PHARMACEUTICAL COMPOSITIONS COMPRISING CANNABINOIDS.

Abstract

The present invention relates to pharmaceutical compositions comprising one or more cannabinoids and optionally one or more pharmaceutically acceptable carriers, diluents, adjuvants, excipients, or any combination thereof. In particular, the compositions of the present invention comprise a mixture of THC and CBD in varying proportions and are preferably in the form of sublingual tablets, sublingual drops, or soft gelatin capsules.

Description

PHARMACEUTICAL COMPOSITIONS COMPRISING CANNABINOIDS Field of Invention The present invention lies in the field of pharmaceutical compositions containing cannabis derivatives. Specifically, the present invention relates to pharmaceutical compositions comprising one or more cannabinoids and optionally one or more pharmaceutically acceptable carriers, diluents, adjuvants, excipients, or any combination thereof. Furthermore, the present invention provides different pharmaceutical compositions for various dosage forms and routes of cannabinoid administration, such as a sublingual composition comprising cannabinoids. Background of the Invention Cannabis is a genus of flowering plants in the Moraceae family that includes three varieties: Cannabis indica, Cannabis sativa, and Cannabis ruderalis, which exhibit morphological differences. Cannabinoids, terpenoids, and other compounds are secreted by glandular trichomes, which are most abundant in the flower calyxes and bracts. The best known variety is Cannabis sativa L. (hemp), whose derivatives have been used worldwide since ancient times due to their multifunctional characteristics, the most important products of which are: i) oil and proteins, used in food production, ii) fibers, used in the paper and textile industries, and iii) resins, which show many important biological / pharmacological activities in humans. Regarding this latter group, the therapeutic activities of cannabis products have been extensively documented, primarily Cannabidiol (CBD) and Tetrahydrocannabinol (THC), which stand out as analgesic agents among several others. There is evidence of their efficacy in the treatment of neuropathic pain, musculoskeletal spasms, cancer pain, and fibromyalgia, among various other acute and / or chronic pain conditions of moderate intensity that rapidly progress to severe. Currently, morphine (obtained from Papever somniferum) is still one of the most widely used options for relieving pain from various conditions. In this sense, opioids are the primary treatment for severe, acute, chronic, and / or exacerbated pain. They are controlled substances, and their acquisition is regulated under Section I of Article 226 of the General Health Law in Mexico. For their use and distribution, all countries adhere to an international regulatory framework, which means that opioids like morphine are subject to international control under the 1961 Single Convention on Narcotic Drugs, signed in New York and amended by the 1972 Protocol. However, more than 60 million people worldwide lack this option, primarily in situations where the patient's critical condition requires its use as pain management. In countries like Mexico, the supply of pRzrnn / zznz / e / Yi This product covers less than 10% of the total estimated demand (20 tons annually) for therapeutic purposes. Furthermore, there is a 62.4% shortage of medicinal morphine for patients requiring palliative care, which is why the use of opioids and morphine is considered insufficient in our country. Thus, considering the entire spectrum of action of Cannabis in the manifestations of acute and / or chronic pain of moderate to severe intensity, it will be beneficial to develop a product that can be used as an alternative to the use of morphine as an analgesic and that constitutes a formulation capable of providing the patient with a sedative effect, equivalent to that currently provided by opioid products. In this regard, there are publications that refer to the use of cannabinoids for the treatment of various disorders. For example, International Patent Application No. WO2016064987A1 discloses, firstly, an extract comprising a mixture of at least 95% total cannabinoids and at least one terpene / flavonoid, in which the cannabinoids comprise at least four cannabinoids selected from the group consisting of tetrahydrocannabinolic acid (THCa), cannabidiolic acid (CBDa), cannabinolic acid (CBNa), cannabichromenic acid (CBCa), tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), and