PL241417B1 - Water dispersible turmeric extract formulation containing curcuminoids, method of its preparation and use of the formulation in food and industrial products - Google Patents

Abstract

The present invention relates to a dry curcumin formulation containing water-dispersible curcuminoids of turmeric extract, a method of its preparation and a curcumin formulation prepared by this method. The invention also relates to a beverage concentrate, beverage, color, dietary supplement, pharmaceutical composition containing the curcumin formulation according to the invention as well as dry form curcumin formulation uses.

Description

PL 241 417 B1

Description of the invention

TECHNICAL FIELD

The subject of the invention is a curcumin formulation in a dry form containing curcuminoids of turmeric extract dispersed in water. The invention also relates to a method for obtaining a curcumin formulation in a dry, water-dispersible form and a beverage concentrate, dye, beverage and dietary supplement containing it. The use of water-dispersible turmeric extract formulations in food products, feed products, dietary supplements and medicinal products is also described.

STATE OF TECHNOLOGY

Curcuma longa, commonly called turmeric, is a tropical plant of the Zingiberaceae family, native to South Asia. Turmeric rhizomes have traditionally been used as a coloring ingredient, but also as a spice. Turmeric is quite commonly used as a spice, but also as an additive to food and beverages (Govindarajan, 1980; Salzer et al., 1975). Dried turmeric rhizomes contain 3-5% essential oils and 0.02-6.0% curcuminoids, such as curcumin, demethoxycurcumin and bisdemethoxycurcumin. These curcuminoids may occur in different amounts and proportions to each other, which depends on the biological and environmental factors related to the cultivation of the rhizome itself, and in the case of oleoresin or extracts, on the technology of their production. In addition to the coloring and spice properties, turmeric, and especially the curcuminoids contained in it, have various medicinal properties confirmed by pharmacological studies conducted on various animals. Turmeric extracts have anti-inflammatory, anti-fungal and anti-cancer effects (Amalraj et al., 2017; Yamamoto et al., 1997; Apisariyakul et al., 1995; Ruby et al., 1995). In order to be able to affect living organisms (humans and animals), curcuminoids must first be delivered to the body and then absorbed from the digestive tract into the bloodstream (Amalraj et al., 2017; Jager et al., 2014).

Curcuminoids are compounds that do not dissolve in water, and what is more, their solubility in vegetable and animal fats is very limited and does not exceed 1 mg ml ^-1 , which significantly hinders the bioavailability of curcuminoids from the gastrointestinal tract. Curcuminoids dissolve best in organic solvents such as acetone, then ethyl acetate, methanol and ethanol (in the case of ethanol, in order to increase the solubility of curcuminoids, it is required to heat the solution to the boiling point, i.e. approx. 78 ° C, which causes thermal decomposition of curcuminoids) (Amalraj et al., 2017; Anderson et al., 2000). Due to the toxicity of solvents, solutions obtained in this form cannot be administered to living organisms. Methods and ways of dissolving or dispersing curcuminoids in water are sought so that they can be introduced into the human or animal body in this form. Studies have shown that the physical or chemical form of curcuminoids plays a key role in their bioavailability. It has been shown that the dispersion of curcuminoids in an aqueous environment significantly improves their bioavailability (Jager et al., 2014). In addition, the purpose of developing water-soluble or dispersible curcuminoid formulations is to facilitate their combination with the appropriate flavor and aroma composition, thanks to which they can be much more willingly consumed by humans and animals. Curcuminoids in concentrated form, like powdered turmeric itself, have a very intense, characteristic taste and are bitter, which practically disqualifies the possibility of eating them directly. In this form, they can either be encapsulated or used as a food supplement. The development of a curcuminoid formulation that enables their dispersion in an aqueous environment is a major technological challenge, also due to the low fat solubility of curcuminoids (fat solubility < 1 mg g ^-1 , while curcuminoids are completely insoluble in water). In the case of products intended for food, the formation of the dispersion system must be carried out with organic solvents allowed in food production, which must then be removed from the final product. Moreover, their content in the final product must meet the legal requirements on the approximation of the laws of the Member States on extraction solvents used in the production of foodstuffs and food ingredients (Directive 2009/32/EC of the European Parliament and of the Council of 23 April 2009).

Many methods of obtaining water-dispersible curcuminoid formulations are described in the world literature. A very common method of obtaining water-dispersible curcuminoids is dissolving them in 70-80% ethanol together with 3-cyclodextrin, and then heating and stirring for at least 4 h at 70°C (Mangolim et al., 2014; Marcolino et al. ., 2011).

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Solvents (ethanol and water) are most often removed by spray drying, but also by vacuum evaporation or freeze-drying. This method of obtaining water-dispersible curcuminoids has several disadvantages. The first one is the unfavorable chemical transformations of curcuminoids in a water-ethanol environment related to their thermal decomposition. Research by Wang et al. (1999) showed that curcuminoids in an aqueous environment under the influence of elevated temperature, even at the most favorable pH of the environment (curcuminoids show the greatest stability at pH between 3 and 6) decompose. Wang et al. (1999) showed that heating curcumin at 37°C for 2 h causes as much as 10% loss of this compound. Formulation of curcuminoids dispersing in water should be carried out at possibly low temperatures, especially in the process of combining them with the water phase. An additional disadvantage of the formulation using β-cyclodextrin is its limited use in food production, β-cyclodextrin (E 459) can be used in the production of e.g. beverages, but its content cannot be higher than 1 g kg ^-1 (Commission Regulation (EU ) No. 1129/2011). This limits the possibility of introducing any amount of curcuminoids into the finished product.

Other formulations of water-dispersing curcuminoids are those compounds adsorbed on silicates, e.g. silicon dioxide (Martins et al., 2013). The use of curcuminoids adsorbed on silicon dioxide (E 551) in the production of e.g. beverages is quite limited, because such a formulation is not thermodynamically stable and such particles sediment quickly. This is due to the high density of silicon dioxide and curcuminoids associated with it.

There are many different formulations of curcuminoids available on the world market, however, not all of them may be suitable for the production of beverages, i.e. their dispersion in water. Meriva® produced by Indena SpA (Italy) consists of 18-20% curcuminoids adsorbed on microcrystalline cellulose with the addition of soy lecithin (Cuomo et al., 2011). This product is more suitable for the preparation of solid preparations or as a food additive, but other than beverages, due to the lack of solubility of microcrystalline cellulose, which falls out of solution and sediments. LongVida® produced by Verdure Sciences (USA) is a preparation that contains approx. 20% of curcuminoids suspended in fat particles with a solid consistency at room temperature with the addition of phosphatidylcholine (Gota et al., 2010). The preparation is basically used for the production of dietary supplements in the form of tablets or capsules, it can also be added to various foods, however, it is not suitable for a stable dispersion of curcuminoids in water. CurQfen® produced by Akay Flavors & Aromatics Pvt. Ltd., MicroActive Curcumin produced by BioActives LLC (USA) contains approx. 25% curcuminoids suspended in short-chain triacylglycerols with the addition of free fatty acids and polyglycerol esters. The formulation is stabilized with hydroxypropyl methylcellulose, sodium alginate and microcrystalline cellulose (Madhavi et al., 2014). This formulation has been developed mainly for the production of tablets/capsules containing highly bioavailable curcumin. Micronized Curcumin produced by Raps GmbH & Co., KG (Germany) contains approx. 25% curcumin powder dispersed in triacetin (glycerol triacetate) and a mixture of lipids obtained from soybean, oil palm and rapeseed (Schiborr et al. , 2014). The preparation is not soluble in water and is not suitable for obtaining stable curcuminoids dispersed in water. NovaSOL® produced by FRUTAROM from Israel is a micellar curcumin with a concentration of approx. 7% in Tween-80 (Schiborr et al., 2014). The preparation cannot be used in food, as Tween-80 is not approved for use in food in many countries, including the EU. CurcuWin® produced by OmniActive Health Technologies (India) contains 20-28% turmeric extract (a mixture of three curcuminoids), which is suspended in a mixture of 63-75% polyvinylpyrrolidone (E1201), 10-40% cellulose derivatives with the addition of 1-3% of natural antioxidants (Jager et al., 2014). The preparation enables the production of tablets/capsules, but is not suitable for the production of beverages. CURCUGREEN® (BCM-95®) produced by Arjuna Natural Extracts Ltd., (India) is an essential oil consisting of 45% ar-turmerone and curcuminoids (Antony et al., 2008). CURCUGREEN® is not soluble in water and is not suitable for the production of beverages. Curcumin C3 Complex® + Bioperine® produced by Sabinsa USA is a mixture of piperine and curcuminoids without any special formulation (Shoba et al., 1998). The preparation is not suitable for dispersion in water. CAVACURMIN® produced by Wacker Chemie AG, (Germany) contains approx. 15% curcuminoids in combination with γ-cyclodextrin (Puroura et al., 1998). This product disperses in water, however, at high temperature, curcuminoids with cyclodextrins conjugates are formed (described earlier), and this promotes the thermal breakdown of curcuminoids. In addition, γ-cyclodextrin is not authorized for use in food in the EU and the preparation cannot be used in the production of food, including beverages. Theracurmin™ manufactured by Theravalues Corp. (Japan) is a preparation

