Loaded granules, method of manufacturing the same, and use of the same

Abstract

The present invention relates to cannabinoid and / or nicotine-loaded granules comprising orally dispersible sugar granules loaded with at least one cannabinoid compound and / or nicotine.

Description

Technology Field

[0001] The present invention relates to orally-dispersible granules containing one or more active cannabinoid compounds, orally-dispersible granules containing nicotine, a method for manufacturing said granules, and the use of said granules as a nutritional complement. The present invention also relates to said granules for use as a medicament. Background Technology

[0002] Plant Cannabis Sativa L. Cannabis Sativa L. ) (also known as marijuana) produces phytocannabinoids, which are natural biochemical compounds characterized by their ability to interact with cannabinoid receptors in brain cells.

[0003] This plant has been known for thousands of years for its effects on the human body. Cannabinoids are primarily consumed by smoking or vaporizing dried cannabis plant material. These delivery systems are harmful to health, inconvenient, and lack proper dosage control. Furthermore, the consumed plant extracts all contain combinations of different phytocannabinoids.

[0004] However, it may be desirable to consume only some of these cannabinoid compounds, for example, those that do not exhibit any psychotropic effects.

[0005] To date, about 110 different types of phytocannabinoids have been identified. Among them, the most abundant are tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), followed by cannabigerol (CBG), cannabichromene (CBC), and cannabinodiol (CBND).

[0006] The most notable cannabinoid is trans-delta-9-tetrahydrocannabinol (Δ9-THC), a potent psychoactive compound responsible for euphoric and mind-altering effects. Another important phytocannabinoid is cannabidiol (CBD), a compound exhibiting numerous pharmacological effects, including non-psychotropic, antipsychotic, analgesic, neuroprotective, anticonvulsant, antiemetic, antineoplastic, anti-arthritic, antioxidant, and anti-inflammatory effects.

[0007] Extraction and isolation techniques for cannabinoids have been developed to utilize each cannabinoid individually, and in particular to utilize the beneficial effects of cannabidiol, which has no psychoactive effects.

[0008] It has been clinically proven that cannabidiol administration has positive effects in alleviating neuropathic pain in individuals with multiple sclerosis, and in cases of anxiety behavioral disorders including psychosis, movement disorder, generalized anxiety disorder (GAD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and obsessive-compulsive disorder (OCD). These anxiety-related disorders constitute a significant social and economic burden (Blessing et al ., 2015).

[0009] Cannabidiol administration is well tolerated in humans over a wide range of doses up to 1500 mg / day (oral), and no psychomotor slowing, negative mood effects, or vital sign abnormalities have been reported (Bergamaschi). et al ., 2011).

[0010] The first FDA-approved drug containing CBD was Epidiolex®, a liquid formulation of highly purified plant-derived cannabidiol intended for the treatment of two rare and severe childhood epilepsy syndromes.

[0011] Outside of the United States, Sativex®, a drug containing CBD and Δ9-THC in a 1:1 ratio, has been approved in numerous countries for the treatment of spasticity caused by multiple sclerosis. This drug is offered in the form of an oromucosal spray.

[0012] Isolated phytocannabinoids can be consumed by ingestion, inhalation, or transdermal delivery. Phytocannabinoids can be extracted from plants with alcohol and then applied orally. They can also be extracted into oil and then administered orally or through the nasal mucosa. Oily formulations may be offered as is, in spray form, contained in gelatin capsules, or included in transdermal compositions.

[0013] Different herbal preparations containing cannabinoids for therapeutic or non-therapeutic (recreational) use have been proposed:

[0014] - U.S. Patent 9,095,563 is a cannabis species ( Cannabis species) A topical composition comprising an extract is described;

[0015] - Patent application WO 2017 / 189375 discloses a chewing gum composition comprising at least one isolated cannabinoid, nicotine, and at least one flavoring agent and one sweetener;

[0016] - Patent application WO 2017 / 208072 discloses a nasal cannabidiol composition comprising an oily vehicle such as vegetable oil;

[0017] - Patent application WO 2017 / 180707 relates to an ingestible film comprising a substance extracted from cannabis sativa, said film comprising a matrix and isolated cannabinoids at a concentration of more than 90%;

[0018] - Patent application WO 2017 / 185038 further discloses an oral CBD formulation comprising a compound intended to obtain the fast-acting physiological effects of CBD;

[0019] - Patent application WO 2018 / 129097 relates to a nutritional complement comprising a synthetic cannabinoid combined with an N-acetylated fatty amino acid that increases the water solubility of the cannabinoid;

[0020] - U.S. Patent 10,434,084 describes a cannabinoid-enriched powder prepared from tiny coated particles of sugars. This powder can be used as a dry premix for preparing beverages or cooked foods;

[0021] - Patent application US 2018 / 344786 relates to an oily composition comprising a combination of cannabinoids and terpenes.

[0022] Pharmacokinetic studies have shown that oral formulations provide the most favorable pharmacokinetic profile compared to transdermal application (Bartner et al ., 2018).

[0023] Nevertheless, the classic oral form can have undesirable side effects, especially:

[0024] - Cannabinoid-containing compositions may induce bad taste and / or dry mouth;

[0025] - Water must be drunk when taking tablets and capsules, and some individuals may find it bothersome to swallow the bulky, standard dosage forms;

[0026] - Dry premixes for beverages or food require water and / or ingredients; they cannot be consumed on their own;

[0027] - Oily formulations are susceptible to leakage from their vials, making their transport complex; furthermore, this formulation lacks adequate dosage control.

[0028] Culinary preparations containing cannabinoid(s), such as cakes and candies, have been proposed; however, these are often loaded with very small amounts of cannabinoids and are not stable over time due to the perishable nature of the foods.

[0029] The object of the present invention is to provide an oral formulation for administering at least one cannabinoid exhibiting the following advantages:

[0030] - Oral formulations allow for easy control of the desired dosage;

[0031] - Oral formulations are pleasant to use;

[0032] - Oral formulations do not produce any unpleasant taste in the oral cavity and do not dry out the buccal mucosa;

[0033] - Oral formulations do not require water for administration; more generally, they require no preparation and can be administered as is under any circumstances (e.g., while traveling).

[0034] Interestingly, this oral formulation is also suitable for nicotine administration; the same advantages as those described above are achieved for nicotine-loaded granules.

[0035] The oral formulation advantageously comprises at least one terpene. Advantageously, the oral formulation according to the present invention is presented elegantly; its administration is pleasant; and consequently, the formulation is consumed in an enjoyable and playful manner. Furthermore, the consumption of the oral formulation is prudent.

[0036] Summary of the Invention

[0037] The present invention relates to cannabinoid-loaded granules composed of orodispersible sugar granules containing at least one cannabinoid compound.

[0038] The present invention also relates to nicotine-loaded granules composed of orally dispersible sugar granules containing nicotine.

