ES1245259U - Hemp Oil Cannabinoid Emulsions (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

An emulsion of hemp oil comprising cannabinoids of a size less than 55 μm, obtained according to the method characterized in that it comprises the following steps: i. treating a hemp oil comprising cannabinoids, with at least one lipase enzyme that transforms lipids of higher molecular mass to di- and monoglycerides of fatty acids, fatty acids and glycerol, for a period of between 1 minute and 72 hours of treatment, and at a temperature of between 2ºC to 60ºC; ii. transesterify the product obtained in step i), using a procedure selected from - a second enzymatic treatment with at least one enzyme, preferably lipases, - by chemical treatment with KOH or NaOH from 0.5% to 1% as catalysts, where the alcohol/oil ratio is from 3: 1 to 6: 1; to transesterify triglycerides of fatty acids, - ethanolysis or methanolysis to produce methyl esters of fatty acids, or - combination between them; iii. add at least one antioxidant; and iv. provide energy, using a method selected from among stirring at a stirring speed of between 100 rpm to 30,000 rpm, where the actuation time is between 10 seconds and 1 hour, or by ultrasound, at a power between 20 and 3,000 watts and a frequency between 10 and 30 kHz for a sonication time of between 5 seconds and 10 minutes. (Machine-translation by Google Translate, not legally binding)

Description

DESCRIPTION

Hemp oil cannabinoid emulsions

TECHNICAL SECTOR

The invention relates to the production of micro and nanoemulsions from hemp oil that contains cannabinoids, mainly cannabidiol (CBD), which uses fewer amounts of surfactants than traditional systems, demanded by consumers and, in addition, uses natural or ecological surfactants. To achieve this goal, the molecular weight of the oil's lipids (triacylglycerols) is decreased with enzymatic or chemical methods. The resulting components di- and monoglycerides, fatty acids and glycerol or ethyl or methyl esters of the fatty acids or combination thereof, help to emulsify the cannabinoids. Under these conditions, a small addition of surfactant, cosurfactant, comparatively to current methods, and energy, produces micro and nanoemulsions of cannabinoids. The process is biochemical and chemical, and the application is framed in the sector of food, food supplements and supplements, cosmetics and medicine.

BACKGROUND OF THE INVENTION

Global demand for cannabinoids is increasing. Most of the naturally derived cannabinoids come from hemp oil. Hemp refers to three species: Cannabis sativa, Cannabis indica and Cannabis ruderalis. Humans have cultivated and consumed 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 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 hemp cannabinoids is to extract the oil from the leaves or trichomes. Different methodologies are used, one of them is the treatment by pressure and, later, they are concentrated with little polar solvents or with supercritical CO ² . Cannabinoids are more soluble in nonpolar fluids. This feature makes it easy to use effective solvents like hexane and methanol 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 then remove the hexane with a rotary evaporator. The final product is a generally solid oil 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 by freezing and thawing cycles, producing an oil that is liquid at room temperature. This methodology allows obtaining an oil with a concentration from 2% to 60% of cannabinoids, preferably from 20% to 50%, depending on the concentration or partial purification process. Subsequently, chromatographic methods can be used to concentrate the cannabinoids, separating them from the rest of the components present in the oil. Chromatographic methods allow cannabinoids to be obtained with a purity degree greater than 95%, even when they are time consuming and have a high cost.

The cannabinoids contained in hemp oil, specifically cannabidiol (CBD), are poorly polar and insoluble in water. This characteristic makes intestinal absorption difficult.

To use cannabinoids more effectively in food, beverages, food supplements or 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 for that can be absorbed by the intestinal villi.

To produce micro and nanoemulsions of the cannabinoids that hemp oil contains, it is necessary to micro and nanoemulsify the total oil that contains the majority of triglycerides of fatty acids. To achieve this goal, a high concentration of nonionic surfactants generally in an oil / surfactant ratio of 1: 9 is needed for the micro and nanoemulsion to be translucent or transparent when dissolved in water, as they not only micro and nanoemulsify cannabinoids but also, it is necessary to 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 be needed to micro and nanoemulsify cannabinoids since di- and monoglycerides, some acids Fatty 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 linoleic acid from 56% to 60%, followed by α-linolenic acids from 16% to 20%, oleic acid from 10% to 15%, palmitic from 5% to 9%, stearic from 2% to 3%, Y-linolenic from 0.6% to 2%, among other components. Most of these fatty acids are esterified with glycerol forming 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 of higher molecular mass require a higher concentration of surfactants to produce micro and nanoemulsions, than lipids of lower molecular mass.

