NL2030822B1

NL2030822B1 - Method for producing a CBD comprising liquid or solid and use thereof

Info

Publication number: NL2030822B1
Application number: NL2030822A
Authority: NL
Inventors: Monica Johanna Willems Jolieke; Elisabeth Brink Karen; Bernardus Cornelius De Heij Wouter
Original assignee: Food4Innovations Ventures B V
Priority date: 2022-01-14
Filing date: 2022-02-04
Publication date: 2023-07-25

Abstract

The invention provides a method for producing a liquid, wherein the method 5 comprises a ﬁrst stage for providing a ﬁrst liquid comprising components, wherein the components comprise water, oil, an emulsiﬁer, and a functional component, wherein the ﬁrst stage comprises: (a) a ﬁrst mixing stage, wherein the ﬁrst mixing stage comprises: combining and mixing water, oil, an emulsiﬁer, and the functional component, to provide a ﬁrst mixture, wherein in the ﬁrst mixing stage a mixer device is applied rotating at a speed of at least 5000 10 RPM, and wherein the functional component comprises Cannabidiol, and (b) a ﬁrst homogenization stage to provide the ﬁrst liquid, wherein the ﬁrst homogenization stage comprises homogenizing in a homogenizer n times the ﬁrst mixture, wherein in the ﬁrst homogenization stage a homogenizer is applied at a pressure of at least 250 bar, wherein n is selected from the range of 1-10. 15

Description

Method for producing a CBD comprising liquid or solid and use thereof

FIELD OF THE INVENTION

The invention relates to a method for producing a liquid, the liquid as such, as well as the use thereof. The invention also relates to a method for producing a solid, and optionally a liquid thereof, as well as its use. The invention also relates to the products obtainable with the herein described method(s).

BACKGROUND OF THE INVENTION

The use of cannabinoid is known in the art. EP3782602, for instance, describes a composition comprising surfactant-enhanced phospholipid vesicles with one or more cannabinoid substance encapsulated therein, wherein one or more surfactant is utilized for enhancing loading and increasing encapsulation efficiency of cannabinoid passenger molecules within phospholipid structures. A method is described for making a surfactant-enhanced phospholipid vesicles with one or more cannabinoid substance encapsulated therein, wherein one or more surfactant is used for enhancing loading and increasing encapsulation efficiency of passenger molecules in phospholipid structures. A method of using surfactant-enhanced phospholipid vesicles with one or more cannabinoid substance encapsulated therein is described wherein one or more surfactants enhance loading and increases encapsulation efficiency of cannabinoid substances in phospholipid structures. A composition and method of making surfactant-enhanced phospholipid vesicles with one or more lipophilic passenger substance encapsulated therein is described wherein one or more surfactant is utilized for enhancing loading and increasing encapsulation efficiency of passenger molecules within phospholipid structures.

SUMMARY OF THE INVENTION

There appears to be a desire to provide a cannabinoid substance in an easily useable form, and preferably with an enhanced uptake. Solutions known in the art may be less desirable in terms of taste, complexity and/or uptake by the human body.

Hence, amongst others it is an aspect of the invention to provide an alternative cannabinoid comprising material and/or method for the production thereof, which preferably further at least partly obviates one or more of above-described drawbacks. The present invention may have as object to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

According to a first aspect, the invention provides a method for producing a liquid. Especially, the method comprises a first stage for providing a first liquid comprising components. The components may comprise water, oil, an emulsifier, and a functional component. In embodiments, the first stage may comprise a first mixing stage and a first homogenization stage. In embodiments, the first mixing stage may comprise: combining and mixing water, oil, an emulsifier, and the functional component, to provide a first mixture.

Especially, in embodiments in the first mixing stage a mixer device, such as especially an ultra

IO turrax, is applied rotating at a speed of at least S000 RPM. Further, in embodiments the functional component comprises Cannabidiol (CBD). Further, in embodiments in the first homogenization stage the first liquid is provided. Especially, in embodiments the first homogenization stage comprises homogenizing in a homogenizer n times the first mixture.

Especially, in embodiments in the first homogenization stage a homogenizer is applied at a pressure of at least 250 bar. Further, in embodiments n may be selected from the range of 1- 10. Hence, especially in embodiments the invention provides a method for producing a liquid, wherein the method comprises a first stage for providing a first liquid comprising components, wherein the components comprise water, oil, an emulsifier, and a functional component, wherein the first stage comprises: (A) a first mixing stage, wherein the first mixing stage comprises: combining and mixing water, oil, an emulsifier, and the functional component, to provide a first mixture, wherein in the first mixing stage a mixer device is applied; and wherein the functional component comprises Cannabidiol, and (B) a first homogenization stage to provide the first liquid, wherein the first homogenization stage comprises homogenizing in a homogenizer n times the first mixture, wherein in the first homogenization stage a homogenizer is applied at a pressure of at least 250 bar; wherein n is selected from the range of 1-10.

Especially, in embodiment the first mixing stage a mixer device is applied rotating at a speed of at least 5000 RPM, more especially wherein the mixer device is an ultra turrax device.

With such method a cannabinoid substance may be provided in an easily useable form, such as after dilution. Further, with such method, a cannabinoid substance may be provided having an enhanced uptake (in the human body). Further, such cannabinoid substance may be more desirable in terms of taste compared to known solutions. Further, the method may be relatively simple. Further, when dilution the cannabinoid, a clear solution may be provided, in embodiments, comparable to water, while nevertheless comprising the cannabinoid substance in a desirable concentration.

As indicated above, the invention provides a method for producing a liquid.

The method especially comprises a first stage, leading to a first liquid, and optionally a second stage, leading to a second liquid. The first liquid may also be concentrate to a solid material, which may optionally be diluted again to obtain the second liquid. Hence, the term “liquid” in the phrase “a method for producing a liquid”, and similar phrases, may refer in embodiments to the first liquid and may in (other) embodiments refer to the second liquid. Here below, the invention 1s especially described in relation to the first liquid and the second liquid, respectively.

Especially, the method may comprise a first stage for providing a first liquid comprising components. The first liquid may not be clear, and may have a kind of milky appearance. After dilution, however, the liquid (then indicated as second liquid, see also below), may be clear.

In embodiments, the components comprise water, oil, an emulsifier, and a functional component. The term “oil” may refer to one or more different oils. Especially, the oils are edible oils. The term “emulsifier” may refer to one or more different emulsifiers.

Especially, the emulsifiers are edible emulsifiers. The term “functional component” may refer to one or more different functional components. Especially, the functional components are edible functional components. The listing of the components water, oil, an emulsifier, and a functional component does not imply that further components may not be available. In embodiments, one or more further components may be available (such as e.g. first premixing stage mixture component, see also below).

In embodiments, the first stage may comprise a first mixing stage. Especially, the first mixing stage may comprise: combining and mixing water, the oil, the emulsifier, and the functional component, to provide a first mixture. Especially, in embodiments in the first mixing stage a mixer device may be applied rotating at a speed of at least 5000 RPM.

Especially, in embodiments the functional component may comprise

Cannabidiol. Cannabidiol is also known as CBD and is considered a phytocannabinoid. CBD may have a positive impact on one or more of anxiety, cognition, movement disorders, and pain. CBD may also have a positive impact on epilepsy disorders.

In embodiments, the first stage may comprise a first homogenization stage to provide the first liquid. Especially, the first homogenization stage may comprise homogenizing in a homogenizer n times the first mixture. In the first homogenization stage a homogenizer may be applied at a pressure of at least 250 bar. Especially, n may be selected from the range of 1-10.

Especially, the first homogenization stage is subsequent to the first mixing stage, though there may be some time between the mixing stage and the subsequent homogenization stage (see also below).

Especially, (1) the components may be selected such and (ii) the first stage may be executed such that the first liquid has a turbidity of not more than 1000 Nephelometric

Turbidity units. Nephelometric Turbidity units are also known as NTUs.

The NTU value may be determined by a nephelometer. Nephelometers are known in the art. As indicated by Wikipedia, a nephelometer or aerosol photometer is an instrument for measuring the concentration of suspended particulates in a liquid or gas colloid.

A nephelometer measures suspended particulates by employing a light beam (source beam) and a light detector set fo one side (often 90°) of the source beam.

More especially, (1) the components may be selected such and (ii) the first stage may be executed such that the first liquid has a turbidity of not more than 500 Nephelometric

Turbidity units.

The term “emulsifier” may in embodiments refer to a first emulsifier and a second emulsifier. Hence, the term “emulsifier” may refer to one or more emulsifier. Hence, in embodiments two or more different emulsifier may be applied.

The term “oil” may especially refer to a food-grade oil. The term “oil” may refer to one or more oils. Hence, in embodiment two or more different oils may be applied.

In embodiments, the components comprise a first emulsifier.

Especially, in embodiments the first mixing stage may comprise a first premixing stage. The first premixing stage may comprise: (1) combining and mixing the

Cannabidiol, a (food-grade) oil, the first emulsifier, and optionally a further first premixing stage mixture component, and optionally (ii) subjecting the thus obtained first premixing stage mixture to a heating stage. Especially, in embodiments the thus obtained mixture (“first premixing stage mixture” or “Cannabidiol comprising premixing stage mixture”) may be subjected to a temperature selected from the range of 20-60 °C. More especially, the thus obtained mixture may be subjected to a temperature selected from the range of 30-60 °C.

Especially, the thus obtained mixture may be subjected to such temperature during a time period of at least 15 minutes. For instance, the time period may be selected from the range of 15-60 minutes. However, other time periods for subjecting the thus obtained mixture to a temperature higher than room temperature (i.e. higher than 20 °C) may also be possible.

In specific embodiments, the first emulsifier may be selected from the group of quillaia, Arabic gum, octenyl succinic anhydride (OSA) modified waxy starch, a polysorbate,

sucrose monostearate, a monoglyceride, soy lecithin, and Kolliphor RH40. In specific embodiments, the first emulsifier may be selected from the group of a polysorbate and

Kolliphor RH40.

In specific embodiments, the first premixing stage may comprise: (i) combining 5 and mixing the Cannabidiol, a (food-grade) oil, the first emulsifier, and optionally a further first premixing stage mixture component, and optionally (ii) subjecting the thus obtained first premixing stage mixture to a heating stage, wherein the first emulsifier at least comprises

Kolliphor RH40, and wherein the heating stage comprises heating to a temperature of at least 30 °C.

The term “the first emulsifier” may also refer to a plurality of different first emulsifiers.

According to BASF, https://pharma.basf.com/products/kolliphor-rh-40,

Kolliphor RH 40 is a nonionic solubilizer and emulsifying agent obtained by reacting 40 moles of ethylene oxide with 1 mole of hvdrogenated castor oil. The main constituent of Kolliphor

RH 40 is glycerol polvethylene glycol oxystearate, which, together with fatty acid glycerol polvglyvcol esters, forms the hydrophobic part of the product. The hydrophilic part consists of polvethylene glvcols and glycerol ethoxylate. Kolliphor RH 40 is a white to vellowish paste at 20°C. The monoglyceride may especially be a glycerin fatty acid ester.

