Field of the invention

The present invention pertains to a chewing gum or lozenge composition comprising CBD (cannabidiol). More in particular, to a liquid filled chewing gum or lozenge composition comprising hemp oil and it’s applications as a delivery vehicle for CBD.

Background of the invention

Cannabis is a family of plants with two primary classes: Indica and Sativa.

All cannabis plants contain certain distinct compounds called Cannabinoids, of which more than a hundred are currently known. Two of the most abundant are Tetrahydrocannabinol (“THC”) and Cannabidiol (“CBD”). Marijuana is derived from both Indica and Sativa plants that contain a high (15-40%) levels of THC and generally low levels of CBD. THC is the primary psychoactive component of the cannabis plant that is responsible for creating the “getting high” effect of smoking marijuana, in addition to other purported neural effects and numerous medical benefits. The consumer interest for CBD products derived from hemp is vast. The products appeal to all adults who lead a health-oriented lifestyle and want a natural way to relieve physical and mental stress, seeking alternative all-natural, eco-friendly health supplements, seeking relief from chronic pain, arthritis and other conditions associated with aging. Hemp is only derived from Sativa plants which are cannabis plants that contain almost no THC (<0.3 wt.% by law) and high levels of CBD. CBD is a non-psychoactive component (no “high”) of the cannabis plant. CBD actually counters the psychoactive properties of THC. Numerous research studies have shown CBD to be effective in various degrees in relieving chronic pain headaches and migraines, insomnia, anxiety disorder, loss of appetite, depression, diabetes, nausea, alzheimer’s, ALS, arthritis, bone health, cancer, epilepsy and seizures. In contrast to the many positive benefits of CBD, there have been almost no credible studies that have shown even mild ill-effects from consuming even high doses of CBD, to the point that many detractors have had to resort to searching for side effects from extreme dosages.

Much of the positive effects of cannabinoids have been thought to occur as part of the human body’s Endocannabinoid System (“ECS”). The ECS is a widely-recognized neuromodulatory system located in the central and peripheral nervous system that regulates a wide range of homeostasis (healthy balance) in key body functions such as mood, sleep cycles, appetite, immune response, metabolism, pain response, cell repair and more. The ECS is a network of neurons, located throughout the brain, most organs and throughout the body, whose neurotransmitters depend on certain cannabinoids to send signals from one neuron to the next. These are the same cannabinoids found in hemp, marijuana and other plants (such as echinacea and flax) and are found in the human nervous system, specifically the ECS. Cannabinoids that are found in the human body are referred to as endocannabinoids, while those same cannabinoids found in plants are referred to phytocannabinoids.

The ECS maintains the body’s homeostasis by keeping a narrow range in blood sugar levels, internal temperature, blood pH, and the retention of water and certain minerals. As the ECS relies on certain endocannabinoids to maintain its function, bodies must constantly produce their own endocannabinoids. If not enough amounts are created, it is thought that clinical endocannabinoid deficiency may occur, which throughout history humans have treated by ingesting phytocannabinoids.

This often has been done by smoking, inhalation, vaping, eating or other means of administration which are sometimes frowned upon, especially in more public areas.

Hence there is a need for products that contain CBD in an easy-to-use form for the above- mentioned health and lifestyle related applications.

Chewing gum and lozenges are well known in the art. Examples can be found in US9253991, US2019/2244117.

US2018/110730, US2011/097283, US2016/158298 describes cannabinoid containing chewing gum compositions wherein the gum is made through a conventional pressing (extrusion) process.

US2017/312261 describes cannabinoid and nicoltine containing chewing gum compositions

Summary of the invention

The present invention now pertains to a chewing gum and/or lozenge composition that delivers CBD and CBD-related compounds. The composition is suitable for oral administration and provides a pre-set dose to the user of a CBD containing composition.

The invention also pertains to a method of making a chewing gum and/or lozenge composition.

The invention further relates to the use of the chewing gum and/or lozenge composition as a medicament or for the treatment of a variety of ailments.

Detailed description of the invention In the present invention, the term “approximately” and “about” generally indicate a variability of about 5% of the number(s) or range. Typically, “approximately” and “about”, indicate a variability from between 0.001 to 10% from the number(s) or range. 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."

