WO2019198001A1

WO2019198001A1 - Method for producing a spheroid comprising cannabidiol

Info

Publication number: WO2019198001A1
Application number: PCT/IB2019/052937
Authority: WO
Inventors: Michel Iderne; Olivier Jacob
Original assignee: Ghs Patents Limited
Priority date: 2018-04-11
Filing date: 2019-04-10
Publication date: 2019-10-17
Also published as: FR3080278B1; FR3080278A1

Abstract

The invention relates to a method for producing a spheroid comprising cannabidiol, in which: the mixing of an isolated active substance, an active solution of plant origin containing said active substance or a precursor thereof with an absorbent and adsorbent substance exhibiting plastic properties is carried out; b) said mixture is extruded until an extruded product is obtained; and c) said extruded product is spheronised until a spheroid is obtained, said method being characterised in that said isolated active substance consists of cannabidiol and in that said active solution of plant origin consists of an active extract of a plant of the genus Cannabis sativa L, containing cannabidiol and/or a precursor of cannabidiol.

Description

PROCESS FOR PRODUCING A SPHEROID COMPRISING CANNABIDIOL

The present invention is in the field of cannabidiol-based drug compositions in the form of spheroids, or cannabidiol-based food supplements in the form of spheroids.

It also relates to a process for manufacturing said spheroids containing cannabidiol, and as such, the spheroids comprising between 3 and 30%, preferably between 3 and 10%, by weight of cannabidiol relative to the total weight percentage.

Finally, it relates to the applications that result for the administration of these spheroids orally, especially in the field of health, pharmacy, cosmetology, for humans or animals.

The molecule of cannabidiol called "CBD" is one of the many cannabinoids present in the composition of hemp, the latter is a plant of the genus Cannabis sativa L.

The term "CBD" in the present application refers to a molecule: 2- (IR, 6R) -2-methyl-prop-1-en-2-ylcyclohex-2-en-1-yl) -5-pentylbenzene. 1,3-diol; with as CAS no .: 13956-29-1).

CBD is a different molecule of delta-9-tetrahydrocannabinol called "THC".

"CBD" is produced in the plant of the genus Cannabis sativa L via the same metabolic route as "THC" except until the last stage. Indeed, the metabolic pathway producing "CBD" or cannabidiol-carboxylic acid ends with a chemical reaction step which is enzymatic catalysis with the enzyme CBDA-synthase, instead of the THCA synthase for making THC .

Below is the chemical representation of the topological formulas of THC and CBD and their synthetic metabolic pathway:

Cannabidiol is a cannabinoid which is cyclohexene which is substituted with a methyl group at the 1-position, a 2,6-dihydroxy-4-pentylphenyl group at the 3-position and a prop-1-en-2-yl group at the 4-position. Administration of CBD to a patient exerts anti-proliferative, anti-angiogenic activity, i.e., prevents cell angiogenesis and pro-apoptotic through a variety of mechanisms. These mechanisms do not imply a priori the signaling by the cannabinoid receptor CBD1 or CBD2, or the vanilloid receptor 1. Indeed, recent studies have shown that CBD acts as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant receptor coupled with G protein (GPCR) in the body. Allosteric regulation of a receptor is achieved by modulating the activity of a receptor at a site that is functionally distinct from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are of therapeutic importance since direct agonists are limited by their psychomimetic effects, whereas direct antagonists are limited by their depressant effects.

CBD is not a psychoactive unlike THC.

In recent years, the molecule "CBD", for example taken in oral form, has demonstrated clinical efficacy especially for patients with epilepsy, especially Dravet syndrome. A drug, Epidiolex ®, which is oral solution of Cannabidiol titrated to 100 mg / ml, has recently been available in France on prescription via a temporary authorization of use said ATU.

In France, the clinical potential of "CBD" has also been recognized, notably by the marketing authorization of a drug, Sativex ®, for spasticity linked to multiple sclerosis, containing a ratio of 1: 1 of "CBD" and THC Tetrahydrocannabinol.