annabichromene (CBC), which serve to relieve symptoms associated with anxiety, post-traumatic stress disorder, chronic pain or opiate dependence, paralysis, neuropathy, Crohn's disease, inflammatory bowel disorders, and glaucoma, seizures, epilepsy, autism, or cancer. Furthermore, the publication of patent application No. US10206888 B2 addresses a plurality of formulations comprising cannabinoids, terpenes, and flavonoids used to mitigate at least one medical problem. Finally, application MX / a / 2021 / 003832 describes methods and compositions for relieving general and chronic fatigue, restoring energy, regenerating muscles that presented pain, and relieving associated pain by administering a composition that includes caffeine and a cannabis compound. As can be seen, while various technologies exist related to the therapeutic activity of cannabinoid derivatives, these are not focused on providing an analgesic solution for various ailments. Furthermore, none of the compositions proposed to date combine cannabinoids in a way that produces a synergistic and potentiating pharmacological interaction to enhance the analgesic effect and reduce the risk of adverse reactions and toxicity. Summary of the Invention It should be understood that both the following summary and the detailed description are illustrative and explanatory and are intended to provide further explanation of the invention as claimed. Neither the summary nor the descriptions that follow are intended to define or limit the scope of the invention to the particular features mentioned in the summary or in pRzrnn / zznz / e / Yi -3 Description. Rather, the scope of the invention is defined by the appended claims. In certain embodiments, the described embodiments may include one or more of the features described herein. To overcome the disadvantages of the prior art, the present invention provides pharmaceutical compositions containing a therapeutically effective amount of one or more cannabinoids and optionally one or more carriers, diluents, adjuvants, pharmaceutically acceptable excipients, or any combination thereof. Preferably, the cannabinoids contained in the compositions of the present invention may be, for example, phytocannabinoids (obtained from plants) and their subclasses, such as cannabigerol, cannabichromene, cannabidiol, and cannabinol (including tetrahydrocannabinol, for example, A9-THC, A8-THC). Other cannabinoids include cannabicyclol, cannabielsoin, cannabinoldiol, and cannabitriol, among others, as well as mixtures thereof. In another aspect, the pharmaceutical compositions of the present invention comprise therapeutically active cannabinoids obtained from Cannabis sativa, Cannabis indica, Cannabis ruderalis, hybrid forms, their derivatives, and / or any related or genetically modified variety. In a preferred embodiment, the cannabinoids are obtained from Cannabis sativa. In an additional aspect, the pharmaceutical compositions of the present invention are available in different dosage forms, such as oral tablets, chewable tablets, soft gelatin capsules, sublingual drops, sublingual tablets, sublingual solutions, among others. In a more preferred aspect, the present invention further provides a mixture of cannabinoids for the manufacture of pharmaceutical compositions and their use in the treatment of moderate to severe pain generated by diseases such as cancer, irritable bowel syndrome, epilepsy, spinal cord disease, Tourette syndrome, symptoms of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, dystonia, dementia, glaucoma, traumatic brain injury, as well as any disease that presents with a painful condition, acute and / or chronic, of moderate to severe intensity, as well as exacerbations of chronic pain. In one further aspect, the cannabinoid mixtures and pharmaceutical compositions containing them, according to the present invention, provide an appropriate ratio of active agents to achieve a synergistic therapeutic effect while avoiding toxicity. In another aspect, the cannabinoid mixtures and pharmaceutical compositions containing them, according to the present invention, do not present side effects or adverse reactions compared to the administration of opiates, which also helps to improve the quality of life in patients who require analgesic treatment. These and other objectives will be evident to the expert in the technological field to which the present invention belongs, based on the following detailed description, the figures that eRzrnn / zznz / e / Yi -4 accompany it, as well as the attached claims. Detailed description of the invention This description details one or more embodiments incorporating features of the invention. The embodiments described, and references in the specification to an embodiment of the present invention, to an embodiment thereof, to an exemplary embodiment, etc., indicate that the described embodiments may include a particular feature, structure, or characteristic. These phrases do not necessarily refer to the same embodiment. When a particular feature, structure, or characteristic is described in relation to an embodiment, persons skilled in the art may understand that feature, structure, or characteristic in connection with other embodiments, whether or not explicitly described. The description should not be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention. It is understood that, although the terms first, second, etc., may be used herein to describe various elements / steps, these elements / steps shall not be limited by these terms. These terms are used only to distinguish one element from another. For example, a first element could be called a second element, and, similarly, a second element could be called a first element, without departing from the scope of the exemplary forms. As used herein, the singular forms of the invention are intended to include the plural forms, unless the context clearly indicates otherwise. The different aspects of the present invention relate to pharmaceutical compositions or formulations containing a therapeutically effective amount of one or more cannabinoids. For the purposes of this application, the term Cannabinoid or Cannabinoids as used herein means any individually identifiable compound or substance that is synthetically or artificially produced, or that can be obtained by any means from any part of any species of Cannabis plant material, including hybrids, genetically modified species and any other plant variant that occurs artificially or naturally that may contain cannabinoids, such as, but not limited to, roots, leaves, thalli, stems, flowers, buds, nodes, etc. Also included within the scope of this application are Cannabinoids as defined above, which can be obtained from any plant material, Cannabis, and any other artificial or natural plant variant. In a more specific aspect, cannabinoids are obtained from plant material harvested from Cannabis sativa, Cannabis indica, Cannabis ruderalis, hybrid forms, their derivatives, and / or any related or genetically modified variety. Preferably, cannabinoids are collected from the female plant. As used in the present description, cannabinoids are a class of various pRzrnn / zznz / e / Yi -5 chemical compounds that act on the cannabinoid receptors of cells that affect the release of neurotransmitters to the brain. The term cannabinoids includes any cannabinoid receptor ligand and related compounds. Thus, the pharmaceutical compositions or formulations of the present invention may include at least one, and / or any combination of two or more cannabinoids selected from the group comprising: Cannabichromenes, which include: Cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarine (CBCV), cannabicyclovarinic acid (CBCVA), Cannabicyclols, which include: cannabicyclocol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarine (CBLV), Cannabidiols, which include: cannabidiol (CBD), cannabidiol monomethyl ether (CBDM), cannabidiolic acid (CBDA), cannabidiocol (CBD-C1), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), Cannabielsoins, which include: cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), acid Cannabielsoin A (CBEA-A), Cannabigerols: Cannabigerol (CBG), Cannabigerol monomethylether (CBGM), Cannabigerolic acid (CBGA),Cannabinol monomethyl ether (CBGAM), Cannabinol gerovarin (CBGV), Cannabigerovarinic acid (CBGVA), Cannabinols and cannabinodiols, including: Cannabinodiol (CBND), Cannabinodivarin (CBVD), Cannabinol (CBN), Cannabinol methyl ether (CBNM), Cannabinol-C2 (CBN-C2), Cannabinol-C4 (CBNC4), Cannabinolic acid (CBNA), Cannabiorcool (CBN-C1), Cannabivarin (CBV), Cannabitriols, including: 10-Ethoxy-9-hydroxy-delta-6α-tetrahydrocannabinol, 8,9-Dihydroxy-delta-6α-tetrahydrocannabinol, Cannabitriol (CBT), Cannabitriolvarin (CBTV), Delta-8-tetrahydrocannabinols, including: Delta-8-tetrahydrocannabinol (Δδ-THC), Delta-8-tetrahydrocannabinolic acid (Δδ-THCA), Delta-9-tetrahydrocannabinols, Delta-9-tetrahydrocannabinol (THC), Delta-9-tetrahydrocannabinol-C4 (THC-C4), Delta-9-tetrahydrocannabinolic acid A (THCA-A), Delta-9-tetrahydrocannabinolic acid B (THCA-B), Delta-9-20-tetrahydrocannabinolic acid-C4 (THCA-C4), Delta-9-tetrahydrocannabinol (THC-C1),Delta-9-tetrahydrocannabinol (THCA-C1), Delta-9-tetrahydrocannabivarin (THCV), Delta-9-tetrahydrocannabivarinic acid (THCVA). 