All wt % are drawn on the weight of the total chewing gum or lozenge composition unless otherwise specified.

The chewing gum composition comprising the CBD or the extract containing CBD comprises a gum base as is commonly used in chewing gum formulations that are commercially available and accepted by the consumer. The CBD or the extract containing CBD may be comprised by a solid material, for instance composed of a cellulose which comprises a well- defined amount of the cannabinoid or the derivative thereof, e.g. in and/or onto voids or pores within the solid material.

Preferably, the chewing gum composition according to the present invention has a high initial release rate of the CBD thereof to provide a rapid adsorption of the CBD. Accordingly, it is preferred that the chewing gum composition according to the present invention releases at least 1 % by weight to not more than 30 % by weight, based on the total weight content of the CBD in the chewing gum composition according to the present invention within five minutes after ingestion. It is also preferred that the onset of the release starts within three minutes after ingestion. A center fill gum in which the CBD is largely incorporated in the liquid fill is an advantageous formulation thereof.

A chewing gum generally refers to a chewable rubber or plastic that provides the structural integrity of the chewing gum. It may comprise natural materials (chicle) or synthetic materials (like paraffin wax and related polymers). Typically, the chewing gum composition is non-disintegrating, i.e. it does not disintegrate during chewing, and it does not crumble. It is currently contemplated that use of a particular gum base in combination with a suitable selection of additives has a significant impact on the non-disintegrating properties of chewing gum compositions. Examples of suitable gum bases having suitable properties and leading to non- disintegrating chewing gum compositions are e.g. gum bases that are or comprise, Gum powder PG 11 TA, Gum powder PG 11 TA New, Gum powder PG 5 TA, Gum powder PG 5 TA New and Gum powder PG N12 TA. The gum base is normally present in the chewing gum composition according to the present invention in an amount of about 25 to about 85 % by weight, preferably about 30 to about 80 % by weight, more preferably about 40% to about 80 % by weight and in particular about 50 to about 80% w/w, based on the total weight of the chewing gum composition. In preferred embodiments of the chewing gum compositions according to the present invention, the chewing gum composition comprises one or more further ingredients, e.g. fats, waxes, emulsifiers, plasticizers, oils, flavouring agents and the like as desirable to modify the texture of the chewing gum.

A lozenge is a solid dosage form (porous or non-porous) that may comprise or consist of ingredients that are typically provided in a matrix and often covered by a coating, usually a soluble coating. The inside of a lozenge may comprise or consist of compressed powers, microcapsules, microencapsulated particles or liquids. Lozenge can be hard or chewable and dissolve complete in the oral cavity.

The term hemp oil refers to a concentrated, optionally purified liquid form of CBD, which has been extracted from the cannabis plant. In some embodiments, the cannabis extract may take the form of a concentrated oil, which may be readily poured or added dropwise to the other gum ingredients during the mixing process. The purity of the hemp oil may range from 50-99%, and is typically 90% pure. Typically, the hemp oil is CBD oil. Typically the THC content is below 0.3 wt%. The hemp oil may also be provided as a powder, microcapsules etc.

The chewing gum and/or lozenge composition may be a center or liquid-filled chewing gum and/or lozenge of the type as described in US9253991.

A center filled chewing gum or lozenge composition is typically composed of a center that has a composition that is substantially different from the surrounding composition (typically a gum). The center can have having distinct functional characteristics. The center can be liquid or semisolid. Various components can be provided in the interior of a gum or lozenge in a liquid or semi-liquid form while the gum or lozenge itself can be of a traditional composition and/or may incorporate various other (or the same) desirable components to supplement and/or co-act with the components contained in the center. The center filled chewing gum or lozenge of the invention may contain CBD in the center in liquid or semisolid form surrounded by a gum base or lozenge base. In one embodiment, the base itself may also contain CBD.

By combining the active ingredient both in the base and in the center, a time-release effect is provided as the contents of the center are almost instantly released while masticating, while the CBD in the base is released during prolonged mastication or consumption. Alternatively or additionally, delayed release capsules may be provided suspended or encapsulated in the center of the base gum.

