and plants resulting from genetic crosses, self-crosses, or hybrids thereof. The term cannabis plant material should be interpreted accordingly as encompassing plant material derived from one or more cannabis plants. For the avoidance of doubt, it is hereby declared that cannabis plant material includes dried cannabis biomass. Preferably, one or more cannabinoids are selected from: cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and tetrahydrocannabivarinic acid (THCVA). More preferably, one or more cannabinoids is CBD or THC. This list is not exhaustive and merely details the cannabinoids identified in this application for reference. To date, more than 120 different phytocannabinoids have been identified that are within the scope of the present invention. Cannabinoids can be divided into different groups as follows: phytocannabinoids; endocannabinoids; and synthetic cannabinoids. Cannabinoid receptors can be activated by three main groups of agonist ligands, for the purposes of the present invention and whether or not explicitly designated as such herein, of a lipophilic nature and classified respectively as: endocannabinoids (produced endogenously by mammalian cells); phytocannabinoids (such as cannabidiol, produced by the cannabis plant); and synthetic cannabinoids (such as HU-210). Phytocannabinoids can be found in their neutral carboxylic acid form or in their decarboxylated form, depending on the extraction method used. For example, heating the carboxylic acid form is known to cause most of it to decarboxylate. Phytocannabinoids can also exist as pentyl (5 carbon atoms) or propyl (3 carbon atoms) variants. For example, the phytocannabinoid THC is known to be a CB1 receptor agonist, while the propyl variant THCV has been found to be a CB1 receptor antagonist, meaning they have almost opposite effects. According to the invention, examples of phytocannabinoids may include cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), and tetrahydrocannabivarinic acid (THCVA). More preferably, one or more of the cannabinoids is either CBD or THC. The formulation according to the present invention may also comprise at least one cannabinoid selected from those described in A. Douglas Kinghorn et al., Phytocannabinoids, vol. 103, Chapter 1, pages 1-30. Examples of endocannabinoids are molecules that activate cannabinoid receptors within the body. Examples include 2-arachidonoylglycerol (2AG), 2-arachidonoylglyceryl ether (2AGE), arachidonoyldopamine, and arachidonoylethanolamide (anandamide). Structurally related endogenous molecules that share similar structural characteristics but exhibit weak or no activity toward cannabinoid receptors have also been identified and are referred to as endocannabinoids. Examples of these endocannabinoid lipids include 2-acylglycerols, alkyl or alkenyl glyceryl ethers, acyldopamines, and N-acylethanolamides containing alternating fatty acid or alcohol moieties, as well as other fatty acid amides containing different head groups. These include N-acylserines, as well as many other N-acylated amino acids.Examples of cannabinoid receptor agonists are neuromodulators and affect short-term memory, appetite, stress response, anxiety, immune function, and analgesia. Synthetic cannabinoids encompass a variety of distinct chemical classes: cannabinoids structurally related to THC, cannabinoids unrelated to THC, such as (cannabimimetics), including aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides, and eicosanoids related to endocannabinoids. Any or all of these cannabinoids may be used in the present invention. The formulation is preferred to comprise one or two primary cannabinoids, preferably selected from the group consisting of cannabidiol (CBD) or cannabidivarin (CBDV), tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), tetrahydrocannabinolic acid (THCA), cannabigerol (CBG), and cannabidiolic acid (CBDA), or a combination thereof. It is preferred that the formulation comprise cannabidiol and / or tetrahydrocannabinol. Preferably, the chewing gum of the present invention can be used for the treatment or relief of pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, toothache, sleep apnea, psychiatric disorders, gastrointestinal disorders, inflammatory bowel diseases, loss of appetite, diabetes, and fibromyalgia. In a further aspect of the present invention, the oral cannabinoid formulation is suitable for use in the treatment of conditions requiring the administration of a neuroprotective or anticonvulsant drug. Oral cannabinoid formulations can be used in the treatment of seizures. The oral cannabinoid formulation can be used in the treatment of Dravet syndrome, Lennox-Gastaut syndrome, myoclonic seizures, juvenile myoclonic epilepsy, refractory epilepsy, schizophrenia, juvenile spasms, West syndrome, infantile spasms, refractory infantile spasms, tuberous sclerosis complex, brain tumors, neuropathic pain, cannabis use disorder, post-traumatic stress disorder, anxiety, early psychosis, Alzheimer's disease, and autism. The following non-limiting examples illustrate different variations of the present invention. The examples are intended to illustrate the inventive concept; therefore, the examples mentioned should not be considered exhaustive at this time. In particular, CBD is used as an exemplary compound, but it could also be another cannabinoid. EXAMPLES EXAMPLE 1 Preparation of rubber base Twenty different water-insoluble gum bases were prepared. The gum bases were prepared according to the procedure described below. The specific compositions of the gum bases are described in the following examples (GB10 to GB29). Elastomers and an elastomeric plasticizer (PVA) were mixed at 120°C along with a filler, either calcium carbonate or talc, in a mixer with horizontally positioned Z-shaped arms. It is noted that the PVA was applied as an elastomeric plasticizer for the elastomers in the composition and not in its pure elastomer form. PVA as an elastomeric plasticizer has special properties in this context. For some of the comparative examples, another comparator polymer was added along with the elastomers and the elastomeric plasticizer and mixed together with the elastomer and the elastomeric plasticizer. Natural resins were added after approximately 30 minutes of mixing the polymers. After the polymers and natural resin had softened in the composition, additional ingredients were added, such as triacetin, emulsifier, wax, antioxidants, and vegetable fat. After a total mixing time of approximately 45-60 minutes, the mixture was discharged into a container and allowed to cool to room temperature. For some of the examples where butyl rubber (BR) was added as an elastomer, the mixing time was optionally extended to a total of approximately 90-105 minutes depending on the amount of optional fillers. In all examples of gum base, the amount of the various ingredients is given as % by weight of the gum base. EXAMPLE 2 Various rubber-based formulations TABLE 1A Rubber-based compositions, PVA = oolivinyl acetate (Vinnapas B 1.5 so., supplied by Wacker); PIB = polyisobutylene glycol B12, supplied by BASF); BR = butyl rubber (isobutylene-isoprene copolymer); nat. resin = ester of hydrogenated gum rosin glycerol; vea fat, = vegetable fat. Number GB GB10 GB11 GB12 GB13 GB14 PVA 25 18 30 10 40 GDP 5 10 5 10 5 BR 5 5 5 5 - Nat. resin. 