[0039] The present invention also relates to cannabinoid and nicotine-loaded granules comprising orally dispersible sugar granules containing at least one cannabinoid compound and nicotine.

[0040] In particular, the granules are composed of lactose, saccharose, xylitol, or a mixture thereof.

[0041] In a preferred embodiment, the cannabinoid and / or nicotine-loaded granules further contain at least one terpene, preferably a combination of at least two terpenes.

[0042] In another aspect, the present invention relates to a method for preparing cannabinoid and / or nicotine-loaded granules as described above, comprising at least the following steps:

[0043] a) a step of adding at least one cannabinoid compound, and / or nicotine, to orally dispersible sugar granules,

[0044] b) Air-drying stage of granules,

[0045] c) a step of repeating the above consecutive steps (a) and (b) at least 20 times,

[0046] d) optionally, a step of coating cannabinoid and / or nicotine-loaded granules with a sugar syrup containing a coloring agent or flavoring agent, natural gum, natural wax, or any combination thereof.

[0047] The present invention also relates to the cannabinoid and / or nicotine-loaded granules for use as medicine.

[0048] The present invention also relates to granules loaded with cannabinoids and / or nicotine for use in the treatment and / or prevention of chronic pain, inflammatory disorders, behavioral disorders, and anxiety disorders.

[0049] In another aspect, the present invention relates to the use of cannabinoid and / or nicotine-loaded granules as a nutritional supplement.

[0050] The present invention also relates to a kit for use as a nutritional supplement, comprising at least two dispensing devices in a single package containing cannabinoid-loaded granules additionally containing at least one terpene, wherein the at least two dispensing devices are distinguished from each other in that the at least one terpene is different in each dispensing device. Specific details for implementing the invention

[0051] Unless otherwise specified, the following terms and phrases as used herein are intended to have the following meanings:

[0052] In this document, the term "about" means a range of more than or less than 10% of the indicated amount.

[0053] In the context of the present invention, "cannabinoid compounds" and "cannabinoids" are used interchangeably and both refer to a class of various chemical compounds that act on cannabinoid receptors in cells. This class includes endocannabinoids (naturally produced in the body by animals), phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (artificially produced).

[0054] In the sense of the present invention, the term "cannabinoid" includes all derived forms of cannabinoids, particularly those chemically derived from phytocannabinoids.

[0055] The most notable phytocannabinoid is tetrahydrocannabinol (THC), the main psychoactive compound in cannabis. Its chemical name is trans-Δ9-tetrahydrocannabinol, and its CAS number is 1972-08-3. THC exhibits the following developed chemical structure:

[0056] Chemical formula (I)

[0057] In this application, the abbreviations Δ9-THC and THC are used without distinction and both mean trans-Δ9-tetrahydrocannabinol.

[0058] Cannabidiol (CBD) refers to the compound mentioned under CAS number 13956-29-1 and represents the chemical structure developed below:

[0059] Chemical formula (II)

[0060] First discovered in 1940, it was isolated from the cannabis sativa plant, where it represents up to 40% of the extract of the said plant.

[0061] Cannabidiol has a broad pharmacological profile, including interactions with several receptors, specifically cannabinoid type 1 receptor (CB1R), serotonin 5-HT1A receptor, and transient receptor potential (TRP) vanilloid type 1 (TRPV1) receptor. In addition, CBD can also directly or indirectly modulate peroxisome prolifera-activated receptor-γ, orphan G-protein-coupled receptor 55, equilibrative nucleoside transporter, adenosine transporter, additional TRP channels, and glycine receptors.

[0062] Cannabidiol is said to have a very low affinity for cannabinoid CB1 and CB2 receptors, but acts as an indirect antagonist to these receptors.

[0063] Synthetic cannabinoids include all chemically synthesized compounds structurally related to THC and cannabidiol, as well as non-classical cannabinoids designated as cannabimimetics.

[0064] Nicotine, also named 3-(N-methyl-2-pyrrolidinyl)pyridine, 1-methyl-2-(3-pyridyl)pyrrolidine, or β-pyridyl-α-N-methylpyrrolidine under CAS number 54-11-5, is a neurostimulant that is naturally produced in some plants, particularly tobacco.

[0065] Nicotine acts as a receptor agonist or antagonist for nicotinic acetylcholine receptors (nAChRs) present in the human brain. After binding to these receptors, nicotine produces psychoactive effects and increases the levels of several neurotransmitters in various brain structures.

[0066] Characteristics of granules

[0067] The present invention relates to cannabinoid and / or nicotine-loaded granules comprising orally dispersible sugar granules loaded with at least one cannabinoid compound and / or nicotine.

[0068] In a first aspect, the present invention relates to cannabinoid-loaded granules comprising orally dispersible sugar granules loaded with at least one cannabinoid compound.

[0069] In the context of the present invention, the phrase "cannabinoid-loaded granules" means granules loaded with at least one cannabinoid compound by any technique known to a person skilled in the art. The loading technique includes the following:

[0070] - "Impregnation" (corresponding to "loading into"), consisting of cannabinoid compounds penetrating into the matrix of granules, and

[0071] - "Sugar-coating" (corresponding to "loading onto"), which consists of aggregation of cannabinoid compounds around granules as an outer layer, and which involves coating granules with sugar syrup and then applying said cannabinoid compounds onto the sugar syrup layer.

[0072] In a second aspect, the present invention relates to nicotine-loaded granules composed of orally dispersible sugar granules loaded with nicotine.

[0073] In the sense of the present invention, the phrase “nicotine-loaded granules” means granules loaded with nicotine or any of its derivatives exhibiting the same psychoactive properties, by any technique known to a person skilled in the art.

[0074] In a third aspect, the present invention relates to cannabinoid and nicotine-loaded granules comprising orally dispersible sugar granules loaded with at least one cannabinoid and nicotine. The cannabinoid and / or nicotine-loaded granules of the present invention are granules containing cannabinoid(s) and / or nicotine, regardless of the loading technique. In other words, the term "containing" as used herein to refer to the granules includes both embodiments of "loading into" and "loading onto".

[0075] In the sense of the present invention, the phrase "cannabinoid and / or nicotine-loaded granules" means granules loaded as follows, by any technique known to a person skilled in the art:

[0076] (i) at least one cannabinoid, or

[0077] (ii) any one of nicotine or its derivatives exhibiting the same psychoactive properties, or

[0078] (iii) At least one type of cannabidiol and nicotine.

[0079] Orally dispersible sugar granules, also referred to as pellets or beads, are generally used as homeopathic medicine supports. Homeopathic pills are actually prepared from granules made of an inert substance such as sugar, on which a drop of liquid homeopathic preparation is placed and evaporated.

[0080] Neutral orally dispersible sugar granules (i.e., without any active compound) are commercially available and are widely known to those skilled in the art. In the sense of the present invention, the phrase "neutral granules" means granules prior to any step of loading.

[0081] In a specific embodiment of the present invention, the orally dispersible sugar-neutral granules are composed of lactose, saccharose, xylitol, or a mixture thereof.

