Method for producing plant extract

Abstract

The present invention generally relates to a method for producing a plant extract(s), preferably a cannabis plant extract. In particular, the present invention relates to a method for producing a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant comprising a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to separate the cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from the flower material. Furthermore, the present invention relates to a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) produced / obtained by the method described herein. Furthermore, the present invention relates to a cannabis plant extract produced / obtained by the method described herein for use in medicine. Furthermore, the present invention relates to a cannabis plant extract produced / obtained by the method described herein for use in the treatment and / or prevention of chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain and complex pain syndrome.

Description

[Technical field]

[0001] The present invention generally relates to a method for producing a plant extract(s), preferably a Cannabis plant extract. In particular, the present invention relates to a method for producing a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from the flower material. The present invention relates to a method comprising the steps of:

[0002] Further, the present invention relates to a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) produced / obtained by the methods described herein.Further, the present invention relates to a cannabis plant extract produced / obtained by the methods described herein for use in medicine.Further, the present invention relates to a cannabis plant extract produced / obtained by the methods described herein for use in the treatment and / or prevention of chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain or complex pain syndrome. [Background technology]

[0003] Cannabis has long been known as a medicinal plant. However, it was only in the 19th century that it began to be more systematically studied and used in medicine. Shortly thereafter, however, in the early 20th century, research on cannabis was again largely halted, as its psychoactive effects and associated abuse were deemed to outweigh its benefits as a medicinal source. Today, cannabis is still considered an illegal drug in most jurisdictions and is therefore subject to extensive legal restrictions. More recently, changes in the perception of its risk profile as a drug of abuse have partially relaxed said legal restrictions in some parts of the world.

[0004] The main active substances that make cannabis meaningful as a medicinal herb are the cannabinoids. Cannabinoids are a class of substances derived from the cannabis plant. One of the most relevant cannabinoids is the psychoactive delta-9-tetrahydrocannabinol (THC). However, to date, more than 100 cannabinoids have been identified in the cannabis plant, many of which lack psychoactive properties. Most of these cannabinoids, like THC, are poorly soluble in water but are highly soluble in organic solvents such as hydrocarbons and alcohols. Many cannabinoids, especially mixtures of cannabinoids with additional substances found in the cannabis plant, have been the subject of research for several medical indications, including but not limited to neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain (Bridgeman, MB & Abazia, DT, “Medical Cannabis: History, Pharmacology, and implications for the acute care setting”, P&T 42(3), 2007, pp. 180-188).

[0005] More specifically, cannabis extracts derived from plants have been found to be superior to placebo in relieving pain in patients with multiple sclerosis, spinal cord injuries, brachial plexus injuries, and limb amputations due to neurofibromatosis. Both THC and cannabidiol (CBD) have been found to be effective, either alone or in a 1:1 CBD:THC ratio (Wade, DT et al., Clin. Rehabil. 2003, 17(1), pp. 21-29).

[0006] Similar results were obtained using the whole plant extract compared to THC and placebo, although the whole plant extract was observed to be slightly more beneficial than THC in treating pain and spasms in patients with multiple sclerosis, although this was not statistically significant (Zajicek J et al., Lancet. 2003, 362(9395), pp. 1517-1526).

[0007] This led to further research into the complex interactions of some cannabinoids with other substances in the cannabis whole plant extract, which revealed that CBD exerts antinociceptive and antihyperalgesic effects, leading to pain relief in rat models. More mechanism-oriented studies argued that further constituents of the extract, such as terpenes and flavonoids, may contribute synergistically to this activity of CBD. It was also found that the pain-relieving effects of cannabis are induced not only by its antinociceptive properties, but also by its anti-inflammatory properties (Comelli F. et al., Phytotherapy Research 2008, 22(8), pp. 1017-1024).

[0008] Therefore, both the anti-inflammatory activity and the complex interactions between the main cannabinoids (such as THC - in the form of its acid tetrahydrocannabinolic acid (THC(A)) and cannabidiol (CBD)) and other components of cannabis extracts were further investigated. The results showed that THC(A) appears to be the main anti-inflammatory at high doses, while CBD has anti-inflammatory effects only at low doses and cytotoxic effects at high doses. Furthermore, in cell culture models using HCT116 cells and CaCO2 cells, cannabis extracts were found to be even more active in reducing inflammation than single cannabinoids alone, although there is already a difference in activity when comparing extracts of fresh and roasted cannabis flowers. Cannabis extracts were fractionated, but there was no dedicated knowledge as to which of the individual compounds in the fractions actually contributed to the primary activity attributed to either CBD and / or THC(A) (Nallathambi R. et al., Cannabis and Cannabinoid Research 2017, 2(1), pp. 167-182).

[0009] Today, it is certain that these cytotoxic (and therefore potentially relevant for cancer treatment) and anti-inflammatory activities are not substantially derived only from the main constituents THC(A) and / or CBD. The aforementioned terpenes also contribute, but vary greatly depending on the specific variety of the cannabis plant (Gallily R. et al., Cannabis and Cannbinoid Research 2018, 3(1), pp. 282-290). In particular, it has been established from plant physiology that cannabis plants, preferably containing CBD, can be differentiated from varieties containing mainly THC(A) also based on the pattern of associated terpenes. Thus, certain cytotoxic effects and possibly other effects (such as anti-inflammatory or anti-nociceptive / anti-hyperalgesic effects) that are derived mainly from CBD and / or THC(A), respectively, are influenced by a specific set of terpenes associated with such main cannabinoids. For example, CBD is active as a cytotoxic agent and is related to the terpenes guaiol and α-bisabolol, which are active only in combination with the dominant phytocannabinoids, while the activity of the major phytocannabinoids can only be increased by these specific terpenes, which has been called the "interentourage effect" of phytocannabinoids (Namdar D. et al., Molecules 2019, 24(3031), pp. 1-17).

[0010] Therefore, research has been carried out on processes for extracting pharmaceutically active substances from cannabis plants. What is desired is a maximum yield of cannabinoids, and optionally terpenes, terpenoids, and / or flavonoids. Moreover, when applied as a pharmaceutical agent, it is beneficial to maintain the relative concentrations of the pharmaceutically active substances so as to preserve potential synergistic effects between the substances. At the same time, it is usually desirable to remove solids and waxes to obtain a pure extract that can be subjected to further purification and / or chemical processing. Several cannabis plant extracts and corresponding uses have been described, but not necessarily accompanied by specific production methods (e.g., WO 2020 / 006598 and WO 2020 / 006599).

[0011] The above objectives are further constrained by general, environmental and economic boundary conditions: for example, it is beneficial to minimize the amount of (organic) solvents and / or energy during the preparation of the extract.

[0012] Thus, sophisticated separation techniques are being evaluated (for example as described in WO 2002 / 064109) using supercritical CO2 as a solvent that can be removed from the final product without (pharmacologically) relevant residues. DE 10337458 A1 discloses a process for extracting a mixture of pharma-ceutical active substances from cannabis plant material using liquid CO2. According to DE 10337458 A1, the use of liquid CO2 is superior to supercritical CO2 since it can improve the separation of wax from the whole plant material mixture. However, when using liquid CO2 or supercritical CO2, special equipment is required to generate and control the high pressure required to work with liquid or supercritical CO2. Furthermore, in order to remove the aforementioned waxes, the process described in DE 10337458 A1 requires a post-treatment of the obtained extract by subjecting it to a treatment with ethanol in a ratio of 2:1 (ethanol to extract) for about 48 hours at -20°C.

[0013] The post-treatment step in DE 10337458 using ethanol (or any other alcoholic solvent at low temperature) is commonly referred to as "winterization" (which is also necessary in processes using supercritical CO2 such as described in WO 2002 / 064109, or any other extraction process using organic and / or alcoholic extraction of cannabis plant material such as for example WO 2013 / 165251).

[0014] Therefore, regardless of the solvent used, all extraction processes that utilize the principle of containing cannabinoids in the extract require subsequent removal of said waxes from the extract by winterization or similar post-processing techniques.

[0015] Alternative extraction techniques are also known, which reverse the principle and extract water-soluble substances from plant material, producing a (necessarily solid) residue rich in cannabinoids. These have been the subject of improvements and related publications, but have a different objective than obtaining a product that can be easily used in a regulated pharmaceutical context. For example, a process has been described that uses cut cannabis plants or cut cannabis flowers, which have been removed from the stems and leaves of the plant, and exposed to cold water in a semi-permeable bag (Cervantes, J., "Marijuana Horticulture, the indoor / outdoor medical grower's bible", Van Patten Publishing 2006, p. 402; "Ice-O-Lator instructions"). However, these techniques do not remove the wax from the fraction containing the cannabinoids.

[0016] Thus, the removal of said waxes from the associated oil phase has become a real problem in the production of cannabis plant extracts. From the above, it is clear that there remains a need for improved processes for producing extracts from cannabis plants suitable for subsequent pharmaceutical use. Such processes should maximize the content of pharma-ceutically active cannabinoids (or their precursors) and maintain their relative concentrations to each other. In other words, the extract is preferably substantially free of waxes and other non-specific lipophilic materials, but contains substantially all the cannabinoids naturally present in the plant, most preferably in substantially the same ratio as they are present in the intact cannabis plant. In the context of the present invention, the extract, preferably the cannabis plant extract or cannabis plant soft extract obtained by the method described herein, preferably contains less than 3% by weight, less than 2.1% by weight, or less than 2% by weight of wax.

[0017] Furthermore, for environmental, commercial and pharmaceutical reasons, the process should involve minimizing the use of solvents and energy.Therefore, there is a need for improved means and methods for the production of cannabis plant extracts. Summary of the Invention

[0018] The technical problem underlying the present invention is to provide improved means and methods for producing cannabis plant extracts.

[0019] The technical problem is solved and the aforementioned needs are addressed by the definition of the embodiments characterized in the claims and provided herein below.

[0020] The present invention relates to a method for producing a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to separate a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from the flower material and the solvent. The present invention relates to a method comprising the steps of:

[0021] Furthermore, the present invention relates to a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) obtained / produced by the method described herein. The cannabis plant extract obtained by the method described herein may also be referred to as cannabis plant extract (hereinafter also referred to as "cannabis plant soft extract").

[0022] The method according to the invention is characterized in that the plant material used is treated in such a way that the material entering the subsequent alcohol and / or organic extraction step is mainly or preferably exclusively composed of flowers / floral material. In the context of the present invention, the term "mainly consisting of" is understood in such a way that at most 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% or 20% of the weight of the plant material is plant material such as leaves, roots, etc. In other words, the term "mainly consisting of" means that at most 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the weight of the plant material is floral material.

[0023] The present invention solves the above identified technical problem since, as described herein, a method has been surprisingly and unexpectedly found that eliminates the need for a winterization step. Thus, the present invention relates to a method for producing a cannabis plant extract without a winterization step. In other words, the present invention relates to a method for producing a cannabis plant extract that does not include a winterization step. The absence of a winterization step reduces the amount of (organic) solvent required for the production of the cannabis plant extract. Furthermore, the absence of a winterization step reduces the amount of energy required for the production of the cannabis plant extract. Despite the absence of a winterization step, the cannabis plant extract or cannabis plant soft extract produced / obtained by the method described herein contains an excellent concentration of pharmaceutically active substances such as cannabinoids. Despite the absence of a winterization step, the cannabis plant extract produced / obtained by the method described herein contains an excellent concentration of THC (such as at least about 70 weight percent of the cannabis plant extract). Furthermore, the cannabis plant extract produced by the method described herein contains an excellent and highly desirable concentration of pharmaceutically active substances relative to each other. In addition, the cannabis plant extract produced by the methods described herein does not contain saponifiable substances or contains only very small amounts (e.g., less than about 8% by weight of the extract). Thus, the cannabis plant extract produced by the methods described herein is a readily medicamentally usable extract.