If the higher molecular mass lipids in hemp oil containing cannabidioides are previously transformed into lower molecular mass lipids by transesterification, a lower concentration of surfactants and cosurfactants will be required to produce the micro and nanoemulsions. The lipids with the highest molecular mass in hemp oil that contains cannabinoids are mainly triglycerides of fatty acids. The triglycerides of fatty acids can be transformed into lipids of lower molecular mass such as di- and monoglycerides of fatty acids and even fatty acids and glycerol. This transformation is called transesterification and can be carried out enzymatically with lipases, or chemically with catalysts such as NaOH, KOH or H ² SO ⁴ , metal oxides or carbonates. Of the previous processes, enzymatic catalysis is characterized in that the final products are purer, there is no soap formation and chemical catalysts that are frowned upon by consumers are not used. Lipases are triacylglycerol acylhydrolases (EC 3.1.1.3) that They can hydrolyze the ester bond of different substrates. They can catalyze hydrolysis and synthesis reactions (esterification and transesterification). In nature they catalyze the hydrolysis of the tri-, di-, and monoglyceride ester linkages to produce fatty acids and glycerol. Lipases have substrate specificity, pH, have activity in the presence of water and organic solvents, are temperature-dependent, and interact with surfactants and cosurfactants. In transesterification, lipases are used either freely or immobilized. In the alcoholysis of oils, the activity also depends on the alcohol: oil molar ratio (generally from 2: 1 to 18: 1), type of alcohol (generally ethanol or methanol), intensity of mixing (generally between 100 and 800 rpm) , humidity (generally from 05 to 30% of water), type of lipase and the concentration of lipase (generally between 50 and 4,000 IU / g).

It is known that the mono and diglycerides of fatty acids have emulsifying capacity and are the most widely used emulsifiers in food. This particular characteristic decreases the necessary concentration of surfactants and cosurfactants to produce micro and nanoemulsions. Sodium or potassium salts of fatty acids are not only the fundamental component of classic water-soluble soaps, but are also used in the food industry to obtain emulsions of fats in water, preferably mixtures of salts of various mono and diglycerides of different fatty acids.

Another way to decrease the molecular mass of lipids is to transform triglycerides into ethyl or methyl esters of fatty acids. Ethyl or methyl esters of fatty acids are produced by ethylation or chemical methylation and also have some emulsifying capacity. This characteristic decreases the necessary concentration of surfactants and cosurfactants to produce micro and nanoemulsions.

It is known that the realization 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 clear dispersion of the phytocannabinoids from hemp oil in water, a weight ratio of phytocannabinoids from hemp oil to nonionic emulsifier of 1: 5 to 1: 10,000 (Water-soluble phytocannabinoid formulations. patent US9907823).

Moreover, lipolysis of hemp oil 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 does not use a mixture of the oil with the surfactant and lipase dissolved in water, as performed in the present invention The surfactant increases the contact surface of lipase with oil and improves the efficiency of glycerolysis In addition, it does not claim its use for hemp oil.

The US patent "Nanoemulsion compositions and methods of use thereof" (US7,118,688) uses a nanoemulsion composition comprising a protein or a protein fragment complex and wherein the nanoemulsion contains hemp oil, and at least a phospholipid selected from a group consisting of phosphatidylserine with a concentration equal to or greater than 40%, it also uses phosphatidylserine because it plays a critical role in maintaining 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 aforementioned patent above, it uses phosphatidylserine as an emulsifier and also at a concentration of less than 40%.

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

The "Cochleates made with soy phosphatidylserine" patent No. US9,775,907 uses soy phosphatidylserine having 40% to 74% purity and a multivalent cation. Phosphatidylserine with a purity of less than 40% is used in the present invention and does not multivalent cations are used.

EXPLANATION OF THE INVENTION

DESCRIPTION

The terms of the present invention are used with the following meanings:

"Hemp oil" refers 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% of cannabidiol.