PL 241 417 B1 nano-colloid containing even 30% of curcuminoids. The preparation additionally contains glycerin and Ghatti gum (Sasaki et al., 2011). The product disperses well in water, is suitable for the production of beverages, however, at the moment it cannot be used for food production, because Ghatti gum is not approved for food production as an additive in the EU. In addition, due to the content of maltose and maltodextrin, Theracurmin™ is characterized by a sweet taste, which limits its use in food products. The content of maltose and maltodextrin in Theracurmin™ preparation, due to their high glycemic index and high calorific value, makes it impossible to use it for the production of low-calorie drinks or for special purposes, e.g. for diabetics or overweight people.

All commercially available curcumin formulations described above were developed in order to maximize the bioavailability of curcuminoids, omitting the technological aspects necessary to develop a formulation suitable for water dispersion and, consequently, for the production of beverages.

DISCLOSURE OF THE INVENTION

TECHNICAL PROBLEM

The technological problem resulting from the state of the art is the lack of a water-dispersible turmeric extract powder formulation, assuming that the turmeric extract contains high concentrations of curcuminoids, preferably min. 90% w/w curcuminoids, including curcumin, demethoxycurcumin and bisdemethoxycurcumin, whose dispersion in water will be stable, with no observable and noticeable sedimentation or creaming process for a long time. After dissolving the formulation in water, the system should be uniformly colored. Preferably, the content of turmeric extract in the final formulation should be at least 10%. All substances used in the production of formulations should be allowed for use in food, including in the EU, in accordance with the currently applicable regulations in this regard. The emulsification process should preferably take place at maximum room temperature (20°C ± 2°C) to avoid thermal degradation of the curcuminoids. Higher temperature results in a decrease in viscosity and thus an increase in particle size distribution, which adversely affects the stability of the dispersion system.

PURPOSE OF THE INVENTION

The object of the invention is to overcome the indicated disadvantages of the state of the art. This goal was achieved by developing a formulation solution as well as the method of its production and the product obtained in this way, enabling the preparation of a water-dispersible formulation of turmeric extract with increased stability and increased homogeneity, while in the method of producing the curcumin formulation in the form of an emulsion solution and in a dry form, all substances used in the production process are substances approved for use in the production of food.

The inventors of the invention surprisingly found that the use of a non-obvious system of auxiliary substances, preferably in the form of starch octenyl succinate and cellulose derivatives as a carrier, and the use of an organic solvent approved for use in the production of food, preferably in the form of ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, especially preferably ethyl acetate allows the homogenization process to produce an emulsion with a narrow and small particle distribution (the vast majority of diameter below 1 μm, preferably in the range of 0.1 to 1 μm), which ensures the creation of a dispersible formulation containing curcuminoids in the spray drying process turmeric extract with desirable physicochemical properties and increased bioavailability.

THE ESSENCE OF THE INVENTION

Innovative research carried out by the creators has shown that the use of a combination of starch octenyl succinate and cellulose derivatives, in particular hydeoxypropyl cellulose or hydroxypropyl methylcellulose, as a carrier for dissolved in an organic solvent approved for use in food production, which is ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol , particularly preferably ethyl acetate, turmeric extract containing curcuminoids, allows to obtain an emulsion in the process of homogenization. In addition, the inventors have found that the addition of a polysaccharide solution, preferably a high viscosity cellulose derivative, particularly preferably carboxymethyl cellulose (CMC), preferably if the solvent is water, stabilizes the emulsion. The obtained emulsion is stable and characterized by a narrow and small distribution of particles with a diameter of less than 1 μm, with no sedimentation or creaming process observable to the naked eye, preferably for a period of not less than 12 months.

PL 241 417 B1

The combination of starch octenyl succinate with modified cellulose as a carrier for turmeric extract dissolved in an organic solvent makes it possible to produce the described curcuma formulation in the form of a narrow and small particle distribution emulsion, even using only turbo-vortex homogenization. In order to obtain the described curcumin formulation in a dry form, most preferably a powder, stabilization of the emulsion system is carried out during drying of the emulsion curcumin formulation consisting in diluting the emulsion produced in an aqueous solution of carboxymethyl cellulose (CMC) with a concentration of 0.001 to 1%, preferably 0.01 to 1%. 0.5%, preferably 0.10 to 0.20%, preferably 0.1-1.4%, in a proportion of not less than 1:6, preferably in a proportion of about 1:8, and drying the emulsion thus stabilized to obtain a powder, e.g. in spray drying. Produced powder - the curcumin powder formulation is still characterized by a narrow and low particle distribution, and after reconstitution of the produced powder, a stable dispersion system is obtained due to prior stabilization by carboxymethyl cellulose.

Surprisingly, it turned out that it is possible to obtain dispersed phase particles for turmeric extract containing curcuminoids with a dispersed phase particle size below 1 µm, which makes it possible to obtain a system that is stable from the point of view of thermodynamics of emulsion systems. The lower particle diameter range of the obtained particles does not affect the stability of emulsion formation, although obtaining the majority of particles in a certain range, preferably in the particle diameter range of 0.1-1 µm, facilitates the industrial processing of such a uniform product at a later stage. With such a small particle size of the dispersed phase for the extract prepared in this way, the sedimentation velocity calculated from the Stokes equation

V=[(2r ² g(p _p -pf)]/(9q) will be low, which is what the final curcumin formulation of the invention provides.

More surprisingly, it turned out that the described curcumin formulation has a higher bioavailability, i.e. it is better absorbed by the body than known and commercially available preparations containing curcumin, as well as having a higher permeability through the intestinal cell layer. Unexpectedly, it turned out that the described curcumin formulation provides improved properties in the regulation of liver function, better activates the action of liver enzymes, especially enzymes from the group of dehydrogenases, including aldehyde dehydrogenase, and also shows greater anti-inflammatory, anti-cancer and anti-depressant activity than known and available curcumin preparations. The following explanations and general definitions refer to the descriptions of preferred embodiments of the invention that follow.

The present invention, as illustrated below, may suitably be practiced in the absence of any element or elements, limitation or limitations not specifically disclosed herein.

When the term "comprising" or "including" is used in this specification and claims, it is not intended to exclude other elements. For purposes of the present invention, the term "consisting of" is considered a preferred embodiment of the term "comprising" "including". When a group is defined below that includes at least a certain number of embodiments, this is also to be understood as disclosing a group that preferably consists only of those embodiments.

The terms "about" or "approximately" in the context of the present invention mean a range of accuracy that a person skilled in the art will understand to be sufficient to still provide the technical effect of a given feature. The term "typically" means a deviation from the indicated numerical value of ±10%, preferably ±5%.