25 20 20 35 15 Calcium carbonate 17 - 17 17 17 Talc - 17 - - - Triacetin - 7 - - - Emulsifier 5 10 5 5 5 Wax 13 13 13 13 13 Vegetable fat. 5 - 5 5 5 Total 100 100 100 100 100 / uuoa jo EXAMPLE 3 Various rubber-based formulations TABLE IB Rubber-based compositions, PVA = polyvinyl acetate (Vinnapas B 1.5 sp·, supplied by Wacker); PIB = polyisobutylene β-ppanol B12, supplied by BASF); BR = butyl rubber (isobutylene-isoprene copolymer); nat. resin = hydrogenated gum rosin ester of 10 glycerol; vegetable fat = vegetable fat Number GB GB15 GB16 GB17 GB18 GB19 PVA 25 25 20 40 15 GDP 5 10 5 5 5 BR 5 5 5 5 - Nat. resin. 25 20 30 10 40 Calcium carbonate 17 17 17 17 17 Talc - - - - - Triacetin - - - - - Emulsifier 5 5 5 5 5 Wax 13 13 13 13 13 Vegetable fat. 5 5 5 5 5 Total 100 100 100 100 100 EXAMPLE 4 Various rubber-based formulations TABLE 1C Rubber-based compositions, PVA = polyvinyl acetate (Vinnapas B 1.5 sp·, supplied by Wacker); PIB = polyisobutylene (Qppanol B12, supplied by BASF); BR = butyl rubber (isobutylene-isoprene copolymer); nat. resin = glycerol ester of hydrogenated gum rosin; veq. fat = vegetable fat; acesulfame K (HIS = high-intensity sweetener); menthol (flavoring); BHT (butylated hydroxytoluene = antioxidant) Number GB GB20 GB21 GB22 GB23 GB24 PVA 18 18 18 18 18 GDP 10 10 10 10 10 BR 5 5 5 5 5 Nat. Resin 20 20 20 20 20 Calcium carbonate - - - - - Talc 14 16.5 13.5 17 14 Triacetin 7 7 7 7 7 Emulsifier 10 10 10 10 10 Wax 13 13 13 13 13 Vegetable fat. - - - - - Acesulfame - 0.5 0.5 - - Menthol 3 - 3 - 3 BHT - - - 0.04 0.04 Total 100 100 100 100 100 EXAMPLE 5 Various rubber-based formulations ID BOX Rubber-based compositions, PVA = polyvinyl acetate (Vinnapas B 1.5 sp·, supplied by Wacker); PIB = polyisobutylene (Qppanol B12, supplied by BASF); BR = butyl rubber (isobutylene-isoprene copolymer); nat. resin = hydrogenated gum rosin glycerol ester; VA-VL = vinyl acetate vinyl laurate copolymer (Vinnapas B 500 / 40VL, supplied by Wacker); ve. fat = vegetable fat Number GB GB25 GB26 GB27 GB28 GB29 PVA 25 18 30 30 20 GDP 5 10 5 3 3 BR 5 5 - 2 2 Nat. resin. 25 20 - - 20 VA-VL - - 20 20 10 Carbonate 17 - 17 17 17 of calcium Talc - 17 - - - Triacetin - 7 - - 2 Emulsifier 5 10 11 11 9 Wax 13 13 12 12 12 Vegetable fat. 5 - 5 5 5 Total 100 100 100 100 100 EXAMPLE 6 CBD Extract 52% ινΐΛ / a / zuz i / uuoa jo The CBD extract with a 52% CBD content, supplied by CBDepot (batch number CSFF 2018 / 5), was preheated to approximately 60°C for about 0.5 to 1 hour until it was in liquid form. The extract contained fatty acids, glycerol, waxes, terpenes, and flavonoids. After preheating, the extract was used directly with additional chewing gum ingredients or incorporated into a premix. EXAMPLE 7 CBD Extract 10% The CBD extract with a 10% CBD content provided by Medical Hemp (batch number MH131B Gold) was preheated to approximately 60°C for about 0.5 to 1 hour until it was in liquid form. The extract contained fatty acids, glycerol, waxes, terpenes, and flavonoids. After the preheating procedure, the extract was used directly with additional chewing gum ingredients or incorporated into a premix. EXAMPLE 8 CBD isolate CBD isolate from cannabis plant tissues (phytocannabinoid) with a CBD content of 98.5%, provided by Medical Hemp (lot number MH18212), was dissolved in a 96% ethanol solution. The ratio of CBD isolate to ethanol was 1:1. Once dissolved in the ethanol, the CBD isolate was used directly along with additional chewing gum ingredients, or the extract was applied in a premix. EXAMPLE 9 Preparation of the cannabinoid sugar alcohol premix A premix was made with CBD and sugar alcohol particles, here sorbitol. The premix was prepared in a 1:5 weight ratio of CBD and sorbitol with any of the forms of CBD described in Examples 6-8. CBD was added to the sugar alcohol particles and gently homogenized. EXAMPLE 10 Preparation of the cannabinoid cyclodextrin premix CBD (extract or isolate) was added and dissolved in a 5% polysorbate 80 solution to obtain a 10% CBD solution. The 10% CBD solution was slowly added to and mixed into a 10% cyclodextrin solution to form a CBD-cyclodextrin complex. The water was removed, after which the complex was used directly with additional chewing gum ingredients or applied in a premix. EXAMPLE 11 Preparation of the cannabinoid microcrystalline cellulose premix A cannabinoid-microcrystalline cellulose (MCC) premix was prepared by first adding free cannabinoid to poloxamer F68 (PF) to obtain a 10% cannabinoid-in-poloxamer F68 mixture. Butylated hydroxytoluene (BHT) (0.5%) was added to 50 grams of the solid cannabinoid-poloxamer F68 mixture and then added to 50 grams of microcrystalline cellulose provided as Avicel PH 102 from FMC Biopolymer. The mixture was then blended in a KitchenAid mixer operated at approximately 30 rpm for approximately 30 minutes at room temperature. This mixture was equilibrated for approximately 30 minutes in a sealed container. A 5% cannabinoid-MCC premix was thus obtained. EXAMPLE 12 Preparation of the cannabinoid chewing gum formulation The gum base (GB) prepared according to Example 1 and formulated according to Examples 2-5 was mixed with a filler, in this case talc, calcium carbonate, or sugar alcohol, in a 60 g mixer having horizontally positioned Z-shaped mixing arms. The mixer was preheated to a temperature of approximately 50°C. Once the contents of the mixer were homogeneous, the chewing gum ingredients were added according to a specified time schedule. EXAMPLE 13 Preparation of cannabinoid chewing gum formulation with specific order The gum base (GB) prepared according to Example 1 and formulated according to Examples 2-5 was mixed with a load, here sugar alcohol, in a 60 g mixer having horizontally positioned Z-shaped mixing arms. The mixer was preheated to a temperature of approximately 50°C. Once the contents of the mixer were homogeneous, the chewing gum ingredients, including the water-soluble ingredient, and the cannabinoids were added according to a specified time schedule as follows: TABLE 1E Specific order of addition in the preparation of chewing gum. Ingredient Content in % by weight Application time in minutes Gum base (GB) 40 0 ​​Sugar alcohol 22.8 0 Maltitol syrup 8 3 Menthol powder 3 5 Eucalyptus powder 2 5 Acesulfame K 0.1 5 Sucralose 0.1 5 Sugar alcohol* 5 8 CBD 52%* 1 8 Sugar alcohol 18 8 Total 100 13 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. Sugar alcohol* was prepared as a premix with CBD according to Example 9. Here, the weight percent content is calculated as the sugar