Medical chewing gum comprising cannabinoid

Abstract

A medical chewing gum including gum base polymers and one or more cannabinoids as an active pharmaceutical ingredient, the gum base polymers including polyvinyl acetate and vinyl laurate-vinyl acetate copolymer in an amount of more than 90% by weight of the gum base polymers, wherein the gum base polymers include 20-95% by weight of polyvinyl acetate and 5-80% by weight of vinyl laurate-vinyl acetate copolymer.

Claims

1. A medical chewing gum comprising gum base polymers and one or more cannabinoids as an active pharmaceutical ingredient, wherein the gum base polymers comprise polyvinyl acetate and vinyl laurate-vinyl acetate copolymer in an amount of more than 90% by weight of the gum base polymers, and the gum base polymers include 20-95% by weight of polyvinyl acetate and 5-80% by weight of vinyl laurate-vinyl acetate copolymer, wherein the chewing gum is a compressed chewing gum comprising granules with a content of gum base and extragranular chewing gum ingredients.

2. The medical chewing gum according to claim 1, wherein the total content of gum base ingredients selected from the list consisting of polyterpene resins, resins based on gum rosin, wood rosin and tall oil resin is less than 5 percent by weight of the chewing gum.

3. The medical chewing gum according to claim 1, wherein the chewing gum contains no polyterpene resins and no resins based on gum rosin, wood rosin or tall oil resin.

4. The medical chewing gum according to claim 1, wherein the one or more cannabinoids is a least partly comprised in said granules.

5. The medical chewing gum according to claim 1, the one or more cannabinoids is a least partly comprised outside the granules.

6. The medical chewing gum according to claim 1, wherein said medical chewing gum comprises gum base granules, said gum base granules comprising gum base polymers.

7. The medical chewing gum according to claim 1, wherein the one or more cannabinoids comprises THC, CBD, and salts, derivatives, analogues and homologues thereof.

8. The medical chewing gum according to claim 1, wherein said chewing gum comprises said cannabinoids in an amount of 0.1-30 mg.

9. The medical chewing gum according to claim 1, wherein the one or more cannabinoids is at least partly contained in a carrier.

10. The medical chewing gum according to claim 1, wherein the chewing gum comprises cellulose as a carrier for said one or more cannabinoids.

11. The medical chewing gum according to claim 10, wherein said carrier cellulose is or comprises microcrystalline cellulose (MCC).

12. The medical chewing gum according to claim 10, wherein said carrier cellulose is provided in the form of particles having an average particle size between 10 and 250 micrometers.

13. The medical chewing gum according to claim 1, wherein said medical chewing gum comprises one or more fillers, wherein said one or more fillers comprises cellulose.

14. The medical chewing gum according to claim 1, wherein the medical chewing gum is substantially free of natural resins.

15. The medical chewing gum according to claim 1, wherein the chewing gum comprises gum base polymers in an amount of between 15 and 80 percent by weight of the chewing gum.

16. The medical chewing gum according to claim 1, wherein the gum base polymers consist of synthetic gum base polymers.

17. The medical chewing gum according to claim 1, wherein the weight ratio between the polyvinyl acetate and the vinyl laurate-vinyl acetate copolymer is from 8:1 to 2:3.

18. The medical chewing gum according to claim 1, wherein the weight ratio between the polyvinyl acetate and the vinyl laurate-vinyl acetate copolymer is from 5:1 to 2:3.

19. The medical chewing gum according to claim 1, wherein the weight ratio between the polyvinyl acetate and the vinyl laurate-vinyl acetate copolymer is from 3:2 to 2:3.

20. The medical chewing gum according to claim 1, wherein the weight ratio between vinyl acetate monomers of the vinyl laurate-vinyl acetate copolymer and vinyl laurate monomers of the vinyl laurate-vinyl acetate copolymer is less than 90:10.

21. The medical chewing gum according to claim 1, wherein the total release of the one or more cannabinoids is increased compared to conventional extruded chewing gum.

22. The medical chewing gum according to claim 1, wherein the release rate of the one or more cannabinoids is increased compared to conventional extruded chewing gum.

23. The medical chewing gum according to claim 1, wherein initial crumbling of the gum facilitates increased total release of the one or more cannabinoids compared to conventional extruded chewing gum.

24. A medical chewing gum comprising gum base polymers and one or more cannabinoids as an active pharmaceutical ingredient, wherein the gum base polymers constitute more than 50% by weight of the total content of gum base ingredients, the total content of gum base ingredients selected from the list consisting of polyterpene resins, resins based on gum rosin, wood rosin and tall oil resin is less than 5% by weight of the chewing gum, and the gum base polymers include 20-95% by weight of polyvinyl acetate and 5-80% by weight of vinyl laurate-vinyl acetate copolymer, wherein the chewing gum is a compressed chewing gum comprising granules with a content of gum base and extragranular chewing gum ingredients.

25. The medical chewing gum according to claim 24, wherein the gum base polymers substantially consist of synthetic gum base polymers.

26. A medical chewing gum comprising gum base with a content of gum base polymers and one or more cannabinoids as an active pharmaceutical ingredient, wherein the gum base comprises 15-45% by weight of polyvinyl acetate and 10-30% by weight of vinyl laurate-vinyl acetate copolymer, the total content of gum base ingredients selected from the list consisting of polyterpene resins, resins based on gum rosin, wood rosin and tall oil resin is less than 5% by weight of the chewing gum, and the gum base polymers include 20-95% by weight of polyvinyl acetate and 5-80% by weight of vinyl laurate-vinyl acetate copolymer, wherein the chewing gum is a compressed chewing gum comprising granules with a content of gum base and extragranular chewing gum ingredients.

