EP4090173A1

EP4090173A1 - Aqueous solution of a lipophilic compound

Info

Publication number: EP4090173A1
Application number: EP21701405.9A
Authority: EP
Inventors: Frank G. M. Collaris; Frederikus Gerardus Josephus Maria van de Wiel
Original assignee: Rrw BV
Current assignee: FYTA COMPANY B.V.
Priority date: 2020-01-13
Filing date: 2021-01-12
Publication date: 2022-11-23
Also published as: WO2021144262A1

Abstract

The invention relates to methods and devices for preparing an aqueous solution of a lipophilic compound, and for preparing a lipophilic compound in water-soluble form. More particularly, the lipophilic compound can be curcumin. The lipophilic compound can further be selected from cinnamon, constituents of cinnamon, carotenoids, in particular astaxanthine, cannabis or constituents of the cannabis plant, such as cannabinoids, in particular cannabidiol.

Description

Aqueous solution of a lipophilic compound

The present invention is generally directed to aqueous solutions of lipophilic compounds. In particular, the invention relates to methods of preparing an aqueous solution of a lipophilic compound. The invention also relates to a method for producing a lipophilic compound in water-soluble form and for improving the water solubility of a lipophilic compound. The invention also relates to aqueous solutions of lipophilic compounds and lipophilic compounds in water-soluble form. The invention also relates to a device for producing an aqueous solution of a lipophilic compound.

Technical background

Lipophilic compounds such as curcumin, ingredients from cinnamon and the cannabis plant are known to be poorly soluble in water. In order to bring the lipophilic compounds into a liquid form, they are dissolved in organic solvents or oil or added to oil-water emulsions or suspensions. However, such processes are undesirable in many applications because additives are necessary so that the lipophilic compounds can be converted into liquid form and remain stable therein, i.e. without precipitating or degrading. However, it is desirable for many applications to achieve lipophilic compounds in high concentrations in aqueous solutions, such as in medicine to improve bioavailability, in the food industry to use lipophilic substances without additives in beverages or food, and in research, to take advantage of new water-based chemical reactions - without sacrificing the amount of end product produced.

One lipophilic compound of interest is curcumin, a yellow dye found in the turmeric rootstock. Curcumin is used as a yellow food color and as a spice. It also has pain-relieving and exercise-promoting properties in osteoarthritis patients. However, curcumin has an extremely low solubility in water, so that it can often only be used in solution in oil or with the use of adsorption mediators. The water solubility of curcumin was investigated in Jagannathan et al., 2012, among others. A slight improvement in solubility was found here by heating, the changes in solubility being attributed to the intramolecular interactions of the curcumin. However, the solution produced only contained very small amounts of curcumin of 1-10 mg / mL, in which the curcumin also agglomerated. Other research has used nanotechnology to break curcumin into nanoparticles and create aqueous suspensions. Here, however, curcumin is not dissolved in the water and the bioavailability is significantly worse than in the dissolved state.

Also of interest are lipophilic compounds, ingredients of cinnamon, the cannabis plant, and carotenoids, especially astaxanthin. Cinnamon is a spice that is extracted from the bark of trees of the genus Cinnamomum. In addition to the taste and olfactory properties of cinnamon, it has beneficial bioactive properties and has an antioxidant, anti-inflammatory, antidiabetic, antimicrobial, cancer-fighting, lipid-lowering and cardiovascular effect. Furthermore, cinnamon regulates blood lipid levels and lowers blood sugar.

Most of the ingredients responsible for this are found in the vegetable oil during extraction and are lipophilic. In particular, the main components cinnamaldehyde and trans-cinnamaldehyde are highly lipophilic with a water solubility of 1.1 g / L (at 20 ° C), which reduces the bioavailability and thus the positive medical effect (Ashakirin et al., IJPSR, 2017; Vol. 8 (6): 2333-2340). Other substances such as carotenoids, especially astaxanthin, or ingredients of the cannabis plant, such as cannabinoids, especially cannabidiol (CBD), are very poorly soluble in water. However, these substances have a large number of bioactive properties that can only develop a relevant effect through improved water solubility and consequently bioavailability.

Against this background, the invention was based on the object of bringing lipophilic substances into water-soluble form so that aqueous solutions of the lipophilic substances can be prepared without the addition of solubilizers.

Summary of the invention

The invention is based on the basic idea of treating lipophilic compounds with a method according to the invention in such a way that the lipophilic compound can dissolve in water, so that an aqueous solution of the lipophilic compound can be produced.

The above object was achieved by a method according to the first aspect, in which the lipophilic compound is first enriched in foam. The powder obtained from the foam by drying has an extremely increased water solubility. By dissolving this powder in water, pure aqueous solutions of the lipophilic compound with a very high concentration can be obtained. In a first aspect, the present invention relates to a method for producing an aqueous solution of a lipophilic compound, comprising the steps:

(i) bringing the lipophilic compound into contact with process water;

(ii) triggering foam formation on the process water surface, the foam containing the lipophilic compound;

(iii) collecting the foam;

(iv) drying the foam to obtain the lipophilic compound; and

(v) Dissolving the lipophilic compound obtained from step (iv) in water to obtain an aqueous solution of the lipophilic compound.

In a second aspect, the present invention relates to an aqueous solution of a lipophilic compound that can be prepared by the method of the first aspect. In particular, the invention relates to an aqueous curcumin solution, consisting essentially of water and curcumin, with a concentration of at least 0.1 g / L curcumin.

In a third aspect, the present invention relates to a method for producing a lipophilic compound in water-soluble form, comprising the steps:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam; and

(iv) drying the foam to obtain the lipophilic compound in water-soluble form.

In a fourth aspect, the present invention relates to a lipophilic compound in water-soluble form, producible by the method of the third aspect.

The methods according to the first and third aspects increase the water solubility of the lipophilic compound. The present invention therefore also relates to a method for increasing the water solubility of a lipophilic compound, comprising the steps:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam; and

(iv) drying the foam to obtain the lipophilic compound with increased water solubility.

In a fifth aspect, the present invention relates to a device for producing a lipophilic compound in water-soluble form or an aqueous solution comprising a lipophilic compound

(i) a water tank;

(ii) a container for holding a lipophilic compound which can be held on the surface of water in the water tank; and

(iii) a gas burner for heating the lipophilic compound in the container; and (iv) an element for foaming within the water tank.

Further purposes, features, advantages and aspects of the present application will become apparent to those skilled in the art from the following description and the appended claims. Various changes and modifications within the spirit and scope of the disclosed invention will become apparent to those skilled in the art from the following illustration.

Detailed description of the invention

The present invention provides methods which are particularly advantageous in the preparation of very pure aqueous solutions which essentially contain water and a lipophilic compound and are free of other components or contain only very small amounts of other components. Very pure aqueous solutions that contain water and the lipophilic compound are particularly advantageous in various areas of application. For example, lipophilic compounds are used in the food industry (e.g. curcumin, which is used as a natural food coloring, or cinnamon, which is used in particular as a healthy flavor). However, its application is severely limited by its low water solubility, particularly in relation to drinks. On the other hand, it is not desirable to use additives (such as some solubilizers) to dissolve the lipophilic compounds in water. Lipophilic compounds are also used in medicine, whereby a basic problem remains the low bioavailability due to the poor solubility in water. For example, curcumin has shown some positive effects in some in vitro studies, which, however, were often not transferable to clinical studies, due to the poor water solubility of curcumin (Her et al., 2018, Med. Aromat Plants (Los Angeles), 7: 6) . These problems are solved by the method according to the invention for the preparation of an aqueous solution of a lipophilic compound.

A lipophilic compound in the context of the invention is in particular a compound which consists predominantly of non-polar groups. In particular, the lipophilic compound is hydrophobic. A lipophilic compound in particular has an n-octanol-water partition coefficient K _ow greater than 1, such as 2 or higher or 3 or higher. K _ow indicates the distribution of a compound between water and n-octanol. Examples of lipophilic compounds include, in particular, curcuminoids such as curcumin, and other ingredients of turmeric. The group of curcuminoids includes in particular curcumin, demethoxycurcumin and bisdemethoxycurcumin. In one embodiment, the lipophilic compound is cinnamon, ingredients of cinnamon, in particular cinnamaldehyde, carotenoids, in particular astaxanthin, cannabis or ingredients of the cannabis plant, such as cannabinoids, in particular cannabidiol (CBD).

In one embodiment, the aqueous solution of the lipophilic compound essentially comprises water and the lipophilic compound. This is particularly advantageous for producing very pure aqueous solutions that do not contain any foreign substances. Consequently, no components have to be used to convert the lipophilic compound into a water-soluble one To move shape. An aqueous solution of the lipophilic compound, which essentially comprises water and the lipophilic compound, in particular has a purity of at least 99%, such as, for example, a purity of 99.5%, 99.7%, 99.8%, 99, 9%. The percentage purity relates in particular to the proportion in mol percent of other substances based on the amount of the lipophilic compound in the aqueous solution. "Other substances" refers in particular to other organic compounds and / or heavy metals.

The preparation of aqueous solutions of a lipophilic compound is achieved in particular by the methods according to the first aspect and the sixth aspect of the invention. Devices according to the fifth or eighth aspect of the invention can be used for this purpose. The aqueous solutions of a lipophilic compound correspond in particular to the solutions according to the second aspect and seventh aspect of the invention. Furthermore, lipophilic compounds in water-soluble form according to the fourth aspect of the invention can be prepared by means of the method of the third aspect.

In a particular embodiment, the aqueous solution contains essentially no or no solubilizers or surface-active substances or surfactants. In particular, the aqueous solution contains essentially no or no liposomes, oils (apart from the oil / oils of the lipophilic compound) or phosphates such as orthophosphates. In one embodiment, the aqueous solution contains essentially no or no piperine.

1. Process for the preparation of aqueous solutions of a lipophilic compound

In a first aspect, the present invention relates to a method for producing an aqueous solution of a lipophilic compound, comprising the steps of:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam;

(iv) drying the foam to obtain the lipophilic compound; and

In particular embodiments, the lipophilic compound is a foam-forming compound, ie it can form foam in conjunction with water. Such embodiments are particularly preferred in the context of the method of the first and third aspects. Examples of lipophilic compounds include, in particular, curcuminoids such as curcumin, and other ingredients of turmeric. The group of curcuminoids includes in particular curcumin, demethoxycurcumin and bisdemethoxycurcumin. For the purposes of the present invention, the term “lipophilic compound” also includes mixtures of several lipophilic compounds, for example mixtures of different curcuminoids. In a particular embodiment, the lipophilic compound is a curcuminoid, in particular curcumin, demethoxycurcumin or bisdemethoxycurcumin. In a further embodiment, the lipophilic compound is a mixture of different cucuminoids, in particular a mixture of curcumin, demethoxycurcumin and / or bisdemethoxycurcumin, for example a mixture of consists of at least 60%, in particular at least 70% curcumin, at most 30%, in particular at most 20% Demethoxycurcumin and a maximum of 10%, in particular a maximum of 5% bisdemethoxycurcumin. For the purposes of the disclosure, “curcumin” is defined as one or more of these three main components of organically sourced curcumin. The term “curcumin” in the context of the present invention thus includes in particular pure curcumin and also mixtures of curcumin, demethoxycurcumin and bisdemethoxycurcumin. The lipophilic compounds mentioned are particularly advantageous because they are of great importance not only in the food industry but also for medicine. However, the low solubility of the lipophilic substances in aqueous solutions reduces their applicability. Therefore, the disclosed method is particularly advantageous in connection with the above lipophilic compounds.