The CBD, optionally in the form of an extract, may be present in the chewing gum or lozenge in an amount of up to 30% by weight, drawn on the total weight of the chewing gum or lozenge. Another embodiment of the present disclosure relates to a (liquid-filled) chewing gum or lozenge including a chewing gum base shell and a liquid filling, wherein the amount of CBD in the (liquid-filled) chewing gum or lozenge is from about 0.1 wt% to about 30 wt %, about 0.2 wt% to about 20 wt % or about 0.5 wt% to about 10 wt%. The liquid filling of the lozenge or chewing gum may contain CBD in an amount of about 0.1 wt% to about 30 wt %, about 0.2 wt% to about 20 wt % or about 0.5 wt% to about 10 wt%. The liquid filling may further comprise additives as exemplified herein elsewhere.

The chewing gum or lozenge of the present invention may be provided in the form of a unit dosage form. A unit dosage formulations of the present invention may be contain about 1 mg to about 100 mg, about 2 mg to about 90 mg, about 3 mg to about 80 mg, about 5 mg to about 70 mg, about 10 mg to about 60 mg or about 50 mg of CBD, preferably in the form of an extract. Unit dosage formulations of the embodiments of the present disclosure can include CBD in the amount about 1 mg to about 100 mg, about 2 mg to about 90 mg, about 3 mg to about 80 mg, about 5 mg to about 70 mg, about 10 mg to about 60 mg or about 50 mg of CBD, preferably in the form of an extract.

In certain preferred embodiments, the chewing gum or lozenge composition is a unit dose and contains hemp oil ( a preferred CBD extract) in an amount of from about 1 mg to about 100 mg. with an average content of 20% CBD in hemp oil, the amount of CBD in a unit dose is preferably from about 0.2 mg to about 20 mg.

A particular chewing gum or lozenge composition according to the invention is one, wherein the chewing gum composition contains: CBD , preferably in the form of an extract, in an amount of from about 0.1 to about 20 wt%; gum base in an amount of from about 25 to about 90 wt%; sweetening, flavouring and/ or additive agents in an amount from about 0.0001 to about 50.wt%; wherein the sum of all ingredients adds up to 100 wt%.

Another particular chewing gum or lozenge composition according to the invention is one, wherein the chewing gum composition contains hemp oil in an amount of approximately about 0.1 to about 20 wt%; gum base in an amount of approximately 25 to about 90 wt%; sweetening, flavouring and/ or additive agents in an amount about 0.0001 to about 50.wt%; wherein the sum of all ingredients adds up to 100 wt%.

In a preferred embodiment of the chewing gum or lozenge composition according to the invention, the CBD is provided in the liquid filling and/or in the gum base. There is a preference for proving CBD in both the liquid fill and the gumbase.

In a preferred embodiment of the chewing gum or lozenge composition according to the invention, at least 50% of the CBD, drawn on the whole amount of CBD is provided in the liquid filing and the remainder in the gum base. In a preferred embodiment of the chewing gum or lozenge composition according to the invention, at least 50% of the CBD, drawn on the whole amount of CBD is provided in the gum base and the remainder in the liquid filling. In another preferred embodiment, the liquid filling contains from 30-70 % of the CBD drawn on the whole amount of CBD and the gumbase contains from 70-30% of the CBD drawn on the whole amount of CBD in the unit formulation.

Hemp oil is one of the main sources for the CBD extract used in the present invention. Hemp oil can contain other active ingredients, such as cannabichromene (CBC); tetrahydrocannabinol; THC, cannabigerol (CBG ); cannabicyclol (CBL ); (8) cannabinodiol (CBND); (9) (10) cannabitriol (CBT) and others. The amount of THC in the CBD extract used in the present invention is below 0.3 wt%.

The chewing gum or lozenge composition may further contain components that that have a positive effect on the dental status on the teeth in the oral cavity. A preferred example is sodium bicarbonate that can be present in an amount of 0.1 to 10 wt%. Sodium bicarbonate in chewing gums or lozenge can typically exert an additional and often synergetic teeth whitening and cleaning effect.

