WO2020229711A1

WO2020229711A1 - Micro- and nanoemulsions of hemp oil cannabinoids

Info

Publication number: WO2020229711A1
Application number: PCT/ES2019/070769
Authority: WO
Inventors: Jaime Antonio FABREGAS CASAL
Original assignee: Elixinol, B.V.
Priority date: 2019-05-10
Filing date: 2019-11-11
Publication date: 2020-11-19
Also published as: ES1245259U; ES1245259Y

Abstract

The invention relates to the method for obtaining a micro- and nano-emulsion of cannabinoids containing hemp oil which converts the oil triglycerides into monoglycerides and diglycerides with emulsification capacity. The method allows the use of a smaller amount of surfactants compared with traditional systems. The cannabinoid-containing micro- and nano-emulsion contains mainly cannabidiol (CBD), as do the beverage, food product, complement or supplement, and cosmetic or pharmaceutical compositions comprising said micro- and nano-emulsions. The method for obtaining these is biochemical and chemical, and the application relates to the fields of food science, food complements and supplements, cosmetics and medicine.

Description

Micro and nanoemulsions of cannabinoids from hemp oil

DESCRIPTION

The invention refers to the procedure for obtaining a micro and nanoemulsion of cannabinoids containing hemp oil that transforms the triglycerides of the oil into mono and diglycerides which have emulsifying capacity. This procedure allows the use of fewer surfactants than traditional systems. The micro and nanoemulsion comprising cannabinoids, mainly contains cannabidiol (CBD), as well as the beverage, food, supplement or supplement, and cosmetic or pharmaceutical compositions comprising said micro and nanoemulsions. The obtaining procedure is biochemical and chemical, and the application is framed in the sector of food, supplements and food supplements, cosmetics and medicine.

BACKGROUND OF THE INVENTION

The global demand for cannabinoids is increasing. Most of the naturally occurring cannabinoids come from! hemp oil. Hemp refers to three species: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Humans have cultivated and used cannabis for thousands of years, from the ancient Romans and Greeks to the Middle East, Africa, China, and India. There are more than 100 cannabinoids from hemp. The best known are the non-psychoactive cannabidiol (CBD) and the psychoactive tetrahydrocannabinol (THC).

Many clinical trials report the health benefits of cannabinoids and, specifically, cannabidiol (CBD).

In general, a first step in concentrating the cannabinoids in hemp is to extract the oil from the leaves or trichomes. Different methodologies are used, one of them is pressure treatment and, subsequently, they are concentrated with little polar solvents or with supercritical CO ₂ . Cannabinoids are more soluble in nonpolar liquids. This feature makes it easy to use solvents effective as hexane and methanol, among others, to dissolve them, since polar dissolves its polar. A traditional extraction is to use a solvent such as hexane that extracts the cannabinoids, but also other molecules of similar polarity and, later, remove the hexane with a rotary evaporator. The final product is an oil that is generally solid at room temperature due to the presence of high molecular mass lipids, generally waxes. Some of these lipids can be separated from the rest of the oil through freeze-thaw cycles, producing an oil that is liquid at room temperature. This methodology makes it possible to obtain an oil with a concentration from 2% to 70% of cannabinoids, preferably from 20% to 65%, depending on the concentration or partial purification process. Afterwards, chromatographic methods can be used to concentrate the cannabinoids, separating them from the rest of the components present in the oil. Chromatographic methods make it possible to obtain cannabinoids with a purity level greater than 95%, even though they are time consuming and costly. The cannabinoids contained in hemp oil, specifically cannabidiol (CBD), are not very polar and are insoluble in water. This characteristic makes intestinal absorption difficult.

To more effectively use cannabinoids in food, beverages, supplements or food supplements, cosmetics or medicine, it is necessary to microcapsulate, nanocapsulate or make micro and nanoemulsions of cannabinoids, among other methodologies and, always with a size smaller than 55 micrometers so that they can be absorbed by the intestinal villi. To produce micro and nanoemulsions of the cannabinoids contained in hemp oil, it is necessary to micro and nanoemulsify the fraction of the oil that mainly contains the triglycerides of fatty acids. To achieve this goal, a high concentration of non-ionic surfactants is needed generally in an oil / surfactant ratio of 1: 9 for the micro and nanoemulsion to be translucent or transparent when dissolved in water, since they are not only micro and nanoemulsified cannabinoids if not also, it is necessary micro and nanoemulsify triglycerides. If we initially transform triglycerides from hemp oil to di- and monoglycerides of fatty acids, simple fatty acids, and glycerol, then a much lower concentration of surfactants will need to be used to micro and nanoemulsify cannabinoids since di- and monoglycerides, some acids Fatty acids and glycerol not only dissolve in water because they are more polar, but also act as surfactants and cosurfactants in the case of glycerol Hemp oils from different sources contain high levels of linoieic acid from 56% to 60%, followed by a-linolenic acids from 16% to 20%, oleic from 10% to 15%, palmitic from 5% to 9%, stearic from 2% to 3%, g-linolenic from 0.6% to 2%, among other components. Most of these fatty acids are esterified with glycerol to form triglycerides. They can also get cannabinoids, usually between 20 and 50%. These esterified fatty acids from hemp oil are low polar, and do not dissolve in water. To micro and nanoemulsify them together with cannabinoids, it is necessary to use high concentrations of surfactants and cosurfactants.