27. The medical chewing gum according to claim 26, wherein the medical chewing gum is substantially free of natural resins.

Description

THE FIGURES

(1) The invention will now be described with reference to drawings, where

(2) FIG. 1 illustrates a method of preparing a cannabinoid-microcrystalline cellulose mixture according to an embodiment of the invention and where

(3) FIG. 2 illustrates a process for preparing chewing gum mass with cannabinoid-microcrystalline cellulose CMC according to an embodiment of the invention

DEFINITIONS

(4) The verb to comprise as is used in this description and in the claims and its conjugations are used in its non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. In addition, reference to an element by the indefinite article a or an does not exclude the possibility that more than one of the elements are present, unless the context clearly requires that there is one and only one of the elements. The indefinite article a or an thus usually means at least one. Additionally, the words a and an when used in the present document in concert with the word comprising or containing denote one or more.

(5) As used herein, by the phrase chewing gum is meant any chewing gum such as extruded chewing gum, center-filled chewing gum, toffee-imitating chewing gum, or compressed chewing gum, slabs or sticks.

(6) By the terms gum base and gum base matrix is meant the mainly water-insoluble and hydrophobic gum base ingredients that are mixed together, typically before the bulk portion of the chewing gum is added. The gum base may contain gum base polymers and plasticizers, waxes, emulsifiers, fats and/or fillers. The gum base may thus designate the typical water-insoluble chewing gum components, which may be manufactured in a first step and subsequently mixed with the mainly water soluble portion in a second step. The term gum base may, evidently, also refer to the relevant gum base components fed into an extruder and forming part of the final chewing gum when mixed with the chewing gum components in the extruder.

(7) The term bulk portion intends to mean the mainly water-soluble and hydrophilic chewing gum ingredients that may be mixed into the gum base matrix, either in a separate process or in a one-step process by means of an extruder.

(8) The term gum base polymer intends to mean resins and elastomers of polymeric origin and does not include, for example, plasticizers, waxes, emulsifiers, fats or fillers although these may also be present in a gum base.

(9) The term weight of the chewing gum or similar wording meaning the same is defined in the present context as weight of the chewing gum, not including the weight of an outer coating, such as a hard coating, soft coating, and the like.

(10) By the phrase texture is meant a qualitative measure of the visco-elastic properties of the chewing gum and of the overall mouth-feel experienced by the user during the chewing process. Thus the term texture encompasses measurable quantities such as hardness and elasticity as well as more subjective parameters related to the chew-feel experienced by a user.

(11) The term natural resin, as used herein, means resinous compounds being either polyterpenes derived from terpenes of natural origin or resinous compounds derived from gum rosin, wood rosin or tall-oil rosin.

(12) The term synthetic polymer, as used herein, means polymers industrially synthesized by appropriate polymerization techniques.

(13) The term buffer, as used herein, refers to pH-control agents.

(14) The average particle size is understood to mean the D50 value as measured by laser diffraction analysis

(15) The term bitterness should be understood as the taste of bitterness, and as being evaluated by a taste panel of 4 persons trained for sensory evaluation. The trained persons chewed the samples at a rate of 60 chews per minute and for each sample evaluated bitterness.

DESCRIPTION

(16) According to embodiments of the invention a preferred amount of gum 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.

(17) The formulation of gum bases can vary depending on the particular product to be prepared and on the desired masticatory and other sensory characteristics of the final product.

(18) Besides the polyvinyl acetate and the vinyl laurate-vinyl acetate copolymer, the gum base may optionally contain further synthetic elastomers in an amount of less than 10% by weight of the gum base polymers such as less than 8% by weight of the gum base polymers or less than about 5% by weight of the gum base polymers.

(19) Such synthetic elastomers may be selected from the group consisting of styrene-butadiene copolymers (SBR), polyisobutylene, isobutylene-isoprene copolymers (IIR also known as butyl rubber, BR), polyurethane and polyethylene.

(20) Preferred synthetic elastomers are styrene-butadiene copolymers (SBR), polyisobutylene and isobutylene-isoprene copolymers (BR).

(21) If non-tack chewing gum is desired, copolymers of methyl vinyl ether and maleic acid and derivatives thereof, such as Gantrez and/or copolymers of polyisoprene-graft maleic anhydride (PIP-g-MA) with polyethylene-glycol (PEG) or methoxy-polyethylene-glycol (MPEG) side chains, such as REV-7 provided by Revolymer, may be among the gum base polymers.

(22) The gum base matrix may further comprise:

(23) 0 to 40% by weight waxes, 5 to 35% by weight softeners other than waxes, such as plasticizers, fats and emulsifiers, 0 to 50% by weight filler, and 0 to 5% by weight of miscellaneous ingredients such as antioxidants, colorants, etc.