"Hemp" or industrial hemp is the name given to the varieties of the Cannabis plant: Cannabis sativa, Cannabis indica and Cannabis ruderalis. "Industrial hemp" refers to Cannabis varieties intended for 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 in the plant, found in varying proportions depending on the strain.

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

"Cannabidiol (CBD)” is a hydrophobic compound. It has a solubility in water of 0.0126 mg / mL. The low solubility limits its oral use. To increase its oral use, it is necessary to make dispersions of cannabidiol in water of less than 55 microns in size. it is the maximum size suitable for absorption by the intestinal villi.

"Clear or transparent" refers to an aqueous solution containing the lipophilic compound in a water-containing solution that is free of visible particles of dispersed (undissolved) compound.

"Emulsion" is a colloidal dispersion of two immiscible liquids, such as oil and water, in the form of drops. If the oil drops are finely dispersed in water, then it is an oil-in-water emulsion. Water is finely dispersed in oil, it is a water-in-oil emulsion.

"Cosurfactant" are generally alcohols or amines within the C4 to C10 range that aid in the formation and stabilization of micro and nanoemulsions. Examples: ethanol (C2), glycerol (C3), xylitol (C5), erythritol (C4).

"Antioxidants" are considered the recognized fat-soluble natural antioxidants (tocopherols, tocotrienols, beta-carotene and coenzyme Q10).

"Micro and nanoemulsions" refers to the production of a mixture of micro and nanoemulsions from hemp oil containing cannabinoids with the same procedure. They are distinguished from an emulsion in that they are thermodynamically stable in the long term without apparent flocculation or coalescence, while an emulsion is only kinetically stable, that is, the speed 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 diameters of nanometers and are transparent.

"Surfactant, surfactant, emulsifier or nonionic dispersant" refers to different synonyms for a generally amphiphilic agent with a hydrophilic head and a hydrophobic tail with the same or different hydrophilic or lipophilic character, which tends to decrease the surface tension between two phases and to be non-ionized in neutral solutions Some examples of nonionic surfactants are Tween 80, Tween 20, Span 80.

It is known that lipids with a higher molecular mass require 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 clear monophasic region.

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 hemp oil have a higher molecular mass than diglycerides and these more than monoglycerides. Furthermore, the di- and monoglycerides have some 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 feature helps decrease the concentration of surfactants to produce micro and nanoemulsions from hemp oil.

An emulsifying effect similar to di and monoglycerides is provided by ethyl and methyl esters of fatty acids (FAME).

The method refers to a process to produce micro and nanoemulsions from hemp oil containing cannabinoids whose lipids have been transformed to di- and monoglycerides of fatty acids or to 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 have a diameter less than 55 micrometers and, in addition, to produce translucent or transparent micro and nanoemulsions in a phase of Water.

The present invention describes a method of producing micro and nanoemulsions from hemp oil containing cannabinoids, by combinations of the different steps including:

i. An initial treatment of hemp oil containing cannabinoids to transform lipids of higher molecular mass to di- and monoglycerides of fatty acids, fatty acids and glycerol, or to ethyl or methyl esters of fatty acids or a combination of them,

ii. An enzymatic treatment with one or more enzymes, preferably lipases, or chemical treatments, to transesterify the triglycerides of the fatty acids, or ethanolisis or methanolisis to produce methyl esters of the fatty acids, or combination of them,

iii. None, one or more surfactants,

iv. None, one or more cosurfactants,

v. One or more antioxidants,

saw. A contribution of energy,

vii. A presentation in liquid or powder form in such a way that the micro and nanoemulsions in liquid or powder can be dispersed in water producing a translucent or transparent emulsion.

It is known that lipase enzymes can, by definition, act at the organic-aqueous interface, catalyzing the hydrolysis of ester-carboxylate bonds and releasing fatty acids and organic alcohols. In general, lipases catalyze the hydrolysis of triacylglycerols to di- and monoglycerols, and to fatty acids and glycerol at random, the intermediates being mono- and diacylglycerols.

Lipases can be of animal (pancreatic, hepatic, and gastric), microbial (bacterial, fungal, and yeast) or plant origin, and vary in their catalytic properties.

There are different types of lipases. Specific lipases: they have glycerol esters as specific substrates. They catalyze the hydrolysis of triacylglycerols, and also di- and monoacylglycerols. Non-specific lipases: catalyze the complete hydrolysis of the triacylglycerols in fatty acids and glycerol in a random way, being the intermediate products mono- and diacylglycerols.