It is known that lipids with a higher molecular mass need a higher concentration of surfactants to produce micro and nanoemulsions than do lipids with a lower molecular mass.

It is known that the production of a micro and nanoemulsion of an oil in water, which is translucent or transparent, requires a high concentration of surfactant. For example, to make a transparent dispersion of hemp oil phytocannabinoids in water, a weight ratio of hemp oil phytocannabinoids to non-ionic emulsifier of 1: 5 to 1: 10,000 (Water-soluble phytocannabinold formulations. Patent number US9907823).

On the other hand, hemp oil lipolysis occurs when lipases are mixed with the oil. In some procedures, such as the patent "Process for producing partial glyceride US 6,337,414", a process of glycerolysis of oil or fat is described using a lipase in the presence of water, but it does not use a mixture of the oil. with the surfactant and the ipase dissolved in water, as performed in the present invention. The surfactant increases the contact surface of the lipase with the oil and improves the efficiency of glycerolysis. Also, it does not claim its use for hemp oil.

The US patent "Nanoemulsion compositions and methods of use thereof (No. 1187,118,688) uses a nanoemulsion composition comprising a protein or protein fragment complex and wherein the nanoemulsion contains hemp oil, and at least one Phospholipid selected from a group consisting of phosphatidylserine with a concentration equal to or greater than 40% in addition, it uses phosphatidylserine because it plays a critical role in the maintenance of optimal mental performance and in addition, the preferred formulation is the inclusion of phospholipids rich in phosphatidylserine in the oil phase after emulsification Hemp oil is also used in the present invention, but unlike the above mentioned patent, it uses phosphatidylserine as an emulsifier and also at a concentration lower than 40%.

The patent application "Pre-spray emulsifies and powders containing non-polar compounds" Number: PCT / US2015 / 051097, also uses phosphatidylserine, but at a concentration of 40% or higher. In the present invention, phosphatidylserine is used at a concentration of less than 40%.

The patent "Cochleates made witb soy phospbatidylserine" No: 1189,775,907 uses soybean phosphatidylserine which is 40% to 74% pure and a multivalent cation. In the present invention phosphatidylserine with a purity of less than 40% is used and multivalent cations are not used.

DESCRIPTION OF THE INVENTION

The first aspect of the present invention is a process for obtaining a micro and nanoemulsion of a size smaller than 55 mm from hemp oil comprising cannabinoids, characterized in that it comprises the following steps: i. treat a hemp oil that contains cannabinoids,

- with at least one lipase enzyme that transforms the lipids with the highest molecular mass to di- and monoglycerides of fatty acids, fatty acids and glycerol, for a time of between 1 minute up to 72 hours of treatment, and at a temperature between 2 ° C and 60 ° C;

or

transesterifying by chemical treatment with KOH or NaOH from 0.5% to 1% by weight as catalysts, where the alcohol / oil ratio is from 3: 1 to 6: 1;

ii. adding at least one antioxidant to the product obtained in step (i); and iii. provide energy to the product obtained in stage (ii), by means of a method selected from stirring at a stirring speed of between 100 rpm and 30,000 rpm, where the action time is between 10 seconds and 1 hour, or by ultrasound, at a power between 20 and 3,000 watts and at a frequency between 10 and 30 kHz for a sonication time of between 5 seconds and 10 minutes.

In the present invention, "emulsion" is understood to be a colloidal dispersion of two immiscible liquids, such as oil and water, in the form of drops. If the oil droplets are finely dispersed in water, then it is an oil-in-water emulsion. When the water droplets are finely dispersed in oil, it is a water-in-oil emulsion.

In the present invention, "micro and nanoemulsions" is understood to refer to the production of a mixture of micro and nanoemulsions of hemp oil containing cannabinoids with the same procedure. They differ from an emulsion in that they are thermodynamically stable in the long term without apparent flocculation or coalescence, whereas an emulsion is only kinetically stable, that is, the rate at which the emulsified phase separates from water is slow. In general, microemulsions are considered to have micrometer diameters and can be transparent or translucent. Nanoemulsions have nanometer diameters and are transparent.

In the present invention, "hemp oil" is understood to refer to oil extracted from hemp, mainly from trichomes and preferably without waxes, where cannabinoids can be present from 5% to 50%. In some examples, hemp oil may contain 20% cannabidiol. In the present invention it is understood by "hemp" or industrial hemp! is the name given to the varieties of the Cannabis plant: Cannabis sativa, Cannabis indica and Cannabis ruderalis. The varieties of Cannabis intended for! Is called "industrial hemp". industrial and food use. Hemp contains cannabinoids among many other components. Cannabidiol, also known as CBD is one of the two most important cannabinoid components of the plant, which is found in variable proportions depending on the strain.