[0082] Preferably, the neutral granules consist of 100% xylitol, a sugar alcohol of CAS number 87-99-0. Xylitol is industrially produced from lignocellulose derived from wood and agricultural waste.

[0083] These granules are dispersible in the mouth (or also defined as oral dispersible, oral soluble, melt-in-mouth, or porous granules), which means that the granules are designed to disperse or disintegrate upon contact with saliva without the aid of water, and then release the active compound(s) they contain.

[0084] These granules are intended for sublingual administration of the active compounds they contain.

[0085] These granules are advantageously useful in conditions where water is unavailable or prohibited, such as before surgery.

[0086] The optimal time for orally dispersed granules to disintegrate into the oral cavity is considered to be less than 1 minute. In most cases, the disintegration time varies from 5 seconds to 30 seconds.

[0087] Neutral granules used to manufacture cannabinoid-loaded granules preferably have a circular shape, such as small beads, balls, or spheres.

[0088] Preferably, the neutral granules and loaded granules of the present invention have a diameter greater than 1 millimeter.

[0089] In a preferred aspect of the present invention, the diameter of each neutral granule is about 2 to 10 millimeters, preferably about 3 to 4 millimeters. In a specific embodiment of the present invention, each granule has a diameter of about 3 to 4 millimeters, particularly 3.7 millimeters.

[0090] In a preferred aspect of the present invention, the weight of each neutral granule is about 30 to 300 milligrams, preferably about 30 to 150 milligrams. Typically, these neutral granules are commercially available in batches of “8 granules per gram” (i.e., about 125 mg per granule), “10 granules per gram” (about 100 mg per granule), “20 granules per gram” (about 50 mg per granule), and “25 granules per gram” (about 40 mg per granule).

[0091] cannabinoid compounds

[0092] In a specific embodiment of the present invention, the cannabinoid used to load neutral granules is selected from the group consisting of cannabidiol (CBD), cannabigerol (CBG), trans-Δ9-tetrahydrocannabidiol (THC), and mixtures thereof.

[0093] According to the first embodiment, the granules contain cannabidiol (CBD). These granules are specifically intended for individuals who wish to consume only cannabidiol via a sublingual administration method.

[0094] In particular, the granules contain products such as pure CBD, which is an isolated product of cannabidiol.

[0095] According to the second embodiment, the granules contain trans-Δ9-tetrahydrocannabidiol (THC).

[0096] According to a third embodiment, the granules contain a mixture of both cannabidiol (CBD) and trans-Δ9-tetrahydrocannabidiol (THC). The mixture may be in any proportion for each component, for example, 50% CBD and 50% THC, or 20% CBD and 80% THC or oppositely, or 90% CBD and 10% THC or oppositely.

[0097] In a specific embodiment, CBD and THC may be combined in specific ratios including CBD / THC of 99:1 to CBD / THC of 1:99, and limit values ​​of this range are included.

[0098] Although CBD and THC act through different mechanisms, they possess many overlapping physiological effects. When combined, CBD and THC can enhance each other's benefits while reducing unwanted effects, including the psychoactive or damaging effects of THC.

[0099] According to a fourth embodiment, the granules contain cannabidiol (CBD), trans-Δ9-tetrahydrocannabidiol (THC), or a mixture thereof, and additional other cannabinoid compounds.

[0100] According to the fifth embodiment, the granules contain cannabidiol (CBD) in combination with cannabigerol (CBG).

[0101] At least one cannabinoid used to load neutral granules may be of natural or synthetic origin.

[0102] Preferably, at least one cannabinoid is a phytocannabinoid of natural origin. In particular, at least one cannabinoid may be a phytocannabinoid extracted from the plant cannabis sativa.

[0103] Preferably, at least one cannabinoid will be in a purified form comprising at least 90% by weight of the cannabinoid. This purified form may be, in particular, an isolated product of the cannabinoid.

[0104] Extracts from the plant cannabis sativa may be in different forms such as emulsions, oils, pastes, liquids, resins, crystals, powders, or pulps.

[0105] These different forms of cannabinoid extracts are classified into two main categories: "full spectrum" or "isolates." "Full spectrum" extracts primarily contain a single cannabinoid, but also contain small amounts of other cannabinoids from plants.

[0106] "Isolates" consist of purified cannabinoids extracted from plants and isolated from other cannabinoids.

[0107] According to a preferred embodiment of the present invention, the isolated material contains at least 95% by weight, preferably at least 99% by weight, and more preferably about 99.9% by weight of the considered cannabinoid relative to the total weight of the isolated material.

[0108] Cannabidiol isolates containing more than 99% CBD are commercially available, for example, from Spectrums Europe or Folium Biosciences (USA).

[0109] These isolates obtained by purifying oily full-range extracts are generally in the form of crystalline powders. This powder is soluble in oil but not in water. Interestingly, these isolates have no taste or flavor. Advantageously, the CBD isolates contain only trace amounts of THC, or preferably contain no THC at all.

[0110] Sugar coating of granules

[0111] In a preferred embodiment of the present invention, the granules are sugars coated with sugar syrup and an extract containing at least one cannabinoid compound and / or nicotine.

[0112] This technique, referred to as "sugar coating" of granules, is a routine procedure for a person of ordinary skill in the field of homeopathic granules as well as for a person of ordinary skill in the field of confectionery. This technique is advantageous because it allows at least one cannabinoid compound and / or nicotine to be uniformly redistributed into an outer layer of sugar formed around the granules.

[0113] This is typically performed using a coating turbine. Coating turbines useful for this step are particularly DRIAM, GLATT, or MANESY type turbines.

[0114] The sugar coating process comprises three steps: coating granules with sugar syrup, then applying an extract containing at least one cannabinoid compound (whole or isolated, preferentially isolated), and / or nicotine onto the granules, and finally air-drying the coated granules.

[0115] The sugar syrup consists of water and at least one type of sugar, such as a polyol, monosaccharide, disaccharide, or any combination thereof. Preferably, the sugar is selected from lactose, saccharose, polyol, or a mixture thereof. In particular, the sugar is a polyol, preferably xylitol.

[0116] In a preferred embodiment of the present invention, the sugar syrup is present at a concentration of about "60 Brix," corresponding to 60 grams of sugar dissolved in 100 ml of water. The sugar syrup may also be a solution of 40, 50, 65, 70, 80, or 90 Brix.

[0117] Advantageously, an extract containing at least one cannabinoid compound is derived from the plant cannabis sativa L.

[0118] Preferably, it is an isolate containing only one type of cannabinoid compound.

[0119] In a preferred embodiment, this isolate comprises at least 95 weight percent of the one type of cannabinoid compound.

[0120] Dosage of loaded cannabinoid

[0121] Dosage is a key factor in achieving the greatest benefits and minimizing adverse effects of cannabis sativa extract. Although individual differences may exist, the optimal (i.e., safe and without any side effects) average daily dose of cannabinoids for adults has been established by physicians and is as follows:

[0122] - In the case of CBD, 25 to 30 milligrams per day; and

[0123] - In the case of THC, 20 to 30 milligrams per day.