[0024] This is particularly surprising since the methods described herein use cannabis flowers / flower material, which typically contains the highest amounts of wax as well as cannabinoids. It was therefore entirely unexpected and surprising that the winterization step could be omitted without affecting the quality of the cannabis plant extract obtained. Furthermore, the methods described herein allow for the production of cannabis plant extracts with excellent THC concentrations (such as at least about 70 weight percent of the weight of the cannabis plant extract) using ethanol as a solvent. The use of ethanol allows for the use of simpler equipment, for example, compared to supercritical CO2 used in prior art methods. [Brief description of the drawings]

[0025] [Figure 1] The cannabis plant soft extract obtained by the method described herein was analyzed as described in section 6 of the Examples section. D9-THC = Delta-9-THC DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] The method described herein allows for the production of cannabis plant extracts with a desired concentration of pharma- ceutical active substances. The method described herein allows for the production of cannabis plant extracts with a desired concentration of cannabinoids. Thus, the method described herein allows for the production of cannabis plant extracts with a desired concentration of CBD and / or THC(A), preferably delta-9-tetrahydrocannabinol. The method described herein allows for the production of cannabis plant extracts with a desired concentration of cannabinoids (preferably delta-9-tetrahydrocannabinol) and / or terpenes. The method described herein advantageously allows for the production of cannabis plant extracts with a desired concentration of pharma- ceutical active substances as described herein and mentioned above, without or with very low amounts of undesirable waxes. Surprisingly and unexpectedly, the method described herein allows for the production of said cannabis plant extracts without a winterization step.

[0027] The present invention will now be described in further detail.

[0028] In particular, the present invention relates to the following:

[0029] [1] A method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from the flower material. The method includes:

[0030] [2] The method of claim 1, wherein the method further comprises evaporating the solvent from the liquid cannabis plant extract to concentrate the extract.

[0031] [3] The method of claim 2, further comprising heating the concentrated cannabis plant extract to a temperature of 50°C to 150°C, preferably 80°C, under reduced pressure, preferably at a pressure of 175mbar to 195mbar, more preferably at a reduced pressure of about 185mbar, to decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC).

[0032] [4] The method according to any one of items 1 to 3, wherein the cannabis plant contains delta-9-tetrahydrocannabinol (THC) in an amount of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or preferably 10 percent (w / w) by dry weight.

[0033] [5] A method according to any one of paragraphs 1 to 4, wherein the drying step of the flower material of the cannabis plant as defined in step (b) of paragraph 1 is carried out at a temperature range of 20°C to 35°C for at least four days (96 hours) or until the moisture content of the flower material is less than 10 percent.

[0034] [6] The process step defined in step (c) of item 1 is: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) maceration for about 24 hours at a temperature between 15°C and 25°C, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) a percolation step, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material. The method according to any one of items 1 to 5, comprising:

[0035] [7] The method according to any one of items 1 to 6, wherein the separation step defined in step (v) of item 6 comprises filtering the cannabis plant extract at a sedimentation velocity of 1.5 μm.

[0036] [8] The method according to any of items 1 to 7, wherein the solvent is selected from the group consisting of ethanol, butanol, alkanes (such as pentane, heptane, and propane), ethyl ether, tertbutyl-methyl-ether, methyl-ethyl-ketone, acetone, ethyl acetate, and CO2, preferably ethanol, more preferably pharmaceutical grade 96% by volume ethanol.

[0037] [9] The method according to any one of items 1 to 8, wherein the cannabis plant is DKJ127 (deposited with the European Plant Varieties Office under application number A202104053).

[0038]

[10] The method according to any one of items 1 to 9, wherein the method does not include a winterization step.

[0039]

[11] A cannabis plant extract containing delta-9-tetrahydrocannabinol (THC), obtained by the method according to any one of items 1 to 10.

[0040]

[12] The cannabis plant extract according to item 11, wherein the plant extract is in liquid form.

[0041]

[13] The cannabis plant extract according to items 11 or 12, wherein the plant extract is in solvent-free, decarboxylated form.

[0042]

[14] The cannabis plant extract according to any of items 11 to 13, or the cannabis plant extract obtainable by the method according to any of items 2 to 10, wherein the cannabis plant extract comprises delta-9-tetrahydrocannabinol (THC) in an amount of at least about 50, 60, or 70 percent by weight of the extract, preferably between about 60 and 80 percent by weight of the extract, more preferably between about 70 and 74 percent by weight of the extract.

[0043]

[15] The cannabis plant extract according to any of items 11 to 14, or the cannabis plant extract obtainable by the method according to any of items 1 to 10, wherein the cannabis plant extract further comprises one or more terpenes selected from the group consisting of α-bisabolol, guaiol, and β-caryophyllene.

[0044]

[16] A cannabis plant extract according to any of items 11 to 15, or a cannabis plant extract obtainable by the method according to any of items 1 to 10, for use in medicine.

[0045]

[17] The cannabis plant extract according to any of items 11 to 15, or the cannabis plant extract obtainable by the method according to any of items 1 to 10, for use in the treatment and / or prevention of chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain, or complex pain syndrome.

[0046]

[18] A method for treating and / or preventing chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain, or complex pain syndrome comprising administering a cannabis plant extract according to any of items 11 to 15, or obtained by a method according to any of items 1 to 10.

[0047] Any disclosure in the context of the methods of the invention described herein is applicable to the corresponding uses, and vice versa.

[0048] As mentioned above, the present invention relates to a method for producing a plant extract, which means that the extract is produced / obtained from a plant material. In other words, the plant extract is produced / obtained by extracting the plant material according to the methods described herein. In particular, the present invention relates to a method for producing a cannabis plant extract(s), which means that the extract is produced from a cannabis plant. In other words, the cannabis plant extract is produced by extracting the cannabis plant material according to the methods described herein.

[0049] The present invention therefore relates to a method for producing an extract of a cannabis plant, comprising the steps of: (a) providing a cannabis plant, preferably containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to separate the cannabis plant extract from the flower material. The present invention relates to a method comprising the steps of:

[0050] The present invention also relates to a method for producing a cannabis plant extract comprising the steps of: (a) providing a cannabis plant, preferably containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material to obtain a trimmed and dried plant material; and (c) treating the flower material of step (b) with a solvent to separate the cannabis plant extract from the flower material. The present invention also relates to a method comprising the steps of:

[0051] The present invention further provides a method for producing a cannabis plant extract comprising the steps of: (a) providing a cannabis plant, preferably containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to separate the cannabis plant extract from the mixture of flower material and solvent. where The processing step defined in step (c) is the next step: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) maceration for about 24 hours at a temperature between 15°C and 25°C, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) a percolation step, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material. The present invention relates to a method comprising the steps of:

[0052] In the context of the present invention, it is envisaged that steps (i) to (v) are carried out in sequential order.

[0053] In the context of the present invention, the term "plant" refers to any photosynthetic eukaryotic multicellular organism belonging to the kingdom Plantae that produces an embryo, contains chloroplasts, has a cellulose cell wall, and lacks the ability to move. As used herein, "plant" includes any plant or part of a plant at any stage of development, and its progeny, that contains cannabinoids, terpenes, and terpenoid compounds. The plant material can be obtained from, but is not limited to, solid plant material. The solid plant material can be obtained from the whole plant or a part thereof, including, but not limited to, plant cells, plant organs, leaves, stems, fruits, roots, meristems, plant seeds, protoplasts, calli, and any group of plant cells organized into a structural and / or functional unit. Alternatively, the plant material can be a plant cell culture, specifically a plant suspension cell culture in a liquid medium. Methods for establishing in vitro plant cell cultures from solid plant material are known to those skilled in the art and include callus formation (Espinosa-Leal et al., Planta (2018), 248, pp. 1-18). It will be clear to those skilled in the art that what is described herein for plants in general can also be applied to cannabis plants.

[0054] "Cannabis plant" may be used interchangeably with "Cannabis plant material". Any part of the cannabis plant may be used, including but not limited to trichomes, flower buds, flower bracts, leaves, stems, and any other plant parts that may contain cannabinoids. Preferred cannabis plant parts that contain cannabinoids are flowers, trichomes, and sugar leaves. Also, both female plants (including "feminized plants") and male plants may be used, although female plants may produce higher concentrations of cannabinoids than male plants. The terms "flower / blossom" and "flower material" may be used interchangeably herein. Those skilled in the art know that in cannabis plants, flowers are arranged in so-called colas. Thus, flower material as used herein shall also refer to said colas.

[0055] The leaves of the cannabis plant can be differentiated into fan leaves and sugar leaves. Fan leaves are the large, primary leaves of the cannabis plant. Sugar leaves develop and emerge during the flowering stage of the cannabis flower. As described in detail below, said sugar leaves or parts thereof can be removed from the flower material by the methods described herein.

[0056] Trichomes (i.e. resin glands) of cannabis plant material are almost microscopic mushroom-like projections that protrude from the surface of the cannabis plant, mainly from the surface of the flower buds. Although relatively complex, trichomes are mainly composed of a stem and a head. The production of cannabinoids, such as THC, occurs mainly in the head of the trichome. The cannabinoids are concentrated in the trichomes of the plant. It is therefore clear to the skilled person that all the methods described herein can be carried out using (isolated) trichomes of the cannabis plant. The isolation of trichomes can be carried out as described in the prior art (e.g. Cerantes, J., "Marijuana Horticulture, the indoor / outdoor medical grower's bible", Van Patten Publishing 20 "6, p. 402; "Ice-O-Lator Instructions").

[0057] In the present invention, when a cannabis plant is used in the methods described herein, the plant material is preferably obtained from the flowers of the plant. Moreover, in the context of the present invention, the plant material used in the methods described herein may be obtained from a natural plant or a genetically modified plant.

[0058] In the context of the present invention, the plant material used to obtain the extract may be fresh, dried, freeze-dried or frozen, but is preferably dried.

[0059] As used herein, "drying" means that the water / moisture in the plant material is reduced. Drying of the plant material can be accomplished by any means, such as by placing the plant material on trays with air flow in a drying chamber at a temperature ranging from 20°C to 35°C (i.e., 20°C, 21°C, 22°C 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, or any part thereof) for at least 1 day, 2 days, 3 days, or 4 days, preferably 4 days (96 hours), or until the moisture content of the flower material is less than 10 percent. Those skilled in the art know how to measure temperature by standard methods. Furthermore, those skilled in the art know how to determine the moisture content of plant material, particularly dried cannabis flowers (e.g., as described in the European Pharmacopoeia 10th Edition, Chapter 2.2.32). Thus, the drying step of the flower material of the cannabis plant as defined in step (b) of the method described herein may be carried out, for example, by placing the plant material, preferably the flower material, in a drying chamber on a tray through which air flows, at a temperature in the range of 20°C to 35°C (i.e. 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, or any portion thereof) for at least 1 day, 2 days, 3 days, or 4 days, preferably 4 days (96 hours), or until the moisture content of the flower material is less than 10 percent.

[0060] Preferably, the plant material is trimmed. Thus, the floral material used in the methods described herein is trimmed.

[0061] As used herein, the term "trimming the floral material" means that the leaves, particularly the sugar leaves and / or fan leaves, are removed from the flowers. In particular, the visible parts of the sugar leaves protruding from the flower are cut off. Trimming the floral material can be carried out as follows:

[0062] The flowers of the cannabis plant can be separated from the rest of the plant by hand (e.g., with scissors) or using a destalker (e.g., MB Bucker 500; Master Bucker 500; www.masterproducts.es).

[0063] The undried flowers are then trimmed to separate the sugar leaves from the flowers, this step can be done manually (e.g. with scissors) or using a trimmer (e.g. MT Tumbler 500 MED; MT Tumbler 500 MED; masterproducts.es).

[0064] Trimmers that can be used in the methods described herein may function as follows: (a) Fresh or dried flowers are placed in a rotating drum made of stainless steel. (b) The transport speed of the flowers through the drum can be adjusted using the tilt angle of the drum. Flowers are also transported towards the outlet by newly added flowers. About a handful of flowers are added every 30 seconds and stay in the drum for about 30 to 45 seconds. (c) Sugar leaves protruding through the opening in the drum are removed by roller blades mounted below the drum.

[0065] To increase the throughput per minute, for example, several trimmers can be connected in series and material added at shorter intervals.