(24) Natural resins are not used according to an embodiment of the invention, or at least only in minute amounts. According to an embodiment of the invention the medical chewing gum is free of natural rosin esters, often referred to as ester gums including as examples glycerol esters of partially hydrogenated rosins, glycerol esters of polymerized rosins, glycerol esters of partially dimerized rosins, glycerol esters of tally oil rosins, pentaerythritol esters of partially hydrogenated rosins, methyl esters of rosins, partially hydrogenated methyl esters of rosins, pentaerythritol esters of rosins, synthetic resins such as terpene resins derived from alpha-pinene, beta-pinene, and/or d-limonene, and natural terpene resins.

(25) In an embodiment of the invention, the medical chewing gum comprises further chewing gum ingredients selected from the group consisting of flavors, dry-binders, tableting aids, anti-caking agents, emulsifiers, antioxidants, enhancers, absorption enhancers, high intensity sweeteners, softeners, colors, active ingredients, water-soluble indigestible polysaccharides, water-insoluble polysaccharides or any combination thereof.

(26) According to embodiments of the invention, said emulsifiers are selected from the group of cyclodextrins, polyoxyethylene castor oil derivatives, polyoxyethylene alkyl ethers, macrogol alkyl ethers, block copolymers of ethylene and propylene oxides, polyoxyethylene alkyl ethers, polyoxyethylene glycols, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene (20) sorbitan monostearates, polyoxyethylene (20) sorbitan monooleates, polyoxyethylene stearates, sorbitan esters, diacetyl tartaric ester of monoglycerides, lactylated monoglycerides, mono- and/or di-glycerides of fatty acids such as glycerol monostearate, Acetem, lecithines or any combination thereof.

(27) In an embodiment of the invention, said chewing gum comprises emulsifiers in an amount in the range of 0.1% to 25% by weight of said chewing gum.

(28) In an embodiment of the invention the chewing gum comprises flavor. Flavor may typically be present in amounts between 0.01 and 10% by weight of the chewing gum, such as between 0.01 and 5% by weight of the chewing gum.

(29) Non-exhaustive examples of flavors suitable in embodiments of the present invention are coconut, coffee, chocolate, vanilla, grape fruit, orange, lime, menthol, liquorice, caramel aroma, honey aroma, peanut, walnut, cashew, hazelnut, almonds, pineapple, strawberry, raspberry, tropical fruits, cherries, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, and mint, fruit essence such as from apple, pear, peach, strawberry, apricot, raspberry, cherry, pineapple, and plum essence. The essential oils include peppermint, spearmint, menthol, eucalyptus, clove oil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and oils of the fruits mentioned above.

(30) Petroleum waxes aid in the curing of the finished gum made from the gum base as well as improve shelf life and texture. Wax crystal size influences the release of flavor. Those waxes high in iso-alkanes have a smaller crystal size than those waxes high in normal-alkanes, especially those with normal-alkanes of carbon numbers less than 30. The smaller crystal size allows slower release of flavor since there is more hindrance of the flavor's escape from this wax versus a wax having larger crystal sizes.

(31) Petroleum wax (refined paraffin and microcrystalline wax) and paraffin wax are composed of mainly straight-chained normal-alkanes and branched iso-alkanes. The ratio of normal-alkanes to iso-alkanes varies.

(32) The normal-alkanic waxes typically have carbon chain lengths >C-18 but the lengths are not predominantly longer than C-30. The branched and ring structures are located near the end of the chain for those waxes that are predominantly normal-alkanic. The viscosity of normal-alkanic waxes is <10 mm2/s (at 100 C.) and the combined number average molecular weight is <600 g/mole.

(33) The iso-alkanic waxes typically have carbon lengths that are predominantly greater than C-30. The branched chains and ring structures are located randomly along the carbon chain in those waxes that are predominantly iso-alkanic. The viscosity of iso-alkanic waxes is greater than 10 mm2/s (at 100 C.) and the combined number average molecular weight is >600 g/mole.

(34) Synthetic waxes are produced by means that are atypical for petroleum wax production and are thus not considered petroleum wax. The synthetic waxes may include waxes containing branched alkanes and copolymerized with monomers such as, but not limited to propylene, polyethylene, and Fischer Tropsch type waxes. Polyethylene wax is a synthetic wax containing alkane units of varying lengths having attached thereto ethylene monomers.

(35) Waxes and fats are conventionally used for the adjustment of the texture and for softening of the chewing gum base when preparing chewing gum bases. In connection with the present invention, any conventionally used and suitable type of natural and synthetic wax and fat may be used, such as for instance rice bran wax, polyethylene wax, petroleum wax (refined paraffin and microcrystalline wax), sorbitan monostearate, tallow, propylene glycol, paraffin, beeswax, carnauba wax, candelilla wax, cocoa butter, degreased cocoa powder and any suitable oil or fat, as e.g. completely or partially hydrogenated vegetable oils or completely or partially hydrogenated animal fats.

(36) Suitable vegetable oils include but are not limited to oils that are based on coconut, palm, palm kernel, cotton seed, rape seed or sunflower and combinations thereof.

(37) Antioxidants prolong shelf life and storage of gum base, finished gum or their respective components including fats and flavor oils.

(38) Antioxidants suitable for use in gum base include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), betacarotenes, tocopherols, acidulants such as Vitamin C (ascorbic acid or corresponding salts (ascorbates)), propyl gallate, other synthetic and natural types or mixtures thereof.