In embodiments, the first premixing stage mixture may comprise the first emulsifier in a ratio of 1:4 relative to the food grade oil up to ratio of 8:1 (in the first premixing stage mixture). In embodiments, the first premixing stage mixture may comprise the first emulsifier in a ratio of 1:2 relative to the food grade oil up to ratio of 4:1 (in the first premixing stage mixture).

In embodiments, the food-grade oil may be selected from the group of cannabis sativa oil, MCT oil, and sunflower oil.

In specific embodiments, the first premixing stage mixture may comprise

Cannabidiol in an amount of 5-40 weight% (relative to the first premixing stage mixture). More especially, in specific embodiments the first premixing stage mixture may comprise

Cannabidiol in an amount of 9-30 weight (relative to the first premixing stage mixture).

Especially, the phrase “relative to the first premixing stage mixture” refers to the total weight of the first premixing stage mixture. Likewise this may apply to similar phrases.

In specific embodiments, the further first premixing stage mixture component may comprise ethanol, and the first premixing stage mixture may comprise ethanol in an amount of 5-85 weight%, such as 15-85 weights, more especially in an amount of 25-75 weight% (relative to the first premixing stage mixture). In other embodiments, the further first premixing stage mixture component comprises ethanol, and the first premixing stage mixture comprises ethanol in an amount of 5-50 weight%, such as 5-50 weight%. In embodiments, the first premixing stage mixture comprises ethanol in an amount of 5-25 weight%.

In embodiments, the emulsifier may comprise a second emulsifier. Note that the presence of a second emulsifier does not necessarily include the presence of the first emulsifier.

Hence, in embodiments the components may comprise a second emulsifier.

Especially, in embodiments the first mixing stage may comprise a second

IO premixing stage. The second premixing stage may comprise combining and mixing the second emulsifier and water to provide a second premixing stage mixture (“substantially aqueous liquid comprising premixing stage mixture”).

In specific embodiments, the second emulsifier may be selected from the group of quillaia, Arabic gum, octenyl succinic anhydride (OSA) modified waxy starch, a polysorbate, sucrose monostearate, a monoglyceride, soy lecithin, and Kolliphor RH40. For further embodiments in relation to the second emulsifier it is also referred to some of the embodiments described in relation to the first emulsifier.

In specific embodiments, the second emulsifier may be selected from the group of quillaia, Arabic gum, octenyl succinic anhydride modified waxy starch, sucrose monostearate, a monoglyceride, and soy lecithin. In further specific embodiments, the second emulsifier may be selected from the group of a sucrose monostearate and soy lecithin.

The term “the second emulsifier” may also refer to a plurality of different second emulsifiers.

In specific embodiments, the second premixing stage mixture may comprise the second emulsifier in an amount of 0.5-10 weight%, more especially 1-5 weight% (relative to the second premixing stage mixture).

As can be derived from the above, the first emulsifier may comprise one or more first emulsifiers and the second emulsifier may comprise one or more second emulsifier.

Especially, in embodiments the composition of the first emulsifier (comprising one or more first emulsifiers) is different from the composition of the second emulsifier (comprising one or more second emulsifiers).

In specific embodiments, the total weight percentage of polysorbate and

Kolliphor RH40 in the first emulsifier is more than 50 wt%, and the total weight percentage of sucrose monostearate and soy lecithin in the second emulsifier is more than 50 wt%.

The phrase “total weight percentage of a and b”, and similar phrases refer to embodiments wherein one of these options a and b is available and to embodiments where both options a and b are available.

Therefore, in specific embodiments a first premixing stage mixture and a second premixing stage mixture may be provided. These two mixtures may be combined (and mixed).

Hence, in embodiments the first mixing stage may comprise: combining and mixing the first premixing stage mixture and the second premixing stage mixture, to provide the first mixture.

Therefore, in embodiments the first mixture may be processed into the first

IO liquid via the first mixing stage and the first homogenization stage. However, in embodiments also the first mixture may be provided by combining first premixing stage mixture and the second premixing stage mixture (which may have been subjected to a heat treatment). This first mixture may then be processed into the first liquid via the first mixing stage and the first homogenization stage.

In embodiments, the second premixing stage mixture and the first premixing stage mixture may be combined in a weight ratio between 1:99-25:75, more especially 5:95- 20:80. Hence, the amount of the Cannabidiol comprising premixing stage mixture may be lower than the substantially aqueous liquid comprising premixing stage mixture,

In embodiments, the first mixture (or the first liquid) may comprise Cannabidiol in an amount of 0.1-10 weight%, such as especially 0.25-10 weight%, more especially in an amount of 0.5-6 weight% (relative to the first mixture). In other specific embodiments, the first mixture (or the first liquid) may comprise Cannabidiol in an amount of 0.25-4 weight%, more especially in an amount of 0.25-2 weight% (relative to the first mixture).

In embodiments, the first mixture (or the first liquid) comprises the oil in an amount of 0.15-40 weight%, such as in an amount of 0.3-20 weight%. In embodiments, the first mixture (or the first liquid) the oil in an amount of at least | weight%o.

In embodiments, the first mixture (or the first liquid) comprises the emulsifier in an amount of 0.1-50 weight%, such as in an amount of 0.25-30 weight%. In embodiments, the first mixture (or the first liquid) comprises the emulsifier in an amount of at least 1 weight%.

In embodiments, the first mixture (or the first liquid) comprises water in an amount of at least about 44 weight%, more especially at least 50 weight%. In embodiments, the first mixture (or the first liquid) comprises water in an amount of at maximum about 99 weight%.

Hence, in specific embodiments the product may comprises the first liquid, wherein the product comprises, relative to the total weight of the product: Cannabidiol in an amount of 0.5-6 weight%; the oil in an amount of 0.3-20 weight%; the emulsifier in an amount of 0.25-30 weight%, and wherein the product further comprises water, and optionally ethanol. Especially, the (first liquid) product may have a turbidity of not more than 500

Nephelometric Turbidity units.

Especially, in embodiments the first emulsifier and the second emulsifier are different (or comprise different compositions). Hence, when the first emulsifier comprises two or more emulsifiers and/or the second emulsifier comprises two or more emulsifiers, then in specific embodiments the first emulsifier and the second emulsifier comprise different compositions.

In embodiments, in the first mixing stage a mixer device may be applied rotating at a speed of at least 10.000 RPM, such as selected from the range of 10.000-25.000. However, other rotational speeds may also be possible.

Especially, in embodiments the mixer device for the first mixing stage may comprise an ultraturrax device.

In embodiments, the mixer device for the first mixing stage may be a high-shear mixing device. In embodiments, the mixing device maybe a low pressure homogenizer, such as up to 15 bar, such as up to 10 bar, like at atmospheric pressure.

In embodiments, the mixer device for the first mixing stage may be of the rotor- stator type, such as especially an ultraturrax device. In embodiments, the mixer device for the first mixing stage may be a rotor-stator homogenizer. Especially, the mixer device for the first mixing stage is a high shear batch mixer, and may comprise a rotating shaft in a stationary cylinder; hereby, drops may be reduced in size between the gap created between these two cylinders due to the shear forces that arise. Especially, the mixer device for the first mixing stage 1s based on the shear forces in the rotor stator homogenizer. Such homogenizer may be a low pressure homogenizer, as the mixing device may in general be operated at ambient pressures, or at least below about 15 bar (see also above).

After the first mixing stage, the first homogenization stage may be executed. In embodiments, after the first mixing stage, and before the first homogenization stage, there may be a resting period. In general, the resting period may be selected from the range of 5 minutes to 300 minutes, such as up to about 120 minutes. A longer resting period is possible, but may be less desirable. The resting period may promote emulsion formation and/or stability.

In specific embodiments, in the first homogenization stage a homogenizer may be applied at a pressure of at least 500 bar.

Good results were obtained when n is be selected from the range of 2-10, such as 2-6, such as in specific embodiments at least 3, like e.g. 3-5. In embodiments, n may be selected from the range of 3-10. In specific embodiments, n may be selected from the range of 3-6.

There are many different types and models of homogenizers depending on the material to be processed. Suitable for homogenization of milk is usually a high-pressure homogenizer machine. This electric milk homogenizing equipment is actually a three-plunger reciprocating pump, which is mainly composed of the main drive shaft, a transmission belt, a body, a seal, a plunger, a suction valve, a homogenizing valve, a valve stem, 4 pressure gauge, a discharge valve, and the like.

Herein, the homogenizer used for the first homogenization stage may especially a high pressure homogenizer, such as using a pressure of at least 250 bar (during the homogenization stage).

Especially, the homogenizer used for the first homogenization stage may be a high pressure homogenizer. Such high pressure homogenizer may comprise a high shear continuous pump. In embodiments, the homogenizer used for the first homogenization stage may be a high pressure pump where at a pressure of typically hundreds to thousands of bars, such as especially at least about 250 bar in the present invention, a liquid is forced through a narrow gap and droplets are broken up by the resulting shear forces.

In the present invention, however, the pressure (used in the homogenization stage) may be substantially higher than for the homogenization for milk.

In specific embodiments, during each homogenization stage the elevated pressure may be applied during a time period selected from the range of 0.05-60 seconds, more especially 0.1-20 seconds.

With the homogenizer in the first homogenization particles may be created in the submicron range. In embodiments, cannabidiol comprising particles may be provided in the first homogenization stage having particle sizes below 500 nm, such as even below 200 nm. In embodiments, at least 50 vol.% of the cannabidiol comprising particles may have particle sizes selected from the range of up to about 200 nm, such as even up to about 100 nm.

The small droplets may improve intake in the human body of the functional component. The small droplets may in embodiments essentially be oil droplets comprising the functional component. Hence, the functional component may especially be comprised by an oil phase. In embodiments, particle sizes may be determined using laser scattering.

In specific embodiments, the components may further comprise one or more of citric acid, ascorbic acid, and sodium benzoate. These may be added for e.g. conservation purposes. Such component(s) may be added before or after homogenization. In embodiments, such component(s) may be added before homogenization.

The thus obtained first liquid may thus be turbid, but may comprise a relatively high concentration of the functional component.

In embodiments, the invention also provides the first mixture per se.

The first liquid may thus essentially be the first mixture after the mixing stage and the first homogenization stage.

Hence, a first mixture may be obtained as such due to combining and mixing the components during a first mixing stage, whereafter the first mixture is homogenized in the first homogenization stage, to provide a homogenized first mixture.

A first mixture may also be obtained by executing the first premixing stage and the second premixing stage, and combining and mixing the first premixing stage mixture and the second stage mixture to provide the first mixture in the first mixing stage, i.e. especially wherein the mixer device is applied rotating at a speed of at least 5000 RPM, whereafter the first mixture is homogenized in the first homogenization stage, to provide a homogenized first mixture.