Technical terms are used in accordance with their usual meaning. If a specific meaning is used, the meaning will be described in detail with respect to the context in which the term is used.

By stability is meant the formation of a dispersed system with a particle size of the dispersed phase <1 pm. The concept of stability is understood as the formation of a dispersion system, homogeneous to the naked eye without a visible process of creaming or sedimentation. The system is considered stable if, during 20 minutes of centrifugation at 5000 rpm, min' ¹ and at 25°C, the amount of sediment at the bottom of the tube does not exceed 30% of the starting weight of the water-dispersed powder formulation.

Dispersion means a system composed of at least two immiscible phases, at least one of which is a finely divided system (dispersed phase), dispersed in a second continuous phase (dispersing phase), called the dispersion medium.

PL 241 417 B1

Solubility means the ability of a solid substance to dissolve in the liquid phase and form a dispersion system, creating a heterogeneous mixture.

The invention relates to a curcumin formulation in a dry form, preferably a powder, soluble in water, giving a dispersion system whose dispersed phase is characterized by a particle size of <1 μm. Additional features of the developed curcumin formulation according to the invention are:

• The formulation is made without the use of ethanol or other alcohols or ketones (eg acetone);

• The formulation is neutral in taste, i.e. no sweet, sour and bitter-scorching taste, i.e. the characteristic taste of turmeric;

• The formulation is made at low temperatures, which favorably affects the chemical stability of the curcuminoids.

The subject of the invention is a curcumin formulation in dry form, comprising:

- starch octenyl succinate in an amount of 0.1-45% w/w, more preferably 25-35% w/w, particularly preferably 28-32% w/w;

- a cellulose derivative in an amount of 0.01-20% w/w in the form of hydroxypropylmethylcellulose, hydeoxypropylcellulose or a mixture thereof, preferably the cellulose derivative is in an amount of 5-15% w/w, particularly preferably 8-10% w/w;

- turmeric extract in the amount of 0.01-20% w/w, wherein the turmeric extract contains at least 90% w/w curcuminoids, including curcumin, demethoxycurcumin and bisdemethoxycurcumin, preferably turmeric extract in the amount of 5-15%, particularly preferably turmeric extract in an amount of 8-10% (w/w);

- β-glucan in an amount of 0.1-10% w/w, preferably 3-5% w/w, particularly preferably 3.8-4.2% w/w;

- a cellulose derivative with a viscosity above 5600 mPas in an amount of 10-70% w/w, preferably in an amount of 30-60% w/w, particularly preferably in an amount of 48-52% w/w, wherein the cellulose derivative with a viscosity above 5600 mPas is selected from carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, ethyl methyl cellulose, cross-linked cellulose gum, preferably the cellulose derivative with a viscosity above 5600 mPas is carboxymethyl cellulose;

- starch octenyl succinate in an amount of 0.1-45% w/w, preferably 25-35%, particularly preferably in an amount of 28-32% w/w; wherein at least 60%, more preferably at least 95% of the particles, preferably at least 99% of the particles are less than 1 Pm in diameter.

In a preferred curcumin formulation in dry form, at least 90%, more preferably at least 95%, preferably at least 99% of the particles have a diameter in the range of 0.1 to about 1 Pm.

The invention also relates to a process for the preparation of a curcumin formulation in dry form, which comprises the following steps:

a) turmeric extract containing min. 90% curcuminoids in a food-approved organic solvent, preferably ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, particularly preferably ethyl acetate;

b) the dissolved turmeric extract from step a) is added to the carrier solution which is a mixture of polymers comprising starch octenyl succinate and a cellulose derivative, preferably the cellulose derivative is hydeoxypropyl cellulose, hydroxypropyl methylcellulose, dissolved in a polar solvent, preferably water, preferably cooling is used, preferably, the temperature of the polymer mixture during the addition of the dissolved turmeric extract is between about 5°C and about 10°C (the use of higher temperatures affects the viscosity of the continuous phase, which consequently contributes to obtaining an emulsion system with an unfavorable particle size distribution, i.e. with a diameter greater than 1 μm);

c) the mixture obtained in step b) is homogenized to obtain an emulsion, preferably at a temperature of about 5°C to about 10°C (the use of higher temperatures affects the viscosity of the continuous phase, which in turn contributes to obtaining an emulsion system with an unfavorable size distribution particles, i.e. diameter greater than 1 μm);

d) the emulsion obtained in step c) is diluted with an aqueous solution of β-glucan (this is a polymer that positively affects the stability of the dispersion system), preferably, at a concentration of 1-8% of β-glucan, preferably from oats or barley, of low viscosity (preferably viscosity in the range of 40-200 mPas) and further homogenized briefly;

e) the emulsion obtained in step d) is stabilized by combining with a high viscosity cellulose derivative (>5600 mPas), preferably 0.1-1.4% aqueous solution of carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, ethyl methyl cellulose, cellulose gum

cross-linked, more preferably high viscosity carboxymethyl cellulose, diluting preferably in a ratio of not less than 1:6, more preferably not less than 1:8, mechanically mixing the whole;

f) the stabilized emulsion of step e) is dried to obtain a curcumin formulation in a dry form wherein greater than 90%, preferably greater than 95%, preferably greater than 99% of the particles obtained have a diameter of less than about 1 Pm, more preferably at least 90%, more preferably at least 95% of the particles, more preferably at least 99% of the particles have a diameter in the range of 0.1 to about 1 Pm.

In the preferred method for preparing the curcumin formulation, the organic solvent used to dissolve the turmeric extract in step a) is ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, more preferably ethyl acetate. In a preferred process, the polar solvent used to dissolve the carrier in step b) is water.

In a preferred method of making the curcumin formulation, the cellulose derivative used to make the carrier is hydeoxypropylcellulose, hydroxypropylmethylcellulose, or a mixture thereof, with the preferred mixture of hydeoxypropylcellulose to hydroxypropylmethylcellulose being in a ratio of 10:1.

In a preferred method of preparing the curcumin formulation in step d), the emulsion is diluted with 1-8% β-glucan, preferably oat or barley β-glucan, or a mixture thereof.

In a preferred method of preparing the curcumin formulation, the high viscosity cellulose derivative is carboxymethyl cellulose (CMC), preferably in a concentration of 0.01 to 0.5%, more preferably in a concentration of 0.10 to 0.20%, more preferably in a concentration of 0.1 up to 1.4% (w/w).

In the preferred method of preparing the curcumin formulation, the carrier solution is obtained by mechanically mixing the polymers, the mixing being preferably carried out for not less than 10 h, preferably about 12 h.

In a preferred method of preparing the curcumin formulation, the carrier solution is dissolved in a polar solvent in a weight ratio of 1:5 to 1:25, preferably 1:10.

In a preferred method for preparing the curcumin formulation, the drying in step f) is carried out using spray drying with an inlet temperature to the dryer in the range of 110-160°C, more preferably about 150°C, and an outlet temperature of not more than 65°C, preferably not more than about 55°C. It has surprisingly been found that the use of low temperatures in the range of 2-20°C, preferably from about 5°C to about 15°C, more preferably from about 5°C to about 10°C, more preferably about 7°C, in step b) and c) has been found to be C or in a water bath, preferably an ice bath, allows the formation of an emulsion with the desired particle size range. Higher temperatures affect the viscosity of the continuous phase, which in turn contributes to obtaining an emulsion system with an unfavorable particle size distribution with a diameter above 1 μm.