(39) Further chewing gum ingredients, which may be included in the medical chewing gum according to the present invention, include surfactants and/or solubilizers. As examples of types of surfactants to be used as solubilizers in a medical chewing gum composition according to the invention, reference is made to H. P. Fiedler, Lexikon der Hilfstoffe fr Pharmacie, Kosmetik and Angrenzende Gebiete, pages 63-64 (1981) and the lists of approved food emulsifiers of the individual countries. Anionic, cationic, amphoteric or non-ionic solubilizers can be used. Suitable solubilizers include lecithin, polyoxyethylene stearate, polyoxyethylene sorbitan 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, saccharose esters of fatty acids, polyglycerol esters of fatty acids, polyglycerol esters of interesterified castor oil acid (E476), sodium stearoyllatylate, sodium lauryl sulfate and sorbitan esters of fatty acids and polyoxyethylated hydrogenated castor oil (e.g. the product sold under the trade name CREMOPHOR), block copolymers of ethylene oxide and propylene oxide (e.g. products sold under trade names PLURONIC and POLOXAMER), polyoxyethylene fatty alcohol ethers, polyoxyethylene sorbitan fatty acid esters, sorbitan esters of fatty acids and polyoxyethylene steraric acid esters.

(40) Particularly suitable solubilizers are polyoxyethylene stearates, such as for instance polyoxyethylene(8)stearate and polyoxyethylene(40)stearate, the polyoxyethylene sorbitan fatty acid esters sold under the trade name TWEEN, for instance TWEEN 20 (monolaurate), TWEEN 80 (monooleate), TWEEN 40 (monopalmitate), TWEEN 60 (monostearate) or TWEEN 65 (tristearate), 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, sodium stearoyllatylate, sodium laurylsulfate, polyoxyethylated hydrogenated castor oil, blockcopolymers of ethylene oxide and propyleneoxide and polyoxyethylene fatty alcohol ether. The solubilizer may either be a single compound or a combination of several compounds. In the presence of an active ingredient, such as the included one or more cannabinoids, the medical chewing gum may preferably also comprise a carrier known in the arts of chewing gum and pharmaceutical ingredients.

(41) Poloxamer F68 is a further highly suitable solubilizer.

(42) In some embodiments, one or more colors can be included in the chewing gum.

(43) High intensity artificial sweetening agents can also be used according to preferred embodiments of the invention. Preferred high intensity sweeteners include, but are not limited to sucralose, aspartame, salts of acesulfame, alitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside and the like, alone or in combination.

(44) In order to provide longer lasting sweetness and flavor perception, it may be desirable to encapsulate or otherwise control the release of at least a portion of the artificial sweeteners.

(45) Techniques such as wet granulation, wax granulation, spray drying, spray chilling, fluid bed coating, conservation, encapsulation in yeast cells and fiber extrusion may be used to achieve desired release characteristics. Encapsulation of sweetening agents can also be provided using another chewing gum component such as a resinous compound.

(46) Usage level of the artificial sweetener will vary considerably and will depend on factors such as potency of the sweetener, rate of release, desired sweetness of the product, level and type of flavor used and cost considerations. Thus, the active level of artificial sweetener may vary from about 0.001 to about 8% by weight (preferably from about 0.02 to about 8% by weight). When carriers used for encapsulation are included, the usage level of the encapsulated sweetener will be proportionately higher. Combinations of sugar and/or non-sugar sweeteners may be used in the chewing gum.

(47) A chewing gum and/or gum base may, if desired, include one or more fillers/texturizers including as examples, magnesium- and calcium carbonate, sodium sulphate, ground limestone, silicate compounds such as magnesium- and aluminum silicate, kaolin and clay, aluminum oxide, silicium oxide, talc, titanium oxide, mono-, di- and tri-calcium phosphates, cellulose polymers, such as wood, and combinations thereof.

(48) According to an embodiment of the invention, one preferred filler/texturizer is calcium carbonate.

(49) A number of chewing gum components well known within the art may be applied within the scope of the present invention. Such components comprise but are not limited to waxes, fats, softeners, fillers, bulk sweeteners, flavors, antioxidants, emulsifiers, coloring agents, binding agents and acidulants.

(50) In an embodiment of the invention, the chewing gum is provided with an outer coating selected from the group consisting of hard coating, soft coating and edible film-coating or any combination thereof.

(51) Cannabinoid may be attached to a carrier in an advantageous embodiment of the invention. One applicable carrier is microcrystalline cellulose.

(52) Microcrystalline cellulose (MCC) may be prepared e.g. by hydrolyzing wood pulp by means of mineral acid. Thereby, microcrystalline cellulose may be obtained as purified, practically depolymerized cellulose. In more detail the manufacturing may typically comprise starting from selected rolls of wood pulp that are diced, or cut, into small particles. The chopped particles may then be hydrolyzed under heat and pressure by mineral acid. Thereafter, the obtained mixture may be washed and filtered.

(53) Also, spray drying may be employed, which can be used to control the particle size distribution and the moisture content.

(54) In some embodiments, microcrystalline cellulose may be obtained from other sources, such as other plant sources. Microcrystalline cellulose with different moisture content may be used. Typical moisture content may for example be about 5%, although other moisture contents, such as e.g. 3% or 1.5%, are also known to work.

(55) Microcrystalline cellulose is commercially available, and may for example be obtained from FMC Biopolymer, e.g. the products known as Avicel PH 101, PH 102, PH 103, PH 105, PH 112, PH 113, PH 200, PH 301, and PH 302.

(56) The chewing gum of the invention may be manufactured as an extruded chewing gum, or as a compressed chewing gum.