alcohol content, excluding the CBD content in the premix. CBD 52%* was prepared according to Example 6. EXAMPLE 14 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. / uuoa jo TABLE 1F CG number CG100 CG101 CG102 CG103 CG104 GB10 40 - - - - GB11 - 40 - - - GB12 - - 40 - - GB13 - - - 40 - GB14 - - - - 40 Sorbitol 45.8 45.8 45.8 45.8 45.8 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to Example 6 EXAMPLE 15 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. TABLE 1G CG number CG105 CG106 CG107 CG108 CG109 GB15 40 - - - - GB16 - 40 - - - GB17 - - 40 - - GB18 - - - 40 - GB19 - - - - 40 Sorbitol 45.8 45.8 45.8 45.8 45.8 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 / uuoa jo It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to example 6. EXAMPLE 16 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. PANEL 1H CG number CG110 CG111 CG112 CG113 CG114 GB20 40 - - - - GB21 - 40 - - - GB22 - - 40 - - GB23 - - - 40 - GB24 - - - - 40 Sorbitol 45.8 45.8 45.8 45.8 45.8 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to example 6. EXAMPLE 17 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. / uuoa jo TABLE II CG number CG115 CG116 CG117 CG118 CG119 GB25 40 - - - - GB26 - 40 - - - GB27 - - 40 - - GB28 - - - 40 - GB29 - - - - 40 Sorbitol 45.8 45.8 45.8 45.8 45.8 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to example 6. EXAMPLE 18 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. / uuoa jo TABLE 1J CG number CG120 CG121 CG122 CG123 CG124 GB10 40 40 GB11 - - 40 40 40 Sorbitol 30 45.8 30 35.8 45.8 Talc 15.8 - 15.8 10 - Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to example 6. EXAMPLE 19 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. TABLE 1K CG number CG125 CG126 CG127 CG128 CG129 GB11 55.8 45.8 35.8 25.8 15.8 Sorbitol 30 40 50 60 70 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to example 6. EXAMPLE 20 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. / uuoa jo 1L BOX Number CG CG130 CG131 CG132 CG133 CG134 GB10 40 40 - - - GB11 - - 40 40 40 Sorbitol 41.8 45.8 46.3 41.8 45.8 Maltitol Syrup 8 8 8 8 8 Menthol Powder 3 3 3 3 3 Eucalyptus Powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD Isolate* - - 0.5 - - CBD 10%* 5 - - 5 - CBD 52%* - 1 - - 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD isolate* was prepared according to Example 8. CBD 10%* was prepared according to Example 7. CBD 52%* was prepared according to Example 6. EXAMPLE 21 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. / uuoa jo PANEL 1M CG number CG135 CG136 CG137 CG138 CG139 GB11 40 40 40 40 40 Sorbitol 45.8 45.6 45.4 45.2 45.0 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.2 0.3 0.4 0.5 Sucralose 0.1 0.2 0.3 0.4 0.5 CBD 52%* 1 1 1 1 1 Total 100 100 100 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to example 6. EXAMPLE 22 Composition of cannabinoid chewing gum The cannabinoid chewing gum based on the procedure in Example 13 was prepared using the formulations indicated in the following examples. The formulations were formed into pieces of chewing gum by extrusion (rolling and scoring). The extruded pieces of chewing gum weighed 1 g each and contained 5 mg of CBD per piece. In all 15 chewing gum examples, the quantity of the various ingredients is given as a percentage by weight of the chewing gum. IN PICTURE CG number CG140 CG141 CG142 CG143 CG144 GB11 40 40 40 40 40 Sorbitol 45.8 36.8 41.8 26.8 44.8 Maltitol syrup 8 8 8 8 8 Menthol powder 3 3 3 3 3 Eucalyptus powder 2 2 2 2 2 Acesulfame K 0.1 0.1 0.1 0.1 0.1 Sucralose 0.1 0.1 0.1 0.1 0.1 CBD 52%* 1 - - - 1 CBD-MCC 5%* - 10 - - CBD-MCC 10%* - - 5 - - CBD-cyclodex* - - - 20 - Self-emulsifying* - - - - 1 Total 100 100 100 100 100 / uuoa jo It was ensured that the CBD was thoroughly mixed into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to Example 6. CBD-MCC 5%* was prepared according to Example 11. CBD-MCC 10%* was prepared according to Example 11 with a higher amount of CBD. CBD-cyclodex* is a CBD-cyclodextrin complex prepared according to Example 10. The self-emulsifier* was prepared with an emulsifier, here polysorbate. EXAMPLE 23 Chewing gum coating A hard coating was prepared for selected samples with the following composition: TABLE 10 Hard Coating 15 Ingredients % by weight Number CG145 CG146 Maltitol 57 57 Water 25.4 25.9 Mannitol 11 11 20 Gum arabic 4 4 Titanium dioxide 1 1 Polysorbate 0.1 0.1 CBD 52%* 1.5 - CBD Isolate* - 0.7 25 Total 100 100 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. CBD 52%* was prepared according to Example 6. Isolate was prepared from CBD* according to example 8. The coating was provided to CG100 samples from example 15. The coating was applied as a preheated suspension, as previously described, to 1 g of extruded chewing gum using the CG100 formulation from Example 15, except that 52% CBD or CBD isolate was replaced with sorbitol in the CG100. Therefore, CBD was not present in the extruded gum, but only in the coating. The coated tablet contained a total of 5 mg of CBD. The suspension was applied in three subsequent steps according to conventional coating techniques, resulting in a total of 0.45 g of coating to 1 g of extruded gum. This corresponds to an extruded gum-to-coating ratio of 70:30. EXAMPLE 24 In vivo release testsA sample was chewed at a rate of 60 chews per minute for 3 or 5 minutes by a test panel of 8 participants. Each participant was a healthy individual selected objectively based on specified requirements. After 3 or 5 minutes, the CBD content in the remaining chewing gum residue was measured. The gum was subjected to triple measurements for each of the 8 participants, resulting in a total of 24 measurements per sample. An average of the 24 measurements was calculated, and the weight percent of the released CBD was calculated based on the original CBD content in the sample. The CBD content was measured in the remaining chewing gum residue. The gum residue was placed in a flask and weighed. An organic solvent was then added for dissolution, and the mixture was stirred overnight on a laboratory shaker. The organic phase was diluted and centrifuged.The supernatant was injected directly into an HPLC system and analyzed using an assay method. EXAMPLE 25 In vitro release assays The in vitro release of CBD was established using a chewing machine (Dissolution Test for Chewing Gum, General Monograph 2.9.25, in the European Pharmacopoeia, 5th ed.). A chewing chamber was filled with 20 mL of pH regulator (phosphate pH regulator, pH 7.4). The chewing gum sample was placed in the chamber, and the chewing machine was started at 20°C with one chew per second. After 3 or 5 minutes of chewing, the machine was stopped, and the chewing gum sample (residue) was placed in a vial. If further release time points (release profile) were required, the chewing pH regulator should be changed by 1 mL of fresh pH regulator every five minutes. The CBD content was measured in the remaining chewing gum residue. The