Preferred embodiments of the process for preparing a curcumin formulation in a dry form to obtain a stabilized emulsion characterized by a narrow and fine particle distribution in the range of about 0.1 to about 1 μm in diameter without appreciable sedimentation or creaming use a starch octenyl succinate polymer carrier and a cellulose derivative. The carrier is made of a mixture of starch octenyl succinate and a cellulose derivative, preferably with a viscosity in the range of 40-200 mPas, particularly preferably hydeoxypropyl cellulose, hydroxypropyl methyl cellulose, preferably in the proportion of 0.1 to 30 g of starch octenyl succinate (e.g. PURITY GUM 2000®) to 0.02 to 20 g of hydeoxypropyl cellulose or hydroxypropyl methylcellulose, or a mixture thereof in the proportions 0:0 to 10:1. After mechanical mixing of the polymers, they are dissolved in a polar solvent, which is particularly preferably water, in the weight proportions 1:5 to 1:25, preferably 1:10. The resulting mixture is stirred mechanically to dissolve and combine the polymers, preferably for proper dissolution and connection of the polymers, for not less than 10 h, preferably about 12 h.

Separately, a turmeric solution with a minimum content of 90% curcuminoids is prepared in a food grade organic solvent, preferably ethyl acetate. The solution is obtained by dissolving 0.01 to 3 g of turmeric extract (min. 90% curcuminoids) in a food grade organic solvent, preferably 0.19 to 60 ml of ethyl acetate. The dissolved curcuminoid extract is added to the polymer mixture (polymer ratio 2 : 3 w/w) and homogenized using e.g. a mechanical homogenizer. Homogenization can be carried out continuously in various ways, for example by gradually increasing the speed of rotation, but most preferably it is carried out in two stages, first making a pre-emulsion and then carrying out the actual homogenization. The two-stage emulsion production is carried out, for example, at a rotational speed in the range of 5000 rpm. rpm ^-1 -15,000 rpm min- ¹ ,

PL 241 417 B1 preferably at a rotational speed of the working element of 10,000 rpm. min ^-1 until the pre-emulsion is produced. The entire mixture from the time the curcuminoids are introduced into the polymer mixture is cooled, for example in an ice water bath. The temperature of the polymer mixture at the time of introduction of the dissolved ethyl acetate extract preferably should not exceed about 10°C and preferably should not be lower than about 5°C. After the pre-emulsion is prepared, it is subjected to proper homogenization using a homogenizer, preferably a turbo-vortex homogenizer, and process parameters in the range of 20,000-24,000 rpm. ^rpm , preferably 22,000 rpm. min ^-1 for 3 min, after this time water or an aqueous β-glucan solution is added, preferably a 1-8% aqueous β-glucan solution, preferably from oats or barley with low viscosity (about 40-200 mPas) in an amount of 0 .5 to 210 ml (1 : 0.25 w/w) and further homogenized, for example for 1 min. The emulsion thus prepared is immediately combined with a polysaccharide solution, preferably a high viscosity cellulose derivative, preferably a solution of 0.1-1.4% aqueous high viscosity carboxymethylcellulose (CMC) solution. This technological procedure enables the production of a stable formulation, i.e. one with a particle size distribution of the dispersed phase <1 μm in diameter (for at least 90% of the particles, preferably for 95%, most preferably for more than 99% of the particles of the dispersed phase). The emulsion is diluted with water in a proportion of not less than 1:6, more preferably not less than 1:8, the whole is stirred mechanically using a stirrer, preferably a propeller stirrer, and the stabilized emulsion is dried, obtaining a curcumin formulation in a dry, preferably powder form. Drying can be carried out by a number of methods known in the art, but preferably spray drying is carried out using an inlet temperature of the dryer in the range of 110-160°C, preferably 150°C and an outlet temperature of not more than 65°C, preferably 55°C .

Also described is a curcumin formulation in dry form obtained by a process for producing a curcumin formulation of the invention.

The formulation obtained as described above is based only on ingredients approved for use in the food industry in accordance with EU law. At the same time, due to the use of only plant ingredients and the complete elimination of ethyl alcohol as a solvent from the production process, the formulation can be certified in accordance with the HALAL procedures, which, if used in food products intended for the markets of Muslim countries, enables their distribution due to the non-use ethyl alcohol as a solvent in the formulation preparation process. The formulation is characterized by an intense orange-yellow color that is natural for turmeric.

In contrast to the known turmeric formulations available on the market, the turmeric formulation according to the invention, the food products produced on its basis, as well as the emulsion produced from it, is characterized by a completely neutral taste - without the bitterness characteristic of turmeric extracts and without the typical sweetish aftertaste for formulations using maltodextrin. and/or maltose, which significantly increases the scope of its application in the food, pharmaceutical and dietary supplement industries. The formulation is stable in dry form and in the form of an aqueous solution, which enables its effective use in a wide range of food products.

The invention relates to a beverage concentrate comprising a curcumin formulation according to the invention. A preferred beverage concentrate comprises at least one of:

- a stabilizing and thickening agent at a concentration of 0-20% w/w, preferably glycerol and/or xanthan gum;

- antioxidant and acidity regulator 0-5% w/w, preferably ascorbic acid;

- acidity regulator 0-5% w/w, preferably citric acid;

- electrolyte and sweetener 0-80% w/w, preferably glucose;

- B vitamins, preferably selected from thiamine, niacin, pyridoxine, folic acid and riboflavin;

- preservatives, preferably benzoic acid, sodium benzoate, potassium sorbate, or a mixture thereof.

The invention also relates to a dye comprising the curcumin formulation of the invention.

The preferred dye is a food dye, used in medicine, cosmetics, food, animal feed.

The invention also relates to a beverage comprising the curcumin formulation according to the invention.

The preferred beverage is a fruit juice based beverage, water, milk based beverage, plant based milk replacer.

The preferred beverage is a functional liver support beverage, with the preferred concentration of curcuminoids in the beverage being 0.01-0.1% w/w.

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The invention relates to a dietary supplement comprising the curcumin formulation according to the invention.

The described dietary supplement favorably supports the work of the liver, and preferably activates the activity of liver enzymes, preferably enzymes from the group of dehydrogenases, preferably aldehyde dehydrogenase.

Also described is a pharmaceutical composition comprising the described curcumin formulation and a pharmaceutically acceptable additive.

Also described is a pharmaceutical composition comprising the described curcumin formulation for use as a medicament.

Preferably, the composition is for use as a drug in the regulation of liver function, an anti-inflammatory, anti-cancer and anti-depressant drug.

Preferably, the composition is for use as a medicament in the regulation of liver function activating the action of liver enzymes, preferably enzymes from the group of dehydrogenases, preferably aldehyde dehydrogenase.

Also described are the uses of the curcumin formulation of the invention as a functional additive to a food beverage, as a colorant, as an active ingredient in a dietary supplement, as an active ingredient in a pharmaceutical composition, as a food additive, as an animal feed additive.

Importantly, due to the increased bioavailability, the food products, in particular the beverages/emulsions, made based on the turmeric formulation of the invention do not require the addition of piperine, which was necessary to increase the bioavailability for prior art turmeric formulations.

The inventors found that the formulation of the invention can be successfully used to produce a stable concentrate containing from 5 to 20% of the formulation concentration and the final concentration of curcuminoids (0.1 to 2.0% w/w) is preferably from 5 to 20 a concentrated concentrate for use in the production of beverages, especially functional beverages, in which the active substance is curcumin, especially beverages that activate the metabolism of acetaldehyde.

Due to the high stability, lack of modification of biological activity and increased bioavailability of curcuminoids, the formulation according to the invention can be used for the production of functional dietary supplements or pharmaceutical preparations, in which one of the active substances is curcumin. Preferably, such preparations include preparations with liver functions regulating activity, activating the activity of enzymes, including enzymes from the group of dehydrogenases, including aldehyde dehydrogenase, anti-inflammatory, anti-cancer and anti-depressant activity.

In a preferred example of application, the formulation is used to produce a functional drink as a dietary supplement supporting liver function, especially in terms of activating enzymes that break down acetaldehyde, preventing some negative aspects of alcohol consumption by lowering the concentration of acetaldehyde in the blood. In a preferred embodiment, the formulation is used at a concentration corresponding to a final curcuminoid concentration of 0.01-0.1% w/w.