[0066] The removal of the sugar leaves is optional. In contrast to fan leaves, sugar leaves have a small amount of trichomes on their surface. Since only a defined amount of material can be loaded into the percolator (extraction vessel), the sugar leaves can be removed in order to obtain the highest possible THC content in the raw material for extraction. A person skilled in the art can easily select the appropriate amount of plant material to load into the percolator. For example, in a 1,000 liter percolator, 10 to 25 kg of plant material can be used.

[0067] In addition to trimming, the plant material used in the methods described herein may be broken down to produce smaller sized plant material. In other words, the plant material may be mechanically crushed during or preferably before mixing with the solvent. All crushing methods known to those skilled in the art that reduce plant material to smaller pieces are suitable, including crushing, pulverizing, milling, powdering, and chipping. However, the methods described herein preferably use whole flowers with the visible part of the sugar leaves trimmed off. Cannabinoids and terpenes are located on the surface of the flower and are easily accessible to the extraction solvent without grinding. Without necessarily being bound by scientific theory, it is assumed that smaller particles have a larger contact area with the solvent, which may lead to an increased amount of extraction of undesirable substances / materials. In other words, extracting smaller parts may result in higher extraction levels of non-active plant ingredients.

[0068] As mentioned above, the cannabis plant extract is preferably produced / obtained by the methods described herein. Thus, the cannabis plant extract is produced by extracting cannabis plant material according to the methods described herein.

[0069] The term "cannabis plant(s)" is used in the broadest sense herein and includes wild-type Cannabis sativa and Cannabis indica, as well as all variants thereof, such as the variants var. Indica and var. Kafirinistanica, Cannabis indica subsp. Indica var. Indica, Cannabis indica subsp. Indica var. himalayansis, Cannabis indica subsp. Indica var. afghanica, and Cannabis indica subsp. Indica var. asperrima. Furthermore, it includes cannabis plants resulting from genetic crosses, self-crosses, or hybrids of the above-mentioned plants and cannabis chemovars. From said cannabis plants, all types of plant material as described above can be used in the methods described herein. Preferably, flower material is used in the methods described herein. The terms "cannabis cultivar" and "cannabis plant cultivar" are used interchangeably herein. Cannabis varieties are known in the art and include, for example, Jack Herer, Chemdawg, Bubba Kush, Trainwreck, Super Silver Haze, Pure Kush, El Nino, Himalayan Gold, Skunk #1, White Widow, Warlock CBD, Pink Kush, OG Kush, Super Lemon Haze, Jack the Ripper, Lemon Skunk, and Hash Plant.

[0070] The preparation of THC- and CBD-containing medicines, i.e. cannabis plant extracts, in convenient ratios is made possible by the cultivation of certain chemovarieties of cannabis. These chemovarieties (plants that are distinguished by the cannabinoids they produce, rather than by the morphological characteristics of the plant) can be bred by various plant breeding techniques that will be familiar to those skilled in the art. Propagating plants by cuttings for material production ensures that the genotype is fixed and that each crop of the plant contains substantially the same ratio of cannabinoids.

[0071] Cannabis plants naturally produce a wide variety of secondary metabolites, including cannabinoids, terpenes and terpenoids, sterols, triglycerides, alkanes, squalene, tocopherols, etc. The mix of these secondary metabolites varies depending on several factors, including the particular cannabis cultivar, the part of the cannabis plant that is extracted, the extraction method, and the processing of the extract.

[0072] Thus, the skilled artisan is well aware that different cannabis varieties contain different amounts / concentrations of (pharmacologically active) substances such as cannabinoids or terpenes. Thus, it is clear to the skilled artisan that the concentration of (pharmacologically active) substances such as cannabinoids or terpenes in the cannabis plant extract produced by the method described herein can be controlled by using a cannabis plant variety that contains a certain concentration of the (pharmacologically active) substance. For example, a cannabis plant extract containing a high concentration of THC can be produced using a cannabis plant variety that contains a high concentration of THC, while a cannabis plant extract containing a high concentration of CBD can be produced using a cannabis plant variety that contains a high concentration of CBD. Thus, the skilled artisan can select a cannabis plant variety depending on, for example, the ratio of cannabinoids to each other. The exact cannabinoid content of any particular cannabis variety can be qualitatively and quantitatively determined using methods well known in the art, such as thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).

[0073] Any of the cannabis varieties described herein or known in the art can be used in the methods described herein. It should be noted that, as will be apparent to one of ordinary skill in the art, mixtures of different cannabis varieties can also be used in the methods described herein.

[0074] Cannabis plants used in the methods described herein can be obtained by selecting for high THC concentrations. Exemplarily, the selection can be performed as follows: seeds of cannabis plants, for example "Jack Herer" seeds, can be commercially obtained. The seeds can be cultivated, for example, for 3 to 14 days until germination, using normal cultivation methods known to those skilled in the art. Based on the germination and growth behavior, the skilled person can select specific seeds for further cultivation. Such a decision can generally be made based on the results of an analysis and / or observations with the cultivar being cultivated. Once the selected seeds have germinated and taken root, they can be cultivated for an additional 3 to 6 weeks using normal cultivation methods known to those skilled in the art to establish a stock of seed plants. Fertilization, watering, pest control, disease monitoring, and trimming of the plants can be optimized by the skilled person. Based on the growth behavior, the skilled person can select specific seed plants for further cultivation. From these selected plants (referred to as individual plants in the following text), cuttings can be taken to secure the genetic material of the individual plants. Individual plants can then be brought into flowering by reducing the daylight hours from more than 18 hours to less than 12 hours. In general, the environmental conditions for the rooting, vegetative and flowering stages must be met. Individual plants can then be finally selected based on the following criteria: growth behavior, flowering behavior, successful cultivation and good rooting behavior of cuttings taken from them, susceptibility to diseases (e.g. gray mold, etc.), and analytical results such as THC content, other cannabinoid content, and terpene profile. As part of the selection process, batch-to-batch consistency can be analyzed based on cannabinoid and terpene profiles.Most preferably, the cannabis cultivar used in the methods described herein is the cultivar referred to herein as DKJ127 and deposited with the European Plant Varieties Office (cultivar deposited by Vertanical GmbH under application number A202104053 (provisional cultivar designation: dk-j127; botanical taxon: Cannabis sativa L.; breeder reference: DK-J127; cultivar name: DKJ127; application number: 2021 / 3223; electronic application number: A202104053; date of receipt by the European Plant Varieties Office: 09 / 12 / 2021)). It should be noted that, as will be apparent to the skilled artisan, progeny of cultivar DKJ127 may also be used in the methods described herein. Said progeny may be selected with even higher THC concentrations than the deposited DKJ127.

[0075] The present invention therefore relates to a method for producing an extract of a cannabis plant, comprising the steps of: (a) providing a cannabis plant of the cannabis variety DKJ127 (i.e. deposited with the European Plant Varieties Office under application number A202104053); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to separate a cannabis plant extract from the flower material. The present invention relates to a method comprising the steps of:

[0076] The present invention further provides a method for producing a cannabis plant extract comprising the steps of: (a) providing a cannabis plant of the cannabis variety DKJ127; (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to extract a cannabis plant extract. where The processing step defined in step (c) is the next step: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) Maceration at a temperature between 15°C and 25°C for approximately 24 hours, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) performing percolation, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material; The present invention relates to a method comprising the steps of:

[0077] Cannabinoids are described as unique terpenophenolic metabolites found only in the cannabis plant (Sirikantaramas and Taura, Springer, 2013). r2017, 1st edition, Chapter 8, p. 183-206). However, alternative cannabinoid-like or cannabimimetic compounds have been proposed, such as Acmella oleracea (Dallazan et al., Inflammopharmacology 2019, 28, pp. 175-186), Echinaceae angustifolia (Raduner et al., J Biol Chem.2006, 281(20), pp. 14192-14206), Echinaceae purpurea (Raduner et al., J Biol Chem.2006, 281(20), pp. 14192-14206), Helichrysum umbraculigerum (Pollastro et al., Fitoterapia 2018, 126, pp. 35-39), Heliopsis helianthoides (Hajdu et al., J Nat Prod. 2014, 77(7), pp.1663-1669), Maca (Lepidium meyenii) (Hajdu et al., J Nat Prod. 2014, 77(7), pp. 1663-1669), kava (Piper methysticum) (Ligresti et al., Pharmacol Res.2012, 6(2), pp.163-1699), pepper (Piper nigrum) (Reynoso-Moreno et al., J Agric Food Chem.2017, 65(43), pp. 9435-9442), Radula marginata (Hussain et al. al., Phytochem rev. (2019), 18, pp. 953-965), Radula perrottetii (Chicca et al., Neurophysiol.2018, 4(10)), Rhododendron anthopogonoides (Iwata and Kitanaka, Chem Pharm Bull.2011, 59(11), pp. 1409-1412), and Tuber melanosporum (Degenhardt et al., Biology, Pharmacology, Diagnosis, and Treatment 2017, Chapter 2, pp. 13-23), (Pacioni et al., Phytochemistry 2015, 110, pp. :104-110). Cannabinoid-like substances or cannabimimetic compounds are considered to be phytochemicals and secondary metabolites that interact with the endocannabinoid system and have pharmacological effects similar to cannabinoids.

[0078] In the context of the present invention, the term "extract" is intended to refer to any form of the extraction product (optionally excluding the extractant), regardless of its physical form (i.e. viscous, pasty, or solid), unless otherwise specified.

[0079] Alternatively, the methods described herein may use plants that are capable of producing cannabinoids, cannabinoid-like substances, or cannabimimetic compounds, and terpenes and / or terpenoids, but do not contain or produce them endogenously. This means that the plants used in the methods described herein may be genetically modified plants that have been genetically modified to produce the desired substances (e.g., cannabinoids and / or terpenes and / or terpenoids). Thus, those skilled in the art will understand that the plants used in the methods described herein may be genetically modified plants or plant cells that differ from those that occur in nature due to genetic modification. Genetically modified plants or plant cells are not naturally occurring, i.e., cannot be found in nature, and differ significantly from naturally occurring plants or plant cells due to the introduction of foreign genetic material, e.g., foreign nucleic acid molecules.

[0080] It is envisaged that the method described herein is for producing a plant extract, preferably a cannabis plant extract, containing (pharmaceutical active) substances, such as cannabinoids, terpenes and / or terpenoids. The term "cannabinoid" as used herein relates to any cannabinoid isolated from a plant or synthetically produced to have activity in the endocannabinoid system, and includes cannabinoid-like substances and / or cannabimimetic compounds. Cannabinoids synthesized by plant sources are considered to be phytocannabinoids, i.e. plant-based cannabinoids. In the context of the present invention, the term "cannabinoid" may be used interchangeably with "phytocannabinoids". The term "cannabinoid profile" is used to describe the combination of cannabinoids, cannabinoid-like substances or cannabimimetic compounds present in a plant extract. To date, more than 100 cannabinoids have been identified in the cannabis plant. A comprehensive, non-limiting list of such cannabinoids found in cannabis is provided in ElSohly MA and Gul W., in Handbook of Cannabis, Oxford University Press (2014), pp. 3-22. Preferred, but non-limiting, examples of cannabinoids include delta-9-tetrahydrocannabinol (THC).

[0081] References to "THC" or "delta-9-tetrahydrocannabinol" and "cannabidiol" or "CBD" or "cannabinoid(s)" as used herein are understood to include pharma- ceutically acceptable salts of such compounds. The term "pharma-ceutically acceptable salts" refers to salts or esters prepared from pharma-ceutically acceptable non-toxic bases or acids, including inorganic bases or acids, organic bases or acids, as is well known to those skilled in the art. Many suitable inorganic and organic bases are known in the art.

[0082] The term "terpene(s)" or "terpenoid(s)" as used herein refers to a class of hydrocarbon molecules (Radwan, MM et al. Molecules 2021, 26(9): 2774). Non-limiting examples of terpenes include α-bisabolol, guaiol, and β-caryophyllene. Further non-limiting examples of terpenes are provided herein below. Terpenoids are terpene compounds that have been further metabolized in plants, typically through an oxidation process, and therefore usually contain at least one oxygen atom (Radwan, MM et al. Molecules 2021, 26(9): 2774). The term "terpene profile" is used to describe the combination of terpene and terpenoid compounds present in a plant extract.