Recent clinical studies have also demonstrated the selective anti-cancer potency of cannabidiol. These studies show that "CBD" only acts on cancer cells by sparing healthy cells. Other studies of "CBD" also show its analgesic and anti-inflammatory effect. Specifically, CBD enhances the generation of reactive oxygen species (ROS), further enhancing apoptosis. This agent also regulates the expression of intercellular adhesion molecule 1 (ICAM-1) and the tissue inhibitor of matrix metalloproteinases-1 (TIMP1) and decreases the expression of the DNA binding inhibitor. 1 (ID-1). This inhibits cancer cell invasion and metastasis.

In addition, it has also been discovered that CBD can also activate the transient receptor potential of vanilloid type 2 (TRPV2), which can increase the uptake of various cytotoxic agents into cancer cells. The analgesic effect of CBD is caused by the binding of this agent to CB1 activation.

Given the clinical potential of "CBD", it is a question of the future to find an ideal and practical galenic form of ingestion of "CBD" for its administration by the patient:

- keeping an efficiency comparable to, or even superior to, conventional dry galenic forms,

- by limiting manufacturing costs,

- by limiting the number of excipients required,

by minimizing the general toxicity while stabilizing the active ingredient of cannabidiol over time,

by facilitating its ingestion, in particular by having a practical dosage form, in particular for patients suffering from spasms or with reduced mobility.

Thus, all of these objectives are achieved by proposing a spheroid more weakly titrated effective active principle of cannabidiol, which has a recognized pharmacological, cosmetic or dietary action, while respecting the doses prescribed by the standards of the pharmaceutical field.

In the usual way in the pharmacological or cosmetological field, when a plant with medicinal potential is discovered, the practice is to identify and isolate the active ingredient responsible for the therapeutic effect for its use in admixture with excipients in a drug.

This active ingredient, isolated and purified from the plant, is rid of its ancillary compounds. It is supposed to have maximum therapeutic activity.

However, in most cases, the isolated active principle derived from the plant is not stable or does not have all the physico-chemical properties required, such as solubility, to be used in the manufacture of a drug.

This active ingredient identified and isolated is then generally:

- Either chemically converted to give an appropriate derivative of the precursor plant compound, then it is used as an active ingredient in the final drug,

- Is obtained by semisynthesis, or total synthesis, to ensure a regular supply and consistent quality.

However, as the therapeutic activity is proportional to the amount of active ingredient contained in the drug, the risks of toxicity or of troublesome side effects for the body increase with the amount of active ingredient in the drug.

The recommended dose of active principle will be defined as being a pharmaceutically acceptable compromise between the clinical efficacy sought for a drug containing the active ingredient, for example CBD, and the risk and the dangerousness of the side effects that may result therefrom.

In view of this, the need exists to have drug formulations based on cannabidiol which while maintaining satisfactory efficacy, would be less toxic to the body, with few side effects.

The invention responds to this need by providing a drug composition based on cannabidiol in a dosage form of a spheroid. Moreover, in addition to the problem of toxicity of a substance containing cannabidiol, it is necessary to reduce its cost of manufacture to make it accessible to a maximum number of people, this even in the countries of the third world.

By decreasing the amount of isolated active ingredient necessary to achieve an effective formulation, the cannabidiol-based spheroids of the invention make it possible to be satisfactory drugs or food supplements because they are obtained directly from a vegetable solution of Cannabis. sativa L low cost and present at a minimum titration of isolated active principle. The manufacturing cost of the cannabidiol-based spheroids of the invention is therefore lower than that of conventional drugs, while retaining the same pharmacological efficacy of the desired "CBD".

It should be noted that the dosage form of a drug containing cannabidiol must be stable and durable over time, especially to maintain the physicochemical and therapeutic properties of "CBD", this is a goal to be achieved for all compositions containing "CBD". In addition, the storage and preservation conditions of a composition or a drug containing cannabidiol should be facilitated, while limiting its manufacturing costs.

Thus, the object of the invention is to provide a dosage form of drug or food supplement containing cannabidiol which is stable over time, inert with respect to the physico-chemical properties and the therapeutic effect of cannabidiol, inexpensive to manufacture, keep, store and package easy.