Especially, the term “first liquid” may refer to the first mixture after the homogenization stage.

In embodiments, the thus obtained first liquid may be diluted to provide a second liquid, or may be concentration for later use in a product. Embodiments thereof are described below.

In embodiments, the method may (further) comprise a second stage for providing a second liquid comprising the first liquid. Especially, the second stage may comprise a second mixing stage. The second mixing stage may comprise combining and mixing the first liquid and an aqueous liquid, to provide the second mixture. This mixing and combining may be with method known in the art, and may not necessarily include high-shear mixing methods as described above in relation to the first mixing stage and/or first homogenization stage.

The second liquid may thus essentially be the second mixture, which may essentially be a dilution of the first liquid (or first mixture after the mixing stage and the first homogenization stage).

Especially, the aqueous liquid may be water. In other embodiments, the aqueous liquid may comprise water and ethanol.

In this way, oil droplets comprising the functional component may be comprised in aqueous (continuous) phase.

In specific embodiments, (1) the first liquid may be selected such and (ii) the second stage may be executed such that the second liquid has a turbidity of not more than 50

Nephelometric Turbidity units. More especially, in embodiments (1) the first liquid may be selected such and (i1) the second stage may be executed such that the second liquid has a turbidity of not more than 25 Nephelometric Turbidity units.

In embodiments, the second mixing stage may comprise diluting the first liquid with the aqueous liquid in the order of 50-4000 times, more especially 100-2000 times, to provide the second mixture.

In specific embodiments, the second mixture may comprise Cannabidiol in an amount of 0.0005-0.06 weight%, such as especially 0.0005-0.04 weight%, more especially 0.001-0.02 weight®% (relative to the second mixture).

In specific embodiments, the second mixture may comprise the oil in an amount of 0.0015-0.4 weight %, more especially 0.003-0.2 weight% (relative to the second mixture).

In specific embodiments, the second mixture may comprise the emulsifier in an amount of 0.0015-0.4 weight%, such as in embodiments 0.0015-0.2 weight%, like especially 0.0015-0.2 weight%o, more especially 0.0025-0.1 weight®% relative to the second mixture). Note that here the term “emulsifier” may thus especially refer to a combination of the first emulsifier and the second emulsifier.

In embodiments, the invention also provides the second mixture (or second liquid) per se.

Hence, in specific embodiments the product may comprises the second liquid, wherein the product comprises, relative to the total weight of the product: cannabidiol in an amount of 0.001-0.06 weight%o; the oil in an amount of 0.003-0.2 weight%; the emulsifier in an amount of 0.0025-0.3 weight%; and wherein the product further comprises water, and optionally ethanol. Further, the (second liquid) product may have a turbidity of not more than 25 Nephelometric Turbidity units.

In embodiments, the invention also provides the first liquid per se (see also above).

In embodiments, the method for producing the first liquid may be followed by a spray drying stage. Hence, in embodiments the method may further comprise a spray drying stage. Especially, the spray drying stage may comprise combining and mixing the first mixture with an additive comprising one or more of a water soluble protein and a water soluble carbohydrate, and spray drying the thus obtained mixture to provide a spray dried product.

In specific embodiments, the additive may comprise one or more of maltodextrin, pea protein, and soy protein. However, other additives are herein not excluded.

Further, combinations of additives may also be possible.

Hence, in embodiments the spray drying stage may comprise combining and mixing the first mixture with an additive comprising maltodextrin, and spray drying the thus obtained mixture to provide a spray dried product. In other embodiments, the spray drying stage may comprise combining and mixing the first mixture with an additive comprising (i) a water soluble protein and (ii) a water soluble carbohydrate, and spray drying the thus obtained mixture to provide a spray dried product.

In embodiments, the method may comprise spray drying at a temperature selected from the range of 80-175 °C.

In embodiments, the spray dried product may have less than 15 weight% water.

Especially, in embodiments the spray dried product may have 5-8 wt% water.

In embodiments, the invention also provides the spray dried product per se.

The spray dried product may in embodiments comprise Cannabidiol in an amount of 0.5-8 weight%, more especially 1-7 weight%o.

The spray dried product may in embodiments comprise the oil in an amount of 0.25-40 weight%, more especially 0.5-25 weight%.

The spray dried product may in embodiments comprise the emulsifier in an amount of 0-25-50 weight%, more especially 0.5-40 weight%.

The spray dried product may in embodiments comprise the additive, comprising one or more of a water soluble protein and a water soluble carbohydrate, in an amount of 15- 95 weight%, more especially 20-95 weight%.

Hence, in embodiments the product comprises the spray dried product, wherein the product comprises, relative to the total weight of the product: - Cannabidiol in an amount of 1-7 weight%; - the oil in an amount of 0.5-25 weight%;

- the emulsifier in an amount of 0.5-40 weight%; - the additive, comprising one or more of a water soluble protein and a water soluble carbohydrate, in an amount of 20-95 weight%, and - less than 15 weight% water.

After spray drying, the spray dried product may be stored and/or transported, etc. For use of the spray dried product, the product may be used as such, or may be diluted with water to provide effectively the above defined second liquid.

Hence, in specific embodiments the method may comprise a third stage for providing a (the) second liquid. Especially, the third stage may comprise: a third mixing stage.

In embodiments, the third mixing stage may comprise combining and mixing the spray dried product and an aqueous liquid, to provide the second mixture.

In an aspect, the invention also provides the use of the second liquid as defined herein, or (the use of) the spray dried product as defined herein, for the preparation of a medicament or a functional food. In yet another aspect, the invention also provides the use of the first liquid as defined herein, for the preparation of a medicament or a functional food.

In an aspect, the invention provides a product comprising one or more of the first liquid obtainable with the method(s) as described herein, or the second liquid obtainable according to the method(s) as described herein, or the spray dried product obtainable with the method(s) as described herein.

In an aspect, the invention also provides a product selected from the group of a medicament and a functional food. Such product may comprise one or more of the first liquid obtainable with the method(s) as described herein, or the second liquid obtainable according to the method(s) as described herein, or the spray dried product obtainable according to the method(s) as described herein, for use in a medical treatment. Instead of the term “medicament” also the term “pharmaceutical composition” may be used.

The product may be used for the treatment of anxiety, movement disorders, and pain. The product may be used for the promotion of cognition. The product may be used for the treatment of epilepsy disorders. The product may be used for the treatment of spasm (i.e. especially a sudden involuntary contraction of a muscle).

In yet a further aspect, the invention also provides an arrangement comprising (1) a mixer device and (ii) a homogenizer, wherein the latter is configured downstream to the former. Especially, the mixer device is an ultra turrax.

In yet a further aspect the invention also provides an arrangement comprising (1) a mixer device and (ii) a homogenizer, wherein the homogenizer is configured downstream to the former, as well as (iii) a second mixing device, wherein second mixing device is configured downstream of the homogenizer. The second mixing device may be configured to dilute the first liquid with the aqueous liquid.

In yet a further aspect the invention also provides an arrangement comprising (1) a mixer device and (ii) a homogenizer, wherein the homogenizer is configured downstream to the former, as well as (iii) a spray dryer device, wherein spray dryer device is configured downstream of the homogenizer.

Amongst others, the invention provides in an aspect (and in embodiments) a production process by which a CBD in water solution can be made with a turbidity of 50 NTU or lower by successively adding the following production steps: - an emulsifying system A is mixed with water; - an emulsifying system B is mixed with a food-grade oil containing CBD dissolved (CBD oil) in a percentage of between 5% and 40% CBD in the relevant food-grade oil. This oil mixture is then heated between 20 and 60 °C and then cooled again; - the water with emulsifying system A and the CBD oil with emulsifying system

B are mixed in a ratio between 95%-5% or 80%-20% by mass, and then this mixture is homogenized with a high-shear mixer (ultraturax) at a speed of at least 10,000 RPM for at least 1 minute; - the homogenized water and oil mixture from the above step is then treated between 2 and 6 times with a high-pressure homogenizer at a pressure between 500 and 1200 bar.

In embodiments, the high pressure homogenized mixture is diluted with water by a factor between 100 times and 2000 times making the turbidity less than 50 NTU and preferably less than 25 NTU.

In embodiments, the emulsifying system A may consist of a mixture comprising sucrose monostearate and/or lecithin in a ratio between 100:0 and 0:100 in a concentration between 2.5% and 15% by mass. Base in the water.

In embodiments, the emulsifying system B may consist of a mixture comprising

Kolliphor RH40 and/or polysorbate in the CBD oil.

In embodiments, the food-grade oil from the second production step may be hemp oil, MCT oil, and/or sunflower oil; optionally mixed with a fraction of ethanol. In embodiments, the CBD concentration in this food-grade oil may be lower than 30% but also higher than 9%.

In embodiments, the homogenization pressure may be between 750 and 1000 bar and the number of high pressure treatments may be between 3x and 5x.

In embodiments, a preservative such as citric acid, sodium benzoate, and/or ascorbic acid may be (finally) added to the high-pressure homogenized water-oil mixture.

In embodiments, a vegetable protein concentrate or isolate (for example from pea, soy, or wheat) or a carbohydrate (for example maltodextrin) may be added to the high- pressure homogenized water, and the (thus obtained) product may then spray dried to a powder.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention will now be described, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbols indicate corresponding parts, and in which: Figs. 1a-1b schematically depict some aspects of the invention. The schematic drawings are not necessarily to scale.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Homogenizer protocol

A stable, optically clear, beverage is desirably obtained. Homogenization is carried out with a pressure of between 300 bar and 1500 bar, preferably about 800 bar. The homogenization pressure may be applied for between 1 and 5 passes. The ratio of emulsifier to carrier oil in the emulsion may be containing an excess amount of emulsifier in oil, which could be used to make an optically clear beverage. An optimal concentration of between 0 and 3 times more emulsifier in contrast to the oil phase will be tested. Cloudy beverages have a high turbidity, e.g., between 200 and 300 NTU, or even as high as 2,000 NTU. The aim is to develop a beverage with a turbidity < 15 NTU. After production of the treatments, the turbidity will therefore be measured by a turbidity meter.

Emulsifiers

Based on literature and information from previous experiments, a list composed of “to be tested’ emulsifiers are shown in the below table 1:

Table 1. List of emulsifiers that will be tested in the lab.