The lipases are produced and come from porcine pancreas, human pancreas, adipose tissue of chicken, bovine milk, wheat germ. Lipases derived from microorganisms of the genera Rhizopus, Aspergillus and Mucor, Rhizopus delemar, Rhizopus oryzae, Rhizopus japonicus, Rhizopus niveus, Aspergillus niger, Asperfillus oryzae, Pseudomonas cepacia, Pseudomonas fluorescens, Candida rugosa, Candida Penicillium camemberti, Mucorjavanicus and Mucor miehei.

Lipase activity is measured in U / mL. They operate 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. Lipase activity 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 can 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 operating time preferably ranges from 10 minutes to 120 hours, more preferably from 1 to 90 hours. The lipases operate from room temperature at 20 ° C to 50 ° C, preferably between 35 ° C and 50 ° C and are deactivated preferably at 90 ° C.

Depending on the activity, 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 mass lipids from hemp oil containing cannabinoids into lower molecular mass products. Lipases do not transform cannabidiol.

One aspect of the present invention comprises transforming most of the lipids in hemp oil containing cannabinoids with a lipase or combination of lipases, to decrease the lipid molecular mass of hemp oil containing cannabinoids.

Another aspect of the present invention is to produce micro and nanoemulsions with low concentration of surfactants. If hemp oil is mixed with lipases and an aqueous phase surfactant, mono and diglycerides of fatty acids are easily formed. The di- and monoglycerides of fatty acids have some emulsifying capacity and decrease the concentration of phospholipids and other surfactants that are necessary to finally produce micro and nanoemulsions.

Another aspect of the present invention comprises the use of proteases, amylases or cellulases to decrease the molecular weights of residual proteins, polysaccharides and cellulose to peptides or amino acids and to monosaccharides.

In some methods of the present invention, lipase or mixtures of lipases dissolved in water are used, and it is mixed with oil and a surfactant using a stirrer or ultrasound. A preferred procedure is agitation.

In other procedures, the lipase is immobilized on a substrate and the oil passes over the substrate so that the lipase acts on the glycerol esters of the oil.

In other procedures, the lipase, or mixture of lipases, is mixed with proteases to reduce proteins, which can be found in the oil, to peptides and amino acids, and can also be mixed with amylases to reduce polysaccharides, which can be found in the oil, to simple sugars.

In another preferred embodiment the enzymes can be used in immobilized format.

In a process of the present invention, the lipase, or mixtures of lipases, dissolves in water and the ratio of oil / water / surfactants / cosurfactants can vary the activity of the lipase. An oil / water ratio of from 1:20 to 1,000: 1, preferably from 1: 4 to 3: 7, and preferably from 10: 2 to 10: 1, and oil / surfactants from 1:20 have been selected in the present invention. up to 1,000: 1 preferably from 100: 5 to 100/1.

In another method of the present invention, the lipase or mixtures of lipases, can be immobilized in different types of carriers such as, for example: alginate, resin, polypropylene, dextran, celite, etc. In general, immobilized lipases are heat resistant and have high durability in 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 patent application number WO2013114178A1, the oil is mixed with an alcohol such as ethanol in a ratio of from 1: 4 to 1: 7.

Another embodiment of the present invention is the production of fatty acid ethyl or methyl esters (FAME) from hemp oil using ethanolysis or methanolysis methodologies. Methanolysis of a compound Fatty, is the result of three consecutive reactions: partial transesterification of triglyceride (TG) to form diglyceride (DG), partial transesterification of DG to form monoglyceride (MG), and partial transesterification of MG to form FAME and glycerol (G ). For the production of FAME, 0.5% to 1% of KOH or NaOH are needed as ethanol or methanol catalyst. 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 0.1 hour reaction time at a temperature of 60 ° C has a FAME production efficiency of 94%.

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

It has been found that a lower concentration of nonionic, natural or ecological surfactants can be used than in current methodologies when hemp oil transformed according to the previous methodologies. For example, a mixture of two phospholipids such as the phosphatidylserine / phosphatidylcholine mixture is added to hemp oil in a ratio of 1:10 to 35:65, preferably 1: 5 in a concentration of 1% to 39% and another non-phospholipid surfactant to produce micro and nanoemulsions. Another example is: phosphatidylserine / phosphatidylcholine and Tween 80, or phosphatidylserine / phosphatidylcholine and modified starch or phosphatidylserine / phosphatidylcholine and gum arabic.