Thus, the present invention aims to overcome the drawbacks of the state of the art, by proposing a method of manufacturing a spheroid in which:

a) an isolated active principle, an active solution of vegetable origin containing said active principle or a precursor thereof, is mixed with an absorbing and adsorbent substance having plastic properties, b) said mixture is extruded until the desired active substance is obtained. 'a product extruded,

c) spheronizes said extruded product until a spheroid is obtained.

According to a specificity of the invention, said isolated active ingredient consists of cannabidiol.

According to the invention, said active solution of vegetable origin consists of an active extract, derived from a plant of the genus Cannabis sativa L, containing cannabidiol and / or a precursor of cannabidiol.

According to the invention, said precursor cannabidiol consists of cannabigerol called "CBG" preferably in its acid form.

According to a preferred embodiment, said active solution of vegetable origin is devoid of THC.

According to the invention, the active solution of plant origin consists of an active extract which is derived from a plant of the genus Cannabis sativa L whose total THC content is less than 0.20%.

According to one variant of the invention, the active solution of vegetable origin consists of an active extract which is derived from a plant of the genus Cannabis sativa L to which an inhibitor of THCA synthase has been added.

Advantageously, the cannabidiol-based spheroids obtained, according to the process of the invention, constitute a very stable galenic form, requiring no particular care for its storage and preservation and being inert with respect to cannabidiol, and therefore not not influencing its physicochemical properties or its desired therapeutic effect.

In addition, according to another characteristic of the process of the invention, after step a) of mixing, said mixture is wetted by means of a humidifying liquid.

The humification liquid has the advantage of allowing the cannabidiol to be transported and deposited to the heart of the absorbent and adsorbent substance, for example within the microcavities of the polymer constituting said substance. Thus, the distribution of cannabidiol within the spheroid is uniform and its dissemination after ingestion by the body will be facilitated.

According to another embodiment of the invention, after the spheronization step c):

• The spheroid is dried, and / or

• We calibrate the spheroid, and / or,

• The spheroid is filmed, and / or

• The spheroids obtained are grouped in a capsule or in a capsule.

The step of drying the spheroid allows, by eliminating moisture, to increase its conservation by limiting the risk of microbiological contamination.

The calibration step makes it possible to obtain spheroids, comprising cannabidiol, of controlled and identical particle size. A controlled granulometry of the cannabidiol spheroids can facilitate its conditioning.

The film-coating step of cannabidiol spheroids makes it possible to increase their behavior and their preservation over time, while facilitating their packaging in capsules, capsules or others.

Advantageously, according to the process of the invention, said active ingredient of cannabidiol represents between 3 and 30% by weight relative to the total weight percentage of said spheroid, preferably between 3 and 10%.

According to another embodiment of the invention, said active ingredient of cannabidiol represents less than 0.20% by weight relative to the total weight percentage of said spheroid.

To limit the risks of toxicity and side effects on the body, as well as the manufacturing costs of the spheroid, part of the amount of cannabidiol consists of the isolated active ingredient, while the other part comes from the active solution of plant origin of the genus Cannabis sativa L.

Also advantageously, said solution of plant origin is a liquid plant extract or a mother tincture from a plant of the genus Cannabis sativa L.

The invention also relates to a spheroid comprising cannabidiol prepared and obtained by the method of manufacturing the aforementioned spheroid.

Advantageously, said spheroid of the invention comprising cannabidiol comprises an active extract derived from a plant of the genus Cannabis sativa L containing cannabidiol and / or a precursor of cannabidiol, in particular cannabigerol, preferably in its acid form, and , an isolated active ingredient of cannabidiol, said cannabidiol represents between 3 and 30% by weight relative to its total weight percentage, preferably between 3 and 10%.

According to another embodiment, for the spheroid of the invention, said cannabidiol represents less than 0.20% by weight relative to the total weight percentage of the spheroid.

According to a particular embodiment of the cannabidiol-based spheroid of the invention, said cannabidiol is of synthetic origin or of natural origin.

Preferably, the spheroid of the invention is free of

THC.

According to the invention, the spheroid of the invention can be used as a medicament.

More specifically, the spheroid of the invention can be used for therapeutic purposes in the treatment of cancer.

The present invention also relates to a medicinal composition comprising cannabidiol in a dosage form of spheroids obtained by the method of manufacturing a spheroid of the invention.