10Oxo-delta-6α tetrahydrocannabinol (OTHC), Cannabibromanol (CBCF), Cannabifuran (CBF), Cannabiglendol, Cannabiripsol (CBR), Cannbicitran (CBT), Dehydrocannabifuran (DCBF), Delta9-cystetrahydrocannabinol (cis-THC), Trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), 3,4,5,6Tetrahydro-7-hydroxy-alpha-2-trimethyl-9-n-propyl-2,6-methane-2H-1-benzoxocin-5-methanol (OH-isoHHCV), and any salt, enantiomer, isomer, aptamer, free acid or free base, and any mixture thereof. In order to provide a better reference to the expert in the field, examples of cannabinoids included in the pharmaceutical compositions of the present invention include, but are not limited to, cannabinols having the following general chemical structure: eRzrnn / zznz / e / Yi eRzrnn / zznz / e / Y where, Ri is H or C3; R2= H or COOH R3= C1, C3, C4 or C5 in side chain Examples of tetrahydrocannabinols include the most commonly known cannabinoid, tetrahydrocannabinol (THC). The most potent stereoisomer occurs naturally as A9-THC, where the two chiral centers at C-6 and C-10 are in a trans configuration as the ()-trans-isomer, and its stereoisomer is also known as dronobinol. There are seven double-bond isomers on the partially saturated carboxylic ring, including A6a-7-tetrahydrocannabinol, A7-tetrahydrocannabinol, AMetrahydrocannabinol, Δ911-tetrahydrocannabinol, A10-tetrahydrocannabinol, and A6a 10'-tetrahydrocannabinol, using the numbering of dibenzopyran: Another example of cannabinol included in pharmaceutical compositions according to the present invention is tetrahydrocannabivarin (THCv), having a propyl side chain or cannabinols with the following general chemical structure: where, Ri= H or COOH -7R2= C1, C2, C3 or C5 side chain R3= H or CH3 Other examples of cannabinoids included in the compositions of the present invention are, for example, cannabidiol (CBD) and its derivatives, such as (-)-trans.cannabidiol (CBD) or cannabidiolic acid (CBDa). Other examples of cannabinoids included in the compositions of the present invention are cannabichromene (CBC) with the following general chemical structure: eRzrnn / zznz / e / Yi where, Ri= H o COOH R2= C3 or C5 side chain. As described, the cannabinoids used to prepare the compositions of the present invention are obtained from any suitable Cannabis species, such as Cannabis sativa, Cannabis indica, Cannabis ruderalis, hybrid forms, their derivatives, and / or any related or genetically modified varieties or species enriched with the desired and appropriate cannabinoids. For example, a Cannabis species may be selected for its CBDa content or for being predominantly THCa. The methods of extraction or separation of the cannabinoids used according to the present invention may be any known to a person skilled in the art or any suitable method. For example, particular separation or extraction methods may be employed to enrich the desired cannabinoid. Processing methods may likewise be employed to enrich the cannabinoid. Furthermore, the cannabinoids used in the present invention also include the carboxylic acid forms of cannabinoids, or acidic cannabinoids. That is, processes are used to obtain preparations of THCa and CBDa (for example), which do not naturally decarboxylate the cannabinoid acids, such as THCa and CBDa. When acidic cannabinoids are desired for the composition, steps such as heating or drying, which result in the decarboxylation of alkaloids, are avoided or minimized to prevent decarboxylation. Other extraction methods that can be applied include solvent extraction, using solvents such as heptane, butane, hexane, isopropyl alcohol, and solid or supercritical fluid dry ice or CO2. Extraction conditions may vary depending on the required concentrations of acidic cannabinoids. Cold extraction can be used. -8 when the acids are desired. The solvent can be removed from the extract by any known method, including vacuum and / or distillation / evaporation. The resulting extract (cannabis preparation) is usually in the form of an oil or viscous oil. Cannabis oil is generally not heated to obtain cannabinoid acids or compressed “a” forms from the carboxylic acid of the substitutions already discussed. Furthermore, cannabis