[0124] Preferably, each single dose should not exceed 10 mg.

[0125] In a specific embodiment, the cannabinoid-loaded granules are prepared to contain a specific amount of at least one cannabinoid or a mixture thereof.

[0126] For example, each granule may contain 5, 10, 15, 20, 25, or 30 mg of cannabinoid, that is, one single cannabinoid or a mixture of at least two cannabinoid compounds.

[0127] Preferably, each granule contains an equivalent dose of one type of cannabinoid of about 2 mg to about 8 mg, preferably about 4 mg to about 6 mg, and more preferably about 5 mg.

[0128] In a specific embodiment of the present invention, the weight of one cannabinoid-loaded granule is about 130 mg, comprising 125 mg of sugar granules and 5 mg of at least one cannabinoid. In this embodiment, at least one cannabinoid represents 3.85% of the total dry weight of the loaded granules.

[0129] In another specific embodiment of the present invention, the weight of one cannabinoid-loaded granule is about 45 mg, comprising 40 mg of sugar granules and 5 mg of at least one cannabinoid. In this embodiment, at least one cannabinoid represents 11.11% of the total dry weight of the loaded granules.

[0130] In a preferred embodiment of the present invention, at least one cannabinoid represents about 2% to 15% by weight of the total dry weight of the cannabinoid-loaded granules.

[0131] Loaded nicotine amount

[0132] Dosage is a key factor in achieving the greatest benefits of nicotine and the least harmful effects. Although it may vary from person to person, it has been established that for smoking suspension or cessation, a doctor should administer about 1 mg of nicotine for every cigarette an individual consumes daily.

[0133] Preferably, each single dose should not exceed 30 mg of nicotine.

[0134] In a specific embodiment, the nicotine-loaded granules are manufactured to contain a specific amount of nicotine. For example, each granule may contain 5, 10, 15, 20, 25, or 30 mg of nicotine.

[0135] According to specific embodiments, the present invention relates to the following:

[0136] - Loaded granules contain cannabidiol (CBD) in combination with nicotine;

[0137] - The loaded granules contain trans-Δ9-tetrahydrocannabidiol (THC) in combination with nicotine;

[0138] - The loaded granules contain a mixture of both cannabidiol (CBD) and trans-Δ9-tetrahydrocannabidiol (THC) and nicotine;

[0139] - Loaded granules contain cannabidiol (CBD) in combination with cannabigerol (CBG) and nicotine.

[0140] Cannabinoid and / or nicotine-loaded granules additionally containing terpenes

[0141] In a specific embodiment of the present invention, the cannabinoid and / or nicotine-loaded granules further contain at least one terpene, preferably a combination of at least two terpenes.

[0142] More specifically, the present invention relates to the following:

[0143] - Cannabinoid-loaded granules further containing at least one terpene, preferably a combination of at least two terpenes;

[0144] - Nicotine-loaded granules further containing at least one terpene, preferably a combination of at least two terpenes; and

[0145] - Cannabinoid and nicotine-loaded granules further containing at least one type of terpene, preferably a combination of at least two types of terpenes.

[0146] Advantageously, the cannabinoid and / or nicotine-loaded granules of the present invention are impregnated with a solution comprising a combination of at least two types of terpenes.

[0147] Terpenes are a class of organic hydrocarbons produced by various plants, particularly conifers, and by some insects. Terpenes and their derivatives, terpenoids, are the main components of essential oils. Terpenes are also the main components of the cannabis sativa plant, which contains at least 120 identified compounds.

[0148] Terpenes possess desirable properties for use in the food and pharmaceutical industries. Although terpenes and terpenoids occur widely, their extraction from natural sources is often problematic. As a result, they are often supplied as synthetic products derived from chemical synthesis.

[0149] In a preferred embodiment of the present invention, the granules are impregnated with a solution comprising at least one terpene selected from the group below: myrcene, d-limonene, alpha-pinene, linalol, borneol, carophyllene, terpinolene, menthol, geraniol, bisabolol, beta-caryophyllene, humulene, linalool, farnesene, α-phelandrene, and any combination thereof.

[0150] The impregnation of granules is a routine procedure for a person skilled in the art of homeopathic granules. This procedure is extensively described in the literature, for example, in U.S. Patent 4,703,717. This technique includes the following uses:

[0151] - A liquid containing an active compound (at least one type of terpene),

[0152] - Porous sugar granules of desired size / weight; and

[0153] - Impregnation device having control means.

[0154] Impregnation devices are commercially available at any homeopathic device shop, such as http: / / www.vanda-france.fr / .

[0155] Advantageously, the granules of the present invention are impregnated with terpene(s) at a ratio of 0.2% to 2%, preferably 0.5%.

[0156] As shown in the Examples section, a typical amount is about 25 grams of terpene per 5,000 grams of xylitol granules, which corresponds to an impregnation rate of 0.5%.

[0157] In a specific implementation of a method for manufacturing cannabinoid and / or nicotine-loaded granules, the granules are first impregnated with a dynamized solution containing at least one terpene, and then loaded with cannabinoid(s) and / or nicotine.

[0158] Optionally, the loaded granules may be coated with a natural gum, for example, gum arabic, immediately after the terpene impregnation step. This optional step is useful for fixing and isolating at least one type of terpene and further helps to solidify the granules.

[0159] additional compounds

[0160] The cannabinoid and / or nicotine-loaded granules according to the present invention may also include at least one additional active compound.

[0161] These active compounds can be selected particularly from mushroom extracts, caffeine, flavonoids, and combinations thereof.

[0162] Mushroom extract is specifically an extract from the following mushrooms:

[0163] - Hydnum lephantum, commonly known as sweet tooth, wood hedgehog, or hedgehog mushroom Hydnum repandum), Basidiomycete of the Hydnaceae family ( Basidiomycete ) Fungus;

[0164] - Lion's mane mushroom, monkey head mushroom, bearded tooth mushroom, satyr's beard, bearded hedgehog mushroom, pom pom mushroom, or Hericium erinaceus, referred to as the bearded tooth fungus belonging to the tooth fungus group ( Hericium erinaceus );

[0165] - Chaga mushroom, that is, from the Hymenochae family, Inonotus obliquus ( Inonotus obliquus );

[0166] - Lingzhi or Ganoderma Lingzhi Ganoderma lingzhi Territory (reishi) also announced as ), Ganoderma ( Ganoderma Polypore fungus belonging to the genus );

[0167] - Coriolus versicala ( Coriolus versicolor ) or polyporous versical ( Polyporus versicolor Trametes Versicala, also announced as ) Trametes versicolor ), polypore mushroom.

[0168] In a specific embodiment, the cannabinoid and / or nicotine-loaded granules according to the present invention further comprise at least one mushroom extract.