Protocol 1. Before starting the experiment, the most optimal solubilizing phase of the emulsifier (organic or in aqueous phase) may be investigated. This could influence the droplet size and is different for every emulsifier (the movement of the emulsifier from the oil phase into the aqueous phase may be important in the formation of nano emulsions by this method). 2. Prepare a pre-emulsion comprising the emulsifier in water or oil phase in order to fully dissolve the emulsifier. When mixing the emulsifier into the solubilizing phase, an

Ultraturrax is used at 10000 rpm (stand 37) for 3 minutes. If needed, the emulsifier and solubilized phase could be heated prior to mixing. 3. Mix the pre-emulsion by slowly adding the oil phase to the aqueous phase while mixing with an Ultraturrax at 12000 rpm (stand 40) for 5 min). 4. Let the pre-emulsion mixture rest for 1 hour 5. Homogenize the emulsion with a homogenizer preferably between 300-1200 bar, and between 3 and 5 passes. 6. Collect the sample and measure the temperature directly. 7. Allow it to cool completely before measuring the turbidity. 8. The concentrated emulsion may especially be made into a ready-to-drink clear beverage by diluting it with water. Therefore, dilute a small amount of the obtained concentrated emulsion from step 6 with water to observe the clarity and turbidity of the final product.

For 5% of oil, the dilution factor will be 165x. 9. Measure the turbidity before and after dilution. 10. Take a picture of the solution before and after dilution. 11. Taste the diluted emulsion for bitterness or other off flavors.

12. Store and look at the shelf life.

Experimental design

Emulsifier type and concentration, emulsifier to oil ratio, addition of essential oil to oil phase and applied pressure are the experimental parameters that will be tested. They are divided over experimental Trial X1 (Table 2) and Trial X2 (Table 3).

Table 2:. Experimental design of Trial XI. "Experimental Treatment description Treatment Emulsifiertype ~~ Bar variable (homogenizor pressure)

Co Emusifieroil 3x2) TA Tween20+OSAstarch gg

Applied pressure © EBnuwlsifieroil 3x21) IB Tweem20+OSAstrch gy ® Emulsifier:oil (3x2:1) IC Tween 20+OSA starch 1000 ce Becanex 20%CBD oil 2A Tween80+OSAstarch 800

Emulsifier:oil (2x2:1) +

Concentration ~~ Becanex20%CBD oil 2B Tween80+OSA starch 800 ratio emulsifiers Emulsifier:oil (3x2:1) + …Becanex 20%CBD oil 2C Tween 80+OSA starch

Emulsifier oil (3.5:1) {tween80=0.5, OSA starch=3) eee Becanex 20%CBD oil 2D Tween80+OSAstarch 800

Emulstfieroil (1:1) + Becanex enn 2006CBD oil A OSAstarch 00

Emulsifier:oil (2:1) + normal

Concentration ~~ MCToil withno CBD 3B OSAsarch 800 ratio emulsifiers Emulstfier oil (3:1) + Becanex enn 2006CBD oil BC OSA starch

Emulstfier:oil (5:1) + Becanex eee CBD ORL ID OSAstarch 800

CT Emulsifieroil (Ratiofrom 4A Qenatwsale a gredion: 14) eee OOO

Concentration Emulsifier oil (1:1) 4B Qematamle gy emulsifier Emulsifier:oil (2:1) 4C Q-naturale 800

EmdsferolG:D 4D Quatmle gg

Emalsifieroil (from literature: 5A Sucrose monostearate oncent ration Emulstfier:oil (1:1) 5B Sucrose monostcarate emulsifier A

Emulsifier:oil (0.5.1) 3C Sucrose monostearate 800

Emalsiferoi il) 6A Monoglyceride gg

Concentration EmdsifierolG:D) 6B Momoglyceride gg emulsifier eee een rn

Emulstfier:oil (1:1) 6C Monoglyceride 800

Experimental Treatment description Treatment Emulsifier type Bar variable (homogenizor pressure)

Emulsifier:oil (3:1) + addition TA 83% Tween 20 + 15%

Concentration Emulsifier.oil (3:1) + addition 7B 65% Tween 20 + 35% ratio emulsifiers ofacoswfactat lecithine 80

Emulsifier:oil (3:1) + addition 7C 100% Tween20 + lecithine

Emulsifier:oil (1:1) based on SA Arabic gum

Concentration literature 800 emulsifier Emulsifieroil(3:D 8B Arabic gum 800

Essential oil : MCT (4:1) 9A Q-naturale (ratio from 4A) 800

Ratioessentialoil: Essentialoil: MCT (1:4) 9B Q-natumle (ratio from 44)

MCT eee eee eee SOO

Essential oil : MCT (1:1) 9C Q-naturale (ratio from 4A) S00

Essential oil : MCT (4:1) + 10A 65% Tween 20 + 35% _Emulsifieroil (11) tie 800

Ratio essential oil : Essential oil : MCT (1:4) + 10B 63% Tween 20 + 35%

MCT _Emulsifieroil (11) lecithine 800

Essential oil : MCT (1:1) + 10C 63% Tween 20 + 35%

Table 3. Experimental design set-up of Trial X2.

Experimental Treatment Treatment Emulsifier type Pressure (Bar) variable description

Emulsifier:oil (1:1) 1A 65% Tween 20 + 35% lecithine 800

Emubsiferoilratio _Bmsisifierol 1) IB 65% Tween20+3S%lecihine go

Emulsifier:oil (3:1) ic 65% Tween 20 + 35% lecithine OR

Emulsifier:oil (1:1) 2A 65% Tween 20 + 35% lecithine OR

Applied pressure Emulsifier:oil (1:1) 2B 65% Tween 20 + 35% lecithine OR (Bar) penne SPIO ened 200

Emulsifier.oil (1:1) 2C 65% Tween 20 + 35% lecithine OR ee SPB DO

Emulsifier:oil (0.5:1) 3A =5C- Sucrose mono stearate i” ee

Emulsifertype+ Emsierel 0.7571) B Sucrose ono sicarais 00 concentration EEE LESSEE EEE e ESSE SEES SSSA SLL snes erase

Emulsifier:oil (0.6:1) 3C 90% sucrose monostearate + 10% ee. mONOglyceride 800

Enmisifier:oil (1:1) 4A 50 % sucrose monostearate + 50%

Emulsifier:oil (1.15:1) 4B 50% sucrose monostearate + 65%

Emulsifiers mixed ~~ tween8 80

Emulsifier:oil (1.1:1) 4C 50% sucrose monostearate + 50% tween 80 + (1% *tolal amount

Le decithimE) 800

Experimental ~~ Treatment Treatment Emulsifiertype = Pressure (Bar) variable description

CT Emudsifieroil (17:1) 4D 29.4 % sucrose monostearate + 29.4% tween 80 + 41.18% g

Emulsifier:oil (1.7:1) 4E 29.4% sucrose monostearate + © Bmulsifieroil (111) 3A 20.7%Tween80 + 33% lecithine gg

Emulsifier Type ~~ Emuisifieroif 2:1) 3B 217%Tween80 +35% lecithine gop

EmoisifieroilG:) 5C 217% Tween80 + 35% lecithine oo

CT BEmalsifieroil (0.511) 6A=5C- sucrose monostearate with 20% CBD from X1

Becanex eee SOL

Emulsifier:oil (1.1:1) GB = 4C- 50% sucrose monostearate + 50% with 20% CBD [rom X2 tween 80 + (1%*total lecithine) 11-2921 Emulsifier:oil (1.1:1) 6D = 4C- 50% sucrose monostearate + 50% with 5% CBD from X2 tween 80 + (1%*total lecithine)

Becanex 800

Emulsifier:oil (1.1:1) 6C= 4C- 50% sucrose monostearate + 50% with 40%CBD X2 — 500 tween 80 + (1%*total lecithine}

CT From Literature = JA KolliphorRH40

Emulsifier:(oil+ethanol 7B Kolliphor RH40 + ethanol

Emulsifier EI) ee SOO concentration Emulsificr.oil (1:1) 7C Kolliphor RH 40 800

Eamlsifieroil 2:1) 7D KolliphorRH40 gg

Emadsifieroil@&:D) 7E OO KollipborRH40 gg

Trial X1: table first part

Experimental | Treatment description Treatment | Emulsifier type variable

Applied Emulsifier:oil (3x2:1) Tween 20+OSA starch pressure (Bar) Emulsifier:oil (3x2:1) Tween 20+OSA starch

Emulsifier;oil (3x2:1) Tween 20+OSA starch

Concentration | Emulsifier:oil (1x2:1) + Becanex 2A Tween 80+OSA starch ratio 20%CBD oil emulsifiers Emulsifier:oil (2x2:1) + Becanex | 2B Tween 80+OSA starch 20%CBD oil

Emulsifier:oil (3x2:1) + Becanex | 2C Tween 80+OSA starch 20%CBD oil

Emulsifier oil (3.5:1) 2D Tween 80+OSA starch (tween80=0.5, OSA starch=3) +

Becanex 20%CBD oil

Experimental | Treatment description Treatment | Emulsifier type variable

Concentration | Emulsifier:oil (1:1} + Becanex 3A OSA starch ratio 20%CBD oil emulsifiers Emulsifier:oil (2:1) + normal MCT | 3B OSA starch oil with no CBD

Emulsifier oil (3:1) + Becanex 3C OSA starch 20%CBD oil

Emulsifier;oil (5:1) + Becanex 3D OSA starch 20%CBD oil

Concentration | Emulsifier:oil (Ratio from 4A Q-naturale emulsifier Ingredion: 1:4)

Concentration | Emulsifier:oil (from literature: 5A Sucrose monostearate emulsifier 0.1:1)

Concentration | Emulsifier;oil (2:1) Monoglyceride emulsifier Enulsifier:oil (3:1) Monoglyceride

Emulsifier:oil (1:1) Monoglyceride

Concentration | Emulsifier:oil (3:1) + additionof a | 7A 85% Tween 20 + 15% lecithin ratio cosurfactant emulsifiers Emulsifier;oil (3:1) + additionofa | 7B 65% Tween 20 + 35% lecithin cosurfactant

Emulsifier:oil (3:1) + additionofa | 7C Tween20 + (1% of lecithin = cosurfactant 1%*300g)

Concentration | Emulsifier:oil (1:1) based on SA Arabic gum emulsifier literature

Ratio essential | Essential oil : MCT (4:1) Q-naturale (ratio from 4A) oil: MCT Essential oil : MCT (1:4) Q-naturale (ratio from 4A)

Essential oil : MCT (1:1) Q-naturale (ratio from 4A)

Ratio essential | Essential oil : MCT (4:1) + 10A 65% Tween 20 + 35% lecithin oil : MCT Emulsifier:oil (1:1)

Essential oil : MCT (1:4) + 10B 65% Tween 20 + 35% lecithin

Emulsifier:oil (1:1)

Essential oil : MCT (1:1) + 10C 65% Tween 20 + 35% lecithin

Emulsifier:oil (1:1)

T) (%) up to pressure) 5x) 0/ 0; 0 oO % 6/

Q

0/ 0; % rr rr rr 6/

Le mE ww

Q

0 = ET A %

I LLL

0 6/ %

I LL LLL

0, [A oO %

T) (%) up to pressure) 5x) % % 7C 5% 15.00% | 80,00 | 10 30 160 5 800 % or /0 8B 5% 15,00% | 80,00 | 10 30 160 5 800 % 6/