In the present invention, "cannabíonoids" are understood to be highly lipophilic molecules with very low levels of aqueous solubility (2-15 mm / mL). They are susceptible to degradation, especially in solution, through the action of light and temperature, as well as through autoxidation. It is found in the Cannabis species. There are more than 100 cannabinoids from hemp. The best known are the non-psychoactive cannabidiol (CBD) and the psychoactive tetrahydrocannabinol (THC). They have a wide range of applications for human and animal health.

In the present invention, "antioxidants" are understood as the recognized fat-soluble natural antioxidants (tocopherols, tocotrienies, beta-carotene and coenzyme Q10).

Hemp oil mainly contains triacylglycerides of fatty acids among other molecules in percentages that can vary, depending on the production method, from 90% to 50%. The triglycerides of the fatty acids in the oil of hemp oil have a higher molecular mass than the diglycerides and these more than the monoglycerides. Furthermore, the di- and monoguerides have a certain emulsifying capacity. Monoglycerides and diglycerides are commonly added to commercial food products in small amounts. They act as emulsifiers, helping to mix insoluble ingredients that would not otherwise mix. This characteristic helps to lower the concentration of surfactants to produce micro and nanoemulsions of hemp oil.

An emulsifying effect similar to the di and monoglycerides ios have ethyl and ios methyl! fatty acid esters (FAME) Therefore, take advantage of the fact that hemp oil contains cannabidiol among other cannabinoids and triglycerides, where both groups can be in different proportions depending on the extraction methodology. As such, the oil (mixture of cannabinoids and triglycerides) is insoluble in water. The advantage provided by this procedure is the initial enzymatic treatment with a lipase to transform the triglycerides into mono and diglycerides that in turn have emulsifying capacity and for this reason it is only necessary to use a very low concentration of other emulsifiers.

The method refers to a process to produce micro and nanoemulsions of hemp oil containing cannabinoids whose iipids have been transformed into di- and monoglycerides of fatty acids or ethyl or methyl esters of fatty acids or a combination of both, to use less concentration of surfactants and cosurfactants so that cannabinoids can be dispersed in a water phase or in a solid food phase, and that they have a diameter less than 55 micrometers and that, in addition, translucent or transparent micro and nanoemulsions are produced in a phase of Water.

In a preferred embodiment of the process of the present invention, the enzymes of step i) are lipases, which produce lipolysis, of animal, microbial or plant origin, from 5 units of lipase per gram of oil to 12,000 units of lipase per gram of oil and they are in an amount of between 0.2 g to 100 g per 100 liters of oil.

Iipase enzymes can act, by definition, at the organic-aqueous interface, catalyzing the hydrolysis of the ester-carboxylate bonds and releasing fatty acids and organic alcohols. In general, the Iipases catalyze the hydrolysis of triacylglycerols to di- and monoglycerols, and to fatty acids and glycerol in a random manner, the intermediate products being mono- and diacylglycerols.

Lipases can be of animal origin (pancreatic, liver, and gastric), microbial (bacterial, fungal, and yeast), or plant, and vary in their catalytic properties. There are different types of lipases. Specific lipases: have glycerol esters as specific substrates. They catalyze the hydrolysis of triacylglycerols, as well as di- and monoacylglycerols. Non-specific lipases: they catalyze the complete hydrolysis of the triacylglycerols into fatty acids and glycerol in a random way, the intermediate products being mono- and diacylglycerols.

Lipases are produced and derived from porcine pancreas, human pancreas, polio adipose tissue, bovine milk, wheat germ. Lipases derived from microorganisms of the genera Rhizopus, Aspergillus, and Mucor, Phizopus delemar, Phizopus oryzae, Rhizopus japonicus, Rhizopus niveus, Aspergillus niger, Asperfillus oryzae, Pseudomonas espacia, Pseudomonas fiáruoresicatica, Candida antifaruoresica, Candida spolyk, fiáruorestica, Candida spolyk, fiáruorestica, Candida antifarica, Candida lipidia. Penicillium camemberti, Mucor javanicus and Mucor miehei.

Lipase activity is measured in U / mL. They act from 5 units of lipase per gram of oil to 12,000 units of lipase per gram of oil, preferably between 100 and 1,200 IU per gram, preferably from 100 U / g to 600 U / g and more preferably from 200 U / g to 400 U / g. The activity of the lipase depends on the origin of the lipases. In other lipases, the activity range varies from 1,200 U / g to 1,800 U / g. In some embodiments, the ratio of porcine type II lipase (100 to 500 Units / mg) to oil may be 5-10 mg / mL, although in another embodiment, it uses 10 grams of oil with 20 mL of water and from 1.5 g to 6 g of lipase. The actuation time preferably ranges from 10 minutes to 120 hours, more preferably 1 to 90 hours. Lipases operate from room temperature to 20 ° C to 50 ° C, preferably between 35 ° C and 50 ° C and are preferably inactivated at 90 ° C.

Depending on the activity, the lipase is added from 0.2 g to 100 g per 100 liters, preferably from 5 g to 20 g per 100 liters, and from 1 minute to 72 hours of treatment, preferably from 1 hour to 24 hours. Temperature can vary from 2 ° C to 60 ° C, preferably from 25 ° C to 40 ° C. Lipases transform the higher molecular weight lipids of hemp oil containing cannabinoids into lower molecular weight products. Lipases do not transform cannabidiol.