Due to the increased bioavailability of curcumin in the form of the described formulation, the use of the formulation makes it possible to eliminate from the recipe of the functional drink concentrate and the functional drink according to the invention substances supporting bioavailability, used in preparations available on the market, in the form of e.g. black pepper extract in the form of piperine (ReadyQ preparations , alcorythm®) adversely affecting the taste of the preparation and substances that additionally induce the activity of enzymes accelerating the decomposition of acetaldehyde, such as DHM (dihydromyricetin) (ReadyQ, Morning Recovery preparations).

The concentrate may also contain excipients in any combination including at least one of the following substances, such as:

- a stabilizing and thickening agent at a concentration of 0-20% w/w, preferably glycerol and/or xanthan gum,

- antioxidant and acidity regulator 0-5% w/w, preferably ascorbic acid,

- acidity regulator 0-5% w/w, preferably citric acid

- electrolyte and sweetener 0-80% w/w, preferably glucose.

The concentrate may also contain B vitamins (including thiamine, niacin, pyridoxine, folic acid and riboflavin) in concentrations for each vitamin not higher than twice the maximum reference intake dose, taking into account the stability surplus, multiplied by the concentration value of the concentrate.

PL 241 417 B1

The concentrate may contain preservatives in any combination including at least one of the following substances, such as, assuming that the total concentration of preservatives, after dilution of the concentrate to the target concentration does not exceed 0.2% w/w, the concentrate may contain examples of preservatives: benzoic acid 0-2% w/w, sodium benzoate 0-2% w/w, potassium sorbate 0-2% w/w or a mixture thereof.

Particularly advantageous was the use of the formulation according to the invention as a yellow dye in the food, pharmaceutical and cosmetic industries for coloring food and pharmaceutical and cosmetic products obtained on the basis of water.

Due to the completely neutral taste, the use of excipients allowed in the food industry, the natural color of the formulation according to the invention resulting from the lack of blockage of chromophoric groups and the high stability of the aqueous solution of the formulation according to the invention, the aqueous solution of the formulation according to the invention can be used at the target concentration of quantum satis, for example as an E100 dye in the production of beverages (including beverages based on natural or reconstituted fruit juices with a pH in the range of 3.0-7.0), for coloring cakes, baked goods, coloring tablet mass and syrups, and cosmetics (e.g. shampoos, creams, masks).

"Golden milk" - a product obtained from an aqueous extract of turmeric rhizomes in milk (ruminant milk) or a plant milk substitute (a drink obtained on the basis of grains, nuts, legumes) is used in unconventional medicine and dietetics based on the medical traditions of the Far East East as a drink that increases the body's immunity, counteracts inflammation. The bitter-scorching taste of turmeric that characterizes the drink discourages the use of the preparation as a prophylactic and therapeutic agent. An additional disadvantage of the drink is the relatively low content and low bioavailability of curcuminoids in the aqueous extract of turmeric rhizome.

Due to the completely neutral taste, the use of excipients allowed in the food industry and bioavailability, the inventors found that the use of the formulation according to the invention to produce beverages, especially milk, allows to avoid the technological problem resulting from the state of the art. The formulation according to the invention forms stable suspensions in animal milk (preferably ruminant milk, especially preferably in cow, buffalo, sheep or goat milk) and in plant milk substitutes in the form of beverages obtained from cereal grains, nuts, legumes (preferably oat, millet, hemp, cashew nuts, pecan nuts, almonds, soybeans), including drinks containing additional and auxiliary substances and supplements in the form of calcium salts, thickeners and stabilizers, and sweeteners.

In a preferred embodiment the milk is cow's milk, almond, soy or oat drink and the concentration of the formulation in the finished product is 0.01%-1.0%, particularly preferably 0.1%. After dissolving the formulation, the product is subjected to the pasteurization process.

DESCRIPTION OF DRAWING FIGURES

For a better understanding of the invention, it is illustrated by non-limiting embodiments and the accompanying drawings, in which:

FIG. 1 shows the particle size distribution of the produced emulsion before spray drying;

FIG. 2 shows the particle size distribution of a reconstituted powder containing 15% curcuminoids.

EXAMPLES

The following examples are provided solely for the purpose of illustrating the invention and explaining particular aspects thereof, not for the purpose of limiting it, and should not be construed as being in its entirety as defined by the appended claims. In the following examples, unless otherwise indicated, standard materials and methods used in the art were used or manufacturers' recommendations for specific materials and methods were followed.

Example 1

Preparation of a curcumin formulation in the form of a powder

6 g of starch octenyl succinate (e.g. PURITY GUM 2000®) and 2 g of hydroxypropyl methylcellulose (a cellulose derivative with a viscosity in the range of 40-200 mPas) were mixed. After mechanical mixing of the polymers, they were dissolved in a polar solvent, which was water, in the amount of 100 ml. The resulting mixture was mechanically mixed to dissolve and combine the polymers, the inventors surprisingly found that this occurs after not less than 10 h, preferably 12 h. 1.6 g of turmeric extract (min. 90% content of curcuminoids) was dissolved in 30 ml of ethyl acetate in boiling point of this solvent. The dissolved curcuminoid extract was added immediately after dissolution to

PL 241 417 B1 of the polymer mixture and homogenized using a mechanical homogenizer at the rotational speed of the working element of 10,000 rpm, until ^a pre-emulsion was produced, i.e. a homogeneous mixture was obtained, assessed with the naked eye. The whole mixture, from the moment of introducing the curcuminoids to the mixture of polymers, was cooled in an ice water bath. The temperature was kept in the range of 5-10°C, preferably 7°C. After the pre-emulsion was prepared, it was subjected to proper homogenization using a turbo-swirl homogenizer and process parameters: ^22,000 rpm for 3 minutes, after which water or a 1.5% aqueous solution of β-glucan from low-density oats or barley was added viscosity (40-200 mPas) in an amount of 50 ml and further homogenized for 1 min. The thus prepared emulsion was immediately combined with a 1% aqueous solution of high viscosity carboxymethyl cellulose (CMC) (>5600 mPas). The emulsion was diluted in 1 L of the solution prepared in this way, with mechanical stirring using a propeller stirrer. For the emulsion solution, the percentage distribution of particle size in the test sample in individual size categories was determined. Results were obtained with a distribution similar to that of Example 2 (greater than 99% of the particles were in the size range of about 0.1 to about 1 µm).

The emulsion solution prepared in this way was subjected to conventional spray drying, using a temperature at the inlet to the dryer of about 150°C, and at the outlet of about 55°C.

For the obtained curcumin formulations in the form of powder after its dissolution, the size of the obtained particles and their size distribution were determined (Table 1, Fig. 2).