[0169] In a specific embodiment, the cannabinoid and / or nicotine-loaded granules according to the present invention further comprise caffeine.

[0170] In a specific embodiment, the cannabinoid and / or nicotine-loaded granules according to the present invention further comprise at least one flavonoid.

[0171] Cannabinoid and / or nicotine-loaded granules may additionally contain additional compounds selected from the group consisting of solubilizers, thickeners, surfactants, coloring agents (especially for granule whitening), flavoring agents, foaming agents, antioxidants, bioadhesive agents, pH modifiers, vitamins, minerals, permeability or penetration enhancers, absorption enhancers, serotonin, caffeine, amino acids, and mixtures thereof.

[0172] Permeability or penetration enhancers and absorption enhancers are added, where present, to improve the absorption of cannabinoids by the individual's mucosal tissues.

[0173] Vitamins are selected particularly from the group consisting of thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, and vitamin K.

[0174] These additional compounds can be added to the granules by impregnation or as part of the sugar coating of the granules.

[0175] Final coating of cannabinoid and / or nicotine-loaded granules

[0176] The final coating of the loaded granules improves the stability of the granules while enabling aesthetic appeal. In particular, if a trace amount of crystalline powder of the cannabinoid isolate is still present around the loaded granules, the final coating can enable the fixation of a trace amount of the powder on the granules.

[0177] In a specific embodiment of the present invention, cannabinoid and / or nicotine-loaded granules are coated with a sugar syrup containing a coloring agent or flavoring agent, natural gum, natural wax, or any combination thereof.

[0178] This optional step makes it possible to obtain bright granules. Additionally, this final coating protects the granules from breakage.

[0179] The technique for obtaining this coating is described above.

[0180] This final coating is an outer layer on the entire surface of the granules with a thickness of less than 10 micrometers. This may specifically include the following:

[0181] - Natural gums, e.g., gum arabic, xanthan gum; or

[0182] - Natural waxes, such as carnauba wax or beeswax; or

[0183] - In the case of sugar coating:

[0184] o Polyol, e.g. xylitol; or

[0185] o Monosaccharides, e.g., glucose or fructose; or

[0186] o Disaccharides, for example, saccharose, lactose, sucrose, or

[0187] - Any combination of these.

[0188] Optionally, the final coating layer may include a coloring agent and / or a flavoring agent.

[0189] The final coating layer may include a colorant selected from suitable synthetic or natural colorants that are widely known to those skilled in the art.

[0190] The final coating layer may also contain flavoring agents selected from synthetic flavor oils and aromatics and / or natural oils. These flavoring agents may be selected from those having one of the following flavors: mint, ginger, anise, cinnamon, peppermint, licorice, honey, vanilla, citrus oils including lemon, orange, grape, lime, and grapefruit, and fruit essences including apple, pear, peach, strawberry, raspberry, cherry, plum, pineapple, and apricot, etc.

[0191] Method for manufacturing cannabinoid and / or nicotine-loaded granules

[0192] The present invention also relates to a method for preparing cannabinoid and / or nicotine-loaded granules as described above, comprising at least the following steps:

[0193] a) a step of adding at least one cannabinoid compound, and / or nicotine, to orally dispersible sugar granules,

[0194] b) Air-drying stage of granules,

[0195] c) a step of repeating the above consecutive steps (a) and (b) at least 20 times,

[0196] d) optionally, a step of coating cannabinoid and / or nicotine-loaded granules with a sugar syrup containing a coloring agent or flavoring agent, natural gum, natural wax, or any combination thereof.

[0197] The step of "adding to orally dispersible sugar granules" may be performed by any technique known to a person skilled in the art. In particular, this step of adding at least one cannabidiol compound and / or nicotine may be as follows:

[0198] - A step of applying an extract containing at least one cannabinoid compound and / or nicotine onto orally dispersible sugar granules; or

[0199] - A step of incorporating at least one cannabinoid compound and / or nicotine onto orally dispersible sugar granules.

[0200] Optional steps may be added at any time during the process described above: for example, a scrubbing step following the terpene(s) impregnation step may be performed before or after the cannabinoid and / or nicotine loading step (a).

[0201] In a specific embodiment of the present invention, a method for preparing cannabinoid and / or nicotine-loaded granules as described above comprises at least the following steps:

[0202] a1) A step of coating orally dispersible sugar granules with sugar syrup, particularly xylitol syrup,

[0203] a2) a step of applying an extract containing at least one cannabinoid compound and / or nicotine onto xylitol-coated granules,

[0204] b) Air-drying stage of granules,

[0205] c) a step of repeating the above consecutive steps (a1), (a2) and (b) at least 20 times,

[0206] d) optionally, a step of further coating the cannabinoid and / or nicotine-loaded granules with a sugar syrup containing a coloring agent or flavoring agent, natural gum, natural wax, or any combination thereof.

[0207] In step (a1), a sugar syrup, such as xylitol syrup, is sprayed onto orally dispersible sugar granules. These granules may have been pre-impregnated with a solution containing at least one type of terpene, preferably a combination of at least two types of terpenes.

[0208] Steps (a1), (a2) and (b) are performed in a coating turbine. These steps are carried out continuously and are repeated at least 20 times, preferably at least 30 times, more preferably at least 40 times, and about 50 times in a preferred manner.

[0209] Step (d) consists of a final sugar-coating of cannabinoid and / or nicotine-loaded granules having a thin outer layer over the entire surface of the granules, comprising:

[0210] - Natural gums, e.g., gum arabic, xanthan gum; or

[0211] - Natural waxes, such as carnauba wax or beeswax; or

[0212] - Sugars containing water and:

[0213] o Polyol, e.g. xylitol; or

[0214] o Monosaccharides, e.g., glucose or fructose; or

[0215] o Disaccharides, for example, saccharose, lactose, sucrose, and

[0216] o Optionally, flavorings and / or colorings, or

[0217] - Any combination of these.

[0218] This step (d) may be repeated at least twice, for example, as follows:

[0219] - Realizing a first sugar-coating step to coat the granules with a flavoring agent;

[0220] - The second coating step is realized with wax to obtain a bright appearance of the cannabinoid and / or nicotine-loaded granules.

[0221] The first sugar-coating step for covering the granules with a flavoring agent can be repeated at least 2 times, at least 5 times, at least 10 times, or at least 20 times or more before performing the second coating step.

[0222] The above coating is performed using a coating turbine. Coating turbines useful for this step are particularly Driam, Glatt, or Manesti type turbines.

[0223] Another implementation of the method according to the present invention is presented in Example 4. This specific method comprises the following steps:

[0224] 1) A step of impregnating orally dispersible sugar granules with at least one type of terpene;

[0225] 2) Step of scrubbing with natural gum;

[0226] 3) A step of loading at least one cannabinoid compound and / or nicotine onto granules;

[0227] 4) A step of coating the granules with a sugar syrup optionally containing a flavoring agent;

[0228] 5) A final coating step of the granules with wax for protection and brightness.