Yo = ee % 9C 5% 1.25% | 93,75 10 2.5 187.5 5 800 % % % 10C 5% 5.00% | 90,00 | 10 10 180 5 300 %

Trial X2 table first part:

Experimental Treatment description Treatment Emulsifier type variable

Emulsifier;oil ratio Emulsifier:oil (1:1) 65% Tween 20 + 35% lecithin OR span80

Emulsifier:oil (2:1) 1B 65% Tween 20 + 35% lecithin OR span80

Emulsifier:oil (3:1) 1C 65% Tween 20 + 35% lecithin OR span80

Applied pressure Emulsifier:oil (1:1) 2A 65% Tween 20 + 35% lecithin OR (Bar) span80

Emulsifier:oil (1:1) 2B 65% Tween 20 + 35% lecithin OR span80

Emulsifier:oil (1:1) 2C 65% Tween 20 + 35% lecithin OR span80

Emulsifier type + | Emulsifieroil (0.5.1)

Experimental Treatment description Treatment | Emulsifier type variable

Emulsifier:oil (0.6:1) 3C 90% sucrose monostearate + 10% monoglyceride

Emulsifiers mixed Emulsifier:oil (1:1) 4A 50 % sucrose monostearate + 50% tween 80

Emulsifier:oil (1.15:1) 4B 50% sucrose monostearate + 65% tween 80

Emulsifier:oil (1.1:1) 4C 50% sucrose monostearate + 50% tween 80 + (1%*total amount lecithin)

Emulsifier:oil (1.7:1) 4D 29.4 % sucrose monostearate + 29.4% tween 80 + 41.18% g lecithin

Emulsifier:oil (1.7:1) 4E 29.4% sucrose monostearate + 17.6% tween 80 + 52.9% lecithin

Emulsifier Type Emulsifier:oil (1:1) 21.7% Tween 80 + 35% lecithin

Emulsifier:oil (2:1) 21.7% Tween 80 + 35% lecithin

Emulsifier:oil (3:1) 21.7% Tween 80 + 35% lecithin with CBD in oil. 2- | Emulsifier:oil (0.5:1) with 6A =5C-X1 | sucrose monostearate 11-2021 20% CBD from Becanex

Emulsifier:oil (1.1:1) with 6B = 4C-X2 | 50% sucrose monostearate + 50% 20% CBD from Becanex tween 80 + (1%*total lecithin)

Emulsifier:oil (1.1:1) with 6D =4C-X2 | 50% sucrose monostearate + 50% 5% CBD from Becanex tween 80 + (1%%*total lecithin)

Emulsifier:oil (1.1:1) with 6C=4C-X2 | 50% sucrose monostearate + 50% 40%CBD - 500 mL tween 80 + {1%*total lecithin)

Emulsifier From Literature = 7A Kolliphor RH 40 concentration emulsifier:oil (9:1) emulsifier:(oil+ethanol Kolliphor RH40 with ethanol (2:1) 2:1)

Emulsifier:oil (1:1) Kolliphor RH 40

Emulsifier:oil (2:1) Kolliphor RH 40

Emulsifier:oil (3:1) Kolliphor RH 40

With CBD in oil Emulsifier:oil (2:1) Kolliphor RH40 + 5%CBD

Emulsifier:oil (2:1) SB | Kolliphor RH40 + 20%CBD

Trial X2 table second part:

Treatment | Oil Concentratio | Water | Qil | Emulsifie | Water | Passes Bar (%) n Emulsifier | (%) (8) | r(g (g) (start (homogenisato (MCT | (%) with 3 r pressure) ) up to 5x) % % % % % % % % 3C 5% 3.00% | 92,00 | 10 6 184 5 800 % % % % % 4E 5% 8,50% | 86,50 | 10 17 173 5 800 % 5A 5% 2.83% | 92,17 | 10 5,667 | 184,33 5 800 % 3 5B 5% 5.67% | 8933 | 10 11.334 | 178.66 5 800 % 6 5C 5% 8.50% | 90,00 | 10 17,001 180 5 800 % 6A = 5C- 5% 2,50% | 92,50 | 10 5 185 5 800

X1 % 6B =4C- 5% 6,00% | 89,00 | 10 12 178 5 800

X2 % 6D = 4C- 5% 6,00% | 89.00 | 10 12 178 5 800

X2 % 6C= 4C-X2 5% 6.00% | 89,00 | 10 12 178 5 800 - 500 mL Yo % %

L Results a) Ratio emulsifier: Oil

Tween 20 + cosurfactant lecithin © Treatment Treatment Emulsifier type ~~ Temp Turbidity Turbidity after description after Before 165x dilution cycles dilution (NTU)

Emulsifier:oil 1A-X2 65% Tween 20 + 49.5 892 25,5

Emulsifier:oil 1B-X2 65% Tween 20 + 49.4 603 12.6

Emulsifier:oil 7B-X1 65% Tween 20 + 50 397 8,9 e For the pre-solution: Tween 20 was solubilized in the organic phase, lecithin was solubilized in the aqueous phase e The solution foamed e The homogenizer was operating at 800 Bar for 5 passes. © 1A with lowest emulsifier:oil ratio showed the highest turbidity (25,5 NTU) e 1B and 7B showed a lower NTU, but tasted very bitter. b) Applied pressure (Bar)

Tween 20 + cosurfactant lecithin

Treatment Treatment Emulsifier Passes Bar ~~ Temp Turbidity Turbidity description type (homogenisation after Before after 165x pressure) cycles dilution dilution

Emulsifier:oil 2A -X2 65% 5 300 31.6 >1000 119,0 (1:1) Tween 20 + 35%

Emulsifier;oil 1A-X2 65% 5 800 49.5 892 25,5 (1:1) Tween 20 +35%

Emulsifier:oil 2B -X2 65% 5 1200 57,5 793 17.9 (1:1) Tween 20 + 35%

Emulsifier:oil 20-X2 65% 3 1500 59 899 20,4 (1: Tween 20 + 35% e For the pre-solution: Tween 20 was solubilized in the organic phase, lecithin was solubilized in the aqueous phase e The homogenizer was operating between 300 and 1500 Bar. The temperature after cycles was measured between 31 and 59 °C, respectively. The homogenizer was operating at 5 passes for bar pressure 300, 800 and 1200. For 1500 bar, 3 passes were conducted. e The solution foamed e Treatment 2A with a pressure of 300 Bar showed the highest turbidity (119 NTU). Based on the pictures before and after dilution, the solution did not look optically clear. e Treatment 1A from a previous experiment with a pressure of 800 bar showed a turbidity of 25,5 NTU. e Treatment 2B with a pressure of 1200 Bar showed a slightly lower turbidity of 17,9 NTU. e Treatment 2C with a pressure of 1500 Bar and only 3 passes showed a turbidity of 20,4

NTU. eo An increase in pressure (Bar) increased the temperature after homogenization. Therefore, a lower pressure is preferred. e When comparing treatment 2B (1200 bar, 5 cycles) and 2C (1500 bar, 3 cycles); a turbidity of approximately 18 and 20 NTU is observed, respectively. Furthermore, a temperature of 58°C for 2B and 59 °C for 2C is measured. This indicates that when lowering the number of passes, the pressure may be increased in order to obtain the same turbidity and thereby clear solution. On the other hand, when a high pressure of 1500 is used, the temperature could increase up to 80 °C (when the number of cycles will be higher than 3). This is not preferred as (in a next step) vitamins will be added to the solution, which are sensitive to heat. e Conclusion: at 800 Bar and 5 passes, the solution showed the most optimal combination of a low NTU and a low temperature. c) Emulsifier type and concentration

Tween 20 + cosurfactant lecithin

Treatment description Treatment ~~ Emulsifier type Temperature Turbidity Turbidity code after cycles before after (°C) dilution dilution (Emulsifier+cosurfactant) 7A -X1 85% Tween 20 + 15% 51 290 5.8 (Emulsifiers + 7B -X1 63% Tween 20 + 33% 50 397 8.9 (Emulsifier + 7C -X1 Tween20 + lecithin (1% of 52 280 5.7 e For the pre-emulsion: Tween 20 was solubilized in the organic phase, lecithin was solubilized in the aqueous phase e The homogenizer was operating at 800 Bar for 5 passes. e Tween 20 makes the solution taste bitter; lecithin does not add bitterness to the solution.

Lecithin tastes like soy, beany, grassy. e The solution foams after shaking © 7C showed the highest bitterness perception compared to 7A and 7B due to a high amount of Tween present in the solution. 7B had the lowest bitterness perception due to a lower amount of Tween used. e All treatments showed a turbidity < 10 NTU. Based on the pictures before and after dilution, all treatments showed optically clear solutions. eo Treatment 7B was chosen as the best treatment due to the lowest bitterness perception and an optically clear solution.

Sucrose monostearate — solubilized in cold water

Treatment description Treatment ~~ Emulsifier type ~~ Temperature Turbidity Turbidity code after cycles before after (°C) dilution dilution

Emulsifier:oil (from …Hiterature: 0.1:1) 54 Xl Sucrose monostearate 4521000 209 ……Bmulsifieroil.(1:1)……. Bz Xl SueTose MOnosIEarale NA NA NA … Emulsifier:oil (0.5:1) SC Xl Sucrose monostearate 48 575 SL … Emulsifier:oil (0.75:1)_3B _X2 sucrosemonostearate 42 383 OO e For the pre-solution: Sucrose monostearate was solubilized in the aqueous phase (cold water), and stored overnight at 4 °C. e The homogenizer was operating at 800 Bar for 5 passes. e Emulsifier:oil (1:1) was way too viscous, therefore treatment SB could not be homogenized. e All treatments tasted like water, no bitterness or off-flavor perceived. However, turbidity is too high e The lowest turbidity of 51 NTU is shown for sample SC-X1. Based on the pictures before and after dilution, all treatments did not show optically clear solutions. eo Treatment 5C-X1 was chosen as the best treatment due to the lowest NTU.

Sucrose monostearate — solubilized in hot water (60-70 C) “Treatment description Treatment Emulsifier type Temperature Turbidity code after cycles after (°C) dilution

Emulsifier:oil (from literate: 8.1:1) SEXE Serose monostearate 45 39 … Emalsifier:oil (1:1)_ SB-X1 Sucrose monostearate 52.00 35

Emulsifieroil 2: SD Sucrose momostearate ST 26 e For the pre-solution: dissolved sucrose monostearate in warm water (62 degrees) (recommended by the supplier, Sisterna B.V.). Leave for 1 hour to solubilize and cool down, add oil phase, homogenized straight after adding oil e The homogenizer was operating at 800 Bar for 5 passes. e The emulsifier concentration could be increased up to Emulsifier:oil (2:1) ratio, due to heating of the sucrose monostearate in the pre-solution. e After homogenization the treatments were still low in viscosity, however, after a couple of days, the hot solubilized treatments all became very viscous (thickness of yoghurt or even thicker with increasing sucrose monostearate concentration). Therefore, future experiments will be conducted with the cold solubilized sucrose monostearate.