(57) The chewing gum may be produced by a conventional batch or extrusion process. The process is well-known in the art. It should be noted that the temperature under which the one or more cannabinoids are added may advantageously be relatively low, e.g. be lower than 70 degrees Celsius

(58) When manufacturing a compressed chewing gum tablet another method is applied, which is basically very different than the extruded chewing gum, but may broadly be described as an initial conventional mixing of the gum base followed by a granulation of the obtained gum base mix. The obtained gum base granules may then be mixed with further chewing gum ingredients, such as sweeteners and flavor. This final granule mix may then be compressed under high pressure into a chewing gum tablet. For each compression a layer is made and in this way it is possible to make multi-layered chewing gums, such as two, three or four layers, wherein each layer may include an individual composition, e.g. cannabinoid or different colors may be used for visual purposes, etc.

(59) The cannabinoid may advantageously be applied in a gum base-containing module or a tablet-module substantially free of gum base. In cases where a high initial release of cannabinoid is desired, the cannabinoid may advantageously be comprised in a tablet module substantially free of gum base whereas e.g. flavors and/or sweeteners advantageously may be added to the gum base-containing module and very often to both types of modules. The flavors and/or sweeteners may both be added as separate particles which are mixed and compressed with gum base-containing particles in one module and it may be incorporated into gum base-containing granules.

(60) In some embodiments of the invention cannabinoids is carried by a carrier. Below the invention will be described with one particular carrier for exemplary purposes, although it should be noted that alternative carriers, such as sorbitol, may be applicable within the scope of the invention.

(61) Referring to FIG. 1, a process for preparing a cannabinoid-microcrystalline cellulose mixture according to an embodiment of the invention is illustrated. The intention is to obtain a material, here cellulose, which comprises a well-defined amount of cannabinoid, salts thereof or derivatives thereof in and/or onto voids or pores within the material.

(62) First a cannabinoid CAN is added to a mixer MIX1 together with microcrystalline cellulose MCC. The mixing ratio between the cannabinoid CAN and the microcrystalline cellulose may in some cases be around 1:1, but may generally vary from about 1:1000 to about 1:1.

(63) The cannabinoid CAN may in some embodiments be cannabinoid as such or, and may in other embodiments be diluted cannabinoid. Diluted cannabinoid may often be simpler to handle, and/or easier to dose in accurate amounts. Examples of diluents may e.g. comprise one or more of propylene glycol, water, ethanol, or one or more solubilizers.

(64) Optionally, one or more anti-oxidants may be added in the cannabinoid-MCC premix step, by adding the one or more anti-oxidants to the mixer MIX1 before, simultaneous with and/or after adding the one more cannabinoids and/or the carrier, such as e.g. microcrystalline cellulose MCC.

(65) The mixer MIX1 may be any type of mixer capable of mixing the cannabinoid CAN and the microcrystalline cellulose MCC.

(66) The mixer MIX1 is operated until an effective mixing of the cannabinoid CAN and the microcrystalline cellulose MCC is obtained.

(67) Thereafter the resulting mixture of the cannabinoid CAN and the microcrystalline cellulose MCC may in some cases be subjected to a further processing PROC. This processing PROC may involve letting the mixture of the cannabinoid CAN and the microcrystalline cellulose MCC rest or soak for a period of time, e.g. in a sealed container, i.e. equilibrating the cannabinoid CAN and the microcrystalline cellulose MCC.

(68) In some cases further mixing, either by means of mixer MIX1 or another mixer, may be employed.

(69) In some cases the processing PROC may be carried out in the mixer MIX1, whereas in other cases the processing is carried out in separate process equipment. It may in some cases be especially advantageous to perform the processing PROC in the mixer MIX1 when further mixing is performed.

(70) The final cannabinoid-microcrystalline cellulose mixture CC may be obtained from the processing PROC, if used, or from the mixer MIX1 if the processing PROC is not used.

(71) Referring to FIG. 2, a process for preparing a chewing gum mass with cannabinoid-microcrystalline cellulose CMC according to an embodiment of the invention is illustrated.

(72) Cannabinoid-microcrystalline cellulose mixture CC obtained in accordance with the embodiment illustrated on FIG. 1 may be used.

(73) First, chewing gum ingredients CGI, including e.g. filler, is added to a mixer MIX2 together with a gum base GB and mixed therein to obtain a chewing gum mass CGM as a mixture of gum base and chewing gum ingredients GCI. The gum base must comprise an effective amount of gum base polymers. It is very important that the gum base is chosen such that the gum base polymers comprise polyvinyl acetate and vinyl laurate-vinyl acetate copolymer in an amount of more than 90% by weight of the gum base polymers. Similarly, the gum base should also be chosen such that the gum base polymers include 20-95% by weight of polyvinyl acetate and 5-80% by weight of vinyl laurate-vinyl acetate copolymer.

(74) Then, the cannabinoid-microcrystalline cellulose mixture CC is added to a mixer MIX2 together with the chewing gum mass CGM. Thereby, a chewing gum mass with cannabinoid-microcrystalline cellulose CMC is obtained.

(75) In some embodiments, the mixers MIX2 and MIX3 are different mixers, whereas in other embodiments they are the same mixer, but where timing divides the use of the mixer into two separate actions, first the mixing of the gum base GB with the chewing gum ingredients CGI, then mixing with the cannabinoid-MCC mixture CC.