In another preferred embodiment of the process of the present invention, the lipase enzymes of step (i) are combined with proteases, amylases or cellulases to decrease the molecular weights of the residual proteins, polysaccharides and cellulose to peptides or amino acids and monosaccharides.

In another preferred embodiment of the process of the present invention the enzymes of step (i) are used in immobilized format.

In another preferred embodiment of the process of the present invention, it also comprises adding at least one surfactant in step (i) in an amount of between 1% and 25% by weight with respect to the initial hemp oil amount.

Immobilized lipases are heat resistant and have high durability over a wide range of concentrations. Many of the immobilized lipases and lipases are readily available as products on the market. The amount of lipase used is preferably 0.1 to 30% by weight, particularly 1 to 15% by weight (200 to 100,000 units per gram of oil or fat) based on the raw materials for the reaction. In another preferred embodiment of the process of the present invention, in the transesterification of step (i) a metonolysis or ethanolysis is produced and it is carried out enzymatically with lipases without the presence of water or in low concentration.

In another preferred embodiment of the process of the present invention, it comprises an additional step (ii ^' ) of adding at least one surfactant after step (ii) and before step (iii), where said surfactant is selected from among natural phosphatidic surfactants and surfactant of animal origin.

In the present invention, "non-ionic surfactant, surfactant, emulsifier or dispersant" refers to different synonyms of a generally amphiphilic agent with a hydrophilic head and a hydrophobic tail with the same or different character. hydrophilic or lipophilic, which tends to decrease the surface tension between two phases and to be non-ionized in neutral solutions. Some examples of non-ionic surfactants are Tween 80, Tween 20, Span 80. It is known that lipids with a higher molecular mass need a higher concentration of surfactants to disperse them in micro and nanoemulsions in an aqueous phase. For example: high molecular volume oils, such as soybean and sunflower oils, can produce a small microemulsion region, while the lower molecular volume triglyceride, tributyrin (butyric + glycerol), produces a large region clear single phase.

In another preferred embodiment of the process of the present invention, if the surfactants of additional step (ii ') are selected from the list consisting of lecithin, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid or their combinations, additionally they are added in combination with at least:

- a non-ionic surfactant, selected from among Tween 20, Tween 40, Tween 80, Tween 80, Tween 21, Tween 85, Tween 65, Tween 81, Tween 61 and Tween 100;

- a surfactant that is selected from the list consisting of Span 20, Span 40, Span 60, Span 85, and Span 85;

- a sulfactant that is selected from the list consisting of starches, milk caseinate, milk powder, soy protein, pea protein and whey protein; or

-any of its combinations; Y

where the weight ratio of total surfactants and hemp oil ranges from 10: 1 to 1: 100.

In another preferred embodiment of the process of the present invention, it comprises adding at least one cosurfactant, where said cosurfactant is selected from the group ethanol, methanol, xylitol, sorbitol, glycerol, maititol or erythritol, or any of their combinations.

In the present invention, "cosurfactant" is generally understood to be alcohols or amines within the C4 to C10 range that help the formation and stabilization of micro- and nanoemulsions. Examples: ethanoi (C2), glycerol (C3), xylitol (C5), erythritol (C4). The production of fatty acid ethyl or methyl esters (FAME) from hemp oil using ethanolysis or methanolysis methodologies. The methanolysis of a fatty compound is the result of three consecutive reactions: partial transesterification of the triglyceride (TG) to form the diglyceride (DG), partial transesterification of the DG to form the monoglyceride (MG), and partial transesterification of the MG to form the FAME and glycerol (G). For the production of FAME, 0.5% to 1% KGH or NaOH are needed as catalyst, ethanol or methanol. Fatty compounds must have an acid value less than 1 mg KOH / g. The alcohol / oil ratio preferably ranges from 3: 1 to 6: 1. The reaction time of 0.1 hours at a temperature of 60 ° C has a FAME production efficiency of 94%.

FAME can be used as solvents and help the dispersion of cannabinoids found in hemp oil and, in this way, a lower concentration of cosurfactants is needed, of surfactants such as iecithins or their derivatives, of biosurfactants, of surfactants natural, certified organic surfactants, and synthetic surfactants such as ios Tweens or Spans, and their combinations, for the production of micro and nanoemulsions of ios cannabinoids present in hemp oil.

It has been found that a lower concentration of non-ionic, natural or ecological surfactants can be used than in current methodologies when using hemp oil processed according to the above methodologies. For example, to hemp oil is added a mixture of two phosphoipids such as the phosphatidiyserine / phosphatidylcholine mixture in a ratio from 1: 10 to 35:65, preferably 1: 5 in a concentration from 1% to 39%. and another non-phospholipid surfactant to produce micro and nano emmisions. Another example is: phosphatidiyserine / phosphatidiicholine and Tween 80, or phosphatidiyserine / phosphatidylcholine and modified starch or phosphatidiyserine / phosphatidylcholine and gum arabic.