In one embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound of at least 0.1 g / L. In particular, the aqueous solution of the lipophilic compound can have a concentration of the lipophilic compound of at least 0.2 g / L, at least 0.5 g / L, at least 1 g / L, at least 1.5 g / L, at least 2 g / L, at least 3 g / L, at least 4 g / L, or at least 5 g / L. In one embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound between 0.1 to 200 g / L, 0.1 to 100 g / L, 0.5 to 50 g / L, 1 to 30 g / L or 2 to 20 g / L, preferably between 2 to 15 g / L. In particular, the lipophilic compound is completely dissolved here. In particular, the lipophilic compound is dissolved without the aid of solubilizers or nanotechnology. In these embodiments, the lipophilic compound is in particular a curcuminoid, for example curcumin. The high concentrations of lipophilic compound in the aqueous solution are particularly advantageous for many applications. For example, the high concentration of the lipophilic compound in water can improve bioavailability in medical fields of application. Furthermore, the high concentration of the lipophilic compound in water is particularly advantageous in order to produce aqueous solutions, for example in the form of beverages. The dissolved lipophilic compound can have various effects. For example, curcumin dissolved in water in high concentrations can not only change the color of beverages in a natural way, but can also have positive effects on health (Pulido-Moran et al., 2016, Molecular, 21: 264).

In step (i) of the method according to the invention, the lipophilic compound is brought into contact with process water.

In a preferred embodiment, the process water used in step (i) of the method is selected from distilled water, double-distilled water, demineralized water, ultrapure water, deionized water. “Distilled water” in the context of the invention is essentially free of salts, organic substances and microorganisms. For example, distilled water can be produced by evaporating and condensing conventional water (e.g. spring water or tap water). Distilled water in the context of the invention is not to be understood as meaning that the water must have arisen from a distillation process, but that it meets the minimum requirements for distilled water. For the classification of distilled water, in particular the measurement of the conductivity in the prior art is used. Thus, water can be used that has a conductivity similar to, equal to, or lower than that of distilled water. For example, distilled water at 25 ° C. has a conductivity of 5 pS / cm or less, for example between 0.5 and 5 pS / cm. Process water which is used in the method according to the invention can consequently have a conductivity of 5 pS / cm or less at 25 ° C., in particular a conductivity of 2 pS / cm or less, 1.5 pS / cm or less, 1 pS / cm or less, or 0.5 ps / cm or less, each at 25 ° C.

Methods other than distillation known in the art can also be used to produce water that is essentially free of salts, organics and microorganisms. In one embodiment, the process water is produced from conventional water by suitable methods. Such methods are known to the person skilled in the art. For example, spring or tap water can be demineralized with the help of ion exchangers and thus correspond to distilled water. Alternatively, upstream reverse osmosis with downstream residual desalination via a mixed-bed filter can be used to demineralize water and thus meet the criteria of distilled water. Other expressions for distilled water in the context of this disclosure are fully demineralized water (also deionized water) or ultrapure water. More highly purified water can also be used as process water, such as highly purified water (Aqua valde purificata) or ultra-pure water.

In one embodiment, in step (i) of the method, the lipophilic compound is a curcuminoid, in particular curcumin, and the process water is demineralized or distilled water.

In a preferred embodiment, the lipophilic compound in step (i) is essentially pure. A lipophilic compound that is essentially pure has a purity of at least 80%, preferably>80%,>85%,>90%,>92%,>94%,>96%,> 98% or> 99% . In one embodiment, the lipophilic compound is a curcuminoid such as curcumin (including mixtures of different curcuminoids) which is essentially pure, preferably having a purity of>90%,>92%,>94%,>96%,> 98% or> 99%. The purity refers to the amount of other substances in the substance used in mol percent. Curcuminoids such as curcumin can be extracted from plants or chemically synthesized using methods known to those skilled in the art. Vegetable curcuminoids can be extracted from plants including Zingiberaceae Curcuma, such as Curcuma longa (turmeric), Curcuma aromatica (wild turmeric), Curcuma zedoaria (Zedoary), Curcuma xanthorrhiza, mango ginger, Indonesian arrowroot, yellow zedoary, black zedoary and galangal can be obtained. Methods for isolating curcuminoids from turmeric are known to the person skilled in the art. In addition, curcumin can be obtained from commercial sources, for example curcumin can be obtained from Sigma Chemicals Co (St. Louis, Mo.).

In a preferred embodiment, the water is provided in a water tank, the water tank in particular holding at least 0.1 L of water. In a preferred embodiment, the water tank holds a volume selected from the range from 0.1 to 1,000 L, in particular 5 L. The water tank can, for example, hold a volume of at least 0.1 L, at least 0.2 L, at least 0.5 L , at least 1 L, at least 2 L, at least 3 L, at least 4 L, at least 5 L, at least 10 L, at least 20 L or at least 50 L. The volume of the water can be selected, for example, from a range of 0.1 L up to 10,000 L. The water tank is preferably designed so that the water does not run out during the process. The water tank preferably comprises an outlet, in particular a tap, suitable for draining the water, the mixture and / or the aqueous solution of the lipophilic compound.

In a preferred embodiment, the water tank is larger in two dimensions than in the third dimension, in particular the x and y axes are larger than the z axis. For example, the water tank is larger in the axes of the stand area than in height. The water tank is preferably designed to be wide and flat, so that a large process water surface is obtained for foam formation. However, the water tank can also be larger in height than in the axes of the standing surfaces. For example, a tall water tank that is narrow in diameter can be selected. A water tank can also be selected that has axes of the same size in all three dimensions.

In one embodiment, at least 10 g of the lipophilic compound per liter of process water are used in step (i). For example, at least 15 g / L, at least 20 g / L, at least 30 g / L or at least 40 g / L can be used. In certain embodiments, between about 20 g and about 200 g of the lipophilic compound are used per liter of process water, for example about 30 g to about 100 g, in particular about 40 g to about 60 g.

In a preferred embodiment, the method comprises the further steps (vi) and (vii) between step (i) and step (ii):

(vi) providing a further small amount of the lipophilic compound, this small amount of the lipophilic compound being held in a container on the process water surface and being in contact with the process water; and

(vii) heating the small amount of the lipophilic compound. A "small amount" of the lipophilic compound in the context of the invention relates, for example, to an amount of about 0.1 g to about 10 g, in particular about 0.5 g to about 8 g, preferably about 2 g to about 6 g, such as, for example 3 g, 4 g or 5 g.

The small amount of the lipophilic compound is held in the container on the process water surface. In particular, the small amount of the lipophilic compound can be kept in a limited area on the process water surface. For example, the small amount of the lipophilic compound can be kept in an area on the process water ^{surface of 20 cm 2} or less. The lipophilic compound is in particular in a container that allows the entry of water, but prevents the exit of the lipophilic compound in the undissolved state or at least slows it down. The container is preferably held at or just below the process water surface. In particular, the container on the

The process water surface or immerse up to 5 cm in the process water. Here, the top of the container is above the process water surface, so that part of the small amount of the lipophilic compound on or on the

Process water surface can float. It can be advantageous to keep the small amount of the lipophilic compound in a limited area on the process water surface, so that it can be heated very specifically in the subsequent heating step. The residues of the heated lipophilic compound can then be removed from the process water with the container.

In a preferred embodiment, the container is a metal sieve. The container is preferably made of a metal which does not or substantially does not give off impurities or constituents into the process water and which does not melt at the temperatures used in the heating step. An example of a suitable metal is stainless steel or stainless steel. A metal sieve preferably has a sieve size that is small enough that the small amount of the lipophilic compound essentially remains in the metal sieve.

The “process water surface” in the sense of the invention includes in particular the air-water interface of the process water. The process water is preferably located in a water tank during the process, the process water surface relating to the surface via which the water is in contact with the air.

In step (vii) of the process according to the invention, the small amount of the lipophilic compound is heated.

For the purposes of the invention, heating the small amount of the lipophilic compound is to be understood as meaning that at least part of the lipophilic compound is heated in the container. However, further components can also be heated. For example, in addition to the lipophilic compound, part of the process water in the environment can be heated. In addition, the container in which the lipophilic compound is located can also be heated. The heating can also be direct and / or indirect take place, where direct heating is defined by the fact that the heat source heats one area directly, and indirect heating is defined by the fact that a heat source heats another area directly, but the small amount of the lipophilic compound indirectly through heat transport from the directly heated area is heated.

In one embodiment, the lipophilic compound is heated directly in the container and, if appropriate, its surroundings. For example, the lipophilic compound and the process water that is in the vicinity of the lipophilic compound are heated directly by a heat source. For example, the lipophilic compound is held in the container and the container including the lipophilic compound is heated. In such an exemplary embodiment, process water can also be heated which is in the direct vicinity of the lipophilic compound and / or further away from the actual heat source - for example by heat transport.

The heating can be done with any suitable heat source. Examples of corresponding heat sources include flames, in particular gas flames, electrical heating elements, sparks, in particular electrical sparks, and heat radiators. In a preferred embodiment of the method, in step (vii) the lipophilic compound in the container is heated to a temperature of at least 250.degree. C., in particular at least 300.degree. C. or at least 350.degree. In particular, the temperature is sufficient to decompose the lipophilic compound. The heat source used is particularly suitable for generating such a temperature.

In a preferred embodiment of the method, in step (vii) the lipophilic compound in the container is heated with a flame, it being possible for a flame to be generated by means known from the prior art. In a specific embodiment of the method, the lipophilic compound is heated with a gas flame in step (vii). In a particular embodiment, a water gas flame is used to heat the lipophilic compound.

A water gas flame within the meaning of the invention is a flame that is created by burning water gas in the air. In particular, a water gas flame can be generated by using a water gas cell. The water gas cell produces water gas, which can be ignited to create a water gas flame.

For the purposes of the invention, water gas essentially consists of the elements hydrogen and oxygen.

In a preferred embodiment, the water gas cell comprises a plurality of metal plates; Rubber seals each arranged between two metal plates and enclosing an interior space between the two metal plates; an inlet for water into the interior space and an outlet for water gas from the interior space; a voltage generator that generates a voltage of approximately 1.5 to 2.5 V per space between two metal plates with a current strength of about 0.005 amperes per cm ² surface for the total number of metal plates, and a line between the outlet and gas burner, which conducts the water gas generated from the water gas cell to the gas burner.