The present invention also relates to a dietary supplement comprising cannabidiol in a dosage form of spheroids obtained by the method of manufacturing a spheroid of the invention.

Other features and advantages of the invention will emerge from the detailed description which follows and non-limiting embodiments of the invention.

The present invention relates to a method of manufacturing a spheroid in which an isolated active principle is mixed, a plant-origin solution containing said active ingredient or a precursor thereof, with an absorbent and adsorbent substance having plastic properties.

According to another specificity of the invention, said active solution of vegetable origin consists of an active extract, derived from a plant of the genus Cannabis sativa L, containing cannabidiol and / or a precursor of cannabidiol.

Preferably, use a plant extract of the genus Cannabis sativa L said "agricultural hemp" or "industrial hemp", no trace of psychoactive THC.

Any known techniques for eliminating psychoactive THC may be implemented to have a plant extract devoid of said THC, for example by using THCA synthase inhibitors.

This allows to have a spheroid with, as the only active ingredient, the "CBD".

According to another embodiment of the invention, the active solution of plant origin consists of an active extract which is derived from a plant of the genus Cannabis sativa L whose total THC content is less than 0.20%.

Thus, the spheroid obtained using the manufacturing method of the invention comprises as active ingredient cannabidiol.

"Active ingredient" is understood to mean any molecule or substance having a therapeutic effect when it is present in a composition, in particular a pharmaceutical composition, in any galenic form.

In the present application, cannabidiol is the active ingredient, it can come from two different sources.

The first source of cannabidiol is an "isolated active ingredient" that is either of natural origin or of synthetic origin.

Cannabidiol as an "isolated active ingredient" of natural origin may be derived and isolated directly from the plant of the genus Cannabis sativa L by any appropriate means known.

Cannabidiol as an "isolated active ingredient" of synthetic origin can be obtained chemically in the laboratory, by semisynthesis or by total synthesis.

Cannabidiol as "isolated active ingredient" can be in any physical form, including solid, liquid, pasty, gel or powder.

According to the invention, the second source of cannabidiol, as "active principle", comes from an active solution of plant origin of the genus Cannabis sativa L. This active solution has the advantage of being inexpensive, of extract easily, which makes it easy to obtain.

This plant-based active solution of the genus Cannabis sativa L is preferably a liquid plant extract of a plant of the genus Cannabis sativa L from which the cannabidiol can be extracted directly, or a precursor thereof to chemically transform it by following in cannabidiol.

This active solution of plant origin containing cannabidiol or a precursor of cannabidiol can be obtained from said plant of the genus Cannabis sativa L by any known means such as by aqueous extraction, alcoholic or hydroalcoholic, or by maceration, infusion, decoction, digestion, lixivation or the like.

Preferably, said active solution of vegetable origin is a liquid plant extract derived from a plant of the genus Cannabis sativa L.

According to the invention, said active solution of plant origin is derived from a plant of the genus Cannabis sativa L containing a THC content of less than 0.20% or zero relative to its total weight percentage.

The THC content may be determined, for example, by the Community method for the quantitative determination of delta-9-tetrahydrocannabinol (9-thc) in the varieties of hemp listed in the Annex to Article 1 of the Decree of 22 August 1990 laying down application of article R.5132-86 of the public health code for cannabis. This method is used to determine the delta-9-tetrahydrocannabinol (9-THC) content of Cannabis sativa L. In this method, for a parcel of Cannabis sativa L varieties, one sample consists of 50 or 200 samples. plants.

Each sample is placed without packing it in a canvas or paper bag and then sent to the laboratory responsible for determining the 9-THC content.

Within 48 hours after sampling, the samples are dried by any known method at a temperature below 70 ° C. to constant weight, the humidity being between 8 and 13%.

Dry samples are kept unpacked in the dark at temperatures below 25 ° C. Then, dry samples are cleared of stems and seeds larger than 2 mm.

Then, the dried samples are milled until a semi-fine powder is obtained in a sieve with a mesh size of 1 mm.

In this method, the maximum retention of the powder is 10 weeks in the dry, in the dark and at a temperature below 25 ° C.

Then, to extract 9-THC, 100 mg of powdered analytical sample is weighed and placed in a centrifuge tube. Then 5 ml of extraction solution containing the internal control is added.