(76) The obtained chewing gum with cannabinoid-microcrystalline cellulose CMC may be used to produce chewing gum. In some embodiments further ingredients are added, e.g. further sweeteners, flavors, fillers etc. In other embodiments, such further ingredients, if needed, are all added to the gum base after adding the cannabinoid-MCC mixture.

(77) The resulting chewing gum produced from the chewing gum mass with cannabinoid-microcrystalline cellulose CMC may be compressed chewing gum or extruded chewing gum.

(78) When making compressed chewing gums, the cannabinoid premix may be added to gum base pellets together with other powders, such as e.g. sweeteners, fillers etc., and then compressed.

(79) As illustrated in connection with FIGS. 1 and 2, MCC and cannabinoid are mixed and equilibrated. The cellulosic fiber and cannabinoid can be mixed in a suitable mixing device for any suitable length of time. In some cases, the cellulosic fiber and cannabinoid can be mixed with a mixing implement rotating at a speed of less than 500 rpm, less than 250 rpm, less than 150 rpm, less than 100 rpm, less than 60 rpm, less than 30 rpm, or less than 10 rpm. For example, the mixer can be a Kitchenaid, Hobart Mixer, ribbon blender, or other mixing apparatus depending on the desired batch size. In some cases, the MCC and cannabinoid can be mixed using a rotating and/or vibrating drum. In some cases, the cellulosic fibers and cannabinoid can be mixed for at least 1 minute, at least 3 minutes, at least 5 minutes, at least 10 minutes, or at 4 least 30 minutes prior to incorporating a resulting MCC-cannabinoid mixture into a chewing gum formulation or gum base formulation.

(80) After mixing cellulosic fiber and cannabinoid, the cellulosic fiber-cannabinoid mixture can be equilibrated in a sealed container. In some cases, the sealed container can be a bag (e.g. a poly bag). In some cases, the MCC-cannabinoid mixture can be equilibrated for at least 30 minutes, at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, or at least 10 hours prior to use or incorporation into an oral product. In some cases, a MCC-cannabinoid mixture can be further mixed or agitated during the equilibrating process. For example, a cellulosic fiber-cannabinoid mixture equilibrating in a poly bag can be agitated during the equilibrating process at a select time (e.g., 2 hours into the equilibrating process).

(81) The following non-limiting examples illustrate different variations of the present invention. The examples are meant for indicating the inventive concept; hence the mentioned examples should not be understood as exhaustive for the present invention.

EXAMPLES

Example 1

(82) Preparation of Cannabinoid Premix

(83) A cannabinoid-microcrystalline cellulose (MCC) premix is made by first adding free cannabinoid to poloxamer F68 (PF) to obtain a 20% solution of cannabinoid in poloxamer F68. Butylated hydroxytoluene (BHT) is added (0.5%) to 50 grams of the cannabinoid-poloxamer F68 solid mix and added to 50 gram of microcrystalline cellulose provided as Avicel PH 102 from FMC Biopolymer. This is then mixed in a Kitchenaid mixer operated at about 30 RPM for about 30 minutes at room temperature. This mixture is equilibrated for about 30 minutes in a sealed container. Thereby, the cannabinoid-MCC mixture is obtained.

Example 2

(84) Preparation of Cannabinoid Premix

(85) A cannabinoid-MCC premix is made by adding first adding free cannabinoid to propylene glycol (PG) to obtain a 10% solution of cannabinoid in propylene glycol. 0.5% of butylated hydroxytoluene (BHT) is added to 50 grams of the cannabinoid-propylene glycol solution and then added to 50 gram of sorbitol. The cannabinoid-propylene glycol solution and the sorbitol are then mixed in a Kitchenaid mixer operated at about 30 RPM for about 30 minutes at room temperature. Finally, the obtained mixture of the cannabinoid-propylene glycol solution and the sorbitol is equilibrated for about 30 minutes in a sealed container. Thereby, the cannabinoid-MCC mixture is obtained.

Example 3

(86) Composition of Gum Bases

(87) Ten different gum bases (GB), given GB numbers 101-110, were prepared by the following process:

(88) The polymers polyvinyl acetate (PVA), vinyl acetate-vinyl laurate copolymer (VA-VL), and optionally polyisobutylene (PIB) are mixed at 120 C. together with filler, here calcium carbonate or talc, in a mixer having horizontally placed Z-shaped arms for mixing.

(89) When the polymers are softened, triacetin is added, followed by addition of emulsifier, wax and vegetable fat.

(90) After a total mixing time of about 45-60 minutes, the mixture is discharged into a pan and allowed to cool to room temperature.

(91) In case of example GB 108, comparative (comp.) example GB 109, and standard (Std.) gum base example GB 110, which include butyl rubber (BR), BR is added in the initial mixing step, and the mixing time is extended to a total of about 90-105 minutes.

(92) In case of comparative (comp.) example GB 109, the natural resin is added before the addition of triacetin, and in case of standard (Std.) example GB 110, the natural resin is added after about 30 minutes before the addition of softeners.