A water gas cell can comprise several metal plates, preferably arranged in parallel, to which an electrical voltage is applied. The metal plates are preferably made of steel, in particular stainless steel such as rust-free stainless steel, for example stainless steel of the alloy AISI 316. The metal plates can have a size of 50 to 400 cm ² , in particular about 200 cm ² . The metal plates can have a thickness of 0.5 mm to 2 mm, in particular about 1 mm to about 1.5 mm. The metal plates are preferably at a distance of 0.5 mm to 2 mm, in particular about 1 mm to about 1.5 mm, from one another. The space between the metal plates is filled with water, from which the water gas is formed. The water preferably has a conductivity of at least 20 pS / cm, for example at least 30 pS / cm such as about 40 pS / cm, at 25 ° C. The water can be, for example, demineralized or distilled water to which a certain amount of salt has been added in order to obtain the desired conductivity. The salt should be as pure as possible and is preferably potassium hydroxide or sodium hydroxide. The metal plates can, for example, be separated from one another by a rubber seal, the rubber seal sealing the space between the metal plates. The electrical voltage per metal plate can be in a range from 0.5 V to 5 V, for example between 1 V and 3 V or between 1.5 V and 2.5 V. The electrical voltage per metal plate is in particular not greater than 2.4 V and is preferably about 2.0 V or about 2.2 V. Furthermore, a current intensity is preferably applied which is in a range from 0.001 to 0.01 amperes per cm ² for the total surface of the metal plates. In particular, the current strength is no greater than about 0.005 amperes per cm ² for the total surface area of the metal plates. The water gas cell can have between 2 and 20 metal plates, in particular between 6 and 8 metal plates, such as 7 metal plates. In addition, the water gas cell preferably comprises an inlet for water into the interior space between the metal plates and an outlet for water gas from the interior space. The water gas cell can also include cooling for the metal plates. In one embodiment, the water gas generated can be fed directly to the gas burner via a line. The device thus comprises, in one embodiment, a line between an outlet of the water gas cell and the gas burner which guides the generated water gas from the water gas cell to the gas burner.

In this water gas cell, water is converted into water gas, which is then used to generate a water gas flame and to heat the lipophilic compound. The water gas generated in this way can either be fed directly to the gas burner, or it can first be collected in a storage tank and later burned in a gas burner to generate the water gas flame. In one embodiment, the water gas produced is passed directly to a gas burner, with the flame of which the lipophilic compound in the container is heated. In a preferred embodiment of the method, in step (vii) the lipophilic compound is heated for a period of time of about 0.5 to 10 minutes, for example at least about 1 minute, at least about 3 minutes or at least about 5 minutes. In particular, the lipophilic compound is heated until at least part of the lipophilic compound has decomposed in the container. The container with the at least partially decomposed lipophilic compound is preferably removed from the process water after the heating has ended.

In one embodiment, steps (vi) and (vii) can also be carried out in a separate water tank. The water treated in this way from the separate water tank is added to the mixture of process water and lipophilic compound in the first water tank after the heating and at least partial decomposition of the lipophilic compound in the container.

In step (ii) of the method according to the invention, foam formation is triggered on the process water surface, the foam containing the lipophilic compound.

In a preferred embodiment of the method, the foam formation is triggered in step (ii) by moving the process water, in particular by stirring or shaking, preferably by stirring. Foaming can be carried out by methods and devices known in the art. For example, a device for mixing liquids can be used. According to one embodiment, a mixer or mixer can be used which is introduced into the water tank. In particular, a vortex is generated in the process water during foam formation.

If the optional step (vii) is carried out, the foam formation can already begin during the heating of the lipophilic compound in the container in step (vii). Alternatively, the foaming begins only after step (vii) has been completed. In a preferred embodiment of the process, the foam formation is carried out in step (ii) for a period of at least 2 minutes. Step (ii) is carried out until sufficient foam formation is achieved. Sufficient foam formation can include, for example, a foam height of at least 2 cm or at least 3 cm.

The foam formed contains at least a portion of the dissolved lipophilic compound. In particular, the foam contains the majority of the lipophilic compound used, for example at least 50%, in particular at least 60%, at least 70%, at least 80% or at least 90% of the amount of lipophilic compound used in step (i).

In step (iii) of the process according to the invention, the foam is collected.

The foam which is produced or arises in the course of the process according to the invention contains part or the entire amount of the lipophilic compound used, this lipophilic compound having a particularly high solubility in after the drying step having aqueous solutions, which is very advantageous for the purposes of the invention. In a preferred embodiment, the foam collected in step (iii) contains a large part of the lipophilic compound used, preferably at least 50%, at least 60%, at least 70%, at least 80% or at least 90% of the amount used in step (i) became.

In step (iii) the foam can be collected by means of skimming, suction, pouring off or peeling off. This step can take place by methods and devices known in the art. For example, a trowel or skimmer can be used to scoop off the foam. Alternatively, the foam can be sucked off and collected by a negative pressure. The exact way in which the foam is collected is not limiting.

“Collecting” the foam within the meaning of the invention includes that the foam located on the process water is essentially removed after step (ii). In particular, the foam is essentially separated from the remaining process water. The foam is preferably collected in a container.

In step (iv) of the process according to the invention, the foam is dried in order to obtain the lipophilic compound.

In a preferred embodiment of the method, the collected foam is dried in a drying cabinet in step (iv). Drying cabinets are known in the prior art and are not limiting in the sense of this disclosure. The drying takes place, for example, at a temperature of 25 ° C to 55 ° C, in particular 30 ° C to 50 ° C, preferably at about 40 ° C. The drying takes place in particular for a time of 0.5 to 5 days, for example for about 20 to about 60 hours, in particular for about 24 to about 48 hours. The drying is carried out in particular until the desired residual moisture is reached.

The foam can be freed from excess water before drying. For example, after skimming the foam, it can be collected on a cloth or sieve. Excess water from the foam is absorbed by the cloth or sieve or drips through here. The foam thus predried can then be dried further as described above.

In a preferred embodiment of the method, in step (iv) the lipophilic compound obtained is in the form of a powder. A “powder” within the meaning of the invention comprises dried solid of the lipophilic compound. A powder can comprise particles, the particles preferably having sizes of less than 5 mm, preferably nano and microparticles. In certain embodiments, the amount of lipophilic compound obtained in step (iv) corresponds to at least 50%, in particular at least 60%, at least 70%, at least 80% or at least 90% of the amount of lipophilic compound used in step (i). In step (v) of the process according to the invention, the lipophilic compound obtained from step (iv) is dissolved in water in order to obtain an aqueous solution of the lipophilic compound.

The lipophilic compound obtained by the process according to the invention from step (iv) has an increased solubility in aqueous solutions compared to the starting substance from step (i). This is a great advantage of the process according to the invention, since the increased solubility is used in a large number of areas. For example, the bioavailability for medical applications can be increased. The increased solubility in water is also advantageous in the food industry, for example in order to dissolve the lipophilic compound in beverages. Accordingly, an essential technical effect of the process according to the invention is the increase in the water solubility of the lipophilic compound. In one embodiment, the water solubility of the lipophilic compound which is obtained in step (iv) is increased compared to the lipophilic compound which is used in step (i). An increased solubility of the lipophilic compound comprises at least an increase by a factor of 2, in particular by a factor of 5, 10, 25, 100, 200 or 500. In one embodiment, the solubility is improved by the method according to the invention by a factor between 500 and 2000, 600 and 1800, 700 and 1400, or 800 and 1200. In these embodiments, the lipophilic compound is preferably a curcuminoid such as curcumin.

In a preferred embodiment of the method, in step (v) the lipophilic compound obtained is dissolved in the water in a concentration of at least 0.1 g / L. In particular, the lipophilic compound is in a concentration of at least 0.2 g / L, at least 0.5 g / L, at least 1 g / L, at least 2 g / L, at least 3 g / L, at least 4 g / L or at least 5 g / L dissolved. In certain embodiments, the concentration of the dissolved lipophilic compound in the aqueous solution is at least 8 g / L, for example about 10 g / L. In these embodiments, the lipophilic compound is preferably a curcuminoid such as curcumin.

The water used in step (v) to dissolve the lipophilic compound is, in particular, water that is as pure as possible. The water can be selected, for example, from distilled water, double-distilled water, demineralized water, ultrapure water and deionized water. Such an embodiment is particularly advantageous since the aqueous solution obtained is very pure and preferably consists essentially of the lipophilic compound and water and does not contain any impurities. For example, the aqueous solution with the lipophilic compound in step (v) essentially comprises water and curcumin. The water which is used in the method according to the invention for dissolving the lipophilic compound in step (v) has in particular a conductivity of 5 pS / cm or less at 25 ° C., for example a conductivity of 2 pS / cm or less, 1 , 5 pS / cm or less, 1 pS / cm or less, or 0.5 ps / cm or less, all at 25 ° C. In further embodiments, the water in step (v) can be selected from tap water, spring water, rain water, ground water, drinking water, process water, Aquifer water, glacier water, treated and untreated water, steam, or atmospheric moisture.

There are also embodiments according to which, in addition to the water and the lipophilic compound in step (v), further components are also present. For example, in alternative embodiments, the lipophilic compound can be dissolved in aqueous solutions selected from milk, soy, vegetable, fruit, coffee and tea beverages, as well as soft drinks, alcoholic or de-alcoholised beverages and other beverages suitable for consumption .

2. Aqueous solution of a lipophilic compound

In a second aspect, the present invention relates to an aqueous solution of a lipophilic compound.

An aqueous solution according to the invention of a lipophilic compound contains water and the lipophilic compound, in particular with a concentration of at least 0.1 g / L and dissolved lipophilic compound. In particular, the concentration of dissolved lipophilic compound is at least 0.2 g / L, at least 0.5 g / L, at least 1 g / L, at least 2 g / L, at least 3 g / L, at least 4 g / L or at least 5 g / L. In certain embodiments, the concentration of the dissolved lipophilic compound in the aqueous solution is at least 8 g / L, for example about 10 g / L. In particular, the lipophilic compound is completely dissolved here. In particular, the lipophilic compound is dissolved without the aid of solubilizers or nanotechnology. In these embodiments, the lipophilic compound is preferably a curcuminoid such as curcumin. The aqueous solution according to the invention is particularly advantageous since very high concentrations of a lipophilic compound can be present. Such high concentrations of lipophilic compounds are interesting and advantageous for a large number of applications. For example, lipophilic compounds often have a reduced bioavailability, so that the medical application is often limited, or further components are required which increase the bioavailability but can have side effects.

The aqueous solution of a lipophilic compound according to the invention can be produced with a particularly high purity. Furthermore, the aqueous solution of a lipophilic compound according to the invention can have wide applicability in the food industry. The preparation of aqueous solutions of a lipophilic compound can be particularly advantageous in the form of beverages. For example, the dissolved lipophilic compound can be curcumin, so that drinks with a particularly high concentration of curcumin can be produced without the need for additional components (eg stabilizers, solubilizers, etc.). As a result, beverages with lipophilic compounds (eg curcumin) can be produced which have a particularly high degree of purity. In a preferred embodiment of the aqueous solution of a lipophilic compound, the lipophilic compound is a compound from the class of curcuminoids, in particular curcumin. In a preferred embodiment of the aqueous solution of a lipophilic compound, the lipophilic compound is curcumin.

In a preferred embodiment of the aqueous solution of a lipophilic compound, the water is selected from distilled water, double-distilled water, demineralized water, ultrapure water and deionized water. In particular, the water has a conductivity of 5 pS / cm or less at 25 ° C., for example a conductivity of 2 pS / cm or less, 1.5 pS / cm or less, 1 pS / cm or less or 0.5 ps / cm or less, each at 25 ° C.

In a preferred embodiment of the aqueous solution of a lipophilic compound, the aqueous solution contains essentially no or no components that support the dissolution of the lipophilic compound (for example stabilizers, solubilizers, surface-active substances, surfactants, etc.). In particular, the aqueous solution contains essentially no or no liposomes, oils or phosphates such as orthophosphates. In one embodiment, the aqueous solution contains essentially no or no piperine. In particular, in such an embodiment, the aqueous solution essentially comprises water and the lipophilic compound. Such an embodiment is particularly advantageous since a particularly pure aqueous solution can be produced.