Monoglyceride

N/A, because monoglyceride has a very low HLB and is therefore suitable for a water in oil emulsion. For this experiment, we are only using emulsifiers for an oil in water emulsion as they perform best.

Tween 80 + cosurfactant lecithin

Treatment description Treatment ~~ Emulsifier type ~~ Temperature Turbidity Turbidity code after cycles before after (°C) dilution dilution 21.7% Tween 80 + 35% co Emulsifieroil (11) SAX2 lecithine B 26 21.7% Tween 80 + 35% … Emulsifier:oil 2:1) SB-X2 lecithine SL 8% 20 21.7% Tween 80 + 35% e For the pre-solution: Tween 80 was solubilized in the organic phase, lecithin was solubilized in the aqueous phase e The homogenizer was operating at 800 Bar for 5 passes. e 65% Tween 80 divided by 3 =21.7%. A lower percentage is added because Tween 80 is three times more concentrated than Tween 20. eo All treatments tasted slightly bitter and foamed. However, bitterness perception is lower compared to Tween 20 treatments. e The lowest turbidity of 10 NTU is shown for sample 5C-X2. e Treatment 5C-X2 was chosen as the best treatment due to the lowest NTU.

O-naturale

Treatment description Treatment ~~ Emulsifier type Temperature Turbidity Turbidity code after cycles before after (°C) dilution dilution

Emulsifier:oil (Ratio 4A-X1 Q-naturale 43 >1000 188 ne HOM INGIEAION 14)

Emulsifier oil (1:1) 4B-X1 Q-naturale 46.6 >1000 163 © Emulsifieroil 2:1) ~~ 4C-X1 ~~ Q-naturale ~~ 486 >1000 115

Emulsifier:oil (3:1) 4D-X1 Q-naturale 50 >1000 117 e For the pre-solution: Q-naturale was solubilized in the aqueous phase e The homogenizer was operating at 800 Bar for 5 passes. e You can taste the Q-naturale (tastes and smells like a sour/rancid off-flavor) for treatment 4B,4C and 4D with an increased potency, respectively. e The Q-naturale samples foamed, except for 4A. e The lowest turbidity was measured at 115 NTU, which does not result in an optically clear solution.

Mix of the best performing emulsifiers so far (Sucrose monostearate + Tween 80)

Treatment Treatment Emulsifier type Temperature Turbidity Turbidity description code after cycles (°C) 165x 500x dilution dilution

Emulsifier:oil Sucrose

Emulsifier:oil 21.7% Tween 80 +

BD IEN Seen 48 AO Ze 50 % sucrose

Emulsifier:oil monostearate + 50% ee BD) AAXD oo tween80 A 23S 50% sucrose

Enwlsifier:oil monostearate + 65%

AAs yo ABX2 een 80 A610 AT 50% sucrose monostearate + 50%

Emulsifier;oil tween 80 + 29.4 % sucrose monostearate +

Emulsifier;oil 29.4% tween 80 +

RTD DX 41 18 g lecithine 48 0236 10 29 4% sucrose monostearate +

Emulsifier:oíl 17.6% tween 80 +

ETD HEX 52.9% lecithine 6 20 A e For the pre-solution: Tween 80 was solubilized in the organic phase, sucrose monostearate and lecithin were solubilized in the aqueous phase e The homogenizer was operating at 800 Bar for 5 passes. e Sample 4A and 4C obtained the same turbidity value with a lower amount of Tween 80 used. Furthermore, sample 4A and 4C are the best performing treatments, as they have a slightly lower bitterness perception and produce a lower amount of foam compared to 5C-X2. e Sample 4D and 4E were produced to lower the % Tween 80 even more and compensate for this with an increase in % lecithin. However, decreasing the amount of Tween 80 to 30% or lower, did not result in a NTU <15 e Sample 4B was produced to check the absence of lecithin. This treatment showed a turbidity of 10 NTU, however, the bitterness perception was equal to 5C-X2. e Conclusion: Sample 4A and 4C are performing better than 5C-X2 because of their lower bitterness perception and a decrease in foam formation, whilst having the same turbidity.

Dilution range with an a) bitter tasting transparant, and b) neutral tasting cloudy treatment

Treatment Treatment Emulsifier type 165x 330x 660x 500x 1000x 2000x description code dilutio dilutio dilutio dilutio dilution dilutio n n n n (NTU) n

Emulsifier:oi Sucrose 54 29,05 19 22 13,20 5.8

Emulsifier:oi 21.7% Tween 80 10 4.28 2.3 2.9 1,6 0.2 50% sucrose monostearate + 50% tween 80 +

Emulsifier:oi (1%*total

MOED 4CX2 lecithine) 102 475 22 25 8 e 165x dilution = would add up to 20 mg CBD in final drink when 20% CBD is used. e 330x dilution = would add up to 20 mg when 40% CBD is used. e 660x dilution = would add up to 20 mg when 80% CBD is used. © 500x dilution = would add up to 10 mg when 20% CBD is used. e 1000x dilution = would add up to 10 mg when 40% CBD is used. e 2000x dilution = would add up to 10 mg when 80% CBD is used. e The samples did not contain the %CBD that is mentioned. In this experiment, only de dilution factors are tested. © The neutral cloudy treatment 5C-X1 has no off-flavor and no foam formation. However, the turbidity is only accepted for 1000x and 2000x dilution (NTU<15). e For the bitter_transparant treatment 5C-X2, the transparency for all the dilution factors is accepted (NTU<15). However, the 330x and the 660x both have a very small bitterness and foam formation. The 1000x and 2000x bitterness is neglected, however the treatments still foam.

e For the bitter transparant treatment 4C-X2, the transparency for all the dilution factors is accepted (NTU<15). However, the 330x and 660x foam and have a light note of nutty due to the lecithin. 330x has a very small bitterness, but lower than 5C-X2. 1000x and 2000x: nutty and bitterness perception can be neglected, but the treatments still foam. e Conclusion: Treatment SC-X1 has no off-flavor or foam formation. Only 1000x and 2000x dilution have transparency (NTU<15). Treatment SC-X2 + 4C-X2 are transparent but all dilutions have foam formation, which makes these treatments less favorable compared to SC-X1. Moreover, 4C-X2 foams less compared to 5C-X2.

Experiment with 5%, 20 and 40% CBD in oil, for an a) bitter transparant and b) neutral cloudy treatment © Treatment Treatment Emulsifier type ~~ Temperature Turbidity Turbidity description code after cycles (°C) 165x 1000x dilution dilution

Emulsifier:oil (0.5:1) with 20% GA-X2 =5C- Sucrose (CBD from Becanex Xl monostearate B 50% sucrose

Emulsifier:oil monostearate + 50% (1.1:1) with 20% 6B-X2 =4C- tween 80 + (1%*total (CBD from Becanex X2 etn) He ee AO 50% sucrose

Emulsifier:oil monostearate + 50% (1.1:1) with 5% 6D-X2 =4C- tween 80 + (1%*total

CBD from Becanex A2 lecithin) oo Tobetested 50% sucrose

Enulsifier:oil monostearate + 50% (1.1:1) with 6C-X2=4C- tween 80 + (1%*total ma BOVCBD B JeC) Pe 100 nA e All treatments with CBD tasted extremely bitter. Especially treatment 4C-X2. e All 20%CBD treatments (MCT+CBD) showed an approximate 2-fold increase in NTU compared to the same treatments with just MCT oil. 5C-X1 without CBD showed a NTU of 54, while 5C-X1 with 20% CBD showed a NTU of 128 (after 165x dilution). © The 40% CBD treatment (6C) showed an approximate 10-fold increase in NTU compared to the same treatment with no CBD.

Kolliphor RH40

The MCT oil phase and surfactant were heated to 50 °C, mixed and stirred at 700 rpm for 5 min to form an isotropic mixture, the pre-emulsion. The pre-emulsion was then left to cool down to room temperature. As a next step, the pre-emulsion was mixed with the aqueous phase using an ultra turrax for 5 min at 12000 rpm and left for 1 hour prior to homogenization. © Treatment Treatment Emulsifier type Temperature Turbidity Turbidity description code after cycles (°C) before after 165x dilution dilution (Emulsifier:oil 0:1) TA-X2 Kolliphor RH40 ee ee .Emulsifier:oil (1:1) 7C-X2 Kolliphor RH40 8 92920 …Emulsifier:oil (2:1) 7D-X2 KolliphorRH40 Ô 07 BT e For treatment 7A: After mixing the aqueous with the oil phase the solution became clearer when letting the mixture rest for +-10 minutes. This can be explained through a phenomenon called spontaneous emulsification. This treatment became clear without any homogenization, however, the bitterness perception was high due to a high ratio of emulsifier to oil used (9:1). e Treatment 7C showed a turbidity of 20 NTU and no bitterness was perceived. © Treatment 7D showed a turbidity of 9 NTU with a very low bitterness perception that could easily be masked by addition of flavors. Treatment 7E showed a lower turbidity (4

NTU) after 165x dilution. Nevertheless, the bitterness perception was higher compared to 7C and 7D. e Treatment 7D was chosen as the best treatment due to a low off-flavor formation and an

NTU<15.

As a next step, 7D-X2 was tested with 5% and 20% CBD added to the oil phase. © Treatment Treatment Emulsifier type Temperature Turbidity Turbidity description code after cycles (°C) before after 165x dilution dilution

Kolliphor RH40 + …Emulsifier:oil 2:1) 8A-X2 S%CBD AS MT

Kolliphor RH40 + …Emulsifieroil 2:1) 8B-X2 2020CBD en He Se ee e Treatment 8A and 8B both showed a turbidity of approximately 5 NTU s Bitterness was perceived, but only due to addition of CBD. e Out of all emulsifiers, Kolliphor RH40 showed the most optimal conditions.