preparation can be carried out using any known method. For example, the cannabis plant is extracted with a solvent, such as heptane, butane, hexane, isopropyl alcohol, and solid dry ice or supercritical fluid CO2. Extraction conditions can vary depending on the required concentrations of acidic cannabinoids. Cold extraction can be used when acids are desired. The solvent can be removed from the extract by any known method, including vacuum and / or distillation / evaporation. The resulting extract (cannabis preparation) is typically in the form of an oil or viscous oil. Cannabis oil is generally not heated to obtain cannabinoid acids or compressed "a" forms from the carboxylic acid, from the substituents already discussed. In a preferred aspect, the compositions of the present invention can be standardized to contain the desired amount of the required cannabinoid. For example, in a cannabinoid preparation, the amount of the cannabinoid of interest is quantified by laboratory tests, and the amount of cannabinoid preparation to be added to the composition is determined by the results of such tests. The addition of the cannabinoids necessary to make the adjustment is then determined by the initial content. For example, if the amount of cannabinoid preparation contains 50% by weight of a desired cannabinoid, the remaining ingredients are adjusted to achieve the desired composition. In another aspect, the pharmaceutical compositions of the present invention optionally include one or more carriers, diluents, adjuvants, pharmaceutically acceptable excipients or any combination thereof, such as cosolvents, which facilitates the solubilization of the different cannabinoid active principles. In some embodiments of the present invention, a propylene glycol / ethanol system is used to improve the overall solubility of the system, which is enhanced compared to the basic water / propylene glycol system. This proportion scheme improves the solubility of polar compounds by up to 40%. In other embodiments, solubility is further improved by using a ternary mixture of ethanol / propylene glycol / PEG 400, achieving a solubility close to 50% while maintaining the homogeneity of the system in the compositions of the present invention. In preferred embodiments the ethanol / propylene glycol / PEG 400 mixture can be found in the following proportions 20:40:0, 40:20:0, 15:0:25, 25:0:15, 0:20:20, 0:30:30, 15:15:15, 30:10:10, 10:30:10. Other examples, not limited to, of excipients used in accordance with this eRzrnn / zznz / e / Yi -9 invention include buffering agents, such as citric acid; fillers or binders, such as dextrose, preservatives, such as p-hydroxybenzoic acid, propylparaben, methylparaben. Water is used both as a solvent and as a formulation vehicle for the compositions of the present invention. For the purposes of this application, "water" encompasses any type of water, including distilled, purified, filtered, non-ionic, acidic, alkaline, hard (D2O), and any other water variant, as it meets the requirements of the compositions of the present invention. The amount of water used to prepare the compositions and presented as part of the compositions may vary from >0% to <100%. Other types of excipients used for the manufacture of the compositions of the present invention include, but are not limited to, medium-chain oils, for example, coconut oil. In another aspect, the compositions of the present invention comprise single or multiple doses containing about 0.1 mg to about 100 mg of cannabinoids, about 0.5 mg to about 50 mg, about 1.0 mg to about 40 mg, about 2 mg to about 20 mg, about 5 mg to about 15 mg, or about 0.1 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 8 mg, 10 mg, 12 mg, 14 mg, 16 mg, 18 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 75 mg, 80 mg, 100 mg and 125 mg per dose. According to a preferred embodiment, the compositions of the present invention comprise CBN, CBDa, CBD, THC, THCa, or mixtures of CBD (or CBDa) and THC (or THCa). The mixtures of CBD or CBDa and THC or THCa may be, for example, in a THC:CBD ratio of 1:1 w / w or any other mixture. Various proportions of the cannabinoids described herein may be used for different dosage forms. Those skilled in the art will understand that the ratios may be adjusted based on the required pharmacological effects. For example, particular cannabinoids may be enriched and / or purified from a cannabis extract by techniques such as fractional distillation or by adjusting the cultivation