In a preferred embodiment of the aqueous solution of a lipophilic compound, the aqueous solution comprises the lipophilic compound in a concentration at which saturation occurs, the lipophilic compound being partially present as a solid in the aqueous solution at concentrations above saturation. The concentration at which the saturation of the lipophilic compound occurs depends on the lipophilic compound and is correspondingly different. In one embodiment, the saturation concentration is> 0.2 g / L,> 0.5 g / L,> 1 g / L,> 2 g / L,> 3 g / L,> 4 g / L or> 5 g / L. In a certain embodiment, the saturation concentration is between 5 and 15 g / L, for example between 8 and 12 g / L. As soon as more lipophilic compound is added in a higher concentration than the saturation concentration, the lipophilic compound can no longer be dissolved and / or partially precipitates, so that part of the lipophilic compound is present as a solid, for example in the form of a dispersion or suspension. Supersaturation can be particularly advantageous if as much lipophilic compound as possible is to be present in the aqueous solution, that is to say that the maximum possible amount is dissolved in the aqueous solution. The part of the lipophilic compound which is then present as a solid can then either remain in the aqueous solution or be removed, depending on the application. For example, it can be advantageous if a part is present as a solid, for example if the aqueous solution is mixed with another aqueous solution so that more water is available for the undissolved lipophilic compound. In such a case, the part of the lipophilic compound which is present as a solid can then go into solution. In a certain embodiment, 5 to 40 g / L or 10 to 30 or 15 to 25 g / L, for example about 20 g / L, of the lipophilic compound are mixed with water, so that an aqueous solution is prepared in which part of the lipophilic compound is present as a solid and a part is dissolved. For example, at least 40%, at least 50%, at least 60%, at least 70%, at least 80% or at least 90% of the lipophilic compound can be dissolved and the corresponding remaining part can be present as a solid. In these embodiments, the lipophilic compound is in particular a curcuminoid such as curcumin.

“Solids” within the meaning of the invention have a solid aggregate state in the aqueous solution and are accordingly not dissolved. Solids can occur in the form of particles or deposits or be distributed in the solution, e.g. in the form of a suspension.

In a preferred embodiment of the aqueous solution of a lipophilic compound, the aqueous solution is produced by a method for producing an aqueous solution of a lipophilic compound according to the first aspect of the invention. The embodiments, features and examples of this method accordingly also relate to the aqueous solution of a lipophilic compound according to the second aspect of the invention.

Further examples of lipophilic compounds include cinnamon, ingredients of cinnamon, carotenoids, in particular astaxanthin, cannabis or ingredients of the cannabis plant, such as cannabinoids, in particular cannabidiol (CBD). In a particular embodiment, the lipophilic compound is cinnamon, ingredients of cinnamon, in particular cinnamaldehyde, carotenoids, in particular astaxanthin, cannabis or ingredients of the cannabis plant, such as cannabinoids, in particular cannabidiol (CBD).

Cinnamon, ingredients of cinnamon, carotenoids, in particular astaxanthin, cannabis and ingredients of the cannabis plant, such as cannabinoids, in particular cannabidiol (CBD) can be extracted from plants or chemically synthesized, using methods which are known to the person skilled in the art. The lipophilic compound is preferably derived from natural sources.

Cinnamon or ingredients in cinnamon preferably come from natural sources. Cinnamon is made up of a variety of ingredients, including cinnamaldehyde, trans-cinnamaldehyde, cinnamic acid and numerous essential oils, including trans-cinnamaldehyde, cinnamyl acetate, eugenol, L-borneol, caryophyllene oxide, B-caryophyllene, L-bornyl acetate, E-nerolidol, a- Cub level, a-terpineol, terpinoia and a-thujene. In one embodiment, the lipophilic compound is an ingredient of cinnamon, especially cinnamaldehyde. In one embodiment, the lipophilic compound is a mixture of an ingredient of cinnamon, a mixture in particular of several cinnamon ingredients disclosed here or in Rao et al. , 2014 disclosed cinnamon ingredients. In an exemplary embodiment, the mixture of cinnamon ingredients comprises a mixture of cinnamaldehyde and eugenol. Astaxanthin is preferably natural astaxanthin. Examples of naturally obtained astaxanthin are derived from algae such as Haematococcus, yeasts such as Phaffia, crustaceans such as shrimp, krill and crabs, cephalopods such as squid and cuttlefish, various seafood; Plants such as Adonis, Paracoccus sp. N81106, Brevundimonas sp. SD212, Erythrobacter sp. Bacteria such as PC6; Gordonia sp. Actinomycetes such as KANMONKAZ-1129; Schizophytrium sp. Astaxanthin from Labyrinthulas such as KH105.

Cannabis or the cannabis plant in the sense of this disclosure refers to the plant species Cannabis sativa, which comprises at least three important subspecies, namely C. sativa sativa, C. sativa indica and C. sativa ruderalis, and includes all naturally occurring cannabis species, hybrids or other varieties, cultures, or clonal varieties derived from or derived from any of these subspecies, including industrial hemp or drug varieties, cultures, or clonal strains. Cannabis is an umbrella term for dried or fresh cannabis flowers, leaves or other plant biomass including trichomes and for all products made from extracts of C. sativa or containing phytocannabinoids that are identical to naturally occurring phytocannabinoids, regardless of the source.

The ingredients of cannabis include, in particular, phytocannabinoids. Phytocannabinoids include decarboxylated phytocannabinoids such as delta-9-tetrahydrocannabinol, cannabidiol (CBD), cannabichromene, cannabielsoin, delta-8-tetrahydrocannabinol, iso-tetrahydrocannabinol, cannabicyclol, cannabicitran. In a preferred embodiment, an ingredient of the cannabis plant is cannabidiol, which can be added to an aqueous solution in the method according to the invention. In one embodiment, the lipophilic compound is an ingredient of cannabis, in particular cannabidiol. In one embodiment, the lipophilic compound is a mixture of an ingredient of cannabis, a mixture, in particular, consisting of several ingredients disclosed here.

The aqueous solution of a lipophilic compound can in particular have one of the following concentrations and lipophilic compounds:

(i) a concentration of at least 2 g / L cinnamon or ingredients of cinnamon, in particular cinnamaldehyde;

(ii) a concentration of at least 0.1 mg / L carotenoids, especially astaxanthin; or

(iii) a concentration of at least 0.1 mg / L cannabis or ingredients of the cannabis plant, such as cannabinoids, in particular cannabidiol (CBD).

In one embodiment, the concentration of dissolved lipophilic compound, in particular cinnamon or one or more ingredients of cinnamon, is at least 10 g / L, at least 20 g / L, at least 50 g / L, at least 100 g / L, at least 200 g / L, at least 250 g / L, e.g. 500 g / L. In one embodiment of the aqueous solution of a lipophilic compound, the aqueous solution is used as a food, drink or cosmetic, preferably as a drink. The aqueous solution of a lipophilic compound is particularly advantageous for the food industry, since the increased solubility of the lipophilic compound in the aqueous solution enables better applicability. In particular, beverages can thereby be produced which contain the lipophilic compound in dissolved form. As a result, lipophilic substances, for example, can be dissolved in drinks, which can have various effects. For example, new or more flavorings can be added that were previously insoluble or poorly water-soluble. Furthermore, lipophilic substances can be added to beverages, which have positive effects on health. In a certain embodiment, curcumin can be used as a lipophilic compound in aqueous solutions, with a particularly high solubility of the curcumin in the aqueous solution being able to be achieved according to the invention. For example, beverages containing curcumin in high concentrations can be produced. Furthermore, beverages can be produced which contain lipophilic compounds (for example curcumin), with no further components having to be added which increase the solubility of the lipophilic compounds. For example, particularly pure aqueous solutions which essentially contain water and the lipophilic compound (eg curcumin) can be used as a drink.

In one embodiment, the aqueous solution of a lipophilic compound is mixed with other aqueous solutions. For example, the aqueous solution of a lipophilic compound can be mixed with aqueous solutions selected from milk, soy, vegetable, fruit, coffee and tea drinks, as well as soft drinks, alcoholic or de-alcoholised drinks and other beverages suitable for consumption .

3. Process for the preparation of a lipophilic compound in water-soluble form

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam; and

(iv) drying the foam to obtain the lipophilic compound in water-soluble form.

The features of the method according to the invention for producing a lipophilic compound in water-soluble form correspond to those of the method for producing an aqueous solution of a lipophilic compound according to the first aspect of the invention, step (v) not being carried out in the second method according to the invention. Consequently, the process according to the third aspect of the invention serves to produce a lipophilic compound in water-soluble form, the lipophilic compound obtained after drying being the end point of the second process according to the invention. in the Subsequently, however, the lipophilic compound obtained can be dissolved in an aqueous solution, if this is desired. However, such a step is not an essential part of the process according to the invention for producing a lipophilic compound in water-soluble form. The embodiments, features and examples described for the method of the first aspect, in particular for steps (i), (ii), (iii), (iv), (vi) and (vii), also apply accordingly to the method of the third Aspect.

The method according to the third aspect of the invention is particularly advantageous for preparing lipophilic compounds which have increased solubility in aqueous solutions. Such compounds can then be used to be placed in aqueous solution. At the same time, the lipophilic compounds are preferably obtained as a solid and are therefore very stable to natural degradation (e.g. hydrolysis). Furthermore, solids can be packaged and transported more easily. A lipophilic compound in water-soluble form, which is preferably obtained as a solid, also enables the solid to be dissolved in any aqueous medium, for example for medical applications or in the food industry, for example as an addition to beverages.

Accordingly, the present invention provides a method of increasing the water solubility of a lipophilic compound comprising the steps of:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam; and

The features of the method according to the invention for increasing the water solubility of a lipophilic compound correspond to those of the method for producing a lipophilic compound in water-soluble form according to the third aspect of the invention. In certain embodiments, the water solubility of the lipophilic compound is increased by a factor of 2, in particular by a factor of 5, 10, 25, 100, 200 or 500. In one embodiment, the solubility is improved by the method according to the invention by a factor between 500 and 2000, 600 and 1800, 700 and 1400, or 800 and 1200. In these embodiments, the lipophilic compound is preferably a curcuminoid such as curcumin.

In the context of the process according to the invention for producing a lipophilic compound in water-soluble form or for increasing the water solubility of a lipophilic compound, the lipophilic compound can in one embodiment be selected from curcuminoids such as curcumin and other ingredients of turmeric. The lipophilic compound is in particular curcumin, demethoxycurcumin or bisdemethoxycurcumin or a mixture thereof, preferably curcumin. As already described above, the lipophilic compound is processed by the method according to the invention in such a way that the solubility in aqueous solutions is significantly increased. For example the lipophilic compound curcumin can be dissolved significantly better in water, so that aqueous solutions can be produced with at least up to 10 g / L or more of dissolved curcumin.

4. Lipophilic compound with increased water solubility

A fourth aspect of the present invention relates to lipophilic compounds in water-soluble form. A lipophilic compound of the present invention in water-soluble form can be produced by a process for producing a lipophilic compound in water-soluble form according to the third aspect of the invention. The embodiments, features and examples of this method accordingly also relate to the lipophilic compound in water-soluble form according to the fourth aspect of the invention. A lipophilic compound in water-soluble form is particularly advantageous for dissolving lipophilic compounds, which are usually not soluble in water, in water. As a result, increased concentrations of lipophilic compounds in water can be achieved without the need for further components that must enable water solubility. Consequently, particularly pure aqueous solutions can be prepared which essentially comprise the lipophilic compound in water-soluble form and the water in which this compound has been dissolved. Lipophilic compounds in water-soluble form are particularly advantageous in medicine, the food industry (especially in beverages), cosmetics and in research.