(93) The gum base compositions were as displayed in table 1A and 1B, the amounts given corresponding to percentages by weight of the gum base:

(94) TABLE-US-00001 TABLE 1A Gum base compositions, VA-VL I = vinyl acetate-vinyl laurate copolymer (Vinnapas B 500/40VL, supplied by Wacker); VA-VL II = vinyl acetate-vinyl laurate copolymer (Vinnapas B 500/20VL, supplied by Wacker); PVA I = polyvinyl acetate (Vinnapas B 1.5 sp, supplied by Wacker); PVA II = polyvinyl acetate (Vinnapas B 30 sp, supplied by Wacker); PIB = polyisobutylene (Oppanol B12, supplied by BASF); BR = butyl rubber (isobutylene-isoprene copolymer); Nat. resin = glycerol ester of hydrogenated gum rosin; Veg. fat = vegetable fat. GB no. 101 102 103 104 105 VA-VL I 20 14 22 VA-VL II 20 22 PVA I 32 33 18 35 33 PVA II 5.0 PIB BR Nat. resin Calcium 19 22 17 Carbonate Talc 20 41 Triacetin 8 8 6 7 2 Emulsifier 5 7 3 8 9 Wax, micro- 13 13 10 12 crystalline Veg. fat 2 3 6 5 Total 100 100 100 100 100

(95) TABLE-US-00002 TABLE 1B Gum base compositions, VA-VL I = vinyl acetate-vinyl laurate copolymer (Vinnapas B 500/40VL, supplied by Wacker); VA-VL II = vinyl acetate-vinyl laurate copolymer (Vinnapas B 500/20VL, supplied by Wacker); PVA I = polyvinyl acetate (Vinnapas B 1.5 sp, supplied by Wacker); PVA II = polyvinyl acetate (Vinnapas B 30 sp, supplied by Wacker); PIB = polyisobutylene (Oppanol B12, supplied by BASF); BR = butyl rubber (isobutylene-isoprene copolymer); Nat. resin = glycerol ester of hydrogenated gum rosin; Veg. fat = vegetable fat. GB no. 109 110 106 107 108 (comp.) (Std.) VA-VL I 21 20 20 10 VA-VL II PVA I 31 30 30 20 25 PVA II PIB 3.0 5.0 3.0 3.0 5 BR 2.0 2.0 5 Nat. resin 20 25 Calcium 17 17 17 17 17 Carbonate Talc Triacetin 2 2 2 2 Emulsifier 9 9 9 9 5 Wax, micro- 12 12 12 12 13 crystalline Veg. fat 5 5 5 5 5 Total 100 100 100 100 100

Example 4

(96) Composition Cannabinoid Chewing Gum

(97) Cannabinoid chewing gum were made as compressed gums, given CM numbers 1001-1010, 1011-1020 and 1021-1030, and as batch mixed gums, given CG numbers 1001-1010, 1011-1020 and 1021-1030, both using gum bases nos. 101-110 from Table 1 has the chewing gum compositions shown in table 2A-2F, the amounts given corresponding to percentages by weight of the chewing gum:

(98) Cannabinoid is added as a 10% cannabinoid-MCC premix as disclosed in Example 1 resulting in a 1 gram chewing gum comprising 10 mg of cannabinoid.

(99) TABLE-US-00003 TABLE 2A Cannabinoid chewing gum compositions; MCC = microcrystalline cellulose. Liquid sweetener may for example be lycasin. Intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. CM and CG no. 1001 1002 1003 1004 1005 GB 101 52 GB 102 52 GB 103 52 GB 104 52 GB 105 52 GB 106 GB 107 GB 108 GB 109 GB 110 Filler 15 15 15 15 15 Cannabinoid-MCC 10.0 10.0 10.0 10.0 10.0 premix Sodium hydrogen 1.0 1.0 1.0 1.0 1.0 carbonate Sodium carbonate 2.0 2.0 2.0 2.0 2.0 Sorbitol powder 14 14 14 14 14 Liquid sweetener 1.5 1.5 1.5 1.5 1.5 Intense sweetener 0.4 0.4 0.4 0.4 0.4 Flavor 4.1 4.1 4.1 4.1 4.1 Total 100 100 100 100 100

(100) TABLE-US-00004 TABLE 2B Cannabinoid chewing gum compositions; MCC = microcrystalline cellulose. Liquid sweetener may for example be lycasin. Intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. CM and CG no. 1009 1010 1006 1007 1008 (Comp.) (Std.) GB 101 GB 102 GB 103 GB 104 GB 105 GB 106 52 GB 107 52 GB 108 52 GB 109 52 GB 110 52 Filler 15 15 15 15 15 Cannabinoid-MCC 10.0 10.0 10.0 10.0 10.0 premix Sodium hydrogen 1.0 1.0 1.0 1.0 1.0 carbonate Sodium carbonate 2.0 2.0 2.0 2.0 2.0 Sorbitol powder 14 14 14 14 14 Liquid sweetener 1.5 1.5 1.5 1.5 1.5 Intense sweetener 0.4 0.4 0.4 0.4 0.4 Flavor 4.1 4.1 4.1 4.1 4.1 Total 100 100 100 100 100

(101) TABLE-US-00005 TABLE 2C Cannabinoid chewing gum compositions; MCC = microcrystalline cellulose. Liquid sweetener may for example be lycasin. Intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. CM and CG no. 1011 1012 1013 1014 1015 GB 101 52 GB 102 52 GB 103 52 GB 104 52 GB 105 52 GB 106 GB 107 GB 108 GB 109 GB 110 Filler 16 16 16 16 16 Cannabinoid-MCC 9 9 9 9 9 premix Sodium hydrogen 1.0 1.0 1.0 1.0 1.0 carbonate Sodium carbonate 2.0 2.0 2.0 2.0 2.0 Sorbitol powder 14 14 14 14 14 Liquid sweetener 1.5 1.5 1.5 1.5 1.5 Intense sweetener 0.4 0.4 0.4 0.4 0.4 Flavor 4.1 4.1 4.1 4.1 4.1 Total 100 100 100 100 100