chewing gum residue was placed in a flask and weighed. Subsequently, an organic solvent was added for dissolution purposes, and the mixture was stirred on a laboratory stirrer overnight.The organic phase was diluted and centrifuged. The supernatant was injected directly into an HPLC system and analyzed using an assay method. EXAMPLE 26 Stability test method For stability testing, the ICH guidelines were used: 25°C / 60% RH (2 years), 30°C / 65% RH (1 year), and 40°C / 75% RH (3 months). All samples were packaged in duma bottles before storage under the specified conditions. All samples underwent sensory and analytical evaluation. The CBD content was measured in the remaining chewing gum residue. The chewing gum residue was placed in a flask and weighed. An organic solvent was then added for dissolution, and the mixture was stirred overnight on a laboratory shaker. The organic phase was diluted and centrifuged. The following method was able to separate and quantify CBD, delta-9 THC, delta-8 THC, and CBN. The supernatant was injected directly into an HPLC system and analyzed using an assay method. EXAMPLE 27 CBD delivered to the oral mucosa An in vivo sample was chewed at a rate of 60 chews per minute for 5 minutes on a test panel of 8 participants. Participants were not permitted to swallow during the procedure. After one minute, saliva was collected from the participant and placed in a container for further analysis. In the 5-minute release tests, the same procedure was followed until the 5-minute mark, at which point the final sample was collected and added to the same container for aggregate analysis. The participant was a healthy individual selected objectively according to specified requirements. The aggregate saliva sample was collected after 5 minutes, and the CBD content in the saliva was measured. The CBD content was also measured in the remaining chewing gum residue. The chewing gum residue was placed in a flask and weighed.Subsequently, an organic solvent was added for dissolution, and the mixture was stirred overnight on a laboratory shaker. The organic phase was diluted and centrifuged. The supernatant was injected directly into an HPLC system and analyzed using an assay method. Chewing gum and saliva were subjected to three triple measurements for each of the eight test subjects, yielding a total of 24 measurements for each sample. An average of the 24 measurements was calculated, and the weight percent release was determined. By comparing the amount of CBD in the remaining chewing gum residue with the amount of CBD in saliva, the amount of CBD reaching the oral mucosa could be estimated. EXAMPLE 28 Sensory evaluation test setup Aside from release measurements, both in vivo and in vitro, as well as stability tests of the extruded chewing gum, sensory tests were also conducted to reveal crucial characteristics and properties. These sensory parameters are important indicators of the chewing gum's composition and its behavior during chewing. Structure is the underlying guide to how closely the chewing gum resembles the structure of a comparative gum, which is established as the standard in the test series; that is, the gums are compared to each other within the test series. The test setup consisted of eight test subjects on a panel. Each test subject was a healthy individual selected objectively according to specified requirements.The sensory analysis was performed in accordance with ISO 4121-2003 under test conditions according to ISO 8589. The result is an average of the results of the 8 individuals. Testers gave a rating from + to +++++, where + is poor and +++++ is excellent and comparable to the standard; that is, +++++ means the chewing gum was comparable to the standard and + means the chewing gum was far from comparable to the standard. 0 indicates that it was not tested. / uuoa jo Five different parameters were tested on a test panel: Initial chewing Texture Flavor Sweetness Unwanted notes Initial chewing: the first impression of the chewing gum when chewed within the first 30 seconds. For example, a very hard and sticky structure gave a very low rating, and a very brittle structure also gave a very low rating. Texture: The overall impression of the gum after 30 seconds of chewing, or when the gum has reached a stable structure. For example, a very hard structure resulted in a very low rating, and a very soft structure also resulted in a very low rating. Taste: The overall impression of the gum during chewing in terms of taste. For example, a very low taste experience resulted in a very low rating, and a taste experience that was too high and not comparable to the standard also resulted in a very low rating. Sweetness: The overall impression of the gum's flavor during chewing in terms of sweetness. For example, if the sweetness was decreasing rapidly, it was given a very low rating of 5, and if the sweetness was too high, giving an uncomfortable sensation, it was also given a very low rating. Unpleasant Notes: The overall impression of unpleasant notes from one or more cannabinoids in the composition during chewing. For example, if unpleasant notes (grassy, ​​bitter, or throat irritation) were experienced in the throat, a low rating of 10 was given, and if other uncomfortable sensations were experienced, a low rating was also given. EXAMPLE 29 Sensory evaluation of cannabinoid chewing gum TABLE 2A Evaluation of examples 14-22 according to example 28 CG Masticación inicial Textura Sabor Dulzura Notas no deseadas CG 100 +++++ +++++ ++++ +++ + ++++ CG 101 +++++ +++++ ++++ +++ + ++++ CG 102 +++++ +++++ ++++ +++ + ++++ CG 103 ++++ +++ +++ +++ + ++++ CG 104 ++++ ++++ ++++ +++ ++++ CG 105 +++++ +++++ ++++ +++ + ++++ CG 106 +++++ +++++ ++++ +++ + ++++ CG 107 +++++ +++++ ++++ +++ + ++++ CG 108 ++++ +++ +++ +++ +++ CG 109 +++ ++++ ++++ +++ +++ CG 110 0 0 +++++ +++ + +++++ CG 111 0 0 ++++ +++++ +++++ CG 112 0 0 +++++ +++++ +++++ CG 113 0 0 ++++ +++ + ++++ CG 114 0 0 +++++ +++ + +++++ CG 115 +++++ +++++ ++++ +++ + ++++ CG 116 +++++ +++++ ++++ +++ + ++++ CG 117 ++ + ++ + + CG 118 + + ++ + + CG 119 ++ ++ +++ +++ ++ CG 120 ++++ ++++ ++ ++ ++ CG 121 +++++ +++++ ++++ +++ + ++++ CG 122 ++++ ++++ ++ ++ ++ CG 123 +++++ ++++ ++++ +++ + ++++ CG 124 +++++ +++++ ++++ +++ + +++ + CG 125 ++++ ++++ ++++ +++ + +++ + CG 126 ++++ ++++ ++++ +++ + +++ CG 127 +++++ ++++ ++++ +++ + +++ + CG 128 ++++ ++++ ++++ +++ + +++ + CG 129 +++ +++ +++ +++ +++ CG 130 ++++ ++++ ++++ +++ + +++ + CG 131 +++++ +++++ ++++ +++ + +++ + CG 132 +++++ +++++ +++++ +++ +++ CG 133 +++++ +++++ +++++ +++++ +++++ CG 134 +++++ +++++ ++++ +++ + +++ + CG 135 +++++ +++++ ++++ +++ + +++ + CG 136 +++++ +++++ ++++ +++ + +++ + CG 137 +++++ +++++ +++ +++ +++ CG 138 +++++ +++++ +++ ++ +++ CG 139 +++++ +++++ ++ + +++ CG 140 +++++ +++++ ++++ +++ + +++ + CG 141 +++++ +++++ ++++ +++ + +++ + CG 142 ++++ ++++ ++++ +++ + +++ + CG 143 +++++ +++++ +++++ +++++ +++++ CG 144 +++++ +++++ +++++ +++++ +++++ EXAMPLE 30 Cannabinoid