Phosphatidiserine is a natural component of all biological membranes and is most concentrated in the brain. The phosphoipids used can be produced synthetically or prepared from natural sources. Lecithins, phosphatidyl choline and phosphatidiyserine are considered Generally Recognized as Safe (GRAS). Both are derived from lecithins of plant or animal origin and are suitable for performing emulsions of micrometric or nanometric range of vegetable and animal oils. In other non-limiting embodiments, phosphatidylserine can be substituted for or combined with phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and phosphatidic acid.

For this reason, surfactants of natural origin such as phospholipids and cosurfactants such as glycerol are used in the present invention to reduce the use of non-ionic surfactants to produce said emulsions. Although non-ionic surfactants are generally safe, consumers demand food, beverages, supplements or food supplements, cosmetics and medicine with low concentrations of non-ionic surfactants and, if possible, natural surfactants and better yet with an ecological name.

In another preferred embodiment of the process of the present invention, it also comprises an additional step (iv) subsequent to step (iii), of adding a drying agent, selected from maltodextrins, glucose, lactose, maltitol, xylitol, erythritol, fructose, methyl cellulose, hydroxypropylmethylcellulose, monophosphate, diphosphate, triphosphate, polyphosphate, citric, citrates, ascorbic, ascorbate, microcrystalline cellulose, whey protein, milk protein, hemp protein, pea protein, soy protein, milk powder or combinations thereof so that the emulsion is in powder form, in an emulsifier / oil weight ratio between 4: 1 to 7: 1, and later grinding in high speed mill, hammer mill, roller mill, disk mill, mill ball, mortar, or any food mill with fine or ultrafine process types. In a more preferred embodiment the desiccant is selected from among monophosphate, diphosphate, triphosphate, polyphosphate, citric, citrates, ascorbic, ascorbate.

When adding any desiccant in the indicated weight ratio, the final volume increases in the order of 10 times the initial volume, however, if the desiccant is selected from among monophosphate, diphosphate, triphosphate, polyphosphate, citric, citrates, ascorbic, ascorbate the volume increases less than double, facilitating the formation of the micro and nanoemulsion.

In another preferred embodiment of the process of the present invention, it also comprises an additional step (v) . of dispersing the product obtained in step (iii) or (iv) in an aqueous phase; or

. to absorb the product obtained in stage (iii) or (iv) in a solid phase from 5 mg in 100 mL to 10 g in 100 mL, producing transparent emulsions.

In the present invention, "clear or transparent" is understood to refer to an aqueous solution containing the lipophilic compound in a water-containing solution that is free of visible particles of dispersed (non-dissolute) compound.

In another more preferred embodiment of the process of the present invention, it further comprises adding at least one cyclodextrin in an amount in percentage by weight of between 5% and 400% with respect to the initial hemp oil, selected from a-Cyclodextrin, b -Cyclodextrin, y-Cyclodextrin, d-Cyclodextrin and derivatives such as 2-Hydroxypropyl- b-cyclodextrin, 2, Hydroxyethyl- b-iclodextrin, 2-Hydroxypropyl- y-cyclodextrin, 2-Hydroxypropyl-a-cyclodextrin, Methyl-b-cyclodextrin , Carboxymethyl-b-cyclodextrin sodium sai, 2-Carboxyethyl-b-iclodextrin, sodium salt, Acetii- b-iclodextrin, Succinyl-cyclodextrin, Succinyl-a-cyclodextrin, Butyl-b-iclodextrin or Butyl-y-cyclodextrin and any combination of the above,

• just before stage (v); or

• the product obtained from step (v);

The liquid or solid emulsion has the characteristic smell and taste of hemp. The removal or suppression of taste and odor can provide an advantage over other procedures. The characteristic hemp odor and taste of the emulsion can be removed or suppressed using cyclodextrins. Cyclodextrins are ring-bound monosaccharides (cyclic oligosaccharides) of 5 or more α-D-glucopyranoside (cyclic glucose) units.

Although cyclodextrins are used in the pharmaceutical industry to increase the solubility of some drugs in water, they can also be used to trap volatile odor-related molecules and taste-related molecules.

A second aspect of the present invention is a micro and nanoemulsion obtained according to the procedure described above. A third aspect of the present invention refers to a micro and nanoemulsion (henceforth the emulsion of the present invention) characterized in that it comprises

• at least one cannabinoid in an amount in percentage by weight with respect to the total emulsion of between 5% and 50%;

• monoglycerides and diglycerides;

• fatty acids;

• glycerol;

• at least one antioxidant;

• ethyl or methyl esters of fatty acids or their combinations; Y

• optionally at least one enzyme, preferably a lipase;

where said micro and nanoemulsions have a size smaller than 55 mm.

In another preferred embodiment of the emulsion of the present invention, the enzyme is a lipase and is selected from lipases of animal, microbial or plant origin.

In another preferred embodiment of the emulsion of the present invention it also comprises other enzymes selected from among proteases, amylases, cellulases and any combination of the above.

In another preferred embodiment of the emulsion of the present invention, the cannabinoid is cannabidiol.

In another preferred embodiment of the emulsion of the present invention it further comprises at least one surfactant, preferably selected from natural phosphatidic surfactant, surfactant of animal origin and any combination, and more preferably natural phosphatidic surfactant in combination with a non-ionic surfactant.