of the source plants. The ratio of the enriched / purified cannabinoids contained in the present invention may be adjusted to, for example, 1:1 w / w THC:CBD.In other preferred modalities the proportions include, but are not limited to, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:10 p / p. Those skilled in the art will also understand that the dosage forms of the compositions of the present invention can be any form according to the bioavailability requirements or the patient's needs. Such dosage forms may include, for example, powdered components, mixed or not, with or without the addition of adjuvants; granules, coated tablets, capsules, lozenges, suspensions, syrups, oils, extracts, aerosols, ointments, creams, solutions, sachets, inhalers, among others, for oral administration. eRzrnn / zznz / e / Yi -10ophthalmic, otic, topical, nasal, among others. Other dosage forms may include injectable solutions, for example, solutions administered intramuscularly, intravenously, subcutaneously, or intradermally. In a preferred embodiment, the compositions of the present invention can be found in the form of sublingual tablets, sublingual drops, and / or soft gelatin capsules so that the cannabinoids contained in the formulation are exposed to the sublingual mucosa, thus resisting the action and flow of saliva. This dosage form optionally includes other excipients such as polymers that also have bioadhesive properties in the formulation. The adhesiveness of the pharmaceutical form is achieved through the composition of the formula of the present invention, which establishes hydrogen bonds and electrostatic interaction between the product system and the mucosal membrane. The hydration provided by saliva promotes the persistence of these interactions, ensuring that the primary route of access for the active components is achieved at the desired site of action. It is well known that traditional pharmaceutical forms can be difficult to swallow for patients suffering from nausea and vomiting. Additionally, pain relief becomes vital, as pain can become unbearable in a relatively short time—a timeframe that is inconvenient for the use of analgesics that require gastrointestinal absorption, before the pain begins and becomes acute. Therefore, the use of novel pharmaceutical forms that provide effective relief via rapid administration routes is required. Sublingual administration of morphine has been attempted; however, the resulting data are not adequately controlled and are inconclusive, making the need to find novel pharmaceutical forms and effective analgesics paramount. In another aspect, the present invention provides a mixture of cannabinoids as described herein, which are used for the manufacture of pharmaceutical compositions and medicines for the prevention, treatment and relief of mild to severe pain caused by various diseases, for example cancer, irritable bowel syndrome, epilepsy, spinal cord injury, Tourette syndrome, symptoms of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, dystonia, dementia, glaucoma and traumatic brain injury, or for treatment in its most general sense. EXAMPLES The present invention will now be described with reference to the following examples, which should not be considered as limiting the scope of the present invention, but will only serve to help the person skilled in the art understand its nature and advantages. eRzrnn / zznz / e / Yi Example 1. Evaluation of the acute toxicological profile of Δ-THC and CBD combinations in rats The toxicological profile of the Δ9-THO and CBD combination was determined in different -11 proportions after a single sublingual administration, which, due to the nature of the administration mechanism, could be mixed with the oral ingestion of the treatments. Acute use of the THC:CBD (1:1) combination maintains the toxicological characteristics of THC (action on the CB1 receptor), although by increasing the proportion of CBD in the 1:2 and 1:3 combination, the CB1 cannabinoid toxicological action is lost until reaching a minimum with the 1:5 THC-CBD combination in both vegetative variables (hypothermia and locomotor activity) and behavioral variables (exploratory activity and inactivity time -sedation-). Example 2. Evaluation of the acute toxicological profile of Δ-THC and CBD combinations in rats under subchronic administration regimen The toxicological profile of the ΔΘ-THC and CBD combination in different proportions was determined after a single sublingual administration, which, due