The chewing gum and lozenge compositions of the invention (e.g., chewing gum and lozenges that can be liquid-filled ) can be used as a medicament or a therapeutic agent. The chewing gum and lozenge compositions of the invention can be used to relieve or alleviate local and/or systemic pain, used as an analgesic and/or to relieve and/or alleviate inflammation. The chewing gum and lozenge compositions of the invention can be orally administered (e.g., placed in the mouth). The chewing gum and lozenge compositions of the invention can include or contain pharmaceutical compositions, including analgesic and/or anti-inflammatory pharmaceutical compositions for the treatment of pain and/or inflammation. The chewing gum and lozenge compositions of the invention typically contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid such as CBD, preferably in the form of an CBD extract, preferably hemp oil. Furthermore, a pharmaceutically acceptable carrier may be present in for example, the liquid fill of the chewing gum or lozenge. The chewing gum and lozenge compositions (e.g. chewing gum and lozenges that may be liquid-filled ) may also include oral care compositions for the treatment of oral or dental pain. This also comprises oral care analgesic and/or anti inflammatory compositions that can play a role in the treatment of oral or dental pain and/or inflammation.

There is a preference for adding buccal adsorption enhancers such as short (C6-C10) and medium chain fatty acids (C12-C14 fatty acids) and salts thereof, preferably sodium and calcium salts. Other suitable components that may be used as buccal adorption enhancers are for instance cetearyl glucosides, glyceryl stearate, cetearyl alcohol, sodium stearoyl lactylate, cetearyl olivate, sorbitan olivate, sodium cholate, sodium glycocholate, sodium glycodeoxycholate, taurodeoxycholate, sodium deoxycholate, sodium lithocholate chenocholate, chenodeoxycholate, ursocholate, ursodeoxy-cholate, hyodeoxycholate, dehydrocholate, glycochenocholate, taurochenocholate, and taurochenodeoxycholate. Other enhancers such as sodium dodecyl sulfate ("SDS"), sodium lauryl sulfate (SLS), salts and other derivatives of saturated and unsaturated fatty acids, surfactants, bile salt analogs, derivatives of bile salts, can be used, alone or in combination.

The buccal adsorption enhancers can be added to the gum compositions in an mount of 0.1-2 wt%, drawn on the gum formulation and can be added to the gum base and/or to the liquid filling. Using buccal adsorption enhancers in the gum of the present invention and preferably in the liquid filling, increases the uptake of CBD via the mucosal tissue and hence enhances the delivery of the CBD.

A fixing agent generally refers to a polyol that allows the gum to have a hard outer coating. The polyol may be sorbitol, maltitol/isomalt, mannitol, starch, and the like.

In order to improve the organoleptic properties of the chewing gum composition according to the present invention, the chewing gum composition preferably comprises a flavouring agent, in an amount of about 0.5 to about 12 % by weight, more preferably about 1 to about 10 % by weight, even more preferably about 1.5 to about 9 % by weight, yet even more preferably about 2 to about 8 % by weight, based on the total weight of the chewing gum composition. Flavouring agents can be e.g., menthol flavour, eucalyptus, mint flavour and/or L-menthol. Other flavors used may be natural or synthetic and may be menthol, peppermint, spearmint, or a sour acid, such as citric, tartaric, malic, lactic, adipic, and fumaric.

In order to increase the gustatory properties of the chewing gum composition according to the present invention, the chewing gum composition preferably comprises a pharmaceutically acceptable sweetener, e.g. sugar alcohols including xylitol, sorbitol and/or isomalt, artificial sweeteners such as e.g. aspartame, sucralose, acesulfame potassium or saccharin. The amount of the pharmaceutically acceptable sweetener is normally preferably at least about 0.05 % by weight, more preferably about 0.075 to about 5 % by weight, even more preferably about 5 to about 35 % by weight, yet even more preferably about 10 to about 35 % by weight, even yet more preferably about 15 to about 35 % by weight and in particular about 20 to about 30 % by weight, based on the total weight of the chewing gum composition. It is highly preferred that the pharmaceutically acceptable sweetener is non-cariogenic as well as non- carcinogenic.

Sweeteners used may include: sugar, dextrose, glucose or corn syrup, erythritol, isomalt, maltitol, mannitol, sorbitol, lactitol, aspartame, acesulfame-K, saccharine, sucralose, neohesperidine, dihydrichalcone.