The extraction solution consists of 35 mg of squalane per 100 ml of hexane.

The internal standard is squalane chromate graphically pure as internal standard.

Then, it is immersed for 20 minutes in an ultrasonic bath. Then centrifuged for 5 minutes at 3000 rpm and the solute 9-THC supernatant. The latter is injected into the chromatography apparatus and the quantitative analysis is carried out. The gas chromatography apparatus is equipped with a split / splitless flame ionization detector and a column allowing a good separation of the cannabinoids, for example a column. 25 m long and 0.22 non diameter glass capillary impregnated with an apolar phase of the 5% phenyl-methylsiloxane type.

It is calibrated with at least 3 points for the sample from the 50 samples or with at least 5 points for the sample from the 200 samples of plants, containing the points 0.04 and 0.50 mg / ml of 9-THC in extraction solution.

The conditions of the chromatography apparatus are given by way of example for the aforementioned column:

- oven temperature: 260 ° C;

- temperature of the injector: 300 ° C;

- detector temperature: 300 ° C;

- volume injected: 1 ml.

The result is expressed with two decimal places, in grams of 9-THC per 100 grams of assay sample, dried to constant weight. The result is assigned a tolerance of 0.03% in absolute value.

According to another embodiment, said active solution of plant origin is a mother tincture from a plant of the genus Cannabis sativa L.

The mother tincture has the advantage of being poorly dosed, therefore better economically speaking while being of satisfactory efficiency.

According to the invention, the isolated active ingredient, an active solution of vegetable origin containing said active principle or a precursor thereof, is mixed with an absorbent and adsorbent substance having plastic properties.

This absorbent and adsorbent substance must have plastic properties compatible with the extrusion and spheronization steps of the following manufacturing process according to the invention.

The absorbent and adsorbent substance is preferably of the polymer type, such as a natural polymer or synthetic polymer, generally in the form of a powder.

For example, as polymers having suitable absorbent and adsorbent properties and satisfactory plastic characteristics include, for example, microcrystalline celluloses, microfine celluloses, starches, modified starches and polysaccharides.

There may also be mentioned a technical excipient formed of a dry homogeneous mixture of weakly substituted hydroxypropyl cellulosic polymer, in particular of a hydroxypropyl cellulose ether weakly substituted at the groups of the 13-O-glucopyranosilic nucleus. This absorbent substance is particularly useful as a polymer when it is desired to obtain fast-dispersing spheroids of cannabidiol or more strongly titrated.

To give it additional properties, it is also possible to add auxiliary substances to the mixture of step a), such as, for example, other excipients, in particular binders, glidants, lubricant compounds, surfactants or the like.

These auxiliary substances may also be compounds intended to improve the results or the quality of the spheroids according to the invention or to give them new properties.

It can thus be vitamins, minerals and / or other organic components. Examples that may be mentioned include simple sugars with a low energy content, and mineral and organic substances that may correspond in particular to lactose, sorbitol, mannitol, maltodextrins, carbonates, citrates, gelatin, polyvinylpyrrolidone or a cellulose derivative (ethyl, methyl or carboxy) and in particular sodium carboxymethylcellulose crosslinked.

All these auxiliary substances can be mixed simultaneously or successively in any order during the mixing step.

According to a preferred embodiment, during step a) of mixing, the mass of dry absorbent substance, for example microcrystalline cellulose, is wetted with a moistening liquid until a paste is obtained. homogeneous and malleable which can undergo the following steps of the process, that is to say an extrusion and spheronization.

According to a preferred embodiment, the active solution of vegetable origin, of the active extract type derived from a plant of the genus Cannabis sativa L, can advantageously serve as humidifying liquid for wetting.

If the amount of liquid provided by the active solution of plant origin is insufficient, the addition of another liquid, aqueous or non-aqueous, may sometimes be necessary.

The moistening liquid also serves as a carrier for transporting and depositing the isolated active ingredient cannabidiol to the core of the absorbent and adsorbent material in the microcavities of the polymer.

According to another characteristic of the process of the invention, after step a) of mixing, the following steps are carried out:

said mixture is extruded until an extruded product is obtained (step b),

said extruded product is spheronized until a spheroid is obtained (step c).