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

The invention refers to the use of a strategy to use surfactants of natural origin such as phospholipids and cosurfactants such as glycerol, to decrease the use of nonionic surfactants to produce said emulsions. Although non-ionic surfactants are generally safe, consumers demand food, beverages, food supplements or supplements, cosmetics and medicine with low concentrations of non-ionic surfactants and, if possible, natural surfactants and even better with an ecological name.

The synthetic surfactants are Tweens and Spans, both are considered GRAS. Examples: Span 80 (sorbitan monooleate) or Tween 80 (ethoxylated sorbitan monooleate).

Natural surfactants can be grouped into biosurfactants derived from microorganisms, surfactants of plant origin, and surfactants of animal origin. Each of them may or may not have an ecological name. Biosurfactants are grouped into glycolipids, lipopeptides, and polymers. The best-known plant-based surfactants are those derived from Durio zibethinus, Quillaja japónica, gum arabic, peptinas, glucomannanas, modified starches, ultramuz, peas, soybeans and corn, lecithin, phosphatidylserine, phosphatidylcholine, phosphatidylininosidic, phosphatidylininosidic, and The best-known surfactants of animal origin are lecithin, casein, and whey.

In another preferred embodiment the surfactants are selected from the group of lecithin, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid or their combinations, preferably the combination of phosphatidylserine / phosphatidylcholine in concentrations from 1% to 39%, preferably from 5 % to 15%, in combination with the group of nonionic surfactants Tween 20, Tween 40, Tween 60, Tween 80, Tween 21, Tween 85, Tween 65, Tween 81, Tween 61 and Tween 100 and the Span 20 surfactants, Span 40, Span 60, Span 65, and Span 85, alone or in their combinations and from the group of starches, milk caseinate, powdered milk, soy protein, pea protein and whey protein, or combinations thereof. The Surfactant / oil ratio can range from 10: 1 to 1: 100, preferably from 1:10 to 4:10.

Micro and nanoemulsions are composed of an oil, water, surfactants, and generally a cosurfactant, generally a short-chain alcohol (C3-C10) such as ethanol, glycerol, methanol, xylitol, sorbitol, maltitol, or erythritol or combinations. Cosurfactants are added to further reduce interfacial tension, facilitating emulsion and system stability.

Preferred surfactants are xylitol, glycerol, or erythritol in an oil / alcohol ratio of 100: 1 to 1: 4.

When phospholipids alone are used as sole surfactants they generally do not form microemulsions when the two phases are water and oil. It is necessary to use a cosurfactant, usually a short-chain alcohol (C3-C10).

In other embodiments, cosolvents like monosaccharides or alcohols like ethanol, sorbitol, or mannitol can be added.

Antioxidants are added to the micro and nanoemulsions, which are obtained in liquid form, before or after the formation of said emulsion. Antioxidants can include tocopherols or coenzyme Q10 or both in combination, from 0.2 to 10 g / kg.

In another embodiment the antioxidant is selected from the group of tocopherols, alpha, beta, gamma or delta tocopherols, tocotrienols, alpha, beta, gamma or delta tocotrienols, astaxanthin, phospholipids, ubiquinol, ubiquinone, glutathione, and combinations thereof.

In general, the production of micro and nanoemulsions requires the use of high energy methods. One procedure is to use mixers with speeds from 100 rpm to 30,000 rpm, preferably from 2,000 rpm to 10,000 rpm and from 1 minute to 20 minutes to micro or nanoemulsify the oil previously emulsified with enzymes. Another procedure uses ultrasound from 10 khz to 2,000 khz with different power outputs and treatment times that can vary from 10 seconds to 10 minutes of treatment.

The energy treatment of the present invention may include low or high speed homogenizer agitation, or ultrasound.

When a lipase is used to transesterify the triacylglycerols, a maximum agitation of 600 rpm is used so as not to deactivate the enzyme. After transesterification is complete, the emulsion is stirred at high speed from 2,000 rpm to 30,000 rpm preferably between 3,000 and 12,000 rpm to produce micro and nanoemulsions.