OSA starch

Emulsifier:oil High (1x2:1) + Becanex ___20%CBD oil 2A-X1 Tween80+OSAstarch 49 20

Emulsifier:oil High (2x2:1) + Becanex

LL 20%CBDoll 2B-Xt Tween80+OSA starch 46 81

Emulsifier:oil High (3x2:1) + Becanex …20%CBD oil 2C-X1 Tween80+OSAstarch NA NA

Emulsifier oil (3.5:1) High (tween80=0.5, OSA starch=3) + Becanex en 20%CBD ol 2D-XT Tween 80+OSA starch ee eee

Emulsifier:oil (1:1) Medium + Becanex 20%CBD eee SART OA aen 6

Emulsifier:oil (2:1) + Medium normal MCT oil …_Withno CBD 5B-Xi OSAstarch 47 9

Emulsifier oil (3:1) Medium + Becanex 20%CBD

Ml IEKE OBA stareh 4634

Enwlsifier:oil (5:1) Medium + Becanex 20%CBD oll DM OSAstacch 7 e | day in advance, solubilize OSA starch in cold water. e Treatment 2A and 2B showed a NTU of 20 and 8.1, respectively. However, treatment 2B separated in 2 layers (oil and aqueous) after homogenization. Treatment 2A did not foam, however, the bitterness is high. © Treatment 2C and 2D were not suitable because 2A showed a too high viscosity for the homogenizer and 2D separated in an oil and aqueous layer after homogenization. e One unanticipated finding was that treatments 3A to 3D, with only OSA starch as emulsifier, showed a masking effect/decrease on the CBD bitterness. However, the NTU of the treatments is too high. eo Treatment 3B, with no CBD added, showed no bitterness or off-flavor from OSA starch itself. In addition, it does not foam.

OSA starch © Treatment Treatment Emulsifier type Temperature after Turbidity description code cycles (°C) after 165x dilution

Emulstfier:oil (3x2:1) + OSA starch + Tween80 … Becanex 20%CBD oil ARID GOO BA ee JO2

Emulsifier:oil (3x2:1) + OSA starch + Tween80 _Becanex 20%CBD oil X3-IDwamm (300Bap 025 83

Emulsifier:oil (3x2:1) + OSA starch + Tween80 … Becanex20%CBD oil AIEE OB) ee 132 e 1 day in advance, solubilize OSA starch in cold water (high foam formation occurred), and stirred overnight. Tween 80 in oil phase. For treatment X3-1Dwarm, the OSA starch was first dispersed in water at 70 C then stirred overnight to enhance the hydration of the starch. e The homogenizer was operating at 300 Bar for 3 passes. e All treatments showed an acceptable turbidity >15 NTU. e However, all treatments showed a phase separation (layer of oil and aqueous). e The bitterness perception of all treatments was high.

Some further text protocols

Lemon-lime 64-X2

Lemon-lime 6A-X2 me Concentrat - before dilution Added after dilutien 1000

Kanegrade

Sucrose monostearate 2.50% 25 lemon juice 0,40% concentrate sweet 30% potassium sorbate . 0.15% LS stevia 0,00% (g/L) AQUEOUS sew Jom

PHASE ivaudon lim

Water (g/L) Hn on ime 0,03% avounng

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Lemon-lime 6B-X2

Lemon-lime 6B-X2 . Concentrat—-before dilution |i Addedaferdilution g B 1000

Kanegrade

Soy lecithin 1,00% 10 lemon juice 0,40% concentrate 30% potassium sorbate | AQUEOUS <0) givaudon lime or (g/L) PHASE 0,15% 1,5 flavouring 0,03%

Water (g/L) | 0

To]

ALOE CoQ) Te res Vida® (Resveratrol) | 0

MCT on + CoD €)

Polysorbate 80 (g/L) 2.50%

OILPHASE| | 0

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Lemon-lime 8B-X2

Concentrat- - before dilution Pod Added after dilution 1000

Kanegrade

Kolliphor RH40 10,00% 100 lemon juice 0,40% concentrate sweet 0/ 1 « (g/L) PHASE — givaudon lime or lo

ALO: (C010 Te] res Vida® (Resveratrol) | 0

I

0 (OSA starch — 2-X1)

Ingredients 00 g 30% OSA starch (g/L) + AQUEOUS | 50 (15% OSA starch + 35% 500 (150 g OSA starch and 70%water= (pre-emulsion) PHASE water) 350 g water)

50% citric acid (g/L) 0.240 30% potassium sorbate (g/L)

Water (g/L) 29.628 296.28

Kanegrade lemon juice Added after dilution concentrate 0.40

Added after dion 0.0040 Added after dilution

Added after dilution

I

ALL-Q® (CoQ10) ee

Vida (Rosen) TT]

MCT oi CBD (61) | OIL PHASE

Poly sorbate 30 (gL)

TTT

EE EE d) Carrier oils - MCT, Hosun, or essential oils

As carrier oils, MCT and Hosun were chosen. These are very neutral in taste and stable. Vegetable oils and flavor oils differ in the chain length of the fatty acids of the triglyceride. Vegetable oils are mostly composed of long-chain fatty acids (C18) and medium- chain fatty acids (C12-C14) while flavor oils mainly contain short-chain fatty acids (<C10). In general, short-chain triglycerides (essential oils) can form emulsions with droplet sizes as small as 10 nm, while with long-chain triglycerides, the smallest particle size is typically around 100 nm, Therefore, in addition to MCT and Hosun, certain treatments could contain addition of an essential oil (e.g., citrus oil).

Addition of essential oils © Treatment Treatment Emulsifier ~~ Temperature Turbidity before Turbidity description code type after cycles (°C) dilution (NTU) after dilution

Essential oil : 10A-X1 65% Tween 47 560 26.3

MCT (4:1) + 20 + 35%

Emulsifier:oil lecithine

Essential oil : 10B-X1 65% Tween 49 867 19,8

MCT (1:4) + 20 +35%

Emulsifier:oil lecithine

Essential oil : 10C-X1 65% Tween 49 555 12,4

MCT (1:1) + 20 + 35%

Emulsifier:oil lecithine e For the pre-solution: Tween 20 was solubilized in the organic phase, lecithin was solubilized in the aqueous phase e The homogenizer was operating at 800 Bar for 5 passes. e The treatments foamed. They tasted bitter and you can taste the lemon from the essential oil. e The turbidity of 10C-X1 was low (12.4 NTU), however the taste of the essential oil was too overpowering, making the addition of essential oils unsuitable for this application.

In embodiments, one or more of the following may apply: e A turbidity of 15 NTU or lower is preferred. e The homogenizer protocol is most optimal when operating at 800 Bar for 5 passes. e Sucrose monostearate performed best in terms of no bitterness perception and no foam formation. However, the solution showed an NTU>15 and became extremely viscous after a couple days of storage, making this treatment unsuitable for future experiments. e Treatments 5C-X2 (Tween 80 + lecithin) and 4C-X2 (sucrose monostearate + tween 80 + lecithin) showed an acceptable turbidity with an NTU of 10. However, both treatments showed a slightly bitter off-flavor and foam formation, which are undesirable characteristics. e When CBD was added, the bitterness perception increased. Furthermore, the turbidity increased by a 2-fold when 20% CBD MCT oil was used. e Treatment 7D-X2 (Kolliphor RH40) with an emulsifier:oil ratio of (2:1) showed a turbidity of 9 NTU whilst having a lower bitterness perception compared to SC-X2 and 4C-X2. Moreover, the low bitterness of 7D-X2 could easily be masked by addition of flavors and sweeteners. When 20% CBD is added to the oil phase, the 165x dilution showed a NTU of 5, with 20 mg CBD in the final drink when 20% CBD is used. e The turbidity and bitterness perception of 7D-X2 are acceptable which makes this the best performing treatment so far.

The following may be possible in embodiments: 1. Using absolute ethanol as a cosurfactant, having an emulsifier:oil ratio of (2:1) and an oil: ethanol ratio of (2:1). This could decrease the turbidity of the solution. 2. Using emulsifier OSA.

3. Using addition of other ingredients, such as sweeteners, flavors, oil soluble vitamins, acidity regulators, and/or preservatives. (For example: citric acid, potassium sorbate, sucralose, vitamin A, D, K, and flavors).

In an example, the first mixture may comprise about 5% oil + CBD, wherein 5S about 5-40 of the oil + CBD is CBD, about 0.5-30% emulsifiers, optional further additives (in embodiments less than about 5 wt%), and the remaining is water (up to 100 wt%).

Figs. 1a-1b schematically depict some aspects of the invention.

Fig. la schematically depicts in embodiments I and II embodiments of a method for producing a liquid, wherein the method comprises a first stage for providing a first liquid comprising components, wherein the components comprise water, oil, an emulsifier, and a functional component, wherein the first stage comprises: (a) a first mixing stage, wherein the first mixing stage comprises: combining and mixing water, oil, an emulsifier, and the functional component, to provide a first mixture, wherein in the first mixing stage a mixer device is applied rotating at a speed of at least 5000 RPM; and wherein the functional component comprises Cannabidiol; and (b) a first homogenization stage to provide the first liquid, wherein the first homogenization stage comprises homogenizing in a homogenizer n times the first mixture, wherein in the first homogenization stage a homogenizer is applied at a pressure of at least 250 bar; wherein n is selected from the range of 1-10.

Here, in embodiment I the first mixing stage all components C are combined and mixed.

Here, in embodiment II the following may apply: (a) the components comprise a first emulsifier, wherein the first mixing stage comprises a first premixing stage comprising: (1) combining and mixing the Cannabidiol, a food-grade oil, the first emulsifier, and optionally a further first premixing stage mixture component, (ii) optionally subjecting the thus obtained first premixing stage mixture to a heating stage, wherein the thus obtained mixture is subjected to a temperature selected from the range of 20-60 °C, especially wherein the thus obtained mixture is subjected to a temperature selected from the range of 30-60 °C during a time period of at least 15 minutes; (b) the components comprise a second emulsifier, wherein the first mixing stage comprises a second premixing stage comprising: combining and mixing the second emulsifier and water to provide a second premixing stage mixture; and (c) the first mixing stage comprises: combining and mixing the first premixing stage mixture and the second premixing stage mixture, to provide the first mixture.

Referring to Fig. 1b, two embodiments are schematically depicted. In the first embodiment, the second liquid is obtained and in the second embodiment a dried product is obtained. The latter may optionally be diluted to arrive at the second mixture / second liquid.

Fig. 1b, embodiment I, schematically depicts an embodiment of the method comprising a second stage for providing a second liquid comprising the first liquid, wherein the second stage comprises: a second mixing stage, wherein the second mixing stage comprises combining and mixing the first liquid and an aqueous liquid, to provide the second mixture; especially wherein the aqueous liquid is water.

Fig. 1b, embodiment II, schematically depicts an embodiment of the method comprising a spray drying stage, wherein the spray drying stage comprises: combining and mixing the first mixture with an additive comprising one or more of a water soluble protein and a water soluble carbohydrate, and spray drying the thus obtained mixture to provide a spray dried product.

Fig. 1b, embodiment II, schematically also depicts an embodiment wherein the method comprises a third stage for providing a second liquid, wherein the third stage comprises: a third mixing stage, wherein the third mixing stage comprises combining and mixing the spray dried product and an aqueous liquid, to provide the second mixture; especially wherein the aqueous liquid is water.

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The term “plurality” refers to two or more.

The terms “substantially” or “essentially” herein, and similar terms, will be understood by the person skilled in the art. The terms “substantially” or “essentially” may also include embodiments with “entirely”, “completely”, “all”, etc. Hence, in embodiments the adjective substantially or essentially may also be removed. Where applicable, the term “substantially” or the term “essentially” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%.