release from extruded chewing gum TABLE 2B CG number CG100 CG101 CG102 CG103 CG104 3 minutes 12 11 12 8 7 5 minutes 17 16 17 12 11 The release of chewing gum samples from Example 14 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). TABLE 2C CG number CG100 CG101 CG102 CG103 CG104 3 minutes 13 12 14 7 6 5 minutes 15 14 16 11 10 The release of chewing gum samples from Example 15 was tested after 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The results show that at the outer end of the ranges according to the invention, the release was lower, but still acceptable (CG103 and CG104). However, the ranges must be considered in combination, so that the range of each of the elastomeric plasticizers and the natural resin contributes to the overall effect and release properties of the chewing gum. Therefore, if a quantity is applied at the outer end of the natural resin range, the amount of elastomeric plasticizer can counteract the negative effect to some extent. EXAMPLE 31 Cannabinoid release from extruded chewing gum / uuoa jo 2D PICTURE CG number CG105 CG106 CG107 CG108 CG109 3 minutes 12 11 11 8 7 5 minutes 17 15 17 13 12 The release of chewing gum samples from Example 15 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). TABLE 2E CG number CG105 CG106 CG107 CG108 CG109 3 minutes 13 11 14 7 6 5 minutes 15 13 16 12 11 The release of chewing gum samples from Example 16 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The results show that at the outer end of the ranges according to the invention, the release was lower, but still acceptable (CG108 and CG109). However, the ranges must be considered in combination, so that the range of each of the elastomeric plasticizers and the natural resin contributes to the overall effect and release properties of the chewing gum. Therefore, if a quantity is applied at the outer end of the natural resin range, the amount of elastomeric plasticizer can counteract the negative effect to some extent. The release of CG 110-114 was comparable to CG105-109. EXAMPLE 32 Cannabinoid release from extruded chewing gum TABLE 2F CG number CG115 CG116 CG117 CG118 CG119 3 minutes 12 11 6 4 7 5 minutes 17 16 7 6 9 / uuoa jo The release of chewing gum samples from Example 17 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). TABLE 2G CG number CG115 CG116 CG117 CG118 CG119 3 minutes 13 12 3 2 6 5 minutes 15 14 6 5 8 The release of chewing gum samples from Example 17 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The result is clear: the addition of VA-VL to the composition provides a much lower release (CG 117-119) than using the polymers and natural resin according to the present invention. Furthermore, the sensory properties of using VA-VL (see above) also clearly demonstrate that VA-VL is not preferred. EXAMPLE 33 Cannabinoid release from extruded chewing gum PANEL 2H CG number CG120 CG121 CG122 CG123 CG124 3 minutes 7 12 6 10 11 5 minutes 8 17 8 12 16 The release of chewing gum samples from Example 18 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). TABLE 21 CG number CG120 CG121 CG122 CG123 CG124 3 minutes 6 13 7 10 12 5 minutes 7 15 8 11 14 The release of chewing gum samples from Example 18 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The addition of talc to the composition was expected to provide greater CBD release, as talc was expected to give the extruded chewing gum a more porous structure and thus promote better CBD release. However, this was not observed (CG120 and CG122), and it appears that the amount of sugar alcohols is more important for the release characteristics than previously expected. EXAMPLE 34 Cannabinoid release from extruded chewing gum / uuoa jo TABLE 2J CG number CG125 CG126 CG127 CG128 CG129 3 minutes 7 11 12 14 18 5 minutes 8 13 17 19 22 The release of chewing gum samples from Example 19 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). 2K FRAME CG number CG125 CG126 CG127 CG128 CG129 3 minutes 6 10 13 15 17 5 minutes 7 12 14 16 21 The release of chewing gum samples from Example 19 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The results show that too low an amount of sugar alcohol in the chewing gum (CG125) caused problems with cannabinoid release, and that a higher amount was desirable. Overall, this was a surprise. However, too high an amount of sugar alcohol (CG129) affected other properties of the chewing gum, as seen in the sensory results, which were unexpected. EXAMPLE 35 Cannabinoid release from extruded chewing gum / uuoa jo 2L FRAME CG number CG130 CG131 CG132 CG133 CG134 3 minutes 19 12 8 18 11 5 minutes 23 17 11 22 16 The release of chewing gum samples from Example 20 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). 2M PANEL CG number CG130 CG131 CG132 CG133 CG134 3 minutes 18 13 7 17 12 5 minutes 22 15 10 21 14 The release of chewing gum samples from Example 20 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The results show that 10% CBD (CG130 and CG133) contributes to a greater release of the extruded chewing gum than 52% CBD (CG130 and CG134). This result is quite surprising and appears to be a general trend that has not been previously recognized. The addition of an isolate (CG132) resulted in a slightly lower, but still acceptable, release from the gum. It seems unknown why the release differs as observed. This result can be used to specifically design a controlled-release profile for cannabinoids. A certain amount of, for example, 52% CBD combined with a certain amount of 10% CBD allows for the design of CBD release, given that the release profiles are different. EXAMPLE 36 Release of cannabinoids from extruded chewing gum TABLE 2N CG number CG135 CG136 CG137 CG138 CG139 3 minutes 11 12 11 12 14 5 minutes 16 17 18 19 20 The release of chewing gum samples from Example 21 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). Generally, a slightly higher release of CBD was obtained with a higher amount of high-intensity sweetener in the extruded chewing gum formulation. This was quite unexpected since the amount of high-intensity sweetener is relatively low in extruded chewing gum. However, as seen in the previous sensory test, when the amount of high-intensity sweetener is at the upper end (such as CG139), it can affect other properties of the extruded chewing gum. / uuoa jo EXAMPLE 37 Cannabinoid release from extruded chewing gum TABLE 20 CG number CG140 CG141 CG142 CG143 CG144 3 minutes 11 5 8 15 18 5 minutes 16 7 10 18 22 The release of chewing gum samples from Example 22 was tested after 3 or 5 minutes of in vivo chewing according to the test method of Example 24. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). TABLE 2P CG number CG140 CG141 CG142 CG143 CG144 3 minutes 12 6 9 14 20 5 minutes 14 7 10 17 25 The release of chewing gum samples from Example 22 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The overall result shows that release-promoting systems, such as a cyclodextrin complex with CBD (CG143) or self-emulsifying systems (CG144), can be particularly advantageous according to the invention if greater release is desired. However, the use of microcrystalline cellulose as a carrier in a 10% MCC system (CG142) provided lower overall release, which was even lower for a 5% MCC system (CG141). EXAMPLE 38 Stability test TABLE 20 CG132 CBD THC LC (mg / piece) % LC LC (mg / piece) % LC 0 months 5 96 0 0 14 days 5 94 0 0 1 month 5 84 0 0 3 months 5 56 0 0 / uuoa jo The chewing gum sample CG132 was tested under extreme conditions, 60°C / 4% RH according to example 26. In this example, CBD was present as CBD isolate according to example 8. Sorbitol was replaced by isomalt in CG132. Comparative studies of other delivery vehicles have shown that CBD degrades to THC and then to CBN under extreme conditions. However, the results of this study show that CBD did not degrade to THC or subsequently to CBN when extruded chewing gum was used as the delivery vehicle. This was very surprising and indicates that CBD is better protected in an extruded chewing gum matrix. EXAMPLE 39 Preparation of cannabinoid chewing gum formulation with specific order The time for adding CBD to 52% according to example 13 was changed in this example. Although the addition time was 8 minutes in example 13, the following additional time chart was prepared to reveal the substantive significance of addition time in cannabinoid release: TABLE 3A Specified order of addition in the preparation of chewing gum (CG100) Ingredient Content in % by weight Application time in minutes CBD 52%* 1 0 CBD 52%* 1 3 CBD 52%* 1 5 CBD 52%* 1 8 CBD 52%* 1 12 Total 13 It was ensured that the CBD was fully blended into the composition and that a homogeneous mixture was obtained. Sugar alcohol* was prepared as a premix with CBD according to Example 9. Here, the weight % content is calculated as the sugar alcohol content, excluding the CBD content in the premix. CBD 52%* was prepared according to Example 6. The chewing gum composition was abbreviated CG100 (Example 14). EXAMPLE 40 Cannabinoid release from extruded chewing gum / uuoa jo TABLE 3B Application time in minutes % release 0 7 3 9 5 10 8 14 12 15 The release of CBD in chewing gum samples from example 14 (CG100) was tested after 5 minutes of in vivo chewing according to the specification of example 13. The test method of example 24 was applied. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The results show that the release of one or more cannabinoids can depend on the order of application during the extruded chewing gum manufacturing process. In this example, applying one or more cannabinoids after half the mixing time was found to be beneficial, provided the cannabinoids were homogeneously distributed throughout the extruded chewing gum. An application time of 8 minutes or even later in this example proved particularly advantageous. EXAMPLE 41 CBD coating TABLE 3C CG number CG145 CG146 3 minutes 60 55 5 minutes 59 61 The release of chewing gum samples from Example 23 was tested after 3 or 5 minutes of in vitro chewing according to the test method of Example 25. The value indicates the % by weight of cannabinoid released from the chewing gum sample (CG). The result was quite surprising, as it was expected that the chewing gum would absorb a large amount of CBD from the coating when chewed. However, the result shows that applying one or more cannabinoids to a coating, such as a hard coating, can be a promising way to deliver cannabinoids. Furthermore, by combining the application of one or more cannabinoids to both the coating and the extruded chewing gum, a controlled release of cannabinoids can be achieved. This can also be used to provide a biphasic release of cannabinoids, with the coating providing an initial high release and a more sustained release being provided by incorporating the cannabinoids into the extruded chewing gum. EXAMPLE 42 CBD delivered to the oral mucosa The tests were performed according to the test method in Example 27. The tests were performed for CG100 and CG101. The CBD content values ​​in saliva and in the chewing gum residue were measured after 5 minutes of chewing. From these values, the CBD content delivered to the oral mucosa could be calculated. / uuoa jo 3D PICTURE CG number CG100 CG101 CBD in saliva 0.1 0.1 CBD in residue 87 88 CBD delivered to the mucosa 12.9 11.9 The chewing gum samples from Example 14 were tested to determine the CBD content delivered to the oral mucosa after 5 minutes of in vivo chewing according to the test method in Example 27. The values ​​indicate the % by weight of cannabinoid based on one or more cannabinoids present in the initial formulation. The test results were quite surprising, as almost all of the CBD released after 5 minutes of chewing was delivered to the oral mucosa. A much higher amount of CBD was expected in the saliva after 5 minutes of chewing, but only a very low amount was found. Based on the amount of CBD released (13% and 12% respectively), it could be calculated that <1% of the released CBD was present in the saliva, and consequently, >99% of the CBD was delivered to the oral mucosa. Therefore, the chewing gum formulation of the invention is very well suited for delivering cannabinoids to the oral mucosa, far better than expected. EXAMPLE 43 CBD delivered to the oral mucosa The tests were performed according to the test method in Example 27. The tests were performed for CG145 and CG146. The CBD content values ​​in saliva and chewing gum residue were measured after 5 minutes of chewing. From these values, the CBD content delivered to the oral mucosa could be calculated. TABLE 3E CG number CG145 CG146 CBD in saliva 35 35 CBD in residue 40 45 CBD delivered to the mucosa 25 30 The chewing gum samples from Example 23 were tested to determine the CBD content delivered to the oral mucosa after 5 minutes of in vivo chewing according to the test method in Example 27. The values ​​indicate the % by weight of cannabinoid based on one or more cannabinoids present in the initial formulation. The test results were surprising, as a very high amount of CBD released after 5 minutes of chewing was delivered to the oral mucosa. A much higher amount of CBD was expected in saliva after 5 minutes of chewing. It was calculated that the total CBD delivered to the oral mucosa was approximately twice the total CBD delivered to the oral mucosa when the CBD was present in the chewing gum (example 42) compared to the coating (example 43). Such a high CBD content was not expected to be delivered to the oral mucosa with the present chewing gum formulation. In fact, the CBD content would be even higher if polysorbate were not applied to the coating suspension, as polysorbate enhances the emulsifying properties of saliva, further preventing the CBD from reaching the oral mucosa. By varying the CBD content in the coating and the CBD content in the chewing gum, a controlled delivery system can be established.