[0083] It is contemplated that the methods described herein are for producing a plant extract comprising, for example, cannabinoids, terpenes, and / or terpenoids, using any plant material known to contain said substances. As mentioned above, a preferred plant material is the cannabis plant, preferably the flower material of the cannabis plant.

[0084] The methods described herein are preferred for the production of cannabis plant extracts containing delta-9-tetrahydrocannabinol (THC).

[0085] Accordingly, the present invention relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. The present invention relates to a method comprising the steps of:

[0086] The present invention relates to a method for producing a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The drying step of the flower material of the cannabis plant defined in step (b) is carried out by placing the plant material on a tray with air flow in a drying chamber at a temperature range of 20 ° C to 35 ° C for at least 1 day, 2 days, 3 days or 4 days, preferably 4 days; It concerns the method.

[0087] The present invention also provides a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The drying step of the flower material of the cannabis plant defined in step (b) is carried out by placing the plant material in a drying chamber on trays through which air flows, at a temperature range of 20°C to 35°C, until the moisture content of the flower material is less than 10 percent; It concerns the method.

[0088] Methods for determining the moisture content can be found in the European Pharmacopoeia (2.2.32) and the German monograph on cannabis flower. For example, it can be determined using 1.0 g of powdered drug by vacuum drying over molecular sieves R at 40 °C and a pressure between 1.5 and 2.5 kPa for 24 hours.

[0089] The term "sufficient amount" as used herein means that the plant, preferably the cannabis plant, has a sufficiently high THC amount such that the plant extract, preferably the cannabis plant extract produced by the method described herein using said plant or cannabis plant, has a desired amount of THC. In other words, "sufficient amount" as used herein means that the plant, preferably the cannabis plant, has a sufficiently high THC concentration such that the plant extract, preferably the cannabis plant extract or the cannabis plant soft extract produced by the method described herein using said plant or cannabis plant, has a desired concentration of THC. Generally, "sufficient amount" as used herein means that the cannabis plant has a THC concentration of at least 1, 2, 3, 4, 5, 6, 7, 9, 10, 20, or 30 percent (w / w) by dry weight. Dry weight as used herein means that the plant material does not contain water. For example, if the THC content is measured on a sample with a moisture content of 10% and the measured THC concentration of the sample is 20% THC, the THC concentration by dry weight will be 22.2%.

[0090] The skilled artisan is well aware how the THC content of cannabis plants or flowers can be determined (e.g. German Pharmacopoeia 2018-Cannabisblueten / Cannabis flos, Announcement in the Federal Gazette: BAnz AT 24.04.2018 B5).

[0091] Generally, when cannabis plants having a THC concentration of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20 or 30 percent by dry weight (w / w) are used in the methods described herein, the resulting / produced cannabis plant extract (or, for example, cannabis plant soft extract after concentration) may have a THC concentration of at least 60 percent by weight of the cannabis plant extract, preferably about 70-74 percent by weight. As already mentioned herein, the skilled person is well aware that different cannabis varieties contain different amounts / concentrations of cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes). Thus, the skilled person may select the cannabis variety to be used in the methods described herein depending on the desired concentration of cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) in the cannabis plant extract produced by said method. Of course, the skilled artisan is also well aware that different parts of a plant contain, for example, cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) in different concentrations, as described elsewhere herein. For example, in cannabis plants, the concentration of THC and / or other (pharmacologically active) substances (e.g. terpenes) is usually higher in the flower material.

[0092] It will therefore be apparent to one skilled in the art that, for example, when only flower material is used to produce a cannabis plant extract in the methods described herein, the concentration of THC in the flower material may be relevant, and one skilled in the art may select the cannabis variety to use depending on the concentration of THC in the flower material, rather than the corresponding concentration in the whole plant.

[0093] The concentration / amount of, for example, cannabinoids (e.g., THC and / or CBD) and / or other (pharmacologically active) substances (e.g., terpenes) in a plant, preferably a cannabis plant used in the methods described herein, can be determined, for example, as a percentage of the fresh or dry weight, preferably dry weight, of the cannabinoids (e.g., THC and / or CBD) and / or other (pharmacologically active) substances (e.g., terpenes). Thus, the concentration / amount of THC in a cannabis plant can be determined as a percentage of THC by dry weight. The concentration / amount of THC in a cannabis plant can be determined as a percentage of THC by dry weight of the whole plant (i.e., leaves, flowers, and stems) or can be determined as a percentage of THC by dry weight of the flower material only.

[0094] The concentration / amount of THC in the flower material of the cannabis plant used in the methods described herein may be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30 percent by dry weight (w / w), preferably at least 10 percent by dry weight. It is clear to the skilled artisan that the THC content as used herein may also refer to the THC equivalent, which is the sum of THC and THCA*0.877. Thus, in the context of the present invention, the term "THC content" encompasses the THC content and the THCA content. The THC and THCA content can be measured by liquid chromatography as described in the art (e.g., German Pharmacopoeia (DAB) 2018, ISBN: 978-3-7692-7217-8; Danish Medicines Standards 2020.0, BEK Nr. 1231 af25 / 11 / 2019; https: / / www.retsinformation.dk / eli / lta / 2019 / 1231). Dry weight is defined as the weight of a material minus losses due to drying (mainly moisture).

[0095] First, the loss on drying is determined. Loss on drying is defined according to the European Pharmacopoeia (2.2.32) as the mass loss after drying under specified conditions (e.g. in an oven). Loss on drying is a measure of the water content (and other volatile compounds) that is removed during the drying step.

[0096] Preferably, the cannabis plant used in the methods described herein contains THC in an amount of at least 10 percent by dry weight (w / w).

[0097] Accordingly, the present invention relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing delta-9-tetrahydrocannabinol (THC) in an amount of at least 10 percent by dry weight (w / w); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. The present invention relates to a method comprising the steps of:

[0098] In the context of the present invention, the amount of THC in any particular cannabis plant described herein can be measured qualitatively and quantitatively using methods well known in the art, such as thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).

[0099] In the methods described herein, the cannabis plant extract is produced / obtained by extraction. Any extraction method can be used, such as solvent extraction, distillation, expression and sublimation, decoction, digestion, percolation, soxlethtation, maceration, or other suitable extraction methods known to those skilled in the art, and combinations thereof.

[0100] Preferred herein is solvent extraction, i.e. extraction using a solvent. It is envisaged that the plant material, preferably the cannabis plant material, is contacted with a solvent, which may also be called an extractant. In other words, the plant material, preferably the cannabis plant material, is treated with a solvent.

[0101] It is envisaged that the desired (pharmacologically active) substances from the plant material will dissolve in the solvent. Thus, for example, it is envisaged that the cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) from the cannabis plant material will dissolve in the solvent. That means that after treating the cannabis plant material with the solvent, for example, the cannabinoids (e.g. THC and / or CBD) and / or other (pharmacologically active) substances (e.g. terpenes) are not present in the cannabis plant material but will dissolve in the solvent. In other words, the solvent "takes out" for example the cannabinoids (e.g. THC and / or CBD) and / or other (pharmacologically active) substances (e.g. terpenes) from the plant material. In other words, for example, the cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) are extracted from the plant material. The solvent containing dissolved, e.g. cannabinoids (e.g. THC and / or CBD) and / or other (pharmacologically active) substances (e.g. terpenes) can then be separated (i.e. extracted) from the plant material. The solvent containing dissolved, e.g. cannabinoids (e.g. THC and / or CBD) and / or other (pharmacologically active) substances (e.g. terpenes) separated from the plant material, preferably cannabis plant material, is called a plant extract, preferably a cannabis plant extract. The cannabis plant extract can be further concentrated as disclosed elsewhere herein and thereafter referred to as a cannabis plant soft extract. Preferably, the solvent used in the methods described herein removes THC from the plant material. Thus, the methods described herein may include treating the (homogenized) flower material of step (b) with a solvent to separate the cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the mixture of flower material and solvent. Preferably, the solvent used in the methods described herein also removes THC and terpenes. Thus, the solvent used in the methods described herein preferably removes THC and one or more of the terpenes selected from α-bisabolol, guaiol, and β-caryophyllene.

[0102] As mentioned above, in the methods described herein, the cannabis plant material may be treated with a solvent. Thus, the methods described herein may include covering the (homogenized) plant material with a solvent, thereby obtaining a mixture of the plant material and the solvent. Said step is referred to herein as the "mixing step."

[0103] Similarly, the methods described herein may include covering the flower material of the cannabis plant with a solvent, thereby resulting in a mixture of the flower material of the cannabis plant and the solvent. In particular, step (c) of the methods described herein may include covering the flower material of the cannabis plant with a solvent, thereby resulting in a mixture of the flower material of the cannabis plant and the solvent. A person skilled in the art can easily determine the appropriate ratio of plant material to solvent. As used herein, a ratio of plant material to solvent of 1:8.4 (w / w) means that 8.4 times the amount of solvent is used relative to the plant material by weight. In other words, 1 g of plant material is overlaid with 8.4 g of solvent. The ratio of cannabis plant material to solvent used in the methods described herein may be any ratio between 1:0.1 (w / w) and 1:100 (w / w), as non-limiting examples. Preferably, the ratio of cannabis plant material to solvent used in the methods described herein is between 1:1 (w / w) and 1:20 (w / w) (i.e. 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, or 1:20 (w / w), or any fraction thereof, e.g., 1:14.7 (w / w)). Preferably, in the methods described herein, the cannabis plant material is overlaid with the solvent in a ratio of 1:8.4 (w / w), thereby obtaining a mixture of cannabis plant material and solvent. Preferably, in the methods described herein, the flower material of the cannabis plant is overlaid with the solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of flower material and solvent. Therefore, step (c) of the method described herein preferably comprises layering the floral material with the solvent in a ratio of 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent.

[0104] It is preferred that the floral material is completely covered with the solvent.

[0105] After a mixture of plant material, preferably cannabis plant material, more preferably flower material of a cannabis plant, and a solvent is obtained, the method described herein may further comprise a step of, for example, dissolving the cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) in the solvent. The mixture of plant material, preferably cannabis plant material, more preferably flower material of a cannabis plant, and a solvent may be incubated to, for example, dissolve the cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) in the solvent. Preferably, said incubation step is maceration (sometimes called static extraction).

[0106] Said step is referred to herein as the "maceration step."

[0107] Maceration can be carried out for minutes, hours, days or weeks, but preferably for hours to days, and therefore for 1 hour to 48 hours (i.e., 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, 36 hours, 37 hours, 38 hours, 39 hours, 40 hours, 41 hours, 42 hours, 43 hours, 44 hours, 45 hours, 46 hours, or 47 hours, 48 ​​hours, preferably 24±1 hours (h)).

[0108] The maceration may be carried out at a temperature between 4°C and 50°C, preferably between 15°C and 25°C (i.e., 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C).

[0109] Maceration is preferably carried out in the dark.

[0110] Thus, step (c) of the methods described herein may involve maceration for about 24 hours at a temperature between 15° C. and 25° C. As used herein, the term "about" with respect to time means 10 percent more or less than the indicated value.

[0111] Preferably, step (c) of the process described herein may comprise maceration at a temperature between 15°C and 25°C for 24±1 hours in the absence of light.

[0112] It is further contemplated herein that the further solvent is added after incubating the mixture of plant material, preferably cannabis plant material, more preferably flower material of a cannabis plant, and solvent, such as by serration. In other words, it is contemplated that the further solvent is added after the "maceration step". Thus, step (c) of the method described herein comprises adding the further solvent to the mixture of plant material, preferably cannabis plant material, more preferably flower material of a cannabis plant, and solvent. Said step is referred to herein as the "additional solvent step." The same or a different solvent can be added. Preferably, the same solvent is added to the mixture. Any amount of solvent can be added such that the ratio of cannabis plant material to solvent after the additional solvent is added is, for example, 1:1 (w / w) to 1:20 (w / w) (i.e., 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, or 1:20 (w / w), or any fraction thereof, for example, 1:14.7 (w / w)). Preferably, the amount of solvent is added so that it is doubled, i.e. if the ratio of cannabis plant material to solvent before the further solvent was added was 1:8.4 (w / w), then the amount of solvent is added so that after the further solvent is added the ratio of cannabis plant material to solvent is about 1:16.8 (w / w).