[0229] The present invention also relates to a method for manufacturing cannabinoid-loaded granules comprising at least the following steps:

[0230] a) a step of freeze-drying a solution comprising at least one cannabinoid compound and one sugar,

[0231] b) A step of forming granules from freeze-dried powder, for example, using a tablet press,

[0232] c) optionally, a step of coating cannabinoid-loaded granules with a sugar syrup containing a coloring agent or flavoring agent, natural gum, natural wax, or any combination thereof.

[0233] This method is particularly useful when at least one cannabinoid compound is THC. This method is exemplified in Example 5.

[0234] Uses of the cannabinoid and / or nicotine-loaded granules of the present invention

[0235] The present invention also relates to cannabinoid and / or nicotine-loaded granules for use as medicine, as described above or obtained by any one of the methods described above.

[0236] Cannabinoid and / or nicotine-loaded granules are intended to be administered sublingually. Interestingly, this delivery route of cannabinoid(s) enables rapid onset of cannabinoid(s) through the oral mucosa.

[0237] In another aspect, the present invention relates to granules loaded with cannabinoids and / or nicotine for use in the treatment and / or prevention of chronic pain, inflammatory disorders, mobility disorders, and anxiety disorders.

[0238] As used herein, the terms “to treat,” “treating,” or “treatment” refer to administering a therapy to an individual in an attempt to reduce the frequency and / or severity of symptoms of said individual’s disease, defect, disorder, or adverse pathological condition.

[0239] As used herein, the terms "prevent," "preventing," or "prevention" refer to administering a therapeutic compound to an individual in an attempt to reduce the likelihood of said individual developing a specific disease.

[0240] In a specific embodiment, the present invention relates to nicotine-loaded granules for use in the treatment of tobacco addiction, intermittently or regularly.

[0241] Nutritional supplements and kits containing the same

[0242] The present invention also relates to the use of cannabinoid and / or nicotine-loaded granules as a nutritional supplement, as described above, or obtained by any one of the methods described above.

[0243] As used herein, the term “nutritional supplement” refers to any dietary supplement added to a normal diet intended to provide a substance that is not usually consumed.

[0244] Individuals consuming the above nutritional supplement may be as follows:

[0245] - "Users of cannabinoids for diversion," and / or

[0246] - Individuals who wish to consume doses of nicotine intermittently or regularly.

[0247] The present invention also relates to a kit for use as a nutritional supplement, comprising at least two dispensing devices in a single package, each comprising cannabinoid-loaded granules additionally containing at least one terpene, wherein the at least two dispensing devices are distinguished from one another in that the at least one terpene is different in each dispensing device.

[0248] In a specific embodiment, the kit further includes means for communicating information or instructions regarding the use of the kit.

[0249] In a specific embodiment, the kit comprises cannabidiol-loaded granules.

[0250] As previously mentioned, the optimal daily dose of cannabinoids such as cannabidiol (CBD) is about 25 mg per day, and consequently, in a specific embodiment, the optimal daily dose is five granules each containing 5 mg of CBD.

[0251] According to this last embodiment, the kit user will select five granules to consume during the day, depending on his / her specific needs: concentration, drowsiness, fatigue, energy-load before exercise, etc.

[0252] If the kit contains three dispensing devices, the user can choose to consume two granules from one dispensing device in the morning, one granule from another dispensing device at noon, and two granules from the last dispensing device before going to bed at night.

[0253] Advantageously, the kit of the present invention contains granules sufficient for administration over one week (35 cannabinoid-loaded granules), two weeks (70 cannabinoid-loaded granules), or even one month (more than 140 cannabinoid-loaded granules), and the number of granules is based on a daily dose of 5 granules per day.

[0254] These granules are distributed to at least two dispensing devices, preferably three, four, five, six, or seven dispensing devices.

[0255] Each dispensing device contains about 5, 10, 15, 20, 25, or 30 cannabinoid-loaded granules.

[0256] Examples

[0257] Although the invention herein has been described with reference to specific embodiments, it should be understood that these embodiments are merely illustrative of the principles and applications of the invention. Accordingly, it should be understood that numerous modifications may be made to the exemplary embodiments and that other arrangements may be devised without departing from the spirit and scope of the invention as defined by the appended claims.

[0258] Example 1. Manufacturing process of cannabinoid-loaded granules

[0259] In this experiment, 5 mg of CBD was loaded onto xylitol granules per granule. The xylitol beads used had a diameter of approximately 3.7 mm and a weight of 0.04 g.

[0260] A - Impregnation of granules with a combination of terpenes.

[0261] A solution containing a combination of pure terpenes (myrcene type) such as limonene, α-pinene, linalool, and carophyllene was used in the following proportions:

[0262] - 1 kg of xylitol beads, and

[0263] - 5 g of terpene solution.

[0264] The dynamization of the solution was repeated three times with 300 succusations for 20 seconds. As is widely known to those skilled in the art, a liquid containing an active ingredient is "dynamized" first before impregnation. In homeopathy, "dynamization" refers to vigorously shaking an alcohol solution containing an active compound by a process called "succusation."

[0265] Impregnation is realized using an impregnation machine or a coating turbine.

[0266] By impregnation machine:

[0267] Supply of terpene solution by bead addition

[0268] Mixing: 30 minutes

[0269] Drying time: 20 to 30 minutes

[0270] By the turbine:

[0271] Supply of terpene solution by bead spray (atomization with an automatic spray gun);

[0272] Mixing: 30 minutes;

[0273] Drying time: 20 to 30 minutes (using mini central air treatment); air temperature is less than 40℃.

[0274] At the end of this process, xylitol beads are impregnated with a combination of at least two types of terpenes (in this case, 5 g of terpenes per 1 kg of beads, i.e., 0.5 wt% of terpenes per bead).

[0275] B - Coating of xylitol beads impregnated with terpenes with xylitol syrup and subsequent application of CBD or any other cannabinoid compound

[0276] In this example, to distribute about 5 mg of CBD to each bead, 2 kg of xylitol beads impregnated with terpene (i.e., about 50,000 beads) were used along with 250 g of cannabidiol (CBD).

[0277] First, a 60 Brix xylitol syrup is prepared with 450 g of xylitol and 300 g of water, heated to 80°C, then the temperature of the syrup is lowered to 50 to 60°C, and the concentration of xylitol is adjusted to 60 Brix.

[0278] Once 60 Brix syrup is obtained, xylitol beads are introduced into the turbine for coating.

[0279] Each cycle of CBD coating and application includes the following sub-steps:

[0280] Spray xylitol syrup onto the beads using an automatic spray gun, then mix for about 30 seconds;

[0281] Apply CBD isolate to the beads; and

[0282] The beads are dried by air treating them with "cold" air at a temperature of about 25°C for 3 to 4 minutes.

[0283] Repeat these consecutive steps about 64 times.