Additives in the present invention, typically refers to non-structural or flavor- related compounds that are added to the cannabis extract chewing gum to impart other desirable properties. These may include various vitamins for imparting healthful effects to the user. Caffeine and gingerol are two additives that might be used. The chewing gum composition according to the present invention preferably comprises a buffering agent. Suitable buffering agents are typically those selected from the group consisting of acetates, glycinates, phosphates, glycerophosphates, citrates such as citrates of alkaline metals, carbonates, hydrogen carbonates, and borates, and mixtures thereof. The chewing gum composition preferably comprises a buffering agent in an amount of about 0.5 to about 5 % by weight, more preferably about 0.75% to about 4 % by weight, even more preferably about 0.75 to about 3 % by weight, yet even more preferably about 1 to about 2% by weight, based on the total weight of the chewing gum composition.

The chewing gum composition according to the present invention preferably further comprises an anti-oxidant, e.g., ascorbyl palmitate and sodium ascorbate, in an amount of about 0.05 to about 0.3 % by weight, more preferably about 0.1 to about 0.25 % by weight, yet even more preferably about 0.15 to about 0.2 % by weight, based on the total weight of the chewing gum composition.

The pharmaceutically acceptable excipients used in the chewing composition according to the present invention are preferably selected from the group of excipients normally used within the pharmaceutical industry for the preparation of tablets, i.e. excipients like fillers, desintegrants, binders, lubricants and the like.

Suitable fillers include celluloses and cellulose derivatives including micro crystalline cellulose, hydroxypropylcellulose and sodium carboxymethylcellulose, lactose, starches including potato starch and maize starch (in the US known as corn starch). Suitable lubricants include stearates including magnesium stearate, talc and colloidal silica dioxide.

The chewing gum of the invention may advantageously also contain softeners or plasticizers. Examples thereof are lecithin, hydrogenated vegetable oils, glycerol ester, lanolin, methyl ester, pentaerythritol ester, rice bran wax, stearic acid, sodium potassium stearates, and the like.

The chewing gum may further comprise gingerol, caffeine, flavourings, and sweeteners, preferably artificial sweeteners. The user masticating the CBD extract chewing gum receives CBD from the chewing gum. The artificial sweeteners may be based on a preference of the user. Moreover, the chewing gum may also comprise vitamins, antibiotics, colorants, etc. The cannabis extract chewing gum ensures delivery of CBD extract to the user who chews it. In some embodiments, the addition of vitamins or antibiotics may provide added benefits to users. When a user chews the CBD containing chewing gum, the absorption may happen through the lining of the mouth and/or by swallowing.

To optimize the adsorption of the active CBD in the gum of the invention, it may be prefreed to administer CBD through the buccal mucosa of the cheek pouch or by sublingual administration. Such administration through the mucosal tissues of the mouth, pharynx, and esophagus of therapeutic drugs possesses a distinct usefulness. Administration of CBD by this route does not expose the drug to the gastric and intestinal digestive juices. In addition, the drugs largely bypass the liver on the first pass through the body, thereby avoiding additional metabolism and/or inactivation of the drug.

The CBD (extract, sucg as hemp oil) may have an unpleasant taste. As a result, in order to allow for buccal or sublingual administration through the oral mucosal tissues, it is therefore advantageously to incorporate the drug into some type of pleasant tasting mass, such as a gum matrix as defined herein.

For effective application of the CBD, the final gum product may contain the drug uniformly distributed throughout in the gum base, the liquid fill or both in order to ensure uniform levels of medication. Alternatively, for some applications, varying concentrations in the gum base or fill within known and controlled ranges may be desired to vary the rate of CBD administration. However, as the CBD may have varying solubility in the various compounds of the gum and/or the liquid fill components, it may be that difficulties are encountered in attempting to blend solid drugs in a uniform or otherwise carefully controlled manner. This may lead to the resultant gum product is often found to in need of improvement of the more uniform or controlled distribution of the drug.

This may be counteracted by the administration of CBD through the oral mucosal tissues.