[0113] Preferably, after further solvent is added, the plant material, preferably cannabis plant material, more preferably cannabis plant flower material, and solvent are present in a ratio of about 1:16.8 (w / w). As used herein, the term "about" means 10 percent more or less than the indicated value.

[0114] Thus, step (c) of the methods described herein may comprise adding further solvent such that the floral material and the solvent are present in the mixture of floral material and solvent in a ratio of about 1:16.8 (w / w).

[0115] In other words, step (c) of the methods described herein may comprise adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w).

[0116] Generally, one of skill in the art will know how to determine the appropriate ratio of plant material to solvent. For example, if powdered or crushed plant or flower material is used, the bulk density of the material will be higher and less extraction solvent will be required.

[0117] Preferably, further solvent is added before percolation. Said step is referred to herein as the "percolation step." The "maceration step" may already be carried out in a percolator. If the "maceration step" is not carried out in a percolator, the mixture of floral material and solvent is transferred into the percolator before the "percolation step".

[0118] The solvent is then flowed through the floral material. In other words, the solvent permeates the floral material. The flow rate can be in the range of 1.0 ml / min to 10.0 ml / min per kg of floral material, preferably 3.55 to 5.45 ml / min per kg of floral material, more preferably 4.0 ml / min to 5.0 ml / min per kg of floral material (i.e. 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, or 5.0 ml / min per kg of floral material), most preferably 4.0 ml / min per kg of floral material. The solvent is pumped and flowed through the floral material several times. The floral material is preferably covered with the solvent at all times. The percolation is continued until the percolate is collected. Percolation may be carried out for 1 to 400 hours, preferably 63 to 97 hours (i.e. 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, or 97 hours), most preferably 86 hours (h). Percolation is a solvent containing substances extracted from cannabis flower material, i.e. a solvent containing dissolved, for example, cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes). The solvent containing dissolved e.g. cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes) is also called miscella.

[0119] The solvent containing dissolved THC recovered from the percolator may already be a cannabis plant extract. The cannabis plant extract may be further concentrated and may also be referred to as a cannabis plant soft extract. However, the solvent containing dissolved THC recovered from the percolator may be subjected to additional purification and / or separation steps, as further described below.

[0120] Further information on percolation can be found in the European Pharmacopoeia (04 / 2019:0765).

[0121] It is envisaged that for example cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g. terpenes, terpenoids (aromas), as well as secondary flower substances such as chlorophyll and flavonoids) from the cannabis flower material are dissolved in the solvent during the "maceration step" and "percolation step". In other words, THC is extracted from the cannabis flower material during the "maceration step" and "percolation step".

[0122] Thus, extraction of dried cannabis flower material can be carried out as follows:

[0123] Dried flowers, which are only trimmed before the drying step, must have a minimum content of delta-9-THC equivalent (delta-9-THC + delta-9-THCA * 0.877) of 10% by weight (i.e., at least 10 percent by dry weight (w / w)). For every 1 kg of dried cannabis flower material, a quantity of 16.7 kg (15.9 kg to 17.5 kg) of pharmaceutical grade ethanol 96% (v / v) is used. The extraction process is carried out in a pharmaceutical grade cylindrical stainless steel extraction vessel with a strainer at the bottom, protected from light, at 15 °C to 25 °C. Extraction is divided into maceration (static extraction) and percolation (moving extraction). Dried cannabis flower material is first soaked in half the amount of ethanol (8.35 kg ± 5% per kg of flower) for 24 hours ± 1 hour during maceration, which allows dissolution of most of the delta-9-THC and other cannabinoids, as well as associated secondary plant materials such as terpenes (aroma), fats, and chlorophyll. After maceration, the remaining half the amount of ethanol is added to the miscella (i.e., the solvent containing dissolved, e.g., cannabinoids (e.g., THC and / or CBD) and / or other (pharmacologically active) substances (e.g., terpenes)) and percolation is initiated. This allows the miscella to percolate through the flower material for 63-97 hours at a flow rate of 4.0-5.0 ml / min per kg of flower, which is then collected through a strainer in the extraction vessel into a pharmaceutical stainless steel mobile buffer tank. The flower material is placed on top of the strainer, and the opening through which the extract flows into the buffer tank is located below the strainer. In addition, the extract is pumped through a pharmaceutical grade filter on its way to the buffer / collection tank. The collected miscella (i.e. the solvent containing dissolved e.g. cannabinoids (e.g. THC and / or CBD) and / or other (pharmaceutical active) substances (e.g. terpenes)) may be a cannabis plant extract, but will not usually have the desired THC concentration. Therefore, the miscella is preferably subjected to further concentration and / or purification and / or separation steps, after which it can be called a cannabis plant soft extract.

[0124] The methods described herein may also include a step of separating the solvent containing dissolved, e.g., cannabinoids (preferably THC) and / or other (pharmacologically active) substances (e.g., terpenes) from the (cannabis flower) plant material. Said step is referred to herein as the "separation step." When the solvent containing dissolved THC is separated from the cannabis plant material, said solvent is called a cannabis plant extract. Thus, in the "separation step", the (cannabis) plant extract is separated from the mixture of plant material, preferably cannabis plant material, more preferably flower material of the cannabis plant, and the solvent. Thus, step (c) of the method described herein may comprise separating the (cannabis) plant extract from the mixture of plant material, preferably cannabis plant material, more preferably flower material of the cannabis plant, and the solvent.

[0125] In other words, step (c) of the methods described herein may involve separating the cannabis plant extract (preferably containing delta-9-tetrahydrocannabinol (THC)) from the flower material.

[0126] In the "separation step", the skilled person can apply any suitable method to separate liquid from solid materials, such as centrifugation, filtration, decantation, and distillation.

[0127] As mentioned above, when percolation is performed, the percolator may include a strainer to separate the cannabis flower material from the solvent. However, the strainer of the percolator removes only the majority of the cannabis flower material, and therefore, additional purification and / or separation steps may be applied. The additional purification and / or separation step may be filtration.

[0128] Preferably, the solvent containing the dissolved THC is further purified by filtration through a pharmaceutical grade polypropylene-based particle filter with a deposition rate of 1.5 μm. Preferably, the operating pressure and temperature should not exceed 5 bar and 50° C., respectively. As with all methods described herein, those skilled in the art can easily measure parameters such as temperature and pressure by standard techniques. Filtration can be performed between percolation and collection in the mobile buffer tank, or it can be performed afterwards by collecting the filtered miscella in a second mobile buffer tank of the same stainless steel grade.

[0129] In the context of the present invention, a preferred method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant comprises the following steps: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The processing step defined in step (c) includes the following steps: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) Maceration at a temperature between 15°C and 25°C for approximately 24 hours, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) performing percolation, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material; Includes.

[0130] The present invention also provides a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing delta-9-tetrahydrocannabinol (THC) in an amount of at least 10 percent by dry weight; (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The processing step defined in step (c) is the next step: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) Maceration at a temperature between 15°C and 25°C for approximately 24 hours, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) performing percolation, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material; The present invention relates to a method comprising the steps of:

[0131] The present invention also provides a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant of the cannabis variety DKJ127; (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. The present invention relates to a method comprising the steps of:

[0132] The concentration / amount of THC in the cannabis plant (preferably cultivar DKJ127) used in the methods described herein can be determined to assess whether the concentration / amount of THC is sufficient, e.g. whether the cannabis plant extract produced by the methods described herein has the desired THC concentration / amount.

[0133] The present invention therefore also relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant of cannabis variety DKJ127, the cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. The present invention relates to a method comprising the steps of:

[0134] In the context of the present invention, a preferred method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant comprises the following steps: (a) providing a cannabis plant of the cannabis variety DKJ127; (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The processing steps defined in step (c) are as follows: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) Maceration at a temperature between 15°C and 25°C for approximately 24 hours, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) performing percolation, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material; Includes.

[0135] As mentioned above, the solvent is used to "pull out" the desired substances (e.g. cannabinoids (e.g. THC and / or CBD) and / or other (pharmacologically active) substances (e.g. terpenes)) from the plant material, preferably the cannabis plant material. Any solvent can be used as long as it is capable of "pulling out" the desired substances from the plant material. In other words, the desired substances must be soluble or dissolvable in the solvent used.

[0136] Non-limiting examples of solvents that may be suitable include alcohols (e.g., methanol, ethanol, propanol, butanol, propylene glycol, etc.), water, hydrocarbons (e.g., butane, hexane, etc.), polar organic solvents (e.g., ethyl acetate, polyethylene glycol, etc.), or supercritical fluids (e.g., liquid CO2), as well as aqueous solutions thereof.

[0137] Suitable non-polar solvents may be C5-C12 straight or branched alkanes, C1-C12 alcohols, or carbonates of C1-C12 alcohols. More volatile solvents may be particularly useful as they can be easily removed from the extract if necessary. It is noted that, as will be perfectly clear to those skilled in the art, mixtures of the aforementioned solvents may also be used in the methods described herein. Preferred solvents for the methods described herein are ethanol, butanol, alkanes (such as pentane, heptane, and propane), ethyl ether, tertbutyl-methyl-ether, methyl-ethyl-ketone, acetone, ethyl acetate, CO2. Highly preferred solvents for the methods described herein are ethanol, especially 96% ethanol by volume. In the context of the present invention, it is preferred to use pharmaceutical grade solvents.

[0138] Accordingly, the present invention relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with ethanol and isolating a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. The present invention relates to a method comprising the steps of:

[0139] In the context of the present invention, a preferred method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant comprises the following steps: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with ethanol and isolating a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The processing step defined in step (c) includes the following steps: (i) layering the floral material with ethanol in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and ethanol; (ii) Maceration at a temperature between 15°C and 25°C for approximately 24 hours, protected from light; (iii) adding additional ethanol, thereby obtaining a mixture of floral material and ethanol in a ratio of about 1:16.8 (w / w); (iv) percolation, in which ethanol is allowed to penetrate the flower material at a flow rate of 3.55-5.45 ml / min per kg of flower material, preferably 4.0 ml / min per kg of flower material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material; Includes.

[0140] In the context of the present invention, a particularly preferred method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant comprises the following steps: (a) providing a cannabis plant of the cannabis variety DKJ127; (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with ethanol and isolating a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. where The processing steps defined in step (c) are as follows: (i) layering the floral material with ethanol in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and ethanol; (ii) Maceration at a temperature between 15°C and 25°C for approximately 24 hours, protected from light; (iii) adding additional ethanol, thereby obtaining a mixture of floral material and ethanol in a ratio of about 1:16.8 (w / w); (iv) percolation, in which ethanol is allowed to penetrate the flower material at a flow rate of 3.55-5.45 ml / min per kg of flower material, preferably 4.0 ml / min per kg of flower material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material; Includes.

[0141] It is further envisaged that the cannabis plant extract produced according to the methods described herein is further concentrated by a concentration step. A "concentration step" in this context means that the solvent is removed from the liquid cannabis plant extract. The solvent can be removed by evaporation or freeze-drying. However, a concentration step (e.g. an evaporation step) may also be part of the method according to the invention and described herein. Thus, the method described herein may further comprise evaporating the solvent from the liquid cannabis plant extract to concentrate the extract. Furthermore, a decarboxylation step may also be part of the method of the invention. It is envisaged that after the concentration step and / or the decarboxylation step, the cannabis plant extract may be referred to as a cannabis plant soft extract.

[0142] Accordingly, the present invention relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. Including, The method further comprises evaporating the solvent from the liquid cannabis plant extract to concentrate the extract, It concerns the method.

[0143] Preferably, the solvent in the cannabis plant extract is evaporated under vacuum using a rotary evaporator (e.g., manufacturer: Buechi; model: Rotavapor R-220 Pro; distillation rate: up to 12 liters ethanol / hour; flask size: 20 liters; maximum flask volume: 12 liters; continuous feed).