[0284] The number of sprays varies depending on the cycle:

[0285] - During the first 10 cycles, administer 8 sprays of xylitol syrup / CBD isolate; during this time, load 4.5 g of xylitol syrup (0.04 liters) and 2.25 g of cannabidiol onto the beads;

[0286] - During 11 to 20 cycles, perform 12 sprays of xylitol syrup / CBD isolate; load 6.75 g of xylitol syrup and 3.375 g of cannabidiol onto beads;

[0287] - From the 21st cycle, 16 sprays of xylitol syrup / CBD isolate are administered, during which 4.5 g of cannabidiol is loaded.

[0288] In this process, 250 g of cannabidiol is gradually introduced onto 50,000 beads.

[0289] Example 2: Additional coating of cannabinoid-loaded granules for flavor, color, and / or brightness

[0290] Advantageously, perform the two steps of "final sugar-coating":

[0291] 1. Coating of xylitol syrup with vanilla flavor (or any other aroma):

[0292] Spray xylitol syrup onto the beads using an automatic spray gun and mix for about 4 minutes;

[0293] Dry the beads with air treatment for about 3 minutes;

[0294] During the final spray, add vanilla flavoring (2 g / kg) to the beads with minimal air;

[0295] Dry the beads

[0296] Repeat this step about 25 times.

[0297] 2. Mix carbauba wax, without any air, with CBD-loaded granules at the following ratio: 500 mg of wax per 1 kg of loaded granules.

[0298] Example 3. Preparation of the kit

[0299] A kit containing xylitol granules loaded with 5 mg of CBD per granule and other active compounds includes 8 dispensing devices.

[0300] Each dispensing device further comprises CBD-loaded granules containing a mixture of terpenes, and the dispensing devices are distinguished from one another in that the mixture of terpenes varies from dispensing device to dispensing device. In this embodiment, each granule contains 0.5 weight% of a terpene mixture.

[0301] Each of the eight distribution devices was designed for a specific use:

[0302] 1) BRAIN FOCUS - "FOCUS"

[0303] CBD-loaded granules further comprise a combination of at least two terpenes selected from alpha-pinene, d-limonene, borneol, and myrcene.

[0304] 2) Sport Booster - "Sport"

[0305] CBD-loaded granules further comprise a combination of at least two terpenes selected from alpha-pinene, d-limonene, terpinolene, menthol, geraniol, and bisabolol.

[0306] 3) Sleep

[0307] CBD-loaded granules further comprise a combination of at least two terpenes selected from alpha-pinene, beta-caryophyllene, humulene, linalool, and myrcene.

[0308] 4) Pain Relief

[0309] CBD-loaded granules further comprise a combination of at least two terpenes selected from alpha-pinene, d-limonene, geraniol, humulene, farnesene, linalool, and myrcene.

[0310] 5) SAFEGUARD Immune System Booster - "IMMUNITY"

[0311] CBD-loaded granules further comprise a combination of at least two terpenes selected from alpha-pinene, d-limonene, beta-caryophyllene, α-phelandrene, linalool, and myrcene.

[0312] 6) Aphrodisiac Stimulant (Sensitive) - "Intimacy"

[0313] CBD-loaded granules further comprise a combination of at least two terpenes selected from alpha-pinene, d-limonene, terpinolene, beta-caryophyllene, humulene, farnesene, linalool, and myrcene.

[0314] 7) Relax

[0315] CBD-loaded granules further contain a combination of at least two terpenes selected from farnesene, beta-caryophyllene, and myrcene.

[0316] 8) "Pure CBD"

[0317] CBD-loaded granules containing a combination of at least two types of terpenes. CBD is called "Pure" because these granules do not contain any cannabigerol (CBG).

[0318] Example 4. Example of an industrial manufacturing process for loaded granules

[0319] Phase 1: Impregnation

[0320] Step 1 - Control

[0321] Air temperature: 20° to 30°

[0322] Humidity measurement: 20% to 35%

[0323] Step 2 - Device Startup

[0324] Granules made of xylitol (5000 g) are placed into a coating device.

[0325] Turn on the device. The mixing speed is set to 30 to 40 rpm (revolutions per minute).

[0326] Step 3 - Inactivation of solution terpene / alcohol

[0327] Mix the following compounds:

[0328] - Natural terpene (approx. 25 g)

[0329] - Ethyl alcohol (approx. 75 g)

[0330] The terpenes and alcohols are mixed by shaking 2 to 6 times / 300 to 500 times.

[0331] Integrating the kinetic solution into the coating device in four steps, and then:

[0332] - Brewing for 10 to 30 minutes

[0333] Drying for 30 to 60 minutes at a temperature of 40℃ to 60℃.

[0334] Part 2: Scrubbing

[0335] Step 1 - Preparation of the main compound (diluted to 2% to 5%)

[0336] · Xylitol powder: Approx. 100 g

[0337] · Distilled water: 25 g to 30 g

[0338] · Gum arabic: 25 g to 30 g

[0339] Step 2 - Preparation of the above sword

[0340] For approximately 100 g of dry powder:

[0341] · Gum arabic: 20 g to 30 g

[0342] · Xylitol powder: 70 g to 80 g

[0343] Blend xylitol powder and gum arabic.

[0344] For approximately 50 ml of solution:

[0345] · Gum arabic: 5g

[0346] · Xylitol powder: 20 g

[0347] · Distilled water: 25 g

[0348] Blend xylitol powder and gum arabic.

[0349] Heat the water to 30° to 45°.

[0350] Mix the powder with water and maintain the temperature.

[0351] Pour the mixture into a coating device and stir for 1 to 5 minutes.

[0352] Pour 100 g of dry powder into the coating device.

[0353] Brewing for about 1 to 5 minutes.

[0354] Dry at 20° to 30°C for about 1 hour.

[0355] Part 3: CBD-CBG Coating

[0356] Step 1 - Raw Material Preparation

[0357] Xylitol powder: 2,700 g to 3,500 g

[0358] Distilled water: 1000 g to 1700 g

[0359] CBD - CBG: Approx. 1400 g

[0360] Step 2 - Preparation of Xylitol Syrup

[0361] · Pour distilled water into the hot beverage machine.

[0362] · Adjust the temperature to 65° to 85°.

[0363] · Pour in the xylitol powder.

[0364] · Check the Brix of the syrup: 60 to 90

[0365] Step 3 - CBD - CBG Coating

[0366] This coating process includes 40 to 70 steps. Each step consists of the following:

[0367] · Pour about 100 ml of xylitol syrup and 20 g of CBD-CBG into the coating device.

[0368] · Mix for about 1 to 5 minutes.

[0369] · Dry at 20° to 30°C.

[0370] Top 4: Xylitol syrup coating

[0371] Step 1 - Raw Material Preparation

[0372] Xylitol powder: 1250 to 1900 g

[0373] Distilled water: 500 to 850 g

[0374] Vanilla flavor: 5 g to 12 g

[0375] Step 2 - Preparation of Xylitol Syrup

[0376] · Pour distilled water into the hot beverage machine.