Claims

1. A chewing gum for delivering cannabinoids to mucous membranes, the chewing gum comprising water-soluble chewing gum ingredients and a water-insoluble gum base, the gum base comprising one or more natural resins in an amount of 10-40% by weight of the gum base, one or more elastomers in an amount of 3-30% by weight of the gum base, and one or more elastomeric plasticizers in an amount of 8-50% by weight of the gum base, wherein the water-soluble chewing gum ingredients comprise one or more sugar alcohols in an amount of 35-80% by weight of the chewing gum, and wherein the chewing gum comprises one or more cannabinoids.

2. Chewing gum according to claim 1, further characterized in that one or more sugar alcohols are present in an amount of 40-70% by weight of the chewing gum.

3. Chewing gum according to any of claims 1 to 2, further characterized in that one or more sugar alcohols are present in an amount of 40-60% by weight of the chewing gum. 4.- Chewing gum according to any of claims 1 to 3, further characterized in that at least 10% by weight of one or more cannabinoids are present in unbound form.

5. Chewing gum according to any of claims 1 to 4, further characterized in that at least 90% by weight of one or more cannabinoids are present in unbound form.

6. Chewing gum according to any of claims 1 to 5, further characterized in that one or more cannabinoids are homogeneously distributed in one or more sugar alcohols.

7. Chewing gum according to any of claims 1 to 6, further characterized in that one or more cannabinoids are embedded in one or more sugar alcohols.

8. Chewing gum according to any of claims 1 to 7, further characterized in that one or more sugar alcohols are present as a free-flowing powder.

9. Chewing gum according to any of claims 1 to 8, further characterized in that one or more sugar alcohols and water-insoluble gum base are partially separated in the chewing gum.

10. Chewing gum according to any of claims 1 to 9, further characterized in that one or more sugar alcohols are partially located in discrete areas of the chewing gum.

11. Chewing gum according to any of claims 1 to 10, further characterized in that one or more sugar alcohols are partially located in one layer of the chewing gum and the water-insoluble gum base is partially located in another layer of the chewing gum.

12. Chewing gum according to any of claims 1 to 11, further characterized in that one or more sugar alcohols are partially located in one layer of the chewing gum and the water-insoluble gum base is located in another layer of the chewing gum.

13. Chewing gum according to any of claims 1 to 12, further characterized in that one or more sugar alcohols are located partially in one layer of the chewing gum and partially in another layer of the chewing gum. 14.- Chewing gum according to any of claims 1 to 13, further characterized in that one or more sugar alcohols are located partly in one layer of the chewing gum and partly in another layer of the chewing gum, and wherein the same type of sugar alcohols is present in both layers.

15. Chewing gum according to any of claims 1 to 13, further characterized in that one or more sugar alcohols are located partly in one layer of the chewing gum and partly in another layer of the chewing gum, and wherein different types of sugar alcohols are present in the layers.

16. Chewing gum according to any of claims 1 to 15, further characterized in that one or more sugar alcohols are mixed into the water-insoluble gum base.

17. Chewing gum according to any of claims 1 to 16, further characterized in that one or more cannabinoids are part of the ingredients of the water-soluble chewing gum comprising one or more sugar alcohols.

18. Chewing gum according to any of claims 1 to 17, further characterized in that one or more cannabinoids are homogeneously distributed in the water-insoluble gum base.

19. Chewing gum according to any of claims 1 to 18, further characterized in that one or more cannabinoids are embedded in the water-insoluble gum base.

20. Chewing gum according to any of claims 1 to 19, further characterized in that the chewing gum is formulated as an extruded chewing gum, wherein the water-soluble chewing gum ingredients are mixed into the water-insoluble gum base.

21. Chewing gum according to any of claims 1 to 20, further characterized in that the release rate of one or more cannabinoids is at least 10% by weight of one or more cannabinoids within the first 5 minutes after oral administration.

22. The chewing gum according to any of claims 1 to 21, further characterized in that the release rate of one or more cannabinoids is at least 20% by weight of one or more cannabinoids within the first 5 minutes after oral administration.

23. The chewing gum according to any of claims 1 to 22, further characterized in that the release rate of one or more cannabinoids is at least 30% by weight of one or more cannabinoids within the first 5 minutes after oral administration. 24.- Chewing gum according to any of claims 1 to 23, further characterized in that the release rate of one or more cannabinoids is at least 50% by weight of one or more cannabinoids within the first 5 minutes after oral administration.

25. Chewing gum according to any of claims 1 to 24, further characterized in that the taste of one or more cannabinoids is partially masked by one or more sugar alcohols.

26. Chewing gum according to any one of claims 1 to 25, further characterized in that one or more sugar alcohols are selected from the group consisting of xylitol, sorbitol, maltitol, erythritol, isomalt and mannitol.

27. Chewing gum according to any of claims 1 to 26, further characterized in that one or more sugar alcohols is sorbitol.

28. Chewing gum according to any of claims 1 to 27, further characterized in that at least two sugar alcohols are part of one or more sugar alcohols.

29. Chewing gum according to any of claims 1 to 28, further characterized in that the gum base comprises less than 50% rubber-based polymers.

30. Chewing gum according to any of claims 1 to 29, further characterized in that one or more elastomeric plasticizers comprise one or more polyvinyl acetate elastomeric plasticizers.

31. Chewing gum according to any of claims 1 to 30, further characterized in that the gum base does not comprise vinyl laurate-vinyl acetate copolymer.

32. Chewing gum according to any of claims 1 to 31, further characterized in that one or more natural resins are present in an amount of 15 to 35% by weight of the gum base.

33. Chewing gum according to any of claims 1 to 32, further characterized in that one or more natural resins are selected from the group consisting of polyterpene resins, resins based on gum rosin, wood rosin or tall oil resin.

34. Chewing gum according to any of claims 1 to 33, further characterized in that one or more elastomers are selected from the group consisting of styrene-butadiene copolymers, polyisobutylene, isobutylene-isoprene copolymers, polyethylene, polyurethane or any combination thereof.

35. Chewing gum according to any of claims 1 to 34, further characterized in that one or more cannabinoids are mixed into the water-insoluble gum base together with sugar alcohols after a period of more than half of the total mixing time.