It should also be noted that pH conditions within the mouth may tend to adversely affect the administration of certain lipophilic drugs by the mucosal administration route. It has been found in the art that administration of drugs through the mucosal tissues generally occurs best when the drug is in the unionized form. Variations in pH affect the percentage of the drug which is unionized at a particular point in time. As a result, the pH conditions within the mouth often limit the effectiveness of certain drugs administered buccally or sublingually in that those conditions cause the drug to exist in the ionized form which is largely unavailable for transfer across the mucosal tissues.

It would be another important advancement in the art of administering CBD, if suitable methods and compositions provided a precise dosage to a precise effect in every consumer.

A related advancement in the art would be to provide such methods and compositions that avoid the disadvantages of overdosing, underdosing, and the immediate metabolism encountered in the "first pass effect".

However, CBD may profit from enhanced diffusione across mucosal membranes if the mucosal membrane is treated with a permeation enhancer. It has also been found that certain permeability enhancers can significantly enhance the permeability of lipophilic and nonlipophilic drugs.

Typical permeation enhancers include bile salts such as sodium cholate, sodium glycocholate, sodium glycodeoxycholate, taurodeoxycholate, sodium deoxycholate, sodium lithocholate chenocholate, chenodeoxycholate, ursocholate, ursodeoxy-cholate, hyodeoxycholate, dehydrocholate, glycochenocholate, taurochenocholate, and taurochenodeoxycholate. Other permeation enhancers such as sodium dodecyl sulfate ("SDS"), dimethyl sulfoxide ("DMSO"), sodium lauryl sulfate, salts and other derivatives of saturated and unsaturated fatty acids, surfactants, bile salt analogs, derivatives of bile salts, or such synthetic permeation enhancers as described in United States Patent No. 4,746,508 may also be used.

However, it is generally believed that bile salts are good enhancers for hydrophilic drugs and long chain fatty acids, their salts, derivatives, and analogs are more suitable for lipophilic drugs. DMSO, SDS, and medium chain fatty acids (C-8 to about C-14) their salts, derivatives, and analogs may work for both hydrophilic and lipophilic drugs.

The permeation enhancer concentration within the dissolvable matrix material may be varied depending on the potency of the enhancer and rate of dissolution of the dissolvable matrix. Other criteria for determining the enhancer concentration include the desired lag time. The upper limit for enhancer concentration is set by toxic effect to or irritation limits of the mucosal membrane.

The following is a list of typical enhancers and an exemplary concentration range for each enhancer: sodium cholate 0.02% - 50% 0.1% -16% sodium dodecyl sulfate 0.02% - 50% 0.1% -2% sodium deoxycholate 0.02% - 50% 0.1% -16% taurodeoxycholate 0.02% - solubility 0.1% -16% sodium glycocholate 0.02% - solubility 0.1% -16% sodium taurocholate 0.02% - solubility 0.1% -16%

DMSO 0.02% - solubility 5% -50%

To accommodate the incorporation of the lipophilic CBD in the fill, various techniques may may be employed, such as spray drying or freeze drying of the CBD, preferably in combination with a wall material selected from the group consisting of maltodextrin, gum arabic, chitosan, citrus fruit fiber, colloidal silicon dioxide, sodium caseinate-soy lecithin, skimmed milk powder, whey protein concentrate, gelatin, alginates. Jeyakumari et al. describes various ways of microencapsulation of bioactive food ingredients,, but do not suggest this for the formulation of CBD in gum formulations (Jeyakumari A, Zynudheen AA, Parvathy U. Microencapsulation of bioactive food ingredients and controlled release-a review. MOJ Food Process Technol. 2016;2(6):214-224. DOI: 10.15406/mojfpt.2016.02.00059).

Examples

Example 7: center-fill chewing gum

The chewing gum composition of example 3 is rolled to a slab. A layer of the encapsulated hemp oil of example 1 is laid on top of the slab and a second slab of the chewing gum composition is laid on top. The slabs are rolled together and subsequently divided into center-filled pieces

Example 8: center-fill chewing gum The chewing gum composition of example 3 is rolled to a slab and placed on a gum press to form the bottom cavity. The bottom cavity is filled with the encapsulated hemp oil and sodium bicarbonate of example 2. A second slab is rolled and placed on top to form the top piece. The gum is punched by a gum press to form the center-filled gum.