In one embodiment, the aqueous solution of a lipophilic compound or the lipophilic compound in water-soluble form is used as a food, drink or cosmetic, preferably as a drink. Lipophilic compounds can be particularly advantageous in foods or beverages and have various positive effects there. For example, curcumin is used as a natural color in foods. However, the application is limited by the fact that curcumin has only a very low solubility in water. In an advantageous embodiment, the lipophilic compound is curcumin, so that the curcumin is converted into a water-soluble form and can thus be better dissolved in water. As a result, curcumin can be added to beverages in a water-soluble form. In a preferred embodiment, the lipophilic compound is curcumin, which is brought into a water-soluble form by a method according to the invention and is dissolved in water in order to produce a beverage. Such a drink is particularly advantageous because it is particularly pure and essentially contains water and curcumin. No other components are necessary to dissolve or stabilize the curcumin in water.

In a preferred embodiment, the lipophilic compound is selected from curcuminoids such as curcumin, and other ingredients of turmeric. The lipophilic compound is in particular curcumin, demethoxycurcumin or bisdemethoxycurcumin or a mixture thereof, preferably curcumin. In one embodiment, the lipophilic compound is soluble in water in water-soluble form in a concentration of at least 0.1 g / L, in particular at least 1 g / L, at least 2 g / L, at least 5 g / L or at least 8 g / L, e.g. about 10 g / L. In this embodiment, the lipophilic compound is preferably a curcuminoid such as curcumin.

5. Device for the production of lipophilic compounds in water-soluble form

In a fifth aspect, the present invention relates to a device for producing lipophilic compounds in water-soluble form or aqueous solutions of lipophilic compounds, comprising:

(i) a water tank;

(ii) a container for holding the lipophilic compound, which can be held on the surface of water in the water tank; and

(iii) a gas burner for heating the lipophilic compound in the container; and

(iv) an element for foaming within the water tank.

In certain embodiments, the water tank can hold at least 1 L of water, in particular at least 4 L of water. The water tank can be made of any suitable material, in particular made of metal such as, for example, stainless steel or stainless steel.

The container is designed in such a way that it enables the water in the water tank to come into contact with the lipophilic compound in the container. In certain embodiments, leakage of the lipophilic compound in undissolved form from the container is prevented or slowed down. An example of a corresponding container is a metal sieve whose meshes are so narrow that the lipophilic compound cannot pass through them, or only in small quantities. The container is in particular made of a material that withstands the heating by the flame of the gas burner undamaged. The container is preferably made of metal, in particular made of steel, for example stainless steel or stainless steel. The container can be a stainless steel sieve, for example.

The gas burner can be any suitable gas burner which can heat the lipophilic compound in the container to a temperature of at least 200 ° C. The gas burner is aimed in particular at the interior of the container so that the flame of the gas burner can heat a lipophilic compound in the container.

In certain embodiments of the device according to the invention, the gas burner is operated with water gas. In these embodiments, the device can comprise a water gas cell. The water gas cell generates the water gas, which is burned in the gas burner to heat the lipophilic compound. The water gas cell can be connected directly to the gas burner, or the water gas generated is first collected in a suitable container and later fed into the gas burner. In one embodiment, the water gas cell has a plurality of metal plates, preferably arranged in parallel, which are each separated from one another in such a way that there is an interspace between the metal plates are created into which water can be introduced. The metal plates are preferably made of steel, in particular stainless steel such as rust-free stainless steel, for example stainless steel of the alloy AISI 316. The metal plates can have a thickness of 0.5 mm to 2 mm, in particular about 1 mm to about 1.5 mm. The metal plates can have a size of 10 to 4000 cm ² , 20 to 2000 cm ² , 30 to 1000 cm ² , 40 to 600 cm ² or 50 to 400 cm ² , in particular about 200 cm ² . The metal plates are preferably at a distance of 0.5 mm to 2 mm, in particular about 1 mm to about 1.5 mm, from one another. The space between the metal plates can be filled with water, from which the water gas is formed. The metal plates can, for example, be separated from one another by a rubber seal, the rubber seal sealing the space between the metal plates. In addition, the water gas cell comprises an inlet for water into the interior space between the metal plates and an outlet for water gas from the interior space.

In addition, the water gas cell comprises a voltage generator which can generate a voltage suitable for generating water gas between the metal plates. The electrical voltage per metal plate can be in a range from 0.5 V to 5 V, for example between 1 V and 3V or between 1.5 V and 2.5 V. In particular, the electrical voltage per metal plate is not greater than 2 .4 V and is preferably about 2.0 V or about 2.2 V. Furthermore, a current intensity is preferably applied which is in a range from 0.001 to 0.01 amperes per cm ² for the total surface of the metal plates. In particular, the current strength is no greater than about 0.005 amperes per cm ² for the total surface area of the metal plates. The water gas cell can have between 2 and 20 metal plates, in particular between 6 and 8 metal plates, such as 7 metal plates. The water gas cell can also include cooling for the metal plates. In one embodiment, the water gas generated can be fed directly to the gas burner via a line. The device thus comprises, in one embodiment, a line between an outlet of the water gas cell and the gas burner which guides the generated water gas from the water gas cell to the gas burner.

In addition, the device according to the invention can have an element for foam formation in the water tank. The element for foam formation can in particular be a stirrer or mixer. It can also be an element for shaking the water tank.

The device is particularly suitable for performing the method according to the first and / or third aspect of the invention. The embodiments, features and examples of these methods also relate to the device according to the invention, in particular with regard to the water tank, the container for the lipophilic compound, the heat source, the water gas cell and the element for foam formation. 6. Alternative process for the preparation of aqueous solutions of a lipophilic compound

In a further aspect, the present invention relates to an alternative method for producing an aqueous solution of a lipophilic compound, comprising the steps of:

(i) contacting the lipophilic compound with water in a water tank, thereby obtaining a mixture;

(ii) heating a portion of the water tank with a water gas flame, the water gas flame being directed to an area on the outside of the water tank;

(iii) mixing the mixture; and

(iv) obtaining an aqueous solution of the lipophilic compound.

In one embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound of at least 0.1 g / L. In particular, the aqueous solution of the lipophilic compound can have a concentration of the lipophilic compound of at least 0.2 g / L, at least 0.5 g / L, at least 1 g / L, at least 1.5 g / L, at least 2 g / L, at least 3 g / L, at least 4 g / L, or at least 5 g / L. In one embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound between 0.1 to 1000 g / L.

In one embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound of between 1 and 1000 g / L. In a preferred embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound of between 1 and 1000 g / L cinnamon. In one embodiment, the aqueous solution of the lipophilic compound has a concentration of the lipophilic compound of between 10 to 1000 g / L, 20 to 900 g / L, 30 to 800 g / L, 40 to 750 g / L, 50 to 700 g / L, 60 to 650 g / L, 80 to 600 g / L, 90 to 550 g / L or 100 to 500 g / L cinnamon. For the purposes of the invention, the term “cinnamon” relates in particular to cinnamaldehyde or to mixtures of cinnamaldehyde with other cinnamon ingredients.

In one embodiment, the aqueous solution of a lipophilic compound has a concentration of the lipophilic compound which is above the saturation concentration. Such an embodiment can be advantageous in order to prepare highly concentrated aqueous solutions of the lipophilic compound. The supersaturated solution can then be mixed with more water so that the supersaturated part of the lipophilic compound can also be dissolved. It can also be advantageous to prepare aqueous solutions of the lipophilic compound that are particularly highly concentrated and then to add the water. Thus, the aqueous solution of the lipophilic compound can be in the form of a concentrate which is subsequently diluted to the desired concentration, for example by the customer or consumer. In step (i) of the process, the lipophilic compound is brought into contact with water in a water tank, whereby a mixture is obtained.

Contacting the lipophilic compound with water can take place in various ways known in the art. For example, the water can first be introduced into the water tank and then a defined amount of the lipophilic compound can be added. The lipophilic compound can also be added first and then the water. The water and the lipophilic compound can also be brought into contact first and then introduced into the water tank. In a preferred embodiment, the water is first introduced into the water tank and then brought into contact with the lipophilic compound.

By bringing the lipophilic compound into contact with water in a water tank in step (i) of the process, a mixture is obtained. This mixture essentially comprises the lipophilic compound and the water. A mixture in the context of the invention is to be understood in such a way that the lipophilic compound and the water are in contact with one another / with one another and the lipophilic compound partially dissolves. However, since the water solubility of the lipophilic compounds is severely limited, the lipophilic compound is largely in the form of a solid. In one embodiment, the lipophilic compound is in the form of a solid, part of the lipophilic compound being dissolved in the water, but at most that part of the lipophilic compound which corresponds to the water solubility known in the prior art.

In a preferred embodiment, the water used in step (i) of the method is selected from distilled water, double-distilled water, demineralized water, ultrapure water and deionized water. The water used in step (i) of the method can furthermore be process water in the sense of the first aspect of the invention.

In a preferred embodiment, the water is provided in a water tank. The water tank preferably corresponds to the water tank that has already been described in the first aspect of the invention. In a preferred embodiment, the water tank holds a volume selected from the range from 0.1 to 1,000 L, in particular 5 L. In a preferred embodiment, the water tank does not consist of a magnetic metal and not of a plastic, in particular plastic. In the method according to the invention, a region of the water tank is heated by a water gas flame. So that the water tank does not melt or deform or be damaged in any other way by the heating, the water tank is preferably selected from a material which can withstand the increased temperatures caused by the water gas flame. The water tank preferably comprises a material that is heat-stable at least as long as the water gas flame is used for heating. For example, when heating for a short period of time, a less heat-stable material is sufficient than when heating for a long period of time. In preferred embodiments, the water tank is made of stainless steel. In one embodiment, at least 10 g of the lipophilic compound per liter of water are used in step (i). For example, at least 100 g, in particular at least 200 g, at least 300 g, at least 400 g or at least 500 g of cinnamon per liter of water of the lipophilic compound can be used. In certain embodiments, between about 10 g and about 1000 g of cinnamon per liter of water are used, for example about 50 g to about 750 g, in particular about 100 g to about 500 g.

In step (ii) of the method according to the invention, an area of the water tank is heated by a water gas flame, the water gas flame being directed at an area on the outside of the water tank.

When heating, an area of the water tank is heated by a water gas flame, the water gas flame being directed to an area on the outside of the water tank. In one embodiment, the area is located below the surface of the water, where underneath is to be understood as meaning that the area is located on the outside of the water tank, but is lower than the surface of the water. In the context of the invention, below the surface is preferably not in the water during the heating step, i.e. the water gas flame is preferably not in direct contact with the water or mixture. In a preferred embodiment, the area of the water tank is on the side, with lateral heating preferably being understood in such a way that the water tank is neither heated from below (e.g. the standing surface) nor from above (e.g. the main opening of the water tank). The lateral surfaces preferably correspond to the surfaces of the water tank that do not represent the standing surface, but are adjacent to it. Further, it is preferable that the portion of the water tank that is heated is an outer surface of the water tank. In one embodiment, the outer surface of the water tank corresponds to an area that is not located on the inside and is not in direct contact with water.