The emulsion can be treated with ultrasound with a power between 20 and 3,000 watts, preferably between 50 and 1,300 watts and at a frequency between 10 and 30 kHz, preferably 20 kHz, to produce micro and nanoemulsions. The sonication time can vary from 5 seconds to 10 minutes. Industrial equipment can process 2,000 liters / hour. Micro and nanoemulsions can be performed at room temperature and at a preferred temperature from 40 ° C to 50 ° C.

Another embodiment is the powder production of the liquid micro and nanoemulsions by mixing them with carbohydrates or proteins from 50% to 2000%, preferably from 400% to 800%. In such a way that a translucent or transparent solution is produced when 100 pL of the liquid format or 500 mg of the powder format are poured into 100 mL of water.

The powder compositions of the present invention are made by adding to the oil, micro and nanoemulsified, soluble dry products that may include sugars, alcohols, oligosaccharides, polysaccharides, or proteins, as well as the excipients of the gelatin capsules as microcrystalline cellulose.

Micro and nanoemulsions, in liquid or powder form, are used in food, beverages, food supplements or supplements, cosmetic and medical products.

Hemp oil contains mostly lipids and cannabinoids. To micro and nanoemulsify the cannabinoids of hemp oil with surfactants, it is also necessary to micro and nanoemulsify the lipids that make up the oil. Transformation to lower molecular mass lipids such as di- and monoglycerides of fatty acids, fatty acids and glycerol or to ethyl or methyl esters of fatty acids or a combination of They increase the emulsifying capacity of hemp oil and decrease the necessary concentration of surfactants and cosurfactants (non-ionic, natural or ecological) compared to current processes, to produce micro and nanoemulsions of cannabinoids, as demanded by consumers.

The present invention relates to the production of micro and nanoemulsions of cannabinoids from hemp oil with a diameter less than 55 microns using low concentration of surfactants. The molecular mass of lipids in hemp oil containing cannabinoids is decreased with lipase enzymes to produce di and monoglycerides of fatty acids, or the methyl esters of fatty acids are produced using chemical methylation, or a combination of both. This transformation not only decreases the molecular mass of lipids and decreases the necessary concentration of surfactant, but also increases the emulsifying capacity of the oil and further decreases the necessary concentration of surfactants to produce micro and nanoemulsions of cannabinoids.

The invention also relates to the process that uses low concentration of surfactants and cosurfactants, compared to traditional procedures, to further micro and nanoemulsify transesterified oil, supplying energy in the form of agitation or ultrasound.

The invention also relates to the process using natural or eco-denominated surfactants and cosurfactants.

The transparent micro and nanoemulsions of cannabinoids in liquid or powder format are used in food, beverages, food supplements or supplements, cosmetic and medical products.

An object of the invention is to decrease the molecular mass of cannabinoid-containing hemp oil lipids by transforming (esterifying) them to di- and monoglycerides of fatty acids, fatty acids and glycerol or transforming them to ethyl or methyl esters of fatty acids, or a combination of them, to achieve two advantages: on the one hand, the emulsifying capacity of the transformed oil is increased, and on the other, a lower concentration of surfactants and cosurfactants is needed to micro and nanoemulsify the hemp oil cannabinoids.

Another object of the invention is to produce micro and nanoemulsions of cannabinoids from hemp oil with a low concentration of surfactants and natural or eco-denominated cosurfactants to respond to consumer demand.

Another object of the invention is to use different intensities of energy of agitation or ultrasound or combination of both, to produce more microemulsions or more nanoemulsions.

Another object of the invention is to produce micro and nanoemulsions of hemp oil cannabinoids that are less than 55 microns in diameter, so that they can be absorbed by intestinal villi.

Another object of the invention is to produce liquid micro and nanoemulsions, from hemp oil containing cannabinoids, which can be dispersed in a water phase and which is translucent or transparent.

Another object of the invention is to produce micro or nanoemulsion in powder form, from hemp oil that contains cannabinoids, that can be mixed with food, cosmetic or medicinal products and that can also be dispersed in a water phase that is translucent or transparent.

Another object of the invention is to produce micro and nanoemulsions, from hemp oil containing cannabinoids, in liquid or powder form that is stable to oxidation through the use of antioxidants.