In another preferred embodiment of the emulsion of the present invention, it further comprises at least one cosurfactant, preferably selected from ethanol, methanol, xylitol, sorbitol, glycerol, maltitol or erythritol, or their combinations.

In another preferred embodiment of the emulsion of the present invention, the antioxidant is selected from tocopherols, alpha, beta, gamma or delta tocopherols, tocotrienols, alpha, beta, gamma or delta tocotrienols, astaxanthin, phospholipids, ubiquinol, ubiquinone, glutathione, and their combinations. In another preferred embodiment of the emulsion of the present invention, it also comprises at least one emulsifying agent, preferably selected from maltodextrin, glucose, lactose, maititol, xylitol, erythrite, fructose, methyl cellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, whey protein, protein milk, hemp protein, pea protein, soy protein, milk powder or their combinations.

In another preferred embodiment of the emulsion of the present invention, it also comprises at least one cyclodextrin in an amount in percentage by weight of between 5% and 400% with respect to the initial hemp oil, selected from a- Cyclodextrin, b- iclodextrin, y-Cyclodextrin, s- Cyclodextrin and derivatives such as 2- Hydroxypropyl b-iclodextrin, 2, Hydroxyethyl- b-iclodextrin, 2-Hydroxypropyl-y- cyclodextrin, 2-Hydroxypropyl-a-cyclodextrin, Methyl-b-iclodextrin Carboxymethii-b- cyclodextrin sodium sodium, 2-Carboxyethyl-b-iclodextrin, sodium salt, Acetyl-b-iclodextrin, Succinyl-b-iclodextrin, Succinyl-a-cyclodextrin, Butyl-b-iclodextrin, or Butyl-and-cyclodextrin and any combination of the above

In another preferred embodiment of the emulsion of the present invention, the monoglyceride and diglyceride, the fatty acids and the glycerol, are the product of the reaction of hemp oil with enzymes.

A fourth aspect of the present invention is a composition comprising the micro and nanoemulsion described according to the present invention.

In a preferred embodiment of the composition, said composition is a food, a beverage, a food supplement or supplement, a cosmetic composition or a pharmaceutical composition.

In an even more preferred embodiment of the composition, the beverage is selected from the group consisting of energy drink, drinking or mineral water, lemonade, tonic water, fruit water, fruit juice, milk, buttermilk, carbonated drink and soft drink. alcoholic. EXAMPLES

In some embodiments, the emulsified hemp oil is present in a formulation dispersed in water, for example, in a beverage at a concentration from 0.001% by weight to 10% by weight, preferably from 0.05% to 0.2 %.

The composition of the formulation can be in any oral or dermal dosage format. Oral liquid preparations include liquids, beverages, syrups, suspensions, gels, etc., suitable for whoever ingests them.

A water soluble formulation as described herein can be sprayed directly onto the skin.

In other non-limiting embodiments of the present invention, the emulsified hemp oil is mixed with, maltodextrin, glucose, lactose, maltitol, xylitol, erythritol, fructose, methyl cellulose, hydroxypropylmefilcellulose, microcrystalline cellulose, whey protein, milk protein, protein of hemp, pea protein, soy protein, milk powder or in their combinations to obtain a dry powder. In these embodiments, the formulation dispersed in water is in a concentration of from 0.005% to 10%, preferably from 0.1% to 2%.

Example 1: micro and nanoemulsions.

Group A: 100 g of hemp oil containing 30% cannabidiol.

Group B: 400 IU / g of pancreatic or bacterial lipase dissolved in 20 mL of water and 5 g of Tween 80.

Group A and B are mixed with stirring for 24 hours and at a temperature of 30 ° C. Heat to 90 ° C to deactivate the enzymes

Add 10 g of phosphatidylserine / phosphatidiicoline in a ratio of 1: 5, 20 g of Tween 80 and 5 g of glycerol.

Shake at 3000 rpm for 5 minutes. In another embodiment, ultrasound can be used. Liquid micro and nanoemulsions are obtained.

In this embodiment, 0.1 mL of the liquid micro and nanoemulsions are dispersed in 100 mL of a beverage. To produce a powdered product of the liquid micro and nanoemulsions, 250 of maltodextrin are mixed with 50 mL of the micro and nanoemulsions. In this embodiment, 0.8 g of the micro and nanoemulsion powder is mixed with 100 g of a food, drink, food supplement or supplement, cosmetic product or medicine.

Example 2: micro and nanoemulsions with previously transesterified hemp oil.

As in example 1, but instead of producing a lipolysis, a methanolysis occurs through a standard transesterification with NaOH and methanol. Excess methanol is removed using a rotary evaporator.

0.1 mL of the liquid micro and nanoemulsions are dispersed in 100 mL of a cosmetic serum.

And on the other hand, to produce powder for the micro and nanoemulsions, 250 ml of cellulose, microcrystalline and magnesium stearate are added with 50 mL of the micro and nanoemulsions.

In this embodiment, 0.8 g of the micro and nanoemulsion powder is mixed with 100 g of a food, drink, food supplement or supplement, cosmetic product or medicine.

Example 3: micro and nanoemulsions with natural surfactants.