to the nature of the administration mechanism, could be mixed with the oral ingestion of the treatments. The THC:CBD (1:1) combination maintains the toxicological characteristics of THC (action on the CB1 receptor), although as the proportion of CBD increases in the 1:2 and 1:3 combinations, the CB1 cannabinoid toxicological action is gradually lost, reaching a minimum with the 1:5 THC-CBD combination in both vegetative variables (hypothermia and locomotor activity) and behavioral variables (exploratory activity and sedation-induced inactivity time). Example 3. Comparative evaluation of the analgesic efficacy of combinations of Δ-THC and CBD in a central sensitization pain model in mice. The central sensitization pain model produced by intraplantar administration of capsaicin elicited transient spontaneous pain-related behaviors (shaking, licking, and shielding) that allowed for the evaluation of the analgesic effect of combinations of Δ-THC and CBD in different ratios. The capsaicin sensory nerve activation model is attractive because the underlying molecular events involved form the basis of the current understanding of various types of chronic pain in humans, such as low back pain. The results obtained when comparing the analgesic efficacy of the ΔTHC and CBD combinations indicated that while all of them cause a reduction in behaviors indicative of pain (individual and cumulative), the corresponding proportions 1:1, 1:2, 1:3 and 1:5 (THC:CBD) cause a significant reduction in such behaviors, therefore greater therapeutic value in the treatment of pain induced by central sensitization. Example 4. Characterization of the pharmacokinetic properties of Δ-THC and CBD in combinations in male Winstar rats. Blood levels of THC and CBD after a single oral mucosal administration showed faster absorption properties (Tmax) than that described for the traditional oral route in the range of THC:CBD combinations from a 1:1, 1:2, 1:3 ratio up to eRzrnn / zznz / e / Yi -121:5. For its part, although the administered dose of THC was essentially the same in the four combinations, an increase was observed in the bioavailability indicator parameters (Cmax and AUC), as the proportion (dose) of CBD increased in the THC:CBD 1:2, 1:3 and 1:5 combinations. Example 5. Sublingual drops that include the THC:CBD mixture - Manufacturing process Weigh Tetrahydrocannabinol in a 50 mL volumetric flask Weigh Cannabidiol in a 50 mL volumetric flask Adjust the weight according to the purity of the active ingredients Add 25 ml of medium-chain triglyceride oil, measured with a graduated cylinder, to each flask. Heat the flask containing cannabidiol and the flask containing tetrahydrocannabinol for 2 minutes at a low temperature. Shake and homogenize the two flasks, let stand for 5 minutes and bring to volume with medium chain triglyceride oil Transfer the above solutions to a 500 mL stainless steel container Measure 100 mL of medium-chain triglyceride oil with a graduated cylinder and add it to the previous mixture. Mix for 5 minutes with a mixer Take 10 mL of sample for analysis using a volumetric pipette Empty 10 mL of the mixture into each of the amber dropper bottles Label samples Analyze finished product Package in secondary packaging and subsequently in cardboard boxes. Store at a temperature not exceeding 30°C and relative humidity not exceeding 65%, protect from light. - eRzrnn / zznz / e / YiAi formulation 1:1 dilution Each milliliter contains: Tetrahydrocannabinol 25 mg, Cannabidiol 25 mg, Medium chain triglyceride oil q.s. Dilution 1:2 Each milliliter contains: Tetrahydrocannabinol 25 mg, Cannabidiol 50 mg, Medium chain triglyceride oil q.s. -13 Dilution 1:3 Each milliliter contains: Tetrahydrocannabinol 25 mg, Cannabidiol 75 mg, Medium chain triglyceride oil q.s. eRzrnn / zznz / e / Yi Dilution 1:5 Each milliliter contains: Tetrahydrocannabinol 25 mg, Cannabidiol 125 mg, Medium chain triglyceride oil q.s.

Claims

1. A pharmaceutical composition characterized in that it comprises: one or a mixture of two or more cannabinoids in a therapeutically effective amount, which are obtained from Cannabis plant material and, optionally, one or more pharmaceutically acceptable carriers, diluents, adjuvants, excipients or any combination thereof, wherein the composition is adapted to be administered in a dosage form that exposes the cannabinoids contained in the formulation to the sublingual mucosa, so as to resist the action and flow of saliva or other pharmaceutical dosage forms.