[0377] · Adjust the temperature to 65° to 85°.

[0378] · Pour in the xylitol powder.

[0379] · Check the Brix of the syrup: 60 to 90

[0380] Step 3 - Xylitol syrup coating

[0381] Refill the granules into the coating device.

[0382] This coating process comprises 10 to 30 steps. Each step consists of the following sub-steps:

[0383] · Pour about 50 ml of xylitol syrup into the coating device.

[0384] · Mix for about 1 to 5 minutes.

[0385] · Dry at 20° to 30°C.

[0386] · Incorporate vanilla flavor between steps 15 and 25.

[0387] Top 5: Protection - Brightness

[0388] Step 1 - Raw Material Preparation

[0389] Carnauba wax: 0.9 g to 2.5 g (for 5000 g)

[0390] Step 2 - Protection - Brightness

[0391] Refill the granules into the coating device.

[0392] · Pour carnauba wax into the coating device.

[0393] · Brewing for about 30 to 60 minutes.

[0394] · Dry at a temperature of 20° to 30°C for about 30 minutes.

[0395] Example 5. Example of another industrial manufacturing process for THC-loaded granules

[0396] This process includes the following steps.

[0397] 1. Preparation of a solution (1) comprising the following:

[0398] · THC (80% concentrated cannabis oil)

[0399] · Food-grade ethyl alcohol

[0400] · terpenes

[0401] - Mix THC oil with ethanol;

[0402] - Incorporate terpenes into a THC and ethanol solution;

[0403] - Next, the solution is homogenized by dynamic mobilization.

[0404] 2. Preparation of the solution (2) made of sugar and water

[0405] - Dilute the polyol and lecithin in water;

[0406] - Heat the water to 70 to 75°C;

[0407] - Mix xylitol into water;

[0408] - Mix lecithin with water;

[0409] - The solution is homogenized by dynamic mobilization.

[0410] 3. Mix Solution 2 into Solution 1:

[0411] - The final solution is homogenized by ultrasonic homogenization;

[0412] - Repeat the above operation until a particle size of 100 to 200 micrometers is obtained.

[0413] 4. Freeze-drying of solution:

[0414] The solution is freeze-dried to produce powder by the following technique:

[0415] - Distribute the solution into the tray.

[0416] - Incubation in a freeze dryer:

[0417] o Freezing for 9 to 12 hours

[0418] o Freeze-drying for 24 to 28 hours

[0419] 5. Preparation and homogenization of the above powder for incorporation into a tablet press.

[0420] The freeze-dried powder is mixed with excipients (mannitol, xylitol, etc.) in the following proportions:

[0421] - 43% freeze-dried powder

[0422] - 57% excipients

[0423] Powder homogenization is performed by dry granulation, a hammer granulator, or a wheel granulator. Particles with a size of 100 to 200 micrometers are obtained.

[0424] 6. Powder molding

[0425] Granules with a diameter of 3 to 4 mm are formed using a tablet press.

[0426] 7. Primary coating of granules

[0427] The coating process consists of 10 to 30 steps.

[0428] Each step consists of the following sub-steps:

[0429] o Add about 50 ml of xylitol syrup (69% xylitol - 31% water) to the coating machine.

[0430] o Stirring for 1 to 5 minutes;

[0431] o Dry at 20° to 30°C.

[0432] 8. Secondary coating of granules for protection and gloss

[0433] - Refill the granules into the coating machine;

[0434] - Add carnauba wax to the granules;

[0435] - Brewing for 30 minutes to 1 hour.

[0436] References

[0437] patent

[0438] US 9,095,563

[0439] WO 2017 / 189375

[0440] WO 2017 / 208072

[0441] WO 2017 / 180707

[0442] WO 2017 / 185038

[0443] WO 2018 / 129097

[0444] US 10,434,084

[0445] US 2018 / 344786

[0446] Bibliographical reference

[0447] Blessing EM, Steenkamp MM, Manzanares J, Marmar CR. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics. 2015 Oct;12(4):825-36.

[0448] Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a constituent of Cannabis sativa. Curr Drug Saf. 2011 Sep 1;6(4):237-49.

[0449] [ PubMed ] Bartner LR, McGrath S, Rao S, Hyatt LK, Wittenburg LA. Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs. Can J Vet Res. 2018 Jul;82(3):178-183.

Claims

Claim 1 A method for manufacturing cannabinoid-loaded granules comprising sugar granules loaded with at least one cannabinoid compound, comprising: a) adding at least one cannabinoid compound to the sugar granules; b) air-drying the granules; c) repeating the consecutive steps (a) and (b) at least 20 times; wherein each sugar granule has a diameter of 2 to 10 millimeters and the loaded granules disintegrate upon contact with saliva to release at least one cannabinoid compound. Claim 2 A method for manufacturing cannabinoid-loaded granules according to claim 1, wherein the sugar granules consist of lactose, saccharose, xylitol, or a mixture thereof. Claim 3 A method for manufacturing cannabinoid-loaded granules according to claim 1, wherein the weight of each of the granules is 30 to 300 milligrams. Claim 4 A method for preparing cannabinoid-loaded granules according to claim 1, wherein at least one cannabinoid compound is selected from the group consisting of cannabidiol (CBD), cannabigerol, trans-Δ9-tetrahydrocannabinol (THC), and mixtures thereof. Claim 5 A method for manufacturing cannabinoid-loaded granules according to claim 1, wherein at least one cannabinoid compound is natural or synthetic. Claim 6 A method for manufacturing cannabinoid-loaded granules according to claim 1, further comprising the step of coating the cannabinoid-loaded granules with a sugar syrup containing a coloring agent or a flavoring agent, a natural gum, a natural wax, or any combination thereof. Claim 7 A method for manufacturing cannabinoid-loaded granules according to claim 1, further comprising the step of sugar-coating the cannabinoid-loaded granules with a sugar syrup and an extract containing at least one cannabinoid compound. Claim 8 In claim 7, an extract containing at least one cannabinoid compound is the plant cannabis sativa L. ( Cannabis Sativa L . ) A method for preparing cannabinoid-loaded granules derived from and comprising at least 95 weight% of the cannabinoid compound. Claim 9 A method for manufacturing cannabinoid-loaded granules according to claim 1, wherein each of the cannabinoid-loaded granules contains at least one cannabinoid compound in a dose of 2 mg to 30 mg. Claim 10 A method for manufacturing cannabinoid-loaded granules according to any one of claims 1 to 9, wherein the cannabinoid-loaded granules are intended for use as a medicament. Claim 11 A method for manufacturing cannabinoid-loaded granules according to any one of claims 1 to 9, wherein the cannabinoid-loaded granules are used for the treatment or prevention of chronic pain, inflammatory disorders, mobility disorders, and anxiety disorders. Claim 12 delete Claim 13 delete Claim 14 delete Claim 15 delete Claim 16 delete