[0144] The water bath temperature, pressure, and rotation speed are, respectively, about 72°C (i.e., 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, or a portion thereof), about 185 mbar (i.e., 175 mbar, 176 mbar, 177 mbar, 178 mbar, 179 mbar, 180 mbar, 181 mbar, 182 mbar, 183 mbar, 184 mbar, 185 mbar, 186 mbar, 187 mbar, 188 mbar, 189 mbar, 200 mbar, 201 mbar, 202 mbar, 203 mbar, 204 mbar, 205 mbar, 206 mbar, 207 mbar, 208 mbar, 209 mbar, 300 mbar, 301 mbar, 302 mbar, 303 mbar, 304 mbar, 305 mbar, 306 mbar, 307 mbar, 308 mbar, 309 mbar, 310 mbar, 311 mbar, 312 mbar, 313 mbar, 314 mbar, 315 mbar, 316 mbar, 317 mbar, 318 mbar, 319 mbar, 320 mbar, 321 mbar, 322 mbar, 323 mbar, 324 mbar, 325 mbar, 326 mbar, 327 mbar, 328 mbar, 329 mbar, 330 mbar, 331 mbar, 3 mbar, 189 mbar, 190 mbar, 191 mbar, 192 mbar, 193 mbar, 194 mbar, 195 mbar, or parts thereof) and about 150 rpm (i.e., 145 rpm, 146 rpm, 147 rpm, 148 rpm, 149 rpm, 150 rpm, 151 rpm, 152 rpm, 153 rpm, 154 rpm, 155 rpm, 156 rpm, 157 rpm, 158 rpm, 159 rpm, or 160 rpm). These conditions result in an ethanol vapor temperature of 41°C to 42°C and an evaporation performance of about 10 L / h. The evaporation can be terminated when the vapor temperature falls below 30°C, indicating that the ethanol is almost completely removed. By evaporating the solvent in several rotary evaporators in parallel, the overall evaporation time can be kept constant, independent of the batch size. The result is a dark green to dark brown resin-type, nearly solvent-free cannabis plant extract consisting primarily of delta-9-THCA and partially activated delta-9-THC.

[0145] In the cannabis plant, THC exists primarily as tetrahydrocannabinolic acid (THCA). Therefore, it may be beneficial or desirable to convert the tetrahydrocannabinolic acid in the cannabis plant extract produced according to the methods described herein to delta-9-tetrahydrocannabinol (THC). The conversion of tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC) is decarboxylation. Decarboxylation is a chemical reaction that releases carbon dioxide. The conversion step (i.e., decarboxylation step) may be part of the methods described herein according to the invention. Thus, the methods described herein may further include heating the cannabis plant extract to a certain temperature to decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC).

[0146] To decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC), the cannabis plant extract may be heated to a temperature between 50°C and 150°C, preferably about 80°C (i.e. 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, or any portion thereof). Preferably, the decarboxylation is carried out under reduced pressure. The reduced pressure is preferably about 185 mbar (i.e., 175 mbar, 176 mbar, 177 mbar, 178 mbar, 179 mbar, 180 mbar, 181 mbar, 182 mbar, 183 mbar, 184 mbar, 185 mbar, 186 mbar, 187 mbar, 188 mbar, 189 mbar, 190 mbar, 191 mbar, 192 mbar, 193 mbar, 194 mbar, 195 mbar, or any fraction thereof). Decarboxylation may be carried out for about 72 hours (i.e., 67 hours, 68 hours, 69 hours, 70 hours, 71 hours, 72 hours, 73 hours, 74 hours, 75 hours, 76 hours, 77 hours, or any fraction thereof).

[0147] After the concentration and decarboxylation steps, the cannabis plant extract may be referred to as a cannabis plant soft extract and is envisaged to have the components as shown in Figure 1 and Tables 1-7. TIFF2025503278000001.tif72170TIFF2025503278000002.tif221170TIFF2025503278000003.tif247170

[0148] Accordingly, the present invention relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. Including, The method further comprises heating the cannabis plant extract to about 80°C under a reduced pressure of about 185mbar to decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC). It concerns the method.

[0149] It is contemplated that at least 90%-100% of the THCA in the cannabis plant extract is decarboxylated to THC (i.e., 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%, or any fraction thereof, e.g., 95.7%).

[0150] The complete conversion of delta-9-THCA to delta-9-THC is preferably carried out by thermally induced decarboxylation in vacuum. A rotary evaporator is therefore used with water bath temperature, pressure and rotation adjusted to 80°C, 185 mbar and 150 rpm, respectively. The decarboxylation time is 72 hours. The cannabis plant extract obtained has a dark green to dark brown resinous nature with an average THC content of about 70-74% by weight. The conversion factor between dried flowers and soft extract is on average 4.7. A conversion factor of 4.7 means that the method described herein results in approximately 5.3 kg of cannabis plant soft extract from 25 kg of cannabis flowers.

[0151] It is envisaged herein that the method according to the invention further comprises evaporating the solvent from the liquid cannabis plant extract to concentrate the extract and heating the cannabis plant extract to a certain temperature to decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC).

[0152] The present invention therefore relates to a method for producing a cannabis plant (soft) extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material; (d) evaporating the solvent from the liquid cannabis plant extract to concentrate the extract; and (e) heating the cannabis plant extract to about 80° C. under a reduced pressure of about 185 mbar to decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC); The present invention relates to a method comprising the steps of:

[0153] As mentioned above, the method described herein eliminates the need for a winterization step. It is therefore envisaged that the method described herein is carried out without a winterization step. "Winterization step" or "winterization" refers herein to a method step in which the temperature of the cannabis plant extract is reduced, in particular to remove, for example, wax. Winterization is frequently carried out after the cannabis plant extract has been concentrated, for example by evaporation. Typically, during winterization, the temperature is reduced to below 10°C, preferably below 0°C, for example to -5, -10, -20 or -25°C. The cannabis plant extract is then typically incubated at low temperature, for example for 48 hours. After the incubation step, the precipitate is removed, for example by centrifugation or filtration. Typically, before the temperature of the cannabis plant extract is reduced, the extract is mixed with an (additional) organic solvent, for example methanol or ethanol. Winterization is described, for example, in DE 10337458 A1 and WO 2002 / 064109 A1.

[0154] The present invention therefore relates to a method for producing a cannabis plant (soft) extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, which does not include a winterization step. The phrases "the method does not include a winterization step" and "does not include a winterization step" are used synonymously with the phrase "no winterization step is performed". The present invention therefore relates to a method for producing a cannabis plant (soft) extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, which does not include a winterization step.

[0155] Accordingly, the present invention relates to a method for producing a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) from the flower material. Including, The method does not include a winterization step. It concerns the method.

[0156] The present invention further provides a method for producing a cannabis plant extract comprising the steps of: (a) providing a cannabis plant, preferably containing a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to separate the cannabis plant extract from the mixture of the flower material and the solvent. Including, The processing step defined in step (c) is the next step: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) maceration for about 24 hours at a temperature between 15°C and 25°C, protected from light; (iii) adding additional solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) a percolation step, in which the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, preferably 4.0 ml / min per kg of floral material, at a temperature of 15°C-25°C, for 63-97 hours, preferably 86 hours, in the dark; and (v) isolating the cannabis plant extract from the cannabis flower material. Including, The method does not include a winterization step. It concerns the method.

[0157] The present invention also relates to a plant extract produced / obtained by the methods and processes disclosed herein.Accordingly, the present invention also relates to a cannabis plant extract produced / obtained by the methods described herein.Accordingly, the present invention also relates to a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) produced / obtained by the methods described herein.

[0158] Thus, the present invention relates to a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) obtained by the methods described herein. The cannabis plant extract may be in liquid form. Thus, the present invention relates to a liquid cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) obtained by the methods described herein. As described elsewhere herein, the cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) obtained by the methods described herein may be in solvent-free, decarboxylated form. Thus, the present invention relates to a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) obtained by the methods described herein in solvent-free, decarboxylated form.

[0159] The present invention also relates to a cannabis plant extract obtained by the methods described herein, comprising delta-9-tetrahydrocannabinol (THC) in an amount of about 70-74 percent by weight of the cannabis plant extract. The term "about" used in the context of THC content means 20 percent more or less than the indicated value. In the context of the present invention, the THC content of any particular cannabis plant described herein can be qualitatively and quantitatively measured using methods well known in the art, such as thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).

[0160] In the context of the present invention, the cannabis plant extract, preferably the cannabis plant soft extract, produced / obtained by the method described herein may be formulated as shown in Figure 1 and Tables 1-7.

[0161] It is envisaged that the cannabis plant extract or cannabis plant soft extract obtained by the methods described herein may be further processed into a composition comprising desired substances of the cannabis plant, such as delta-9-tetrahydrocannabinol (THC) and / or terpenes. However, it is also envisaged that the cannabis plant extract obtained by the methods described herein may be used directly (i.e. without further processing), for example in medicines or formulations. A cannabis plant extract without further processing may be referred to as a natural extract. Thus, as used herein, the term "a composition comprising desired substances of the cannabis plant, such as delta-9-tetrahydrocannabinol (THC) and / or terpenes, obtained by the methods described herein" may refer to a cannabis plant extract obtained by the methods described herein, but may also refer to a cannabis plant extract obtained by the methods described herein that has been further processed. Thus, "a composition obtained by the methods described herein" may be used synonymously with "a cannabis plant (soft) extract obtained by the methods described herein". In other words, it is envisaged that the cannabis plant extract obtained by the methods described herein will be used directly in a pharmaceutical preparation, i.e. directly incorporated into a medicine or formulation, or alternatively, the cannabis plant extract obtained by the methods described herein will first be further processed into a composition, which will then be used in a pharmaceutical preparation. Processing the cannabis plant extract obtained by the methods described herein into a composition may be necessary, for example, to enable storage and / or transport of said cannabis plant extract.

[0162] The cannabis plant extract can be treated, for example, but not limited to, by changing the pH or adding one or more solvents at a preferred concentration. In some cases, the extract described herein can also be filtered to remove particulate matter, for example, by passing the extract through a filter paper or fine sieve with a pore size suitable for filtration. Thus, the compositions of the present invention are preferably provided in liquid form. As will be appreciated, one or more additional compounds (e.g., cannabinoid, terpene, or terterpenoid compounds) may be added to the compositions described herein. The addition of compounds may be made to compensate for natural variations in the relative amounts of certain compounds expressed by the cannabis plant providing the extract. The added compound can be a natural or synthetic version of the desired compound(s).

[0163] However, it is also envisaged to use the cannabis plant extract, i.e. the natural extract, obtained by the method described herein itself, as a pharmaceutical preparation.

[0164] Thus, all that is disclosed herein about compositions and pharmaceutical formulations also applies to the cannabis plant extract or the cannabis plant soft extract and vice versa. When reference is made herein to a "cannabis plant (soft) extract", it is clear to the skilled person that a reference is also intended to "cannabis plant (soft) extract obtained by the method described herein".

[0165] The cannabis plant extract or soft extract of the cannabis plant obtained by the methods described herein can be analysed by methods known in the art.

[0166] The color of the cannabis plant soft extract can be determined by visual inspection and may be yellow to green.

[0167] The extracts can be further analyzed by TLC according to Ph.Eur.2.2.27 and the DAB monograph "Eingestellter Cannabisextrakt". The extracts can be further analyzed by comparison of the cannabinoid profile with the retention times of reference standards and reference chromatograms of this product according to an internally validated method based on HPLC according to Ph.Eur.2.2.29 and "Eingestellter Cannabisextrakt".

[0168] The extracts can be further analysed by GC according to Ph.Eur.2.2.28 and an internally validated GC-MS method, comparing the terpene / terpenoid profile with the retention times of reference standards and reference chromatograms of this product.

[0169] Moisture content can be determined according to Ph.Eur.2.5.12 (Karl Fischer), ethanol content can be analyzed according to Ph.Eur.2.2.28 and an internally validated GC method, and microbial impurities can be analyzed according to Ph.Eur.5.1.4-2 including Ph.Eur.2.6.12 and 2.6.3.