Another object of the invention is to produce micro and nanoemulsions, from hemp oil containing cannabinoids, in liquid or powder format so that they can be mixed with food, beverages, supplements or food supplements, cosmetic products and medicines.

Another object of the invention where the micro and nanoemulsion is dispersed in an aqueous phase or absorbed in a solid phase from 5 mg in 100 mL to 10 g in 100 mL, preferably from 50 mg in 100 mL to 300 mg in 100 mL, producing transparent emulsions.

In a preferred embodiment in which the aqueous phase or the base material are selected from the group consisting of energy drink, mineral water, lemonade, tonic water, minerals, fruit water, fruit juice, milk, whey, carbonated drink , alcoholic beverage and as a preparation of drinking water.

In another preferred embodiment where the micro and nanoemulsion where the aqueous or solid phase is selected from food, beverages, supplements or supplements or cosmetics.

Another object is a product where micro and nanoemulsions mix with other components (solid phase) to produce a powder product. The components are selected from the group of maltodextrin, glucose, lactose, maltitol, xylitol, erythritol, fructose, methyl cellulose, hydroxypropylmethyl cellulose, microcrystalline cellulose, whey protein, milk protein, hemp protein, pea protein, soy protein, milk powder or in combinations to obtain a dry powder. In these embodiments, the ratio of the solid phase to the micro and nanoemulsions is preferably from 4: 1 to 7: 1. The final blend is milled in a high speed mill, hammer mill, roller mill, disc mill, ball mill, mortar, or any food mill with fine or ultra-fine process types, producing a transparent and instantaneous emulsion.

In a more preferred embodiment in which the micro and nanoemulsions are mixed with a base material selected from the group consisting of energy drink, mineral water, lemonade, tonic water, minerals, fruit water, fruit juice, milk, whey , carbonated drink, alcoholic beverage and as a preparation of drinking water.

In another preferred embodiment where the micro and nanoemulsion powder is used in food, beverages, supplements or supplements, cosmetics and medicine.

PREFERRED EMBODIMENT OF THE INVENTION

In some embodiments, the emulsified hemp oil is present in a formulation dispersed in water, for example, in a beverage at a concentration of 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. Liquid oral preparations include liquids, beverages, syrups, suspensions, gels, etc., suitable for whoever eats them.

A water soluble formulation as described herein can be sprayed directly on 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, hydroxypropylmethyl cellulose, microcrystalline cellulose, whey protein, milk protein, protein hemp, pea protein, soy protein, milk powder or in combinations to obtain a dry powder. In these embodiments, the water dispersed formulation 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 30 ° C temperature. Heat to 90 ° C to deactivate enzymes

Add 10 g of phosphatidylserine / phosphatidylcholine in 1: 5 ratio, 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 is dispersed in 100 mL of a beverage.

To produce a powder product of the liquid micro and nanoemulsions, 250 maltodextrin is 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 lipolysis, methanolysis is produced by standard transesterification with NaOH and methanol. The excess methanol is removed by means of a rotary evaporator.

In this embodiment, 0.1 mL of the liquid micro and nanoemulsions is dispersed in 100 mL of a cosmetic serum.

To produce powder from the micro and nanoemulsions, 250 microcrystalline cellulose 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, Japanese Quillaja (6%) is used as the surfactant and glycerol (6%) as the cosurfactant.

In this embodiment, 0.1 mL of the liquid micro and nanoemulsions is dispersed in 100 mL of a cosmetic serum.

To produce powder from the micro and nanoemulsions, 250 skimmed milk powder 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 4: ecological micro and nanoemulsions

As in example 3, but all components have an ecological certificate.

In this embodiment, 0.1 mL of the liquid micro and nanoemulsions is dispersed in 100 mL of an organic drink.

To produce powder from the micro and nanoemulsions, 250 hemp protein with ecological certification are added to 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 5: Direct micro and nanoemulsions

To 100 g of hemp oil containing 30% cannabidiol, 1,000 IU / g of bacterial lipase are added with 0.1% water and 4% of the glycerol cosurfactant. 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. Subsequently, the enzyme is 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 is dispersed in 100 mL of a beverage.

To produce a powder product of the liquid micro and nanoemulsions, 250 maltodextrin is 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.