2. The composition according to claim 1, characterized in that the cannabinoids are selected from the group consisting of Cannabichromenes, which include: Cannabichromene (CBC), Cannabichromenic acid (CBCA), Cannabichromevarine (CBCV), Cannabicyclovarinic acid (CBCVA), Cannabicyclols, which include: Cannabicicol (CBL), Cannabicyclolic acid (CBLA), Cannabicyclovarine (CBLV), Cannabidiols, which include: Cannabidiol (CBD), Cannabidiol monomethyl ether (CBDM), Cannabidiolic acid (CBDA), Cannabidiocol (CBD-C1), Cannabidivarin (CBDV), Cannabidivarinic acid (CBDVA), Cannabielsoins, which include: Cannabielsoic acid B (CBEA-B), Cannabielsoin (CBE), Cannabielsoin A (CBEA-A) , Cannabigerols: Cannabigerol (CBG), Cannabigerol monomethylether (CBGM), Cannabigerolic acid (CBGA), Cannabigerolic acid monomethylether (CBGAM), Cannabigerovarin (CBGV), Cannabigerovarinic acid (CBGVA), Cannabinols and cannabinodiols, including: Cannabinodiol (CBND), Cannabinodivarin (CBVD),Cannabinol (CBN) 8,9-Dihydrox¡-delta-6a-tetrahydrocannabinol, Cannabitriol (CBT), Cannabitriolvarin (CBTV), Delta-8-tetrahydrocannabinols, including: Delta-8-tetrahydrocannabinol (Δδ-THC), Delta-8-tetrahydrocannabinolic acid (Δδ-THCA), Delta-9tetrahydrocannabinols, Delta-9-tetrahydrocannabinol (THC), Delta-9-tetrahydrocannabinol-C4 (THC-C4), Delta-9-tetrahydrocannabinolic acid A (THCA-A), Delta-9-tetrahydrocannabinolic acid B (THCA-B), Delta-9-20 tetrahydrocannabinolic acid-C4 (THCA-C4), Delta-9-tetrahydrocannabinol (THC-C1), Delta-9-tetrahydrocannabinol (THCA-C1), Delta-9-tetrahydrocannabivarin (THCV), Delta-9-tetrahydrocannabivarinic acid (THCVA). 10Oxo-delta-6a tetrahydrocannabinol (OTHC), Cannabicromannon (CBCF),Cannabifuran (CBF), Cannabiglendol, Cannabiripsol (CBR), Cannbicitran (CBT), Dehydrocannabifuran (DCBF), Delta-9-cystetrahydrocannabinol (cis-THC), Trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), 3,4,5,6-Tetrahydro-7-hydroxy-alpha-2-1 / n-methyl-9-n-propyl-2,6-methane-2H-1-benzoxocin-5-methanol (OH-isoHHCV), and any salt, enantiomer, isomer, aptamer, free acid or free base, and any mixture thereof. eRzrnn / zznz / e / Yi, 3. The composition according to claim 1, characterized in that the single or multiple doses contain about 0.1 mg to about 100 mg of cannabinoids, about 0.5 mg to about 50 mg, about 1.0 mg to about 40 mg, about 2 mg to about 20 mg, about 5 mg to about 15 mg, or about 0.1 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 8 mg, 10 mg, 12 mg, 14 mg, 16 mg, 18 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 75 mg, 80 mg, 100 mg and 125 mg per dose.

4. The composition according to claim 1, characterized in that the plant material is obtained from varieties of Cannabis sativa, Cannabis indica, Cannabis ruderalis, hybrid forms, their derivatives and / or any related or genetically modified variety.

5. The composition according to claim 1, characterized in that it is in the form of sublingual drops, sublingual tablets and soft gelatin capsules, adapted to be administered orally.

6. The composition according to claim 1, characterized in that it is further in the form of powdered components, mixed or not, with or without the addition of adjuvants; granules, dragees, tablets, capsules, lozenges, suspensions, syrups, oils, extracts, aerosols, ointments, creams, solutions, sachets, inhalers; adapted to be administered orally, ophthally, otically, topically or nasally.

7. The composition according to claim 1, characterized in that it is further in the form of an injectable solution, adapted to be administered via intramuscular, intravenous, subcutaneous or intradermal routes.

8. A mixture of two or more cannabinoids for the manufacture of the composition according to claim 1, wherein said mixture comprises Δ-THC and CBD in a ratio of 1:1, 1:2, 1:3 and 1:

5.

8. The mixture according to claim 7 for use in the prevention, treatment and relief of moderate to severe pain caused by diseases such as cancer, irritable bowel syndrome, epilepsy, spinal cord disease, Tourette syndrome, symptoms of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, dystonia, dementia, glaucoma, traumatic brain injury, as well as any disease that presents with a painful condition, acute and / or chronic, of moderate to severe intensity, as well as exacerbations of chronic pain, or for use in the prevention, treatment and relief of general pain.