In other words, after step a) of mixing, the wet mass of mixture is extruded through a calibrated orifice die, then made spherical, that is to say that the extruded product is spheronized. .

During the extrusion process, the wetted mass is compacted and stretched into compact filaments of generally cylindrical and defined section called "extrudates".

To obtain spheroids, the "extrudates" are placed in a cylindrical apparatus called "spheronizer" containing, at its lower part, a disc rotating at a variable and controlled speed. Under the effect of the centrifugal force exerted by the rotation of the rotating disk, the "extrudates" are fragmented regularly and then turn into spheres by a rolling-binding effect.

It has been found that the possibility of transforming "extrudates" into spheroids of homogeneous sphericity, of regular particle size previously defined, depends as much on the plastic characteristics of the extrudates, and therefore the plastic characteristics of the wetted mass, than characteristics related to the actual spheronization operation, ie the speed of rotation of the rotating disk and the duration of its rotation.

According to a characteristic of the invention, to obtain a suitable plasticity, compatible with the extrusion and spheronization techniques, the moistening liquid mass is preferably between 3 and 5 times the mass of absorbent substance used.

A particular characteristic of the invention mentioned by way of example consists in preparing spheroids with a particle size of between 350 microns and 1250 microns, for a yield of at least 95% of the mass of spheroids produced.

In this case, the die of the extruder has orifices of 1000 microns in opening diameter and 1000 microns in length (thickness of the die). The extrusion speed is 100 rpm for a twin screw or other type extruder apparatus.

The spheronization cycle for a spheronization apparatus of 25 cm diameter or other is then of a duration of 5 minutes with a rotation speed of 1040 rpm.

According to a preferred embodiment, the spheroids may then undergo a drying step, preferably at a temperature in the region of 35 ° -40 ° C. They may otherwise simply be left in the open air for a certain time.

According to another embodiment, the spheroids may be calibrated, that is to say passed through a calibration device, constituted for example by a set of sieves, in order to obtain spherical multi-particle particle size systems. controlled.

Spheroids containing cannabidiol as the active ingredient obtained are stable over time, easy to control and reproducible. They are of simple and practical use. They can be stored without care or special care and are easily transportable because they are light, compact and not very fragile.

The spheroids according to the present invention can be presented as such or coated in bulk, dosing dispensers, capsules, tablets, sachets or any other suitable form.

Preferably, they are grouped into capsules or capsules, corresponding to an amount of active ingredient determined according to the specific dosage of the composition and allowing an easier unit setting.

Prior to their packaging, for example in capsule form, these spheroids may, in addition, be film-coated during an additional optional step of the process according to the invention.

This operation consists in covering them with a resistant coating film making it possible to protect the molecules of active principle, for example sensitive to the low pH of the stomach or degraded by the enzymes of the intestinal lumen.

It also makes it possible to regulate the release of the active ingredient of cannabidiol into the body. The release can thus be delayed in order to deliver the cannabidiol selectively to certain levels of the digestive system, for example gastric and upper parts of the small intestine.

By using different types of coatings for the spheroids of the same capsule, it is also possible to successively deliver several doses of cannabidiol by means of a single dose of composition.

Advantageously, the method according to the invention makes it possible to obtain a dosage form for solid cannabidiol that is easy to use and in particular that can be administered orally. In addition, this dosage form ensures the physical and chemical stability over time of cannabidiol used even under unfavorable storage conditions.

Surprisingly, with the composition according to the invention, a reinforced activity of cannabidiol is observed, which makes it possible to produce formulations that are more effective or comparable in their effectiveness, but less dosed and therefore less effective. toxic to the body.

This overactivity can be explained on the one hand by the exceptional bioavailability of cannabidiol loaded onto the spheroids according to the invention. Indeed, after oral absorption of the composition according to the invention, a rapid release of cannabidiol takes place in the stomach, the gastric fluid performing the necessary leaching. The entire active ingredient is released very quickly, in a controlled and reproducible manner.

On the other hand and in an essential manner to the invention, the combination of the two sources of cannabidiol within the same composition achieves a synergy that increases the therapeutic effectiveness of cannabidiol.