36. Chewing gum according to any of claims 1 to 35, further characterized in that one or more cannabinoids are mixed into the water-insoluble gum base as part of a premix with water-soluble chewing gum ingredients. 37.- Chewing gum according to any of claims 1 to 36, further characterized in that one or more cannabinoids are not part of a premix with microcrystalline cellulose.

38. Chewing gum according to any of claims 1 to 37, further characterized in that one or more cannabinoids are present in an amount of 0.1 to 200 mg.

39. Chewing gum according to any of claims 1 to 38, further characterized in that one or more cannabinoids comprise one or more cannabinoids selected from the group consisting of cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), salts and derivatives thereof.

40. Chewing gum according to any of claims 1 to 39, further characterized in that one or more cannabinoids comprise one or more cannabinoids selected from the group consisting of tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), salts and derivatives thereof.

41. Chewing gum according to any of claims 1 to 40, further characterized in that one or more cannabinoids comprise cannabigerol (CBG), salts and derivatives thereof. 42.- Chewing gum according to any of claims 1 to 41, further characterized in that one or more comprise at least two cannabinoids.

43. Chewing gum according to any of claims 1 to 42, further characterized in that one or more cannabinoids are present in solid form.

44. Chewing gum according to any of claims 1 to 43, further characterized in that one or more cannabinoids are present in liquid or semi-liquid form.

45. Chewing gum according to any of claims 1 to 44, further characterized in that one or more cannabinoids are present in granules.

46. ​​Chewing gum according to any of claims 1 to 45, further characterized in that one or more cannabinoids are present in a premixture with one or more sugar alcohols.

47. Chewing gum according to any of claims 1 to 46, further characterized in that one or more cannabinoids form part of a complex with cyclodextrin.

48. Chewing gum according to any of claims 1 to 47, further characterized in that one or more cannabinoids comprise at least one phytocannabinoid that is part of an extract. 49.- Chewing gum according to any of claims 1 to 48, further characterized in that the chewing gum further comprises terpenes, such as at least one terpene that is part of an extract.

50. Chewing gum according to any of claims 1 to 49, further characterized in that one or more cannabinoids comprise at least one isolated cannabinoid.

51. Chewing gum according to any of claims 1 to 50, further characterized in that one or more cannabinoids comprise at least one water-soluble cannabinoid.

52. Chewing gum according to any of claims 1 to 50, further characterized in that the chewing gum comprises one or more emulsifiers.

53. Chewing gum according to any of claims 1 to 52, further characterized in that the chewing gum comprises one or more solubilizers.

54. Chewing gum according to any of claims 1 to 53, further characterized in that the chewing gum comprises a self-emulsifying agent. 55.- Chewing gum according to any of claims 1 to 54, further characterized in that the chewing gum comprises a polymeric vehicle for one or more cannabinoids.

56. Chewing gum according to any of claims 1 to 55, further characterized in that the chewing gum comprises a lipid vehicle for one or more cannabinoids.

57. Chewing gum according to any of claims 1 to 56, further characterized in that the chewing gum comprises enzyme inhibitors.

58. Chewing gum according to any of claims 1 to 57, further characterized in that the chewing gum comprises one or more antioxidants.

59. Chewing gum according to any of claims 1 to 58, further characterized in that one or more cannabinoids have a systemic effect.

60. Chewing gum according to any of claims 1 to 59, further characterized in that one or more cannabinoids have a local effect.

61. Chewing gum according to any of claims 1 to 60, further characterized in that one or more cannabinoids are comprised in an outer coating of the chewing gum. 62 - Chewing gum in accordance with any of claims 1 to 61 for the treatment or relief of a medical condition.

63. Chewing gum according to claim 62 for the treatment or relief of pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, toothache, sleep apnea, psychiatric disorders, gastrointestinal disorders, inflammatory bowel disease, loss of appetite, diabetes, and fibromyalgia.

64. A package comprising a chewing gum according to any of claims 1 to 63, the package comprising a material that acts as a barrier to one or more cannabinoids and oxygen, preferably an acrylonitrile and methyl acrylate copolymer.

65. The package comprising a chewing gum according to claim 64, further characterized in that the package includes a liquid or a semi-solid to provide a preventative environment therein.

66. The package comprising a chewing gum according to any of claims 64 to 65, further characterized in that the package is a bubble wrap package.

67. A method for relieving or treating a medical condition comprising administering chewing gum in accordance with any of claims 1 to 61.

68. The method for relieving or treating a medical condition according to claim 67, further characterized in that the condition is pain, epilepsy, cancer, nausea, inflammation, congenital disorders, neurological disorders, oral infections, dental pain, sleep apnea, psychiatric disorders, gastrointestinal disorders, inflammatory bowel disease, loss of appetite, diabetes, and fibromyalgia.

69. A method for producing chewing gum of any of claims 1 to 61, the method comprising the steps of providing a water-insoluble gum base, water-soluble chewing gum ingredients and one or more cannabinoids, and mixing the ingredients at elevated temperature for a period of time, and subsequently extruding the final composition to obtain chewing gum.

70. The method according to claim 69, further characterized in that the method comprises mixing a first quantity of water-soluble chewing gum ingredients into the water-insoluble gum base at elevated temperature to obtain a mixture of the gum base and the water-soluble chewing gum ingredients, and mixing a second quantity of water-soluble chewing gum ingredients into the mixture after a period of time and mixing one or more cannabinoids into the mixture after a period of time. 71.- The method according to any of claims 69 to 70, further characterized in that the first quantity of water-soluble chewing gum ingredients comprises one or more sugar alcohols. 72.- The method according to any of claims 69 to 71, further characterized in that the second quantity of water-soluble chewing gum ingredients comprises one or more sugar alcohols.

73. The method according to any of claims 69 to 72, further characterized in that one or more cannabinoids are mixed into the mixture at approximately the same time as the second quantity of water-soluble chewing gum ingredients is mixed into the mixture.

74. The method according to any of claims 69 to 73, further characterized in that one or more cannabinoids are mixed into the mixture after a time period of more than half of the total mixing time.

75. The method according to any of claims 69 to 74, further characterized in that one or more cannabinoids are mixed into the mixture as close as possible to the end of the mixing while at the same time ensuring that the one or more cannabinoids are homogeneously distributed in the water-insoluble gum base.

76. The method according to any of claims 69 to 75, further characterized in that one or more cannabinoids are included in a premix prior to mixing, the premix comprising one or more sugar alcohols. 5 77. The method according to any of claims 69 to 76, further characterized in that the method comprises a step of adding an outer coating to the chewing gum, which optionally comprises a portion of one or more cannabinoids.

78. The method according to claim 77, further characterized in that one or more cannabinoids are included in the outer coating of the chewing gum.

79. The method in accordance with any of claims 69 to 78, further characterized in that the chewing gum is formulated in accordance with any of claims 1 to 61.