Table 1

Percentage distribution of particle size in the tested sample (powder after reconstitution), in particular size categories

^lP Lower limit of the range (pm) Average particle size in the range |pm) % particles L-P- Lower limit of the range (pm) Average particle size in the range (pm) % particles Lp- Lower limit of the range (pm) Average particle size in the range (pm) % particles 1 0 0.025 0 23 1.24 1.34 0 45 35.56 38.495 0 2 0.05 0.055 0 24 1.44 1.56 0.07 46 41.43 44.85 0 3 0.06 0.063 0 25 1.68 1.815 0.31 4/ 48.2/ 52.25 0 4 0.07 0.075 0 26 1.95 2.115 0.43 48 56.23 60.87 0 5 0.08 0.085 0 27 2.28 2.465 0.43 49 65.51 70.915 0 6 0.09 0.1 0 28 2.65 2.87 0.36 50 76.32 82.615 0 7 0.11 0.12 0 29 3.09 3.345 0.28 51 88.91 96.245 0 8 0.13 0.14 0.01 thirty 3.6 3,895 0.2 52 103.58 112.125 0 9 0.15 0.16 0.07 31 4.19 4.535 0.13 53 120.67 130.625 0 10 0.17 0.185 0.51 32 4.88 5.285 0 54 140.58 152.175 0 11 0.2 0.215 2.39 33 5.69 6.16 0 55 163.77 177.285 0 12 0.23 0.25 7.71 34 6.63 7.175 0 56 190.8 206.54 0 13 0.27 0.29 15.99 35 7.72 8.36 0 57 222.28 240.615 0 14- 0.31 0.335 21.02 36 9 9.74 0 58 258.95 280.315 0 15 0.36 0.39 19.72 37 10.48 11.345 0 59 301.68 326.57 0 16 0.42 0.455 15.52 38 12.21 13.215 0 60 351.46 380.455 0 17 0.49 0.535 9.77 39 14.22 15.395 0 61 409.45 443.23 0 18 0.58 0.625 4.02 40 16.57 17.94 0 62 477.01 516.36 0 19 0.67 0.725 1 41 19.31 20.9 0 63 555.71 601.56 0 twenty 0.78 0.845 0 42 22.49 24.345 0 64 647.41 700.82 0 21 0.91 0.985 0 43 26.2 28.365 0 65 754.23 816.45 0 22 1.06 1.15 0 44 30.53 33.045 0 66 878.67 878.67 0

Surprisingly, the formulation obtained as described above has a particularly favorable particle size distribution in the range of about 0.1 to about 1 [mu]m in diameter (greater than about 95% of the particles, preferably greater than 97%, preferably 100% of the particles), with curcuminoids in the range (from 0.01% to 15%), which increases its dispersion properties in the aqueous environment, enabling the preparation of emulsions with a high degree of homogeneity.

The quantitative and qualitative composition of the obtained dried (up to 5% moisture) formulation prepared according to the above example was as follows:

starch octenyl succinate 29.5% (w/w) hydroxypropyl methylcellulose (as a cellulose derivative) 9.8% (w/w) turmeric extract (min. 90% curcuminoids) 7.9% (w/w) β-glucan 3, 7% (w/w) carboxymethylcellulose 49.1% (w/w);

with greater than 97% of the reconstituted particles having a size in the range of about 0.1 to about 1 µm.

PL 241 417 B1

The formulation was characterized by an intense orange-yellow color, was neutral in taste and easily dissolved in water, creating a uniform suspension.

Example 2

Preparation of a curcumin formulation in the form of a powder

The formulation of the mixture was obtained as in example 1 with the difference that:

after mechanical mixing of the polymers, they were dissolved in a polar solvent, which was water, in the amount of 90 ml;

- 2 g of turmeric extract (min. 90% content of curcuminoids) was dissolved in a mixture of ethyl acetate and acetone in a ratio of 5:1 in the amount of 35 ml at the boiling point of the mixture.

The resulting mixture was mechanically mixed to dissolve and combine the polymers, not less than 10 h, preferably 12 h. The dissolved curcuminoid extract was added immediately after dissolution to the polymer mixture and homogenized using a mechanical homogenizer at the rotational speed of the working element of 10,000 ^rpm'1 until the formation of pre-emulsion, i.e. obtaining a homogeneous mixture assessed with the naked eye. The whole mixture, from the moment of introducing the curcuminoids to the mixture of polymers, was cooled in an ice water bath. The temperature was kept in the range of 5-10°C, preferably around 7°C. For the curcumin emulsion formulations obtained, the particle size and size distribution of the obtained particles was determined (Table 2, Fig. 1). The inventors have surprisingly found that the formulation obtained as described above has a particularly favorable particle size distribution in the range of from about 0.1 to about 1 µm in diameter (greater than about 95% of the particles, preferably 100% of the particles), with curcuminoid content in the range (from 0.01% to 20%), which increases its dispersion properties in an aqueous environment, enabling the preparation of emulsions with a high degree of homogeneity.

Table 2

Percentage distribution of particle size in the test sample (emulsion), in particular size categories

ip- Lower limit of the range (μπι) Mean particle size in the fam range) % particles ip- The lower limit of the range (pmj Mean particle size in the fam range) % particles no. Lower limit of the range /pm/ Mean particle size in the fam range) % particles 1 0 0.025 0 23 1.24 1.34 0 45 35.56 38.495 0 2 0.05 0.055 0 24 1.44 1.56 0 46 41.43 44.85 0 3 0.06 0.065 0 25 1.68 1.815 0 47 48.27 52.25 0 4 0.07 0.075 0 26 1.95 2.115 0 48 56.23 60.87 0 5 0.08 0.085 0 27 2.28 2.465 0 49 65.51 70.915 0 6 0.09 0.1 0 28 2.65 2.87 0 50 76.32 82.615 0 7 0.11 0.12 0 29 3.09 3.345 0 51 88.91 96.245 0 8 0.13 0.14 0.02 thirty 3.6 3,895 0 52 103.58 112.125 0 9 0.15 0.16 0.11 31 4.19 4.535 0 53 120.67 130.625 0 10 0.17 0.185 0.57 32 4.88 5.285 0 54 140.58 152.175 0 11 0.2 0.215 2.26 33 5.69 6.16 0 55 163.77 177.285 0 12 0.23 0.25 6.53 34 6.63 7.175 0 56 190.8 206.54 0 13 0.27 0.29 12.97 35 7.72 8.36 0 57 222.28 240.615 0 14 0.31 0.335 17.42 36 9 9.74 0 58 258.95 280.315 0 15 0.36 0.39 17.9 37 10.48 11.345 0 59 301.68 326.57 0 16 0.42 0.455 16.65 38 12.21 13.215 0 60 351.46 380.455 0 17 0.49 0.535 13.67 39 14.22 15.395 0 61 409.45 443.23 0 1S 0.5S 0.625 8.53 40 16.57 17.94 0 62 477.01 516.36 0 19 0.67 0.725 3.38 41 19.31 20.9 0 63 555.71 601.56 0 twenty 0.78 0.845 0 42 22.49 24.345 0 64 647.41 700.82 0 21 0.91 0.985 0 43 26.2 28.365 0 65 754.23 816.45 0 22 1.06 1.15 0 44 30.53 33.045 0 66 878.67 878.67 0

The quantitative and qualitative composition of the obtained dried (up to 5% moisture) formulation prepared according to the above example was as follows:

starch octenyl succinate 28.9% w/w;

hydroxypropyl methylcellulose 9.6% w/w;

turmeric extract (min. 90% curcuminoids) 9.6% w/w;

β-glucan 3.6% w/w;

carboxymethylcellulose 48.3% w/w;

wherein for this emulsion composition, 100% of the particles had a particle size in the range of about 0.1 to about 1 µm.

PL 241 417 B1

For the obtained curcumin formulation in the form of powder, the size of the obtained particles and their size distribution after reconstitution were determined. More than 98% of the particles after reconstitution of the powder had a size in the range of about 0.1 to about 1 μm. Thus, results with a distribution similar to the results from example 1 were obtained.

The formulation was characterized by an intense orange-yellow color, was neutral in taste and easily dissolved in water, creating a uniform suspension.

Example 3

Preparation of a curcumin formulation in the form of a powder

The formulation of the mixture was obtained as in example 1 with the difference that:

- after mechanical mixing of the polymers, they were dissolved in a polar solvent, which was water, in the amount of 90 ml;

- the prepared emulsion solution was subjected to freeze drying using the following process parameters: drying pressure 0.5 mbar, shelf temperature program: from 0 to 2 h -20°C, 2-3 h 20°C, 3-18 h 20°C, 18-19 h 40°C, 18-19 h pressure 0.2 mbar, 19-24 h 40°C end of process. For the curcumin formulations obtained in the form of emulsion and powder, after dissolving the powder, the size of the obtained particles and their size distribution were determined. The distribution of results was similar to that of examples 1 and 2.