The active solution of vegetable origin, in addition to providing an additional quantity of cannabidiol, provides the composition according to the invention with all the other compounds present in the plant and accompanying the cannabidiol or its precursor in its natural state. Cannabidiol, thus enriched with the compounds initially present at its sides in the plant, is enhanced by a real synergistic effect.

For all these reasons, the spheroids comprising cannabidiol according to the invention constitute an original formulation and of great interest for preventive and curative medicine.

It is thus possible to reduce the toxicity of a drug treatment based on cannabidiol, but especially to reduce considerably the price, which is a crucial aspect for the underdeveloped countries.

Thus, the present invention has the advantage of proposing a new pharmaceutical means; inexpensive, low toxicity, limiting the risk of side effects for the body, easy preservation, easy ingestion by patients; to use cannabidiol as the active ingredient of a drug, for example an analgesic, an anti-inflammatory, an anti-cancer.

Claims

A method of manufacturing a spheroid comprising cannabidiol wherein

a) an isolated active principle, an active solution of plant origin containing said active principle or a precursor thereof, is mixed with an absorbing and adsorbent substance having plastic properties,

b) extruding said mixture until an extruded product is obtained,

c) spheronizes said extruded product until a spheroid is obtained,

characterized in that said isolated active ingredient consists of cannabidiol and said active solution of vegetable origin consists of an active extract, derived from a plant of the genus Cannabis sativa L, containing cannabidiol and / or a precursor of cannabidiol .

2. A method of manufacturing a spheroid comprising cannabidiol, according to the preceding claim, characterized in that said active solution of plant origin consists of an active extract from a plant variety of the genus Cannabis sativa L whose delta content 9-tetrahydrocannabinol is less than 0.20% by weight relative to the total weight percentage of said plant variety.

3. A method of manufacturing a spheroid comprising cannabidiol according to any one of the preceding claims, characterized in that said precursor cannabidiol is cannabigerol, preferably in its acid form.

4. A method of manufacturing a spheroid comprising cannabidiol according to any one of the preceding claims, wherein after step a) of mixing, said mixture is wetted by means of a humidifying liquid.

A method of manufacturing a spheroid comprising cannabidiol according to any one of the preceding claims, wherein after the spheronization step c): - The spheroid is dried, and / or

- We calibrate the spheroid and / or,

- We film the spheroid and / or

- We group together the spheroids obtained in a capsule or in a capsule.

6. A method of manufacturing a spheroid comprising cannabidiol, according to any one of the preceding claims, characterized in that said isolated active ingredient cannabidiol is between 3 and 30% by weight relative to the total weight percentage of said spheroid.

7. A method of manufacturing a spheroid comprising cannabidiol, according to any one of the preceding claims, characterized in that said active solution of plant origin is a liquid plant extract or a mother tincture from a plant of the genus Cannabis sativa L.

8. Spheroid comprising cannabidiol, characterized in that it is obtained and prepared by the method of manufacturing a spheroid comprising cannabidiol, according to any one of the preceding claims.

9. Spheroid comprising cannabidiol, according to the preceding claim, characterized in that it comprises an active extract derived from a plant of the genus Cannabis sativa L containing cannabidiol and / or a precursor of cannabidiol, and an active ingredient isolated from cannabidiol, said cannabidiol represents between 3 and 30% by weight relative to its total weight percentage.

10. Spheroid comprising cannabidiol according to claim 8, characterized in that it is free of delta-9-tetrahydrocannabinol.

11. Spheroid comprising cannabidiol according to claim 8, characterized in that said cannabidiol is of synthetic origin or of natural origin.

A spheroid comprising cannabidiol according to claim 8 or 10, characterized for use as a medicament.

13. Spheroid comprising cannabidiol, according to the preceding claim, characterized for its use in the treatment of cancers or tumors.

14. A medicinal composition comprising cannabidiol, characterized in that it is in a dosage form of spheroids comprising cannabidiol obtained by the method according to any one of claims 1 to 5.

15. Dietary supplement comprising cannabidiol, characterized in that it is in a dosage form of spheroids comprising cannabidiol obtained by the method according to any one of claims 1 to 5.