Claims (12)

1. An emulsion of hemp oil comprising cannabinoids of a size less than 55 pm, obtained according to the method characterized in that it comprises the following steps: i. treating a hemp oil comprising cannabinoids, with at least one lipase enzyme that transforms lipids of higher molecular mass to di- and monoglycerides of fatty acids, fatty acids and glycerol, for a period of between 1 minute and 72 hours of treatment , and at a temperature between 2 ° C to 60 ° C; ii. transesterify the product obtained in step i), using a procedure selected from -a second enzymatic treatment with at least one enzyme, preferably lipases, -by chemical treatment with KOH or NaOH from 0.5% to 1% as catalysts, where the alcohol / oil ratio is from 3: 1 to 6: 1; to transesterify triglycerides of fatty acids, -ethanolysis or methanolysis to produce methyl esters of fatty acids, or -combination between them; iii. add at least one antioxidant; and iv. provide energy, through a method selected from among stirring at a stirring speed of between 100 rpm to 30,000 rpm, where the actuation time is between 10 seconds and 1 hour, or by ultrasound, at a power between 20 and 3,000 watts and a frequency between 10 and 30 kHz for a sonication time of between 5 seconds and 10 minutes. 2. The emulsion according to claim 1, wherein the enzymes of stage i) and ii) are lipases, which produce lipolysis, of animal, microbial or vegetable origin, from 5 units of lipase per gram of oil to 12,000 units of lipase per gram of oil and are in an amount of between 0.2 g to 100 g per 100 liters of oil. 3. The emulsion according to claim 2 where the lipase enzymes combine with proteases, amylases or cellulases to decrease the molecular weights of the proteins, polysaccharide and cellulose residual to peptides or amino acids and to monosaccharides. 4. The emulsion according to any of claims 1 to 3, wherein the enzymes are used in immobilized format. 5. The emulsion according to claims 1 to 3, wherein the methanolysis or ethanolysis of step ii) are carried out enzymatically with lipases without or with the presence of water. 6. The emulsion according to any of claims 1 to 5, wherein it comprises an additional step of adding at least one surfactant after step (ii) and before step (iii), wherein said surfactant is selected from among natural phosphatidic surfactants and surfactant of animal origin. 7. The emulsion according to claim 6 wherein if the surfactants are selected from the group of lecithin, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid or their combinations, they are additionally added in combination with a nonionic surfactant, selected from Tween 20 , Tween 40, Tween 60, Tween 80, Tween 21, Tween 85, Tween 65, Tween 81, Tween 61 and Tween 100 and the surfactants Span 20, Span 40, Span 60, Span 65, and Span 85 alone or in combinations and from the group of starches, milk caseinate, milk powder, soy protein, pea protein and whey protein, or their combinations, where the weight ratio of the surfactant and oil varies from 10: 1 to 1: 100. 8. The emulsion according to any of claims 6 or 7, wherein it comprises adding at least one cosurfactant, wherein said cosurfactant is selected from the group ethanol, methanol, xylitol, sorbitol, glycerol, maltitol or erythritol, or in their combinations. 9. The emulsion according to any of the preceding claims, wherein it comprises an additional step after step (iv), of adding an emulsifying agent, selected from maltodextrins, glucose, lactose, maltitol, xylitol, erythritol, fructose, methyl cellulose, hydroxypropylmethyl cellulose, microcrystalline cellulose, whey protein, milk protein, hemp protein, pea protein, soy protein, milk powder or in their combinations so that the emulsion is in powder form, in an emulsifying / oil weight ratio. between 4: 1 to 7: 1, and then grinding in high speed mill, hammer mill, rollers, disc mill, ball mill, mortar, or any food mill with fine or ultra-fine process types. 10. The emulsion according to any of claims 1 to 9, wherein the emulsion is dispersed in an aqueous phase or absorbed in a solid phase from 5 mg in 100 mL to 10 g in 100 mL producing transparent emulsions. 11. A beverage or base material comprising the emulsion according to claim 10, wherein the aqueous phase or base material is selected from the group consisting of energy drink, mineral water, lemonade, tonic water, fruit water, juice of fruit, milk, whey, carbonated drink, alcoholic beverage and as a preparation of drinking water. 12. A composition comprising the emulsion according to claim 10, wherein the aqueous or solid phase is selected from food, beverages, supplements or supplements or cosmetics.