The inventors have surprisingly found that the formulation obtained as described above has a particularly favorable particle size distribution in the range of about 0.1 to about 1 μm in diameter (greater than about 95% of the particles, preferably 100% of the particles), with a content of curcuminoids in the range (from 0-101% to 20%), which increases its dispersion properties in an aqueous environment, enabling the preparation of emulsions with a high degree of homogeneity.

The quantitative and qualitative composition of the obtained dried (up to 5% moisture) formulation prepared according to the above example was as follows:

starch octenyl succinate 26.5% (w/w) hydroxypropyl methylcellulose 9.8% (w/w) turmeric extract (min. 90% curcuminoids) 16.4% (w/w) β-glucan 3.7% (w/w) w) carboxymethyl cellulose 43.6% (w/w) with more than 97% of the particles having a particle size in the range of about 0.1 to about 1 μm after reconstitution.

The formulation was characterized by an intense orange-yellow color, was neutral in taste and easily dissolved in water, creating a uniform suspension.

Example 4

Curcumin formulation aqueous solution

The curcumin powder formulation prepared according to Examples 1-3 was dissolved in water at certain concentrations and their physico-chemical properties were tested. Based on the obtained results, it was found that the formulations form a stable suspension in the aqueous environment, in the concentration range from 0.01% to 30% w/w. Preferably the concentration is 0.05-10.00%, particularly preferably 0.5%-1.5% (w/w). At the indicated concentrations, especially at the preferred concentrations, the formulation forms an optically homogeneous suspension, at room temperature after 24 hours, optically no visible precipitate was observed.

The aqueous solution of the formulation in the right concentrations is characterized by chemical stability (the study was carried out on the basis of the observation of color changes, indicating oxidation processes of the active substance and color changes in an acidic environment, in the pH range equal to or higher than 3.0 and less than 7.0, which makes it possible to use it in food production.

In aqueous solutions, the formulation remains stable for a period of min. 12 months, as shown in aging tests under accelerated aging conditions (according to ICH Q1A (R2) Stability testing of new drug substances and drug products - EDQM recommendations).

In order to confirm the stability of the suspension and determine the level of sedimentation, a study was carried out consisting in centrifugation of a suspension with a concentration of 0.5% curcuminoids in 15 ml of distilled water at a speed of 5000 rpm for 20 minutes at a temperature of 25°C in the REF 11778 rotor of the MPW380R centrifuge MPW.

Suspensions compared:

a) the test formulation of Examples 1-3

b) turmeric extract containing 95% curcuminoids

c) Cavacurmin by Wacker and CurQfen by Akay Group Ltd.

PL 241 417 B1

The suspensions were standardized to a total curcuminoid concentration of 0.5% w/w.

Table 3

Stability results for the developed formulation and similar formulations available on the market. P1, P2, P3 formulation prepared according to example 1,2,3, respectively

Tested product sample concentration (volume of sample subjected to stability test 15 ml) concentration of curcuminoids in water suspension (15 ml) % of substance in the form of sediment after centrifugation at 50,000 rpm at 25°C and after 20 min The formulation according to the invention P1 (7.9% curcuminoids*) 949.33 mg in 15 ml of water 0.5% 20.4% P2 (9.6% curcuminoids*) 781.22 mg in 15 ml of water 0.5% 19.9% P3 (16.4% curcuminoids*) 457.3 mg in 15 ml of water 0.5% 19.5% CAVACURMIN® (16.4% curcuminoids*) 457.3 mg in 15 ml of water 0.5% 100% CurQfen® (47.1% curcuminoids*) 159.2 mg in 15 ml of water 0.5% 95% turmeric extract (% curcuminoids*) 81.5 mg in 15 ml of water 0.5% The extract floats on the surface of the water

*Curcuminoid content was measured spectrophotometrically at λ = 420 nm. The solution in which the curcuminoids were extracted from the formulation and measured spectrophotometrically was water : acetone 30:70 v/v.

The results unequivocally indicate a greater suspension stability of the formulation according to the invention.

Example 5

Bioavailability of the aqueous suspension of the formulation

The inventors conducted a study of the bioavailability of the formulations of the invention in the form of a suspension in water. The study was conducted using the in vit.ro method on a cellular model of absorption and penetration through the epithelial cell layer of the intestinal epithelium, using the Caco-2 cell line, according to the protocol described in: Frank, J., 2017. The study compared the bioavailability of turmeric extract, the test formulation according to the invention and Cavacurmin® (Wacker Chemie AG) and CurOfen®. Bioavailability was tested on suspensions normalized to the final content of curcuminoids - concentration of 10 pg/ml.

Table 4

Absorption and permeability of curcuminoid formulations through a monolayer of Caco-2 cells in 60 min. P1, P2, P3 formulation prepared according to example 1,2,3, respectively

Initial concentration of curcuminoids time (minutes) % of curcumin absorbed by cells % curcumin that penetrated the cell monolayer CurQufen® 10µg/ml 60 39.64% ±0.22% 0.66% ± 0.04% CAVACURMIN® 10µg/ml 60 21.61%±0.15% 0.00% ± 0.00% Formulation acc. invention P1 P2 P3 10µg/ml 60 42.57% ± 1.21% 44.23% ± 0.89% 43.62% ± 0.07% 0.63% ± 0.80% 0.72% ± 0.40% 0.67% ± 0.50%

PL 241 417 B1

The study clearly demonstrated the increased bioavailability of the formulations of the invention compared to CAVACURMIN® and CurQfen®. The formulation according to the invention is absorbed by cells at a level more than 2 times higher than CAVACURMIN® and more than 10% higher than CurQfen® (in studies, CurQfen® has been shown to have 45- to 270-fold higher bioavailability than native turmeric extract - Kumar et al. 2016). At the same time, the formulation according to the invention shows 1.5% higher permeability through the cell monolayer than CurQfen®, measured over 60 minutes.

Example 6

Concentrate for use in the production of beverages using a formulation prepared according to one of the methods described in examples 1, 2 and 3

A 5-fold concentrated concentrate containing:

formulation according to the invention: 5% w/w prepared according to example 1:

xanthan gum: 1.1% w/w;

glycerol: 26.5% w/w;

citric acid: 2.5% w/w;

sodium benzoate: 0.5% w/w;

potassium sorbate: 0.5% w/w;

glucose: 40% w/w;

water: up to 100% w/w.

The concentrate showed high stability, confirmed by pH and microbiological tests. Changes in pH and growth of mesophilic bacteria, molds and yeasts have not been demonstrated during storage up to 6 months. Neither the color of the concentrate nor its other organoleptic properties changed. To prepare the final drink, the concentrate should be diluted 1 : 4 (concentrate : liquid), using water or reconstituted fruit juice from the concentrate, preferably mango, peach, orange juice or a mixture of these juices.

Example 7

Use of the formulation according to the invention as a dye

The formulation according to the invention was used as a food coloring E-100 (curcumin) in accordance with the concentrations allowed in the food law, i.e. 100 mg/l(kg) in juice-based drinks, 150 mg/l(kg) in milk-based products.

a) 5-fold concentrated fruit juice concentrate (preferably orange, peach, pineapple, particularly preferably orange) was mixed with the formulation prepared according to example 1 so that the final concentration of the formulation in the finished product was 0.01% w/w, the mixture was supplemented with water so as to obtain 1-fold final concentration of juice.

b) to fruit yoghurt (preferably peach or mango flavor) the formulation according to the invention was added to a final concentration of 0.015% w/w. The resulting mixture was mixed and homogenized.

Example 8

Use of the formulation according to the invention for the production of a milk-based curcumin drink or a plant-based milk-replacement drink

a) 10 times condensed cow's milk was mixed with the formulation prepared according to example 1 so that the final concentration of the formulation in the finished product was 0.015%, the mixture was supplemented with water so as to obtain 1 times the final concentration of milk.

b) A 10-fold concentrated milk-replacement plant drink concentrate (preferably soy, almond, oat drink) was mixed with the formulation prepared according to example 1 so that the final concentration of the formulation in the finished product was 0.01%. The mixture was supplemented with water so as to obtain 1-fold the final concentration of the beverage.