As in example 1, but instead of using Tween 80, Quillaja japonica (8%) is used as surfactant and glycerol (8%) as cosurfactant.

Next, 0.1 mL of the liquid micro and nanoemulsions are dispersed in 100 mL of a cosmetic serum.

And on the other hand, to produce powder from the micro and nanoemulsions, 250 of skimmed milk powder are added with 50 mL of the micro and nanoemulsions and 0.8 g of the micro and nanoemulsion powder are mixed with 100 g of a food, drink , food supplement or supplement, cosmetic product or medicine.

Example 4: micro and nanoemulsions

Group A: 100 g of hemp oil when the amount of cannabidiol is less than 20%. Group B: 400 lil / g of pancreatic or bacterial lipase dissolved in 20 mL of water.

Liquid micro and nanoemulsions are obtained.

Example 5: Micro and direct nanoemulsions

To 100 g of hemp oil containing 30% cannabidiol, 1,000 IU / g of bacterial lipase with 0.1% of water and 4% of the cosurfactant glycerol are added. The pH is adjusted to 7 with NaOH. The mixture is incubated at a temperature of 50 ° C for 14 hours and at 600 rpm. The enzyme is subsequently deactivated at 90 ° C. The emulsion is stirred at 3,000 rpm for 5 minutes.

In this embodiment, 0.1 mL of the liquid micro and nanoemulsions are dispersed in 100 mL of a beverage.

To produce a powder product of the liquid micro and nanoemulsions, 250 of maltodextrin are mixed with 50 mL of the micro and nanoemulsions. In this embodiment, 0.8 g of powdered micro and nanoemulsion ias is mixed with 100 g of a food, drink, food supplement or supplement, cosmetic product or medicine.

Example 6: Eliminate or suppress the taste and odor of the emulsion

To the product obtained in Example 1, an amount of 100 g of a-Cyclodextrin is added, to eliminate or suppress the smell and taste of the emulsion, to the 0.8 g of the micro and nanoemulsion powder and they are added to the 100 g of a food, drink, food supplement or supplement, cosmetic product or medicine.

Claims

1. Procedure for obtaining a micro and nanoemulsion with a size smaller than 55 pm of hemp oil that comprises cannabinoids, characterized in that it comprises the following steps:

i. treat a hemp oil that contains cannabinoids,

with at least one lipase enzyme that transforms the lipids with the highest molecular mass into di- and monoglycerides of fatty acids, fatty acids and glycerol, for a time of between 1 minute and 72 hours of treatment, and at a temperature between 2 ° C up to 60 ° C;

or

2. The process according to claim 1, wherein the enzymes of step i) are lipases, which produce lipolysis, of animal, microbial or plant origin, from 5 lipase units per gram of oil to 12,000 lipase units per gram of oil and they are in an amount of between 0.2 g to 100 g per 100 liters of oil.

3. The process according to claim 2 wherein the lipase enzyme of step (i) is combined with proteases, amylases or cellulases to decrease the molecular weights of the residual proteins, polysaccharide and cellulose to peptides or amino acids and to monosaccharides.

4. The method according to any one of claims 1 to 3, wherein the enzymes of step (i) are used in immobilized format.

5. The process according to any of claims 1 to 4, wherein it further comprises adding at least one surfactant in step (i) in an amount of between 1% and 25% by weight relative to the initial hemp oil amount.

6. The process according to claim 1, wherein in the transesterification of step (i) a metonolysis or ethanolysis occurs and is carried out enzymatically with lipases without the presence of water or in low concentration.

7. The process according to any of claims 1 to 6, wherein it comprises an additional step (ii ') of adding at least one surfactant after step (ii) and before step (iii), wherein said surfactant is selected from among natural phosphatidic surfactant and surfactant of animal origin.

8. The process according to claim 7, wherein if the surfactants of additional step (ii ') are selected from the list consisting of lecithin, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid or their combinations, they are additionally added in combination with at least:

- a non-ionic surfactant, selected from Tween 20, Tween 40, Tween 60, Tween 80, Tween 21, Tween 85, Tween 65, Tween 81, Tween 61 and Tween 100;

- a surfactant that is selected from the list consisting of Span 20, Span 40, Span 60, Span 65, and Span 85;

-any of its combinations; Y

9. The process according to any of claims 7 or 8, wherein it comprises adding at least one eosurfactant, wherein said eosurfactant is selected from the group ethanol, methanol, xylitol, sorbitol, glycerol, maititol or erythritol, or any of their combinations.

10. The process according to any of claims 1 to 9, wherein it further comprises an additional step (iv) subsequent to step (iii), of adding an agent desiccant, selected from maltodextrins, glucose, lactose, maititol, xylitol, erythritol, fructose, methyl cellulose, hydroxypropyl methyl cellulose, monophosphate, diphosphate, triphosphate, polyphosphate, citric, citrates, ascorbic, ascorbate, whey protein, milk protein, cellulose , hemp protein, pea protein, soy protein, milk powder or their combinations so that the emulsion is in powder form, in an emulsifier / oil weight ratio of between 4: 1 to 7: 1, and subsequently grind in high speed mill, hammer mill, roller mill, disc mill, ball mill, mortar, or any food mill with fine or ultrafine process types.