In a preferred embodiment, part of the mixture in the water tank is also heated in step (ii) adjacent to the heated area of the water tank. Heating of the mixture is preferably indirect, so that the mixture is not in direct contact with the water gas flame. In a preferred embodiment, the heating of a region of the water tank transfers the heat to the mixture, so that the mixture is heated indirectly. The heating preferably takes place indirectly, with indirect heating being defined by the fact that a heat source directly heats another area, but the mixture is heated indirectly by heat transport from the directly heated area.

In a preferred embodiment, part of the mixture which has a temperature of more than 50 ° C, more than 60 ° C, more than 70 ° C, more than 80 ° C or more than 90 ° C is also heated in step (ii) or a temperature at which the water starts to boil. Part of the mixture that is adjacent to the area of the water tank that is heated in step (ii) is heated and can reach a temperature of more than 50 ° C, more than 60 ° C, more than 70 ° C , has more than 80 ° C or more than 90 ° C or a temperature at which the water begins to boil. The heat can be distributed through heat transport, so that not only the adjacent part is heated, but also the remaining part of the mixture. There can be gradients in the temperature within the mixture. Parts of the mixture can be more heated than other parts of the mixture in step (ii) of the process.

In a preferred embodiment of the method, the heating takes place by means of a water gas flame. The water gas flame can in particular be generated by a gas burner, the gas burner in particular being introduced to gas that is generated by a water gas cell. Gas burners are known in the prior art and the exact structure of the gas burner is not limiting in terms of the method according to the invention. In a preferred embodiment of the method, the gas burner is designed in such a way that the water gas flame can be emitted in a targeted manner onto an area of the water tank. For example, the gas burner comprises at least one outlet channel through which the water gas emerges. Furthermore, the water gas can be ignited when it exits through the outlet channel, so that a water gas flame is created. A water gas flame can be defined by the size and geometry of the outlet channel, as well as by the water gas itself (e.g. in a mixture) and the volume flow of the water gas. A gas burner can be adapted to the size of the water tank, e.g. by using a larger gas burner (e.g. with a larger outlet duct) with a higher water tank (e.g. 1000 L) than with a smaller water tank (e.g. 1 L).

In particular, a water gas flame can be generated by using a water gas cell. The water gas cell produces water gas, which can be ignited to create a water gas flame. Water gas cells have already been described in the context of the first and fifth aspects of the invention, to which reference is made here.

The water gas flame used is particularly suitable for generating a temperature of, for example, at least 250 ° C, in particular at least 300 ° C or at least 350 ° C. In a preferred embodiment of the method, heating is carried out in step (ii) for a period of time of about 0.5 to 10 minutes, for example at least about 1 minute, at least about 3 minutes or at least about 5 minutes.

In step (iii) of the process according to the invention, the mixture is mixed.

The mixture can be mixed in various ways. In particular, the mixture can be stirred. Agitation of the mixture to mix may be performed at a speed of 10 RPM (revolutions per minute), 20 RPM, 30 RPM, 40 RPM, 50 RPM or more. Mixing of the mixture in step (iii) can take place by stirring, which is carried out by a device selected from a propeller stirrer, inclined blade stirrer, disc stirrer, swash plate stirrer, hollow blade stirrer, impeller stirrer, cross-beam stirrer, anchor stirrer, blade stirrer, grid stirrer with exchangeable blade stirrers, gas inlet stirrers with truncated or pointed ends, stirrers with movable glass or PTFE blades, spiral stirrers, toothed disk stirrers, residual quantity stirrers or other stirring devices known in the prior art. A homogenizer can also be used for mixing. In a preferred embodiment, the stirrer can be inserted and operated in the kettle.

In step (iv) of the method according to the invention, an aqueous solution of the lipophilic compound is obtained.

In a preferred embodiment, the aqueous solution of the lipophilic compound is obtained in step (iv) by removing it from the water tank. The aqueous solution of the lipophilic compound can be obtained in step (iv) in various ways. For example, the aqueous solution can be obtained through an outlet, for example a tap, of the water tank. To do this, the outlet is opened and the aqueous solution of the lipophilic compound flows from the water tank into a container that is used for extraction. In an alternative embodiment, the water tank can also be swiveled so that the aqueous solution of the lipophilic compound flows out of the water tank and is preferably collected in a container. In a further embodiment, a receiving device, in particular a trowel or a spoon, can be used to obtain the aqueous solution of the lipophilic compound in step (iv).

The lipophilic compound obtained by the process according to the invention from step (iv) has an increased solubility in aqueous solutions compared to the starting substance from step (i). This is a great advantage of the method according to the invention, since the increased solubility in aqueous solutions is used in a large number of areas. For example, the bioavailability for medical applications can be increased. The increased solubility in water is also advantageous in the food industry, for example in order to dissolve the lipophilic compound in beverages. An increased solubility of the lipophilic compound comprises at least an increase by a factor of at least 1.5, at least 2, at least 5, at least 10, at least 25, at least 100, at least 200 or at least 500. In one embodiment, the solubility of cinnamon or increases one or more ingredients of cinnamon (for example cinnamaldehyde) in water by the method according to the invention by a factor of at least 10, at least 50, preferably at least 100, for example by 250 to 400 or 300 to 350.

In one embodiment of the method, the aqueous solution of the lipophilic compound obtained in step (iv) has a dissolved concentration of at least 0.1 g / L of the lipophilic compound. In particular, the lipophilic compound is in a concentration of at least 0.2 g / L, at least 0.5 g / L, at least 1 g / L, at least 2 g / L, at least 3 g / L, at least 4 g / L or at least 5 g / L dissolved. In certain embodiments, the concentration of the dissolved lipophilic compound in the aqueous solution is at least 8 g / L, for example about 10 g / L. In one embodiment, the aqueous solution comprises the lipophilic compound has a concentration of cinnamon or one or more cinnamon ingredients (e.g. cinnamaldehyde) of at least 10 g / L water, at least 20 g / L water, at least 50 g / L water or at least 100 g / L water, for example selected from the range 100 to 1000 g / L water, such as 500 g / L.

After the aqueous solution of the lipophilic compound has been obtained in step (iv) of the method, the aqueous solution of the lipophilic compound can be processed further. For example, the aqueous solution of the lipophilic compound can be transferred to collecting and / or storage containers. In one embodiment, the aqueous solution of the lipophilic compound is filled into bottles or similar containers known in the art. The aqueous solution of the lipophilic compound can be filled in plastic containers, for example in bottles or bags made of plastic.

The aqueous solution of the lipophilic compound can also be processed further by adding additional components, in particular further water. This allows a highly concentrated aqueous solution of the lipophilic compound to be diluted. For example, the aqueous solution of the lipophilic compound can be diluted to such an extent that the dilute aqueous solution of the lipophilic compound can be consumed or drunk. Other fields of application of the diluted or nondiluted aqueous solution of the lipophilic compound are also possible and are not limiting in the context of the invention. For example, the aqueous solution of the lipophilic compound can be used in medicine or as a cosmetic. There are also embodiments according to which further components are present or added in addition to the water and the lipophilic compound. For example, in alternative embodiments, the lipophilic compound can be diluted in aqueous solutions selected from milk, soy, vegetable, fruit, coffee and tea beverages, as well as soft drinks, alcoholic or dealcoholized beverages and other beverages suitable for consumption .

According to the present invention, the expression “approximately” means that a value can have a deviation of up to +/- 10%, in particular a deviation of up to +/- 5%. “About 10” thus relates to a range from 9 to 11, in particular from 9.5 to 10.5. According to the present invention, the expression “substantially” means that the corresponding characteristic is mainly fulfilled, in particular to at least 95%, to at least 97% or to at least 99%.

7. Uses of the lipophilic compounds in therapeutic applications

The aqueous solutions of lipophilic compounds and the lipophilic compounds in water-soluble form as described herein have various uses in the art. One important area of application is medicine. The present invention therefore provides the use of the aqueous solutions of a lipophilic compound as described herein for the manufacture of a medicament for the treatment or prevention of a Illness ready. In addition, the present invention provides the use of the lipophilic compound in water-soluble form as described herein for the manufacture of a medicament for the treatment or prevention of a disease.

The lipophilic compound can in particular be a compound as described herein. In particular embodiments, the lipophilic compound is a curcuminoid such as curcumin. In further embodiments the lipophilic compound is a cannabinoid such as CBD or THCA. In further embodiments the lipophilic compound is a carotenoid such as astaxanthin. In further embodiments the lipophilic compound is cinnamon or a cinnamon ingredient. The features and embodiments of the lipophilic compound described herein also apply to the described use for the manufacture of a medicament.

In certain embodiments, the disease is amyloidosis. Amyloidosis is a condition in which proteins accumulate. The enriched proteins form insoluble deposits (amyloid) such as fibrils. In particular embodiments, amyloidosis is a tauopathy. In tauopathies, the tau protein is deposited in nerve and glial cells. The group of tauopathies includes in particular Alzheimer's disease, chronic traumatic encephalopathy (CTE), Parkinson's disease, corticobasal degeneration and frontotemporal dementia. In a preferred embodiment, the amyloidosis is Alzheimer's disease. In Alzheimer's disease, plaques consisting of incorrectly folded beta-amyloid (Aß) peptides form in the brain of the person affected, and defective tau proteins attach themselves to the axons from the cell body.

Treatment is given to a patient who needs it. These are especially patients with amyloidosis such as Alzheimer's disease. The treatment can take place with the beginning of the disease as well as with advanced disease. Prevention can be done on any individual. In particular, prevention is used in older people, such as those aged 60, 65, 70 or 75 years of age. However, individuals of younger age can also benefit from the prevention, e.g. individuals aged at least 20 years, at least 30 years, at least 40 years or at least 50 years. In individuals with incipient or undiagnosed amyloidosis, prevention and treatment can merge. The patients and individuals are especially humans.

For the treatment or prevention of amyloidoses such as Alzheimer's disease, in particular an aqueous solution of a lipophilic compound can be used, which is selected from the group consisting of curcuminoids such as curcumin, cannabinoids such as CBD and THCA, carotenoids such as astaxanthin, cinnamon and a cinnamon ingredient, and mixtures of this. Furthermore, for the treatment or prevention of amyloidoses such as Alzheimer's disease, in particular a lipophilic compound in water-soluble form can be used, which is selected from the group consisting of curcuminoids such as Curcumin, cannabinoids such as CBD and THCA, carotenoids such as astaxanthin, cinnamon and a cinnamon ingredient, and mixtures thereof.

In certain embodiments, the disease is inflammation or an inflammatory disease. Inflammatory diseases include, for example, atherosclerosis, osteoarthritis, autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, Crohn's disease, psoriasis and ulcerative colitis. In particular, an aqueous solution of a curcuminoid such as curcumin can be used to treat or prevent inflammation or inflammatory diseases.

8. Uses of the lipophilic compounds as dietary supplements

The aqueous solutions of lipophilic compounds and the lipophilic compounds in water-soluble form can be used as food or food supplements or as an ingredient in food or food supplements. The present invention therefore provides a food or dietary supplement that contains an aqueous solution of a lipophilic compound or a lipophilic compound in water-soluble form as described herein.