Literature

Amalraj, A., Pius, A. Gopi, S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives - A review. Journal of Traditional and Complementary Medicine 2017, 7, 205-233.

Anderson, A.M. Mitchell, M.S. Mohan, R.S. Isolation of curcumin from turmeric. J Chem Educ. 2000, 77, 359-360.

Claims (19)

PL 241 417 B1 Antony, B. Merina, B. lyer, V.S. Judy, N. Lennertz, K. Joyal, S. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm. sci. 2008, 70(4), 445-449. Apisariyakul, A.; Vanittanakom, N.; Buddhasukh, D. Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae). J. Ethnopharmacol. 1995, 49, 163-169. Cuomo, J. Appendino, G. Dem, A.S. Schneider, E. McKinnon, T.P. Brown, M.J. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod. 2011,74(4), 664-9. Frank, J.; Schiborr, C; Kocher, A.; Meins, J.; Behnam, D.; Schubert-Zsilavecz, M.; Abdel-Tawab, M. Transepithelial Transport of Curcumin in Caco-2 Cells Is Significantly Enhanced by Micellar Solubilisation. Plant Foods Hum Nutr (2017) 72:48-53. Gotha, V.S. Maru, G.B. Sonia, T.G. Gandhi, T.R. Kochar, N. Agarwal, M.G. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J. Agric. Food Chem. 2010, 58(4), 2095-2099. Govindarajan, V.S. Turmericschemistry, technology and quality. CRC Crit. Rev. Food Science. Nutr. 1980, 12, 199-501. Jager, R. Lowery, R.P. Calvanese, A.V. Joy, J.M. Purpura, M. Wilson, J.M. Comparative absorption of curcumin formulations. Nutrition Journal 2014, 13:11, 1-8. Krishnakumar, I.M. Ravi, A. Kumar, D. Kuttan, R. Maliakel, B. An enhanced bioavailable formulation of curcumin using fenugreek-derived soluble dietary fiber. J Funct. Food 2012, 4(1), 348-357. Madhavi, D. Kagan, D. Bioavailability of a sustained release formulation of curcumin. integr. Med. (Encinitas) 2014,13(3), 24-30. Mangolim, C.S. Moriwaki, C. Nogueira, A.C. Sato, F. Baesso, L.M. Neto, A.M. Matioli, G. Curcumin-e-cyclodextrin inclusion complex: Stability, solubility, characterization by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chemistry 2014,153, 361-370. Marcolino,V.A. Zanin, G.M. Durrant, L.R. Benassi, M.T. Matioli, G. Interaction of Curcumin and Bixin with e-Cyclodextrin: Complexation Methods, Stability, and Applications in Food. J. Agric. Food Chem. 2011, 59, 3348-3357. Martins, R.M. Pereira, S.V. Siqueira, S. Salomao, W.F. Freitas, L.A.P. Curcuminoid content and antioxidant activity in spray dried microparticles containing turmeric extract. Food Research International 2013, 50, 657-663. Purpura, M., Lowery, R.P. Wilson, J.M. Mannan, H. Munch, G. Razmovski-Naumovski, V. Analysis of different innovative formulations of curcumin for improved relative oral bioavailability in human subjects. Euro. J Nutr. 2018, 57(3), 929-938. Ruby, A.J.; Kuttan, G.; Baby, K.D.; Rajasekharan, K.N.; Kuttan, R. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995, 94, 79-83. Salzer, D. LL; Haarne, G.; Reimer, G. Analytical evaluation of seasoning extracts (oleoresins) and essential oils from seasonings. Flavors 1975, July/Aug, 206-210. Sasaki, H. Sunagawa, Y. Takahashi, K. Imaizumi, A. Fukuda, H. Hashimoto, T. Innovative preparation of curcumin for improved oral bioavailability. Biol. pharma. bull. 2011, 34(5), 660-665. Schiborr, C. Kocher, A. Behnam, D. Jandasek, J. Toelstede, S. Frank, J. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Moth. Nutr. Food Res. 2014, 58(3), 516-527. Shoba, G. Joy, D. Joseph, T. Majeed, M. Rajendran, R. Srinivas, P.S. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. plant. Med. 1998, 64(4), 353-356. Yamamoto, H.; Hanada, K.; Kawasaki, K.; Nishijima, M. Inhibitory effect on curcumin on mammalian phospholipase D activity. FEBS Lett. 1997, 417, 196-198. Patent claims 1. A curcumin formulation in dry form, characterized in that it comprises - 0.1-45% w/w starch octenyl succinate; - 0.01-20% w/w of a cellulose derivative selected from hydroxypropylmethylcellulose, hydroxypropylcellulose, or a mixture thereof; PL 241 417 B1 - 0.01-20% w/w turmeric extract, the turmeric extract containing at least 9 0% w/w curcuminoids, including curcumin, demethoxycurcumin and bisdemethoxycurcumin, - 0.1-10% w/w β-glucan; - 10-70% w/w of a cellulose derivative with a viscosity > 5600 mPas selected from carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, ethyl methyl cellulose, cross-linked cellulose gum; wherein at least 90%, more preferably at least 95% of the particles, preferably at least 99% of the particles are less than 1 Pm in diameter. 2. The curcumin formulation in dry form according to claim 1, characterized in that it comprises - starch octenyl succinate in an amount of 25-35% w/w, more preferably 28-32% w/w; - a cellulose derivative in the form of hydroxypropylmethylcellulose, hydroxypropylcellulose or a mixture thereof in an amount of 5-15%, preferably in an amount of 8-10%; - turmeric extract in an amount of 5-15%, preferably in an amount of 8-10%, wherein the turmeric extract contains at least 90% w/w curcuminoids, including curcumin, demethoxycurcumin and bisdemethoxycurcumin; - β-glucan in an amount of 3-5% w/w, preferably in an amount of 3.8-4.2% w/w; - carboxymethyl cellulose with a viscosity above 5600 mPas in an amount of 30-60% w/w, preferably in an amount of 48-52% w/w; - starch octenylsuccinate in an amount of 25-35%, particularly preferably in an amount of 28-32% w/w. 3. A curcumin formulation in dry form according to claim 1-2, characterized in that in the curcumin formulation in dry form at least 90%, more preferably at least 95% of the particles, more preferably at least 99% of the particles have a diameter in the range of 0.1 to 1 μm. 4. A method for producing a curcumin formulation in dry form, which includes the following steps: (a) a turmeric extract with a minimum content of 90% curcuminoids is dissolved in an organic solvent selected from ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, approved for use in the manufacture of food; b) the dissolved turmeric extract of step a) is added to a carrier solution which is a mixture of polymers comprising starch octenyl succinate and a cellulose derivative selected from hydroxypropyl cellulose, hydroxypropyl methylcellulose, or mixtures thereof dissolved in water; wherein the temperature of the carrier solution during the addition of the dissolved turmeric extract is between 5°C and 10°C, preferably cooling is used to maintain this temperature of the resulting mixture; c) homogenizing the mixture obtained in step b) into an emulsion by homogenizing at a temperature of 5°C to 10°C; d) the emulsion obtained in step c) is diluted with an aqueous solution of β-glucan having a viscosity in the range of 40-200 mPas and then homogenized briefly; e) the emulsion obtained in step d) is stabilized by dilution with an aqueous solution of a cellulose derivative with a viscosity above 5600 mPas selected from carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, ethyl methyl cellulose, cross-linked cellulose gum, diluting in a ratio of not less than 1:6, preferably not less than 1 : 8, mixing the whole mechanically; and f) the stabilized emulsion of step e) is dried to obtain a curcumin formulation in a dry form, wherein greater than 90%, preferably greater than 95%, preferably greater than 99% of the particles obtained have a diameter of less than 1 Pm; more preferably at least 90%, more preferably at