[0170] The cannabis plant extract or cannabis plant soft extract obtained by the methods described herein can be analysed for wax as follows:

[0171] 1.00 kg of the soft extract can be mixed with 1.75 kg of ethanol and stirred for 30 minutes. The resulting solution can be filtered through a 71 μm metal mesh sieve and ethanol can be added to obtain a solution of soft extract and ethanol in a ratio of 1:2.3. The solution can be placed in a freezer for 48 hours (winterization). After 48 hours, there may not be a noticeable fat layer on the top and only a few small streaks of opaque plaque / strings may be visible. Filtration can be performed using a 50 μm metal mesh sieve and a second 21 μm metal mesh sieve. The dark fatty material can be collected. The collected dark fatty material can be dissolved in about 30 ml of ethanol and centrifuged. For example, if 20 grams of wax is obtained, the wax content of the cannabis plant extract is about 2%.

[0172] The cannabis plant extract obtained by the method described herein is preferably substantially free of or contains very little wax and other non-specific fat-soluble substances, but preferably contains substantially all of the cannabinoids naturally present in the plant, most preferably in substantially the same proportions as they are present in the intact cannabis plant. In other words, the cannabis plant extract obtained by the method described herein is preferably substantially free of or contains very little saponifiable substances. Saponifiable substances as used herein may refer to lipids including free fatty acids, triglycerides, and waxes (monoesterified fatty acids). The cannabis plant extract obtained by the method described herein preferably contains less than 10% by weight, less than 9% by weight, less than 8% by weight, less than 7% by weight, less than 6% by weight, less than 5% by weight, less than 4% by weight, less than 3% by weight, less than 2% by weight, or less than 1% by weight of saponifiable substances, most preferably less than 8% by weight. The cannabis plant extract or cannabis plant soft extract obtained by the method described herein preferably contains less than 3% by weight, less than 2.1% by weight, or less than 2% by weight of wax.

[0173] As mentioned above, the cannabis plant extract obtained by the methods described herein preferably contains THC.

[0174] Thus, the composition (i.e. cannabis plant extract or cannabis plant soft extract) is envisaged to contain THC as the predominant cannabinoid, but does not exclude the optional presence of other cannabinoids including, but not limited to, cannabidiol (CBD), D-8-tetrahydrocannabinol (delta-8-THC), cannabidiolic acid (CBDA), cannabichromene (CBC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabinol (CBN), cannabigerolic acid (CBGA), and cannabigerol (CBG). In particular, it will be appreciated that compositions of the invention that contain THC as the predominant cannabinoid may contain small amounts of CBD, for example less than 10% CBD by weight of the composition, or less than 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.2%, or 0.1% CBD by weight of the composition, or may contain no measurable CBD at all. In the present invention, it is preferred that the composition contains less than 0.5% CBD by weight of the composition, less than about 3.1% CBG, and less than about 2.5%, 2.2%, 2.1%, 2.0%, 1.9%, 1.8%, 1.7%, 1.6%, or 1.5% other cannabinoids, preferably less than about 1.7% other cannabinoids by weight of the composition. Total cannabinoids, i.e., the cannabinoid fraction, typically comprise the majority of the compounds present in the compositions of the present invention. Preferably, the cannabinoid fraction, excluding THC as the predominant cannabinoid, may be present in an amount of about 6% or less by weight of the extract.

[0175] As already mentioned, the cannabis plant extract obtained by the methods described herein may contain THC. The cannabis plant extract may contain THC in an amount of at least about 60, 65, 70, 75, or 80 percent, preferably at least about 70 percent by weight of the cannabis plant extract. Preferably, the cannabis plant extract obtained by the methods described herein contains THC in an amount of about 70-74 (70, 71, 72, 73, 74, or any part thereof, e.g., 70.5, 71.5, 72.5, 73.5) percent by weight of the cannabis plant extract. Preferably, the cannabis plant extract contains THC in an amount of at least about 70 percent. Thus, the present invention relates to a cannabis plant extract obtained by the methods described herein that contains delta-9-tetrahydrocannabinol (THC) in an amount of at least about 70 percent by weight of the cannabis plant extract. The term "about" used in the context of THC amount means 20 percent more or less than the indicated value. In the context of the present invention, the amount of THC in any particular cannabis plant described herein can be measured qualitatively and quantitatively using methods well known in the art, such as thin layer chromatography (TLC) or high performance liquid chromatography (HPLC).

[0176] It is clear to the skilled artisan that during the methods described herein (especially during the maceration and / or percolation steps), not only THC but also other substances of the cannabis plant are removed from the cannabis plant material, preferably the cannabis flower material. In other words, in addition to THC, other substances from the cannabis flower material are dissolved in the solvent, preferably ethanol. As already mentioned herein, it is envisaged that the cannabis plant extract obtained by the methods described herein may further comprise terpenes and / or terpenoids. Non-limiting examples of terpenes are α-bisabolol, guaiol, β-caryophyllene, α-pinene, camphene, β-pinene, β-myrcene, delta-3-carene, α-terpinene, p-cymene, limonene, eucalyptol, ocimene, γ-terpinene, terpinolene, linalool, isopulegol, geraniol, α-humulene, nerolidol, caryophyllene oxide, terpineol, valencene, phellandrene, fenchol, borneol, phytol, sabinene, camphor, isoborneol, menthol, cedrene, and / or squalene. Thus, the cannabis plant extract obtained by the methods described herein may further comprise α-bisabolol, guaiol, β-caryophyllene, α-pinene, camphene, β-pinene, β-myrcene, delta-3-carene, α-terpinene, p-cymene, limonene, eucalyptol, ocimene, γ-terpinene, terpinolene, linalool, isopulegol, geraniol, α-humulene, nerolidol caryophyllene oxide, terpineol, valencene, phellandrene, fenchol, borneol, phytol, sabinene, camphor, isoborneol, menthol, cedrene, and / or squalene. Preferably, the cannabis plant extract obtained by the methods described herein comprises α-bisabolol, guaiol, and / or β-caryophyllene.

[0177] Furthermore, the cannabis plant extract obtained by the methods described herein may further comprise flavonoids, non-limiting examples of which include kaempferol, quercetin, orientin, vitexin, apigenin, hyperoside, rutoside, luteolin-7-glucoside, myricetin, isovitexin, isoquercitrin, apiin, luteolin, cannflavin A, and cannflavin B.

[0178] Furthermore, the cannabis plant extract obtained by the methods described herein may further comprise phytosterols and / or vitamins. Non-limiting examples of phytosterols and / or vitamins include β-sitosterol, campesterol, stigmasterol, and α-tocopherol (vitamin E).

[0179] Cannabis plant extracts obtained by the methods described herein may have concentrations of the above substances in the concentrations shown in Figure 1 and Tables 1-7.

[0180] It is therefore envisaged that the cannabis plant extract obtained by the methods described herein comprises delta-9-tetrahydrocannabinol (THC) and terpenes and / or terpenoids. The cannabis plant extract obtained by the methods described herein may comprise delta-9-tetrahydrocannabinol (THC) and terpenes selected from the group consisting of alpha-bisabolol, guaiol and beta-caryophyllene. The invention therefore relates to a cannabis plant extract obtained by the methods described herein comprising delta-9-tetrahydrocannabinol (THC) and terpenes selected from the group consisting of alpha-bisabolol, guaiol and beta-caryophyllene.

[0181] The cannabis plant extract obtained by the method described herein preferably naturally contains THC and α-bisabolol, guaiol, and / or β-caryophyllene. Thus, the cannabis plant extract obtained by the method described herein is preferably an extract derived / obtained from a plant that contains or produces THC and α-bisabolol, guaiol, and / or β-caryophyllene endogenously. Such a plant extract may be derived / obtained from a plant that contains or produces cannabinoids, cannabinoid-like substances, and / or cannabimimetic compounds, and terpenes and / or terpenoids endogenously, provided that it is capable of producing THC and α-bisabolol, guaiol, and / or β-caryophyllene. Alternatively, the cannabis plant extract obtained by the method described herein is an extract derived / obtained from a plant that can produce cannabinoids, cannabinoid-like substances, or cannabimimetic compounds, and terpenes and / or terpenoids, but does not contain or produce them endogenously. Thus, the cannabis plant extract obtained by the methods described herein may be derived from a genetically modified plant capable of heterologously producing THC and α-bisabolol, guaiol, and / or β-caryophyllene in a biosynthetic process.

[0182] As already mentioned, the present invention also relates to a pharmaceutical formulation comprising a plant extract, preferably a cannabis plant extract obtained by the methods described herein. The pharmaceutical formulation may have the chemical composition of the cannabis plant extract obtained by the methods described herein, or may comprise the cannabis plant extract obtained by the methods described herein and further substances, including but not limited to carriers, surfactants, thickeners, adjuvants, etc., in any suitable concentration. The solvents described herein can be completely or partially removed before incorporating the cannabis plant extract into the pharmaceutical formulation, for example by heating the extract under reduced pressure (e.g. under vacuum). The skilled person will recognize that some of the volatile plant metabolites may be removed with the solvent. Alternatively, the solvent may be included in the pharmaceutical formulation as a carrier.

[0183] The term "pharmaceutical formulation" as used herein generally defines a formulation suitable for application / administration to the body for the treatment, care, or improvement of the appearance of the body. The pharmaceutical formulation of the present invention is specifically intended to be applied / administered to a subject that is a patient, preferably a human patient. However, it is also envisaged that animals, particularly companion animals, are treated with the cannabis plant extracts described herein. The term "pharmaceutical formulation" can be used interchangeably with "medicine".

[0184] It is envisaged that the compositions or pharmaceutical formulations described herein are for medical use.

[0185] Likewise, it is envisaged that the plant extract, preferably the cannabis plant (soft) extract, obtained by the method described herein is for use in medicine. Thus, the present invention relates to the cannabis plant (soft) extract, obtained by the method described herein, for use in medicine.

[0186] In other words, the present invention relates to a method of treatment comprising administering to a subject in need thereof a cannabis plant (soft) extract obtained by the method described herein.

[0187] The pharmaceutical formulations described herein can be used in the treatment and / or prevention of pain-related conditions and / or diseases.

[0188] In particular, the present invention relates to a cannabis plant (soft) extract obtained by the method described herein for use in the treatment and / or prevention of cancer pain, acute non-cancer pain, chronic non-cancer pain, and / or complex pain syndrome, more specifically chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain, and / or complex pain syndrome. Particular examples of cancer pain may include chronic cancer pain. Particular examples of acute non-cancer pain include somatic pain, including pain caused by / resulting from tooth extraction, minor skin surgery, skeletal trauma, orthopedic surgery, or tension headaches, and visceral pain, including pain caused by / resulting from dysmenorrhea, acute pancreatitis, or renal / biliary colic, etc. Specific examples of chronic non-cancer pain include neuropathic pain, such as central neuropathic pain, including pain caused by post-stroke thalamic pain or spinal cord injury, and peripheral neuropathic pain, including pain caused by post-herpetic neuralgia, diabetic painful neuropathy, trigeminal neuralgia, idiopathic small fiber polyneuropathy, or antiretroviral therapy-induced neuropathy, etc. Specific examples of complex pain syndromes include fibromyalgia syndrome, complex regional pain syndrome, and migraine headaches.

[0189] In other words, the present invention relates to a method of treating cancer pain, acute non-cancer pain, chronic non-cancer pain and / or complex pain syndrome, more specifically chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain and / or complex pain syndrome comprising administering to a subject in need thereof a cannabis plant extract obtainable by the methods described herein.

[0190] As used herein, the terms "therapy", "treatment" and the like are understood to be acting on a subject, tissue, or cell to obtain a desired pharmacological and / or physiological effect in terms of partial or complete cure of a disease or associated symptoms. The terms "prophylaxis", "prevention" and the like are understood to be prophylactic treatment of a subject in terms of completely or partially preventing the onset of a disease or associated symptoms, arresting its progression, or reducing its severity. As used herein, the term "subject" refers to a mammal, preferably a human.