The lipophilic compound can in particular be a compound as described herein. In particular embodiments, the lipophilic compound is a curcuminoid such as curcumin. In further embodiments the lipophilic compound is a cannabinoid such as CBD or THCA. In further embodiments the lipophilic compound is a carotenoid such as astaxanthin. In further embodiments the lipophilic compound is cinnamon or a cinnamon ingredient. The features and embodiments of the lipophilic compound described herein also apply to the described use as a component of a food or food supplement.

The food or dietary supplement can additionally contain further constituents, in particular constituents commonly used for foods or dietary supplements. In certain embodiments, the food or dietary supplement contains, in addition to the aqueous solution of a lipophilic compound or the lipophilic compound in water-soluble form, a probiotic bacterium.

The probiotic bacterium can be any probiotic bacterium as well as mixtures of different probiotic bacteria. A “bacterium” in the context of the present invention generally relates to a large number of bacterial cells and not to a single bacterial cell. In certain embodiments, the term "bacterium" refers to a plurality of bacterial cells of the same genus, species, or strain. Probiotic bacteria, in particular, are live bacteria that provide health benefits when given in adequate quantities.

In particular embodiments, the probiotic bacterium is selected from the group consisting of bacteria of the genus Lactobacillus and bacteria of the genus Streptococcus, bacteria of the genus Bifidobacterium, bacteria of the genus Enterococcus, bacteria of the genus Pseudomonas, and mixtures of bacteria containing bacteria of one or more of these genera. The probiotic bacterium can be selected, for example, from the group consisting of bacteria of the genus Lactobacillus, bacteria of the genus Streptococcus, bacteria of the genus Bifidobacterium and bacteria of the genus Enterococcus. In specific embodiments, the probiotic bacterium is a lactic acid bacterium. In particular, the probiotic bacterium can be a bacterium of the genus Lactobacillus or a bacterial mixture containing a bacterium of the genus Lactobacillus.

In certain embodiments, the probiotic bacterium is selected from the group consisting of Enterococcus faecium, Bifidobacterium longum, Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, bacteria containing one or more of these bacteria, Pseudomonas fluorescens, and mixtures of these. The probiotic bacterium can be selected, for example, from the group consisting of bacteria of the species Enterococcus faecium, Bifidobacterium longum, Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus and Bifidobacterium breve. In particular embodiments, the probiotic bacterium is a bacterium of the species Lactobacillus plantarum or Lactobacillus rhamnosus or a bacterial mixture containing a bacterium of the species Lactobacillus plantarum and / or Lactobacillus rhamnosus. In other embodiments the probiotic bacterium is a bacterium of the species Pseudomonas fluorescens.

Figure description

Figure 1 shows a water gas cell made of rubber seals (1) and stainless steel plates (2).

Figure 2 shows a device for producing an aqueous solution of a lipophilic compound with a container (3), e.g. a stainless steel sieve, for receiving a lipophilic compound, a gas flame (4) directed at the lipophilic compound, and a water tank (5) .

Figure 3 shows a device for producing an aqueous solution of a lipophilic compound with a water tank (7) for receiving a lipophilic compound and the water. The lipophilic compound can be present on the surface of the water (6) right at the beginning. A gas flame (8) is directed to a side area of the outside of the water tank for heating.

Figure 4 shows the effects of paralysis in C. elegans nematodes that accumulate Aβ plaques. L4 animals were exposed to the indicated compound and analyzed for loss of neuronal activity. During each point in time, 30 animals per treatment were evaluated as to whether they show a direct reaction to a touch stimulus. A control: healthy nematodes. B control: nematodes with Aβ accumulation (strain CL2006). C control: CL2006 and solvent (water). D CL2006 and 0.25% (w / v) curcumin. E CL2006 and 0.25% (w / v) CBD. F CL2006 and 0.25% (w / v) cinnamon.

Figure 5 shows the quantification of a learning and memory assay. Nematodes of the C. elegans strain CL2355 served as an Alzheimer's model. The chemotaxis index for butanone is plotted on the Y axis. The higher the chemotaxis index, the better the nematodes had learned that the butanone odor is associated with food.

Figure 6 shows the secretion of pro-inflammatory cytokines in an inflammation assay with macrophages. An inflammatory response was induced with LPS and the amount of TNF-a (A) and interleukin-6 (B) in the cell supernatant was determined. Unstimulated macrophages served as controls (left side). The release of the cytokines was measured depending on the treatment of the macrophages with test substances. The mean value of 6 measurements ± SD is shown. n.d. not detectable. ** p <0.1. *** p <0.01. Control: no test substance added. PC Dexa: positive control with dexamethasone.

Examples

In the following, the invention is described by way of example on the basis of exemplary embodiments and figures, but without being restricted to these.

Example 1: Devices for performing the method according to the invention

An embodiment of a water gas cell is shown schematically in Fig. 1. The water gas cell is made up of several stainless steel plates (2) (AISI 316) with a thickness of 1.5 mm, which are separated from one another by rubber seals (1) with a thickness of 1 mm. The gap between the metal plates is sealed by the rubber seals. Water can be fed into the space through an inlet in the lower part of the metal plate and the water gas produced can escape through an outlet in the upper part. An electrical voltage of about 2.2 V per neutral stainless steel plate and a current strength of not more than 0.005 amperes per cm ^{2 is applied} for the total surface of the neutral plates. Water is converted into water gas in the water gas cell.

In Fig. 2 a device for the production of an aqueous solution with the dissolved lipophilic compound (eg curcumin water) can be seen. The water tank (5) is filled with process water and the lipophilic compound, with the process water reaching almost to the edge. A stainless steel sieve (3) is used on the surface of the water. A small amount of the lipophilic compound (eg curcumin powder) is placed in this sieve (3). The water gas flame (4) is then directed at the lipophilic compound (eg curcumin powder) floating in the stainless steel sieve (3). The powder is heated and decomposes. This is followed by the triggering of foam formation on the process water surface by a mixer, the foam containing the lipophilic compound. The mixer is used and controlled in such a way that a vortex is created in the middle of the process water, whereby the water does not flow over the The edge of the water tank sloshes. You can now see that the lipophilic compound (in powder form) quickly disappears in the process water and is completely absorbed. Mixing also creates foam. The mixer can then be turned for an additional minute or several minutes. Then the mixer is removed from the process water. The foam is then collected, for example with a skimmer. Most of the lipophilic compound (e.g. curcumin) is in this foam. After collecting the foam, the process can be repeated, checking whether the water level is still sufficient to process the next load of lipophilic compound (e.g. curcumin powder). It is not necessary to reheat and decompose a small amount of the lipophilic compound in the stainless steel sieve (3). To repeat the process, only another lipophilic compound is added to the process water, the foam formation is triggered and the foam is skimmed off. If the water level is too low, it will be compensated for by adding more process water. In the next step, the foam is dried to obtain the lipophilic compound, for example in a drying cabinet. Slow drying is preferred.

Example 2: Production of curcumin water

In an exemplary embodiment of the process, curcumin water was produced. For this purpose, a water gas flame was aimed at a point in the boiler. The water gas was generated by a water gas cell as described in Example 1 (Fig. 1).

The water tank (5) was filled with 5 L demineralized process water and approx. 250 g curcumin from a biological source was added to the process water. At the edge of the water tank, a stainless steel sieve with about 5 g of curcumin in powder form was inserted so that it floats on the surface of the process water. Then water gas was generated with a water gas cell and the resulting water gas was fed into a gas burner. The water gas flame was aimed at the stainless steel sieve with curcumin. This burned the curcumin powder. A mixer was then added to the process water and turned on, which led to foam formation. As soon as enough foam had formed, the mixer was removed and the foam was removed with a skimmer. The foam contained most of the water-soluble curcumin. The foam was collected on a cloth to remove more water and then placed in a drying cabinet. To obtain the water-soluble curcumin, the foam was slowly dried at approx. 40 ° C. for 2 days.

The curcumin powder was dissolved in distilled water by stirring to obtain curcumin water with a very high concentration. The foam that formed on dissolution was removed. 20 g of the curcumin processed according to the method were dissolved in 1 L of distilled water, an excess of curcumin being achieved so that part of the curcumin settles.

The concentration of dissolved curcumin in water was measured by liquid chromatography tandem mass spectrometry (LC-MS / MS, Waters ^® ACQUITY UPLC I-Class and Waters ^® Xevo TQ-S) in Multiple Reaction Monitoring (MRM) mode. The chromatographic separation was performed with a standard gradients within 5 minutes on a Waters UPLC BEH C18 ^® ACQUITY column (2.1 x 100 mm, 1.7 pm) is performed. 2 mM ammonium formate with 0.2% formic acid and 2 mM ammonium formate with 0.2% formic acid in acetonitrile were used as eluents. The calibration was carried out with an analytical curcumin standard from Sigma-Aldrich. Diazepam-D5 was used as an internal standard.

The results showed that there was 10.4 g / L of curcumin in dissolved form in the curcumin water. This high amount of dissolved curcumin shows that, with the aid of the method according to the invention, a significantly higher amount of curcumin can be dissolved than was to be expected. For example, in Jagannathan et al. , 2012 described that a maximum of 1-10 mg / L curcumin can be dissolved. Consequently, the process according to the invention has led to an enormously improved solubility of curcumin (here an improvement by more than a factor of 1000). Furthermore, a very pure curcumin water could be produced, which essentially contained curcumin and water. Neither additives such as solubilizers nor technologies such as micelle formation or nanodispersion were necessary.

The specific parameters of the process can also be adapted so that, in principle, other lipophilic compounds can be brought into solution with water. The process described above is particularly suitable for improving the solubility of curcumin in aqueous solutions.

Example 3: Devices for carrying out the alternative method

In Fig. 3 a device for the production of an aqueous solution with the dissolved lipophilic compound (eg cinnamon water) can be seen. The water tank (7) is filled with water and the lipophilic compound, the lipophilic compound (for example in the form of a powder) preferably being applied to the water. The water reaches almost to the edge so that the water surface (6) is just below the edge. The water gas flame (8) is then directed at a level slightly below the water level (6) on an area of the outside of the water tank. Heating with the water gas flame (8) helps dissolve the lipophilic compound in the water. Furthermore, a mixing process by means of a mixer can assist in dissolving the lipophilic compound. The mixer is used and controlled in such a way that a vortex is created in the middle of the water, whereby the water does not spill over the edge of the water tank. You can now see that the lipophilic compound (in powder form) quickly disappears in the water and is completely absorbed. The mixer can then be turned for an additional minute or several minutes. Then the mixer is removed from the water. The aqueous solution of the lipophilic compound obtained therefrom can be liquid or pasty, depending on the amount used. The aqueous solution of the lipophilic compound can then optionally be brought into contact with water, so that a dilute aqueous solution of the lipophilic compound can be obtained. Example 4: Preparation of cinnamon water

In an exemplary embodiment of the method, cinnamon water was produced. A device as described in Example 3 was used for this purpose. A water gas flame was aimed at a location on the outside of the water tank just below the water level. The water gas was generated by a water gas cell as described in Example 1 (Fig. 1). The water tank (7) was filled with 5 liters of demineralized water and approx. 500 g of cinnamon per liter of water. Then water gas was generated with a water gas cell and the resulting water gas was fed into a gas burner. The water gas flame was aimed at the kettle at a point just below the water level. A mixer was then added to the water and turned on. Once the lipophilic compound has dissolved, the mixer is removed. The pulpy product represents the cinnamon water that is obtained. The cinnamon water can then be further diluted by adding water. The cinnamon water obtained was very pure and essentially contained cinnamon and water. Neither additives such as solubilizers nor technologies such as micelle formation or nanodispersion were necessary.