(102) TABLE-US-00006 TABLE 2D Cannabinoid chewing gum compositions; MCC = microcrystalline cellulose. Liquid sweetener may for example be lycasin. Intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. CM and CG no. 1019 1020 1016 1017 1018 (Comp.) (Std.) GB 101 GB 102 GB 103 GB 104 GB 105 GB 106 52 GB 107 52 GB 108 52 GB 109 52 GB 110 52 Filler 16 16 16 16 16 Cannabinoid-MCC 9 9 9 9 9 premix Sodium hydrogen 1.0 1.0 1.0 1.0 1.0 carbonate Sodium carbonate 2.0 2.0 2.0 2.0 2.0 Sorbitol powder 14 14 14 14 14 Liquid sweetener 1.5 1.5 1.5 1.5 1.5 Intense sweetener 0.4 0.4 0.4 0.4 0.4 Flavor 4.1 4.1 4.1 4.1 4.1 Total 100 100 100 100 100

(103) TABLE-US-00007 TABLE 2E Cannabinoid chewing gum compositions; MCC = microcrystalline cellulose. Liquid sweetener may for example be lycasin. Intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. CM and CG no. 1021 1022 1023 1024 1025 GB 101 52 GB 102 52 GB 103 52 GB 104 52 GB 105 52 GB 106 GB 107 GB 108 GB 109 GB 110 Filler 14 14 14 14 14 Cannabinoid-MCC 11 11 11 11 11 premix Sodium hydrogen 1.0 1.0 1.0 1.0 1.0 carbonate Sodium carbonate 2.0 2.0 2.0 2.0 2.0 Sorbitol powder 14 14 14 14 14 Liquid sweetener 1.5 1.5 1.5 1.5 1.5 Intense sweetener 0.4 0.4 0.4 0.4 0.4 Flavor 4.1 4.1 4.1 4.1 4.1 Total 100 100 100 100 100

(104) TABLE-US-00008 TABLE 2F Cannabinoid chewing gum compositions; MCC = microcrystalline cellulose. Liquid sweetener may for example be lycasin. Intense sweetener may for example be sucralose. Flavor may for example be pepper mint flavor. CM and CG no. 1029 1030 1026 1027 1028 (Comp.) (Std.) GB 101 GB 102 GB 103 GB 104 GB 105 GB 106 52 GB 107 52 GB 108 52 GB 109 52 GB 110 52 Filler 14 14 14 14 14 Cannabinoid-MCC 11 11 11 11 11 premix Sodium hydrogen 1.0 1.0 1.0 1.0 1.0 carbonate Sodium carbonate 2.0 2.0 2.0 2.0 2.0 Sorbitol powder 14 14 14 14 14 Liquid sweetener 1.5 1.5 1.5 1.5 1.5 Intense sweetener 0.4 0.4 0.4 0.4 0.4 Flavor 4.1 4.1 4.1 4.1 4.1 Total 100 100 100 100 100

Example 5

(105) Preparation of Batch Mixed Cannabinoid Chewing Gum

(106) Gum base and filler according to Example 4 are mixed in a mixer having horizontally placed Z-shaped arms for mixing. The mixer was preheated to a temperature of up to approximately 50 C. When the content of the mixer is homogeneous, the other ingredients according to Example 4 are added according to a specified time schedule. The processed compositions are finally cut into conventionally mixed chewing gum cores CM1001-CM1010, CM1011-CM1020 and CM1021-CM1030. The process corresponds largely to the process disclosed in international patent application WO 02/076230 A1, hereby incorporated by reference.

Example 6

(107) Preparation of Compressed Cannabinoid Chewing Gum

(108) Gum base and filler according to Example 4 formed into gum base granules by a granulation process. The cannabinoid premix is then adsorbed to the gum base granules, optionally together with other liquid chewing gum ingredients. The other ingredients according to Example 4 are mixed with the gum base particles into a homogeneous mix of gum base granules and chewing gum particles. The mixed gum base granules and chewing gum ingredients are then compressed into chewing gum tablets CG1001-CG1010, CG1011-CG1020 and CG1021-CG1030. Liquid ingredients may in some cases be mixed into the gum base. The process corresponds largely to the process disclosed in international patent application WO 2004/004479 A1, hereby incorporated by reference.

Example 7

(109) Evaluation of Cannabinoid Chewing Gum

(110) Different examples of the medical chewing gum were evaluated with respect to stability, texture, robustness, release of flavor and cannabinoid, taste profile and other important features.

(111) The medical chewing gum is highly suitable as delivery vehicle for cannabinoid.

LIST OF FIGURE REFERENCES

(112) CAN. Cannabinoids MCC. Microcrystalline cellulose MIX1. Mixer MIX2. Mixer MIX3. Mixer PROC. Processing CC. Cannabinoid-microcrystalline cellulose mixture GB. Gum base CGI. Chewing gum ingredients CGM. Chewing gum mass CMC. Chewing gum mass with cannabinoid-microcrystalline cellulose mixture