The term “comprise” also includes embodiments wherein the term “comprises”

IO means “consists of”.

The term “and/or” especially relates to one or more of the items mentioned before and after “and/or”. For instance, a phrase “item 1 and/or item 2” and similar phrases may relate to one or more of item 1 and item 2. The term "comprising" may in an embodiment refer to "consisting of" but may in another embodiment also refer to "containing at least the defined species and optionally one or more other species".

Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

The devices, apparatus, or systems may herein amongst others be described during operation. As will be clear to the person skilled in the art, the invention is not limited to methods of operation, or devices, apparatus, or systems in operation.

It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims.

In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

Use of the verb "to comprise" and its conjugations does not exclude the presence of elements or steps other than those stated in a claim. Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

The article "a" or "an" preceding an element does not exclude the presence of a plurality of such elements.

The invention may be implemented by means of hardware comprising several distinct elements, and by means of a suitably programmed computer. In a device claim, or an apparatus claim, or a system claim, enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. In yet a further aspect, the invention (thus) provides a software product, which, when running on a computer is capable of bringing about (one or more embodiments of) the method as described herein.

The invention also provides a control system that may control the device, apparatus, or system, or that may execute the herein described method or process. Yet further, the invention also provides a computer program product, when running on a computer which is functionally coupled to or comprised by the device, apparatus, or system, controls one or more controllable elements of such device, apparatus, or system.

The invention further applies to a device, apparatus, or system comprising one or more of the characterizing features described in the description and/or shown in the attached drawings. The invention further pertains to a method or process comprising one or more of the characterizing features described in the description and/or shown in the attached drawings.

The various aspects discussed in this patent can be combined in order to provide additional advantages. Further, the person skilled in the art will understand that embodiments can be combined, and that also more than two embodiments can be combined. Furthermore, some of the features can form the basis for one or more divisional applications.

Claims

Conclusions:

A method of producing a liquid, the method comprising a first stage of providing a first liquid comprising components, the components comprising water, oil, an emulsifier, and a functional component, the first stage comprising: - a first mixing stage, the first mixing stage comprising: combining and mixing water, oil, an emulsifier, and the functional component to provide a first mixture, the first mixing stage using a mixer device rotating at a speed of at least least 5000 RPM; and wherein the functional component comprises Cannabidiol; - a first homogenization stage to provide the first liquid, the first homogenization stage comprising homogenizing the first mixture n times in a homogenizer, the first homogenization stage using a homogenizer with a pressure of at least 250 bar; where n is selected from a range of 1-10.

The method of claim 1, wherein the components are selected and the first stage is configured such that the first liquid has a turbidity of no more than 1000 nephelometric turbidity units.

The method according to any one of the preceding claims, wherein the components are selected and the first stage is arranged such that the first liquid has a turbidity of not more than 500 nephelometric turbidity units.

The method according to any of the preceding claims, wherein the components comprise a first emulsifier, wherein the first mixing stage includes a first pre-mixing stage comprising: (1) combining and mixing the Cannabidiol, a food grade oil, the first emulsifier, and optionally a further first premixing phase mixture component, (ii) optionally exposing the first premixing phase mixture thus obtained to a heating phase, the first premixing phase mixture thus obtained being exposed to a temperature selected from the range of 20-60°C, in the in particular wherein the first premixing phase mixture thus obtained is exposed to a temperature selected from the range of 30-60°C, for a period of time of at least 15 minutes.

The method of claim 4, wherein the first emulsifier is selected from the group consisting of quillaia, gum arabic, octenylsuccinic anhydride-modified waxy starch, a polysorbate, sucrose monostearate, a monoglyceride, soy lecithin, and Kolliphor RH40.

The method according to any of the preceding claims 4-5, wherein the first emulsifier is selected from the group of a polysorbate and Kolliphor RH40.

The method according to any of the preceding claims 4-6, wherein the first pre-mixing phase mixture comprises the first emulsifier in a ratio of 1:2 to the food grade oil to a ratio of 4:1.

The method according to any of the preceding claims 4-7, wherein the food grade oil is selected from the group of cannabis sativa oil, MCT oil and sunflower oil.

The method according to any one of claims 4-8, wherein the first premix phase mixture comprises Cannabidiol in an amount of 9-30% by weight.

The method according to any of the preceding claims 4-9, wherein the further first premix phase mixture component comprises ethanol, and wherein the first premix phase mixture comprises ethanol in an amount of 5-50% by weight.

The method according to any of the preceding claims, wherein the components comprise a second emulsifier, the first mixing stage comprising a second premixing stage comprising: (i) combining and mixing the second emulsifier and water to form a second premixing stage mixture. provide.

The method of claim 11, wherein the second emulsifier is selected from the group consisting of quillaia, gum arabic, octenylsuccinic anhydride-modified waxy starch, a polysorbate, sucrose monostearate, a monoglyceride, soybean lecithin, and Kolliphor RH40.

The method according to any of the preceding claims 11-12, wherein the second emulsifier is selected from the group consisting of a sucrose monostearate and soya lecithin.

The method according to any of the preceding claims 11-13, wherein the second premix phase mixture comprises the second emulsifier in an amount of 1-5% by weight.

The method of any of claims 4-10 and of any of claims 11-13, wherein the first mixing stage comprises: combining and mixing the first premixing stage mixture and the second premixing stage mixture to provide the first mixture.

The method according to claim 15, wherein the first mixture comprises Cannabidiol in an amount of 0.5-6% by weight.

The method according to any of the preceding claims 15-16, wherein the first emulsifier and the second emulsifier are different or comprise different compositions.

The method according to any one of the preceding claims, wherein in the first mixing stage a mixer device is used that rotates at a speed of at least 10,000 RPM; and wherein the mixer device comprises an ultraturrax device.

The method according to any of the preceding claims, wherein a homogenizer with a pressure of at least 500 bar is used in the first homogenization phase; where n is selected from a range of 3-10; wherein during each homogenization phase the elevated pressure is applied for a period of time selected from a range of 0.1-20 seconds.

The method of any preceding claim, wherein the components further comprise one or more of citric acid, ascorbic acid, and sodium benzoate.

The method according to any of the preceding claims, wherein the method comprises a second phase of providing a second liquid comprising the first liquid, the second phase comprising: a second mixing phase, the second mixing phase comprising combining and mixing of the first liquid and an aqueous liquid to provide the second mixture; in particular wherein the aqueous liquid is water.

The method according to claim 21, wherein the first liquid is selected such and the second phase is carried out such that the second liquid has a turbidity of not more than 50 nephelometric turbidity units, in particular wherein the first liquid is selected and wherein the second stage is carried out such that the second liquid has a turbidity of not more than 25 nephelometric turbidity units.

The method of any of claims 21-22, wherein the second mixing stage comprises diluting the first liquid with the aqueous liquid on the order of 100-2000 fold to provide the second mixture.

The method according to any of claims 21-23, wherein the second mixture comprises Cannabidiol in an amount of 0.001-0.02% by weight.

The method of any one of claims 21-23, wherein the second mixture comprises the oil in an amount of 0.003-0.2% by weight.

The method according to any one of claims 21-23, wherein the second mixture comprises the emulsifier in an amount of 0.0025-0.1% by weight relative to the second mixture.

The method of any one of claims 1 to 20, further comprising a spray drying stage, the spray drying stage comprising: combining and mixing the first mixture with an additive comprising one or more of a water soluble protein and a water soluble carbohydrate , and spray-drying the resulting mixture to provide a spray-dried product.

The method of claim 27, wherein the additive comprises one or more of maltodextrin, pea protein and soy protein.

The method according to any of the preceding claims 27-28 comprises spray drying at a temperature selected from the range of 80-175°C.

The method according to any one of claims 27-28, wherein the spray-dried product contains less than 15% water by weight, in particular when the spray-dried product contains 5-8% water by weight.

The method of any one of claims 27-30, wherein the method comprises a third stage for providing a second liquid, the third stage comprising: a third mixing stage, the third mixing stage comprising combining and mixing the spray-dried product and an aqueous liquid to provide the second mixture; Particularly when the aqueous liquid is water.

Use of the second liquid as defined in any of claims 21-26 and 31, or the spray-dried product obtainable by the method of any of claims 27-30, for the preparation of a medicament or a functional food.

33. A product containing one or more of the first liquid obtainable according to the method according to any one of claims 1-20, or the second liquid obtainable according to any one of the preceding claims 21-26 and 31, or the spray-dried product , obtainable according to the method according to any of the preceding claims 27-30.

34. A product selected from the group consisting of a medicinal product and a functional food product, wherein the product is one or more of the first liquid obtainable by the method according to any one of claims 1-20 or the second liquid obtainable according to any of the preceding claims 21-26 and 31, or the spray-dried product obtainable by the method according to any of the preceding claims 27-30, for use in a medical treatment.

The product according to any one of the preceding claims 33-34, wherein the product comprises the first liquid, wherein: - the product has a turbidity of not more than 500 nephelometric turbidity units; - wherein the product comprises, in proportion to the total weight of the product: - Cannabidiol in an amount of 0.5-6% by weight; - the oil in an amount of 0.3-20% by weight; - the emulsifier in an amount of 0.25-30% by weight; and - wherein the product further comprises water and optionally ethanol.

The product according to any one of the preceding claims 33-34, wherein the product comprises the second liquid, wherein: - the product has a turbidity of no more than 25 nephelometric turbidity units; and - wherein the product comprises, in proportion to the total weight of the product - Cannabidiol in an amount of 0.001-0.06% by weight; - the oil in an amount of 0.003-0.2% by weight; - the emulsifier in an amount of 0.0025-0.3% by weight; and - wherein the product further comprises water and optionally ethanol.

The product according to any of the preceding claims 33-34, wherein the product comprises the spray-dried product, wherein the product comprises, in proportion to the total weight of the product: - Cannabidiol in an amount of 1-7% by weight ; - the oil in an amount of 0.5-25% by weight; - the emulsifier in an amount of 0.5-40% by weight; - the additive, consisting of one or more of a water-soluble protein;

- and a water-soluble carbohydrate, in an amount of 20-95% by weight, and; - less than 15% water by weight.

38. A method of producing a liquid, the method comprising a first phase to provide a first liquid comprising components, the components comprising water, oil, an emulsifier, and a functional component, the first phase comprising: a first mixing stage, the first mixing stage comprising: combining and mixing water, oil, an emulsifier, and the functional component to provide a first mixture, the first mixing stage employing a mixer device, the mixer device having a ultraturrax device; and wherein the functional component comprises Cannabidiol; - a first homogenization stage to provide the first liquid, the first homogenization stage comprising homogenizing the first mixture n times in a homogenizer, the first homogenization stage using a homogenizer at a pressure of at least 250 bar; where n is selected from a range of 1-10.