The specific parameters of the process can also be adapted so that, in principle, other lipophilic compounds can be brought into solution with water. The process described above is particularly suitable for improving the solubility of cinnamon or cinnamon ingredients in aqueous solutions, but also for other lipophilic compounds such as carotenoids, especially astaxanthin, cannabis or ingredients of the cannabis plant, such as cannabinoids, especially cannabidiol (CBD) .

Example 5: Therapeutic effect of the lipophilic compounds against Alzheimer's disease

One of the neuropathologies of Alzheimer's disease is the accumulation of extra-neural amyloid plaques (Aβ). An Alzheimer's model was created by expressing the human Aβ protein in C. elegans nematodes. Due to the accumulation of Aβ, the nematodes become paralyzed over time and show defects in neuronal activity. The nematode strain used with Aβ accumulation (CL2006) was exposed to two different concentrations of different lipophilic substances from the L4 larval stage. The aqueous solutions of the substances were prepared using the methods described herein. The touch reaction test was performed after exposure for 24 hours. Touch reaction tests measure the neural response to a stimulus (touch). In the case of defects in the neural activity, the reaction to the neural activation is reduced (reduced touch reaction). When controlled, nematodes respond to soft touches in the head area by immediately moving backwards, in the opposite direction of the touch (reverse movements, see Fig. 4A). In the case of the CL2006 exposure, this backward reaction is greatly reduced as a result of the Aβ accumulation (see Fig. 4B and C). About 100% of the animals showed no or a very slow response to touch. Both curcumin water and CBD water and cinnamon water were able to inhibit the neuronal defects caused by the Aß accumulation in the CL2006 strain for a certain time, i.e. to delay the onset of paralysis (see Fig. 4D to F). This showed that the aqueous solutions of curcumin, CBD, and cinnamon have a therapeutic effect in combating amyloidoses such as Alzheimer's disease.

In a further assay, the effects of the lipophilic compounds on the loss of memory and learning ability due to Alzheimer's disease were determined. In C. elegans strain CL2355, plaques accumulate in the neurons of the nematode brain. As a result, the nematodes lose their ability to remember and learn. The Aβ accumulation in this strain can be induced by a heat shock to 25 ° C. In the assay, the nematodes were grown to the L4 larval stage and then treated with 25 ° C. heat shock to induce Aβ accumulation. When hungry, they were then put on their food, either with or without an olfactory stimulus (butanone). The memory and learning test was carried out 2 hours later. The nematodes were placed between two different smells (ethanol and butanone) and it was observed whether they migrated to the smell associated with food (learning effect). If the ability to learn and remember is prevented, the nematodes migrate randomly, while if the ability to learn and remember is intact, the nematodes migrate to the learned smell (butanone). The number of nematodes for butanone minus the number for ethanol divided by the total number of nematodes gives the chemotaxis index.

Control animals were not trained with butanone. Untreated nematodes showed only a very low chemotaxis index for butanone. The treatment of the nematodes with an aqueous solution with curcumin or astaxanthin, prepared as described herein, significantly increased the animals' ability to learn and remember, which was evident from a sharply increased chemotaxis index for butanone in the treated and trained animals (see Fig . 5). The aqueous solutions described herein with curcumin or astaxanthin thus showed a therapeutic effect for improving the ability to learn and remember in Alzheimer's disease.

Example 6: Therapeutic effect of the lipophilic compounds in inflammatory diseases

The anti-inflammatory effect of aqueous curcumin solutions, prepared according to the method described herein, was examined in an inflammation assay. For this purpose, THP-1 cells (a human monocyte cell line) were sown in 6-well plates and differentiated into macrophages with phorbol-12-myristate-13-acetate (PMA) within 48 hours. The differentiated cells were exposed to the test substance for 24 h and then the inflammatory process was triggered by treatment with lipopolysaccharides (LPS) for one hour. After 24 hours of incubation, the cell supernatant was collected and frozen for analysis. The concentrations of the pro-inflammatory cytokines TNF-α and interleukin-6 were determined using ELISA kits. Dexamethasone served as a positive control for that Anti-inflammatory. Various dilutions of an aqueous curcumin solution (20 g / l) were used as the test substance.

As shown in Fig. 6, the release of TNF-α and IL-6 was extremely low in unstimulated cells. In the case of stimulated cells, there was a clear inflammatory reaction in the release of TNF-α and IL-6. Dexamethasone reduced this release to some extent. However, the addition of the aqueous curcumin solution suppressed the TNF-α and IL-6 secretion of the cells to a significantly greater extent. The IL-6 secretion was completely suppressed at all concentrations used and the TNF-α secretion was reduced as a function of the concentration, the highest concentration also causing complete inhibition. Thus, the aqueous curcumin solution described herein was shown to have a potent anti-inflammatory effect.

List of reference symbols

1 rubber plate

2 stainless steel plate

3 container for holding a lipophilic compound (e.g. stainless steel sieve)

4 gas flame 5 water tank

6 water surface

7 water tank

8 gas flame

Claims

1. A method for preparing an aqueous solution of a lipophilic compound comprising the steps of:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam;

(iv) drying the foam to obtain the lipophilic compound; and

2. A process for the preparation of a lipophilic compound in water-soluble form, comprising the steps of:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam; and

(iv) drying the foam to obtain the lipophilic compound in water-soluble form.

3. A method for increasing the water solubility of a lipophilic compound comprising the steps of:

(i) bringing the lipophilic compound into contact with process water;

(iii) collecting the foam; and

(iv) drying the foam to obtain the lipophilic compound in water-soluble form.

4. The method according to claim 1, characterized in that the aqueous solution of the lipophilic compound consists essentially of water and the lipophilic compound; and / or has a concentration of the lipophilic compound of at least 0.1 g / L, in particular at least 5 g / L.

5. The method according to any one of claims 1 to 4, characterized in that the lipophilic compound is a curcuminoid, in particular curcumin.

6. The method according to any one of claims 1 to 5, characterized in that in step (i) the process water is demineralized or distilled water; the lipophilic compound is essentially pure; and or at least 10 g, in particular at least 20 g or at least 30 g, is used per liter of process water of the lipophilic compound.

7. The method according to any one of claims 1 to 6, comprising the further steps (vi) and (vii) between step (i) and step (ii):

(vi) providing a further small amount of the lipophilic compound, this small amount of the lipophilic compound being kept in a container on the process water surface and being in contact with the process water, the small amount of the lipophilic compound preferably being an amount of about 0.5 g is up to about 10 g, more preferably about 2 g to about 6 g; and / or the container is preferably a metal sieve, in particular a sieve made of stainless steel; and

(vii) heating the small amount of the lipophilic compound, optionally the small amount of the lipophilic compound being heated with a flame, in particular with a gas flame, e.g., a water gas flame; the small amount of the lipophilic compound is heated to a temperature of at least 250 ° C; the small amount of the lipophilic compound is heated for a period of at least 30 seconds, in particular at least 1 minute or at least 2 minutes; and / or the small amount of the lipophilic compound is heated in such a way that at least partial decomposition of the lipophilic compound is obtained.

8. The method according to any one of claims 1 to 7, characterized in that in step (ii) the foam formation is triggered by stirring the process water; the foaming is carried out for a period of about 1 minute to about 30 minutes, in particular about 2 minutes to about 15 minutes; and / or the foam formed contains at least 70% of the amount of lipophilic compound used in step (i); and / or in step (iii) the foam is collected by means of skimming; and / or in step (iv) the collected foam is dried in a drying cabinet; and / or the lipophilic compound obtained is in the form of a powder.

9. The method according to claim 8, characterized in that the drying in the drying cabinet at a temperature of about 30 ° C to about 50 ° C, in particular at a temperature of about 40 ° C; the drying takes place in the drying cabinet for a period of 0.5 to 4 days, in particular for a period of about 24 to 48 hours; and / or excess water is separated from the collected foam before drying in the drying cabinet, for example by dripping off.

10. The method according to any one of claims 1 to 9, characterized in that steps (i) to (iv) are repeated one or more times.

11. The method according to any one of claims 1 and 4 to 10, characterized in that in step (v) the water is selected from distilled water, double-distilled water, demineralized water, ultrapure water and deionized water; and / or the lipophilic compound obtained is dissolved in the water in a concentration of at least 0.1 g / L, in particular at least 5 g / L.

12. An aqueous curcuminoid solution, consisting essentially of water and a curcuminoid or a mixture of several curcuminoids, with a concentration of at least 0.1 g / L curcuminoid, in particular of at least 5 g / L.

13. An aqueous solution of a lipophilic compound, producible by a method according to any one of claims 1 and 4 to 11, wherein the lipophilic compound is preferably a curcuminoid, in particular curcumin.

14. The aqueous solution according to claim 12 or 13 for use as a food, drink or cosmetic, preferably as a drink.

15. A lipophilic compound in water-soluble form, producible by a method according to any one of claims 2 to 11.

16. The lipophilic compound of claim 15 for use in the manufacture of foods, beverages or cosmetics.

17. An apparatus for producing a lipophilic compound in water-soluble form or an aqueous solution of a lipophilic compound, comprising

(i) a water tank;

(ii) a container for holding a lipophilic compound which can be held on the surface of water in the water tank;

(iii) a gas burner for heating the lipophilic compound in the container; and

(iv) an element for foaming within the water tank.

18. An aqueous solution of a lipophilic compound, consisting essentially of water and the lipophilic compound with a concentration of at least 0.1 g / L, in particular one of the following concentrations and lipophilic compound:

(ii) a concentration of at least 0.1 mg / L carotenoids, especially astaxanthin; or (iii) a concentration of at least 0.1 mg / L cannabis or ingredients of the cannabis plant, such as cannabinoids, in particular cannabidiol (CBD).

19. The aqueous solution according to any one of claims 12, 13, 14 and 18, wherein the aqueous solution does not contain any further components that support the dissolution of the lipophilic compound.

20. Use of an aqueous solution of a lipophilic compound according to any one of claims 12 to 14, 18 and 19 for the manufacture of a medicament for the treatment or prevention of a disease.

21. Use of a lipophilic compound in water-soluble form according to claim 15 or 16 for the manufacture of a medicament for the treatment or prevention of a disease.

22. Use according to claim 20 or 21, wherein the disease is an amyloidosis such as

Alzheimer's disease, chronic traumatic encephalopathy, Parkinson's disease, corticobasal degeneration and frontotemporal dementia, particularly Alzheimer's disease; or where the disease is inflammation or an inflammatory disease such as atherosclerosis and osteoarthritis, or a

Autoimmune disease like rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, Crohn's disease, psoriasis, and ulcerative colitis.

23. Use according to any one of claims 20 to 22, wherein the lipophilic compound is a curcuminoid such as curcumin.

24. Food or dietary supplement containing an aqueous solution of a lipophilic compound according to one of claims 12 to 14, 18 and 19, or a lipophilic compound in water-soluble form according to claim 15 or 16.

25. Foodstuff or dietary supplement according to claim 24, further comprising a probiotic bacterium, the probiotic bacterium preferably being selected from the group consisting of Enterococcus faecium, Bifidobacterium longum, Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus plantarum, Lactobacillus fluoresobacterium, Pseudosacterium rifhamnomonas Bacillus , and mixtures of bacteria containing bacteria of one or more of these species.