11. The process according to claim 10, wherein the desiccant is selected from among monophosphate, diphosphate, triphosphate, polyphosphate, citric, citrates, ascorbic, ascorbate.

12. The process according to any of claims 1 to 11, wherein it further comprises an additional step (v)

* of dispersing the product obtained in step (iii) or (iv) in an aqueous phase; or

• to absorb the product obtained in stage (iii) or (iv) in a solid phase from 5 mg in 100 mL to 10 g in 100 mL, producing transparent emulsions.

13. The process according to claim 12, wherein it further comprises adding at least one cyclodextrin in an amount in percentage by weight of between 5% and 400% with respect to the initial hemp oil, selected from a- Cyclodextrin, b- iclodextrin, y-Cyclodextrin, s- Cyclodextrin and derivatives such as 2- Hydroxypropyl-b-iclodextrin, 2, Hydroxyethyl-b-iclodextrin, 2-Hydroxypropyl-y- cyclodextrin, 2-Hydroxypropyl-a-cyclodextrin, Methyl-b-iclodextrin Carboxymethii-b- cyclodextrin sodium salt, 2-Carboxyethyl-b-iclodextrin sodium salt, Acetyl-b-cyclodextrin, Succinyl-b-iclodextrin, Succinyl-a-cyclodextrin, Butyl-b-iclodextrin or Butii-y-cyclodextrin and any combination of the above,

- just before stage (v); or

to the product obtained from step (v);

14. A micro and nanoemulsion obtained according to the process described in any one of claims 1 to 13.

15. A micro and nanoemulsion characterized by comprising

• at least one cannabinoid in an amount in percentage by weight with respect to! total emulsion between 5% and 50%;

• monoglycerides and diglycerides;

• fatty acids;

• glycerol;

• at least one antioxidant;

• ethii or methyl esters of fatty acids or their combinations; Y

• optionally at least one enzyme, preferably a lipase;

where said micro and nanoemulsions have a size smaller than 55 mm

18. Micro and nanoemulsion according to claim 15, wherein the enzyme is a lipase and is selected from lipases of animal, microbial or plant origin.

17. Micro and nanoemulsion according to any of claims 15 or 16, wherein it also comprises other enzymes selected from proteases, amylases, cellulases and any combination of the foregoing.

18. Micro and nanoemulsion according to any of claims 15 or 17, wherein the cannabinoid is cannabidiol.

19. Micro and nanoemulsion according to any of claims 15 to 18, wherein it also comprises at least one surfactant, preferably selected from among natural phosphatidic surfactant, surfactant of animal origin and any combination, and more preferably natural phosphatidic surfactant in combination with a non-surfactant. ionic.

20. Micro and nanoemulsion according to any of claims 15 to 19, wherein it also comprises at least one cosurfactant, preferably selected from ethanol, methanol, xylitol, sorbitol, glycerol, maltitol or erythritol, or in their combinations.

21. Micro and nanoemulsion according to any of claims 15 to 20, wherein the antioxidant is selected from among tocopherols, alpha, beta, gamma tocopherols or delta, tocotrienols, alpha, beta, gamma or delta toeotrieneols, astaxanthin, phospholipids, ubiquinol, ubiquinone, glutathione, and their combinations.

22. Micro and nanoemulsion according to any of claims 15 to 21, where it also comprises at least one emulsifying agent, preferably selected from maltodextrin, glucose, lactose, maititol, xylitol, erythritol, fructose, methyl cellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, protein whey, milk protein, hemp protein, pea protein, soy protein, milk powder or their combinations.

23. Micro and nanoemulsion according to any of claims 15 to 22, wherein it also comprises at least one cyclodextrin in an amount in percentage by weight of between 5% and 400% with respect to the initial hemp oil, selected from a- Cyclodextrin, b-Cyclodextrin, y-Cyclodextrin, d- Cyclodextrin and derivatives such as 2-Hydroxypropyl- b-cyclodextrin, 2, Hydroxyethyl-b- cyclodextrin, 2-Hydroxypropyl-y-cyclodextrin, 2-Hydroxypropyl-a-cyclodextrin, Methyl b- cyclodextrin, Carboxymethyl-b-cyclodextrin sodium salt, 2-Carboxyethyl-b-cyclodextrin sodium salt, Acetyl-p-cidodextrin, Succinyl-b-iclodextrin, Succinyl-a-cyclodextrin, Butyl-b-cyclodextrin or Butyl-y- cyclodextrin and any combination of the above.

24. Micro and nanoemulsion according to any of claims 15 to 23, wherein the monoglyceride and diglyceride, fatty acids and glycerol, are the product of the reaction of hemp oil with enzymes.

25. A composition comprising the micro and nanoemulsion according to any of claims 15 to 24.

26. The composition according to claim 25, wherein the composition is a food, a beverage, a food supplement or supplement, a cosmetic composition or a pharmaceutical composition.

27. The composition according to claim 26, wherein the drink is selected from the group consisting of energy drink, drinking or mineral water, lemonade, tonic water, fruit water, fruit juice, milk, buttermilk, soda and alcoholic beverage.