[0191] Such methods and uses include administering to a patient in need thereof an effective amount of the cannabis plant extract, formulation or pharmaceutical preparation described herein. The term "effective amount" is understood as an amount of the drug sufficient to achieve the desired effect when administered to a patient. A "therapeutically effective amount" can be determined by the treating physician.

[0192] The cannabis plant extract, composition, or pharmaceutical formulation disclosed herein may be administered locally or systemically. It may be administered by any suitable means, including oral, buccal, rectal, nasal, topical (including dermal, buccal, and sublingual), vaginal, or parenteral (including intramuscular, subcutaneous, and intravenous) administration, or in a form suitable for administration by inhalation or insufflation. The pharmaceutical formulations disclosed herein are preferably administered orally, buccal, or topically, as well as by inhalation. The pharmaceutical formulations disclosed herein are most preferably administered by oral administration.

[0193] The cannabis plant extract obtained by the methods described herein can be further processed by any means known in the art to obtain a composition and / or pharmaceutical formulation suitable for administration to animals or humans. In other words, the pharmaceutical formulation can be prepared by any means known in the art. In yet another way, the pharmaceutical formulation can be prepared from the cannabis plant extract obtained by the methods described herein by any means known in the art. It can be prepared as a solid, such as a tablet or filled capsule, or as a liquid, such as a solution, suspension, emulsion, elixir, or capsule filled with these (all of which are for oral administration), in the form of a suppository for rectal administration, or in the form of a sterile injectable solution for parenteral (including subcutaneous) use. Formulations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions.

[0194] Those skilled in the art will understand that the pharmaceutical formulations described herein are formulated to be suitable for application to patients, compatible with the pharmacologic active substances present in the composition, and not to raise undue safety or toxicity concerns.The pharmaceutical formulations described herein can be administered to subjects in appropriate doses.The administration regimen will be determined by the attending physician and clinical factors.

[0195] The invention is also illustrated by the accompanying non-limiting figures and examples. EXAMPLES

[0196] The following examples illustrate the invention.

[0197] 1. Cultivation of cannabis plant material Cultivation was performed in a sealed greenhouse with filtered air supplied through an HVAC stem. To prevent the spread of disease, beneficial insects were used in cultivation, and trained horticulturists regularly visually inspected the plants for disease. Cannabis plants can be propagated by taking cuttings from the mother plant. Thus, the mother plant was kept as a stock of production plants. Cuttings taken from the mother plant were inserted into rockwool cubes and rooted for 3 weeks at a temperature of about 25-29°C and high humidity (usually about 70-90% relative humidity). After rooting, the plants entered a vegetative growth phase, where the plants were allowed to grow larger for about 2 weeks at a temperature of about 22-28°C and a relative humidity of about 60-80%. Once the plants were large enough and ready to flower, the light hours were reduced from 18 hours per day to 12 hours per day to initiate the flowering phase. At the end of flowering (after 8-9 weeks), the female flowers were harvested from the stem. The stem was cut at the bottom and the flowers were separated from the stem. The separated flowers were trimmed and dried in a drying chamber at 26°C for 96 h by constant removal of humid air. TIFF2025503278000004.tif29170

[0198] 2. Dried flower extraction Flowers were trimmed before the drying step, with a minimum content of delta-9-THC equivalent (delta-9-THC + delta 9-THCA * 0.877) of 10 percent by weight. A quantity of 16.7 kg (15.9 kg - 17.5 kg) of pharmaceutical grade ethanol 96% (v / v) (Kraul & Wilkening u. Stelling GmbH) was used per kg of dried flowers. The extraction process was carried out in cylindrical pharmaceutical grade stainless steel extraction vessels (custom-made by Edelstahlbau Tannroda GmbH) with a strainer at the bottom, protected from light, at 15 °C - 25 °C. The extraction was divided into maceration (static extraction) and percolation (moving extraction). Dried flowers were first soaked in half the volume of ethanol (8.35 kg ± 5% per kg of flower) for 24 hours ± 1 hour during maceration, which allowed the dissolution of most of the delta-9-THC and other cannabinoids, as well as associated secondary plant matter such as terpenes (aroma), fats, and chlorophyll. After maceration, the remaining half volume of ethanol was added to the miscella and percolation was started. This allowed the miscella of ethanol and cannabis extract to percolate through the flower material for 69-86 hours at a flow rate of 4.0-5.0 ml / min per kg of flower and was collected in a pharmaceutical stainless steel mobile buffer tank (custom-made by Edelstahlbau Tannroda GmbH).

[0199] 3. Percolate filtration Small floral residues not separated by the strainer of the extraction vessel were removed by filtering the percolate through a pharmaceutical grade polypropylene-based particle filter with a deposition rate of 1.5 μm (Pall GmbH, order no. AB2A0157PH4). The filter was inserted into a stainless steel housing and the percolate was pumped through the filter by a peristaltic pump and collected in a stainless steel tank. The operating pressure and temperature must not exceed 5 bar and 50° C., respectively.

[0200] 4. Percolate Concentration The extraction solvent was evaporated under vacuum using a rotary evaporator (manufacturer: Buechi; model: Rotavapor R-220 Pro; distillation rate: up to 12 liters ethanol / h; flask size: 20 liters; maximum flask volume: 12 liters; continuous feed). Water bath temperature, pressure, and rotation speed were 72 °C, 185 mbar, and 150 rpm, respectively. These conditions resulted in an ethanol vapor temperature of 41 °C to 42 °C and an evaporation performance of about 10 L / h. Evaporation was terminated when the vapor temperature fell below 30 °C, indicating that the ethanol had been almost completely removed. A soft extract was obtained that was almost solvent-free, of dark green to dark brown resin type nature, consisting mainly of delta-9-THCA and partially activated delta-9-THC.

[0201] 5. Decarboxylation of solvent-free soft extracts The complete conversion of delta-9-THCA to delta-9-THC was performed by thermally induced decarboxylation in vacuum. A rotary evaporator was therefore used with water bath temperature, pressure and rotation adjusted to 80 °C, 185 mbar and 150 rpm, respectively. The decarboxylation time was 72 h. The resulting soft extract still had a dark green to dark brown resin type nature, with an average delta-9-THC content of the extract of 70-74 weight percent. The conversion factor between the dried flowers and the soft extract was 4.7 on average.

[0202] 6. Analysis of the obtained extract The cannabis plant soft extract was visually inspected and confirmed to be yellow to green in color.

[0203] The extract was further analyzed by TLC according to Ph.Eur.2.2.27 and the DAB monograph "Eingestellter Cannabisextrakt". The extract was further analyzed by HPLC according to Ph.Eur.2.2.29 and an internally validated method based on "Eingestellter Cannabisextrakt" by comparing the cannabinoid profile with the retention times of reference standards and by the reference chromatogram of this product.

[0204] The extracts were further analyzed by GC according to Ph.Eur.2.2.28 and an internally validated GC-MS method, comparing the terpene / terpenoid profile with the retention times of reference standards and reference chromatograms of the product.

[0205] Moisture content was determined according to Ph.Eur.2.5.12 (Karl Fischer), ethanol content was analyzed according to Ph.Eur.2.2.28 and an internally validated GC method. Microbial impurities were analyzed according to Ph.Eur.5.1.4-2 including Ph.Eur.2.6.12 and 2.6.3.

[0206] The analytical results of the obtained extract are shown in FIG. 1 and Tables 1-7.

[0207] 7. Analysis of the obtained extract for wax 1.00 kg of the soft extract was mixed with 1.75 kg of ethanol and stirred for 30 minutes. The resulting solution was filtered through a 71 μm metal mesh sieve and ethanol was added to obtain a solution of soft extract and ethanol in a ratio of 1:2.3. The solution was placed in a freezer for 48 hours (winterization). After 48 hours, there was no significant fat layer on top, only a few small streaks of opaque plaque / strings were visible. Filtration was performed using a 50 μm metal mesh sieve and a second 21 μm metal mesh sieve. The dark fatty material was collected. The collected dark fatty material was dissolved in about 30 ml of ethanol and centrifuged. About 20 grams of wax was obtained, which means that the wax content was about 2%.

Claims

1. 1. A method for producing a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from a cannabis plant, comprising the steps of: (a) providing a cannabis plant comprising a sufficient amount of delta-9-tetrahydrocannabinol (THC); (b) trimming and drying the flower material separated from the remaining plant material; and (c) treating the flower material of step (b) with a solvent to isolate a cannabis plant extract comprising delta-9-tetrahydrocannabinol (THC) from the flower material. The method includes:

2. 13. The method of claim 1, further comprising evaporating the solvent from the liquid cannabis plant extract to concentrate the extract.

3. 3. The method of claim 2, further comprising heating the concentrated cannabis plant extract to a temperature of 50°C to 150°C to decarboxylate tetrahydrocannabinolic acid (THCA) to delta-9-tetrahydrocannabinol (THC).

4. 4. The method of any one of claims 1 to 3, wherein the cannabis plant comprises delta-9-tetrahydrocannabinol (THC) in an amount of at least 1 percent by dry weight (w / w).

5. 5. A method according to any one of claims 1 to 4, wherein the drying step of the flower material of the cannabis plant as defined in step (b) of claim 1 is carried out at a temperature range of from 20°C to 35°C until the moisture content of the flower material is less than 10 percent.

6. The processing step defined in step (c) of claim 1 comprises the steps of: (i) layering the floral material with a solvent in a ratio of about 1:8.4 (w / w), thereby obtaining a mixture of floral material and solvent; (ii) maceration for about 24 hours at a temperature between 15°C and 25°C, protected from light; (iii) adding more solvent, thereby obtaining a mixture of floral material and solvent in a ratio of about 1:16.8 (w / w); (iv) percolation, where the solvent is allowed to penetrate the floral material at a flow rate of 3.55-5.45 ml / min per kg of floral material, at a temperature of 15° C.-25° C., for 63-97 hours, in the absence of light; and (v) isolating the cannabis plant extract from the cannabis flower material The method of any one of claims 1 to 5, comprising:

7. 7. The method according to any one of claims 1 to 6, wherein the separation step defined in step (v) of claim 6 comprises filtering the cannabis plant extract at a sedimentation velocity of 1.5 μm.

8. Solvents include ethanol, butanol, alkanes (such as pentane, heptane, and propane), ethyl ether, tert butyl-methyl-ether, methyl-ethyl-ketone, acetone, ethyl acetate, and CO ２ The method of any one of claims 1 to 7, selected from the group consisting of:

9. 9. The method according to any one of claims 1 to 8, wherein the method does not include a winterization step.

10. 10. A cannabis plant extract containing delta-9-tetrahydrocannabinol (THC) obtainable by a method according to any one of claims 1 to 9.

11. 11. The cannabis plant extract according to claim 10, wherein the plant extract is in liquid form.

12. 12. The cannabis plant extract according to claim 10 or 11, wherein the plant extract is in solvent-free, decarboxylated form.

13. 13. A cannabis plant extract according to any one of claims 10 to 12, or obtainable by the method of any one of claims 2 to 9, comprising delta-9-tetrahydrocannabinol (THC) in an amount of at least about 60 percent by weight of the extract.

14. 14. A cannabis plant extract according to any one of claims 10 to 13, or a cannabis plant extract obtainable by a method according to any one of claims 1 to 9, further comprising one or more terpenes selected from the group consisting of α-bisabolol, guaiol, and β-caryophyllene.

15. 15. A cannabis plant extract according to any one of claims 10 to 14, or a cannabis plant extract obtainable by a method according to any one of claims 1 to 9, for use in medicine.

16. 15. The cannabis plant extract according to any one of claims 10 to 14, or obtainable by the method according to any one of claims 1 to 9, for use in the treatment and / or prevention of chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain or complex pain syndrome.

17. 15. A method for the treatment and / or prevention of chronic cancer pain, somatic pain, visceral pain, central neuropathic pain, peripheral neuropathic pain or complex pain syndrome comprising administering a cannabis plant extract according to any one of claims 10 to 14, or a cannabis plant extract obtainable by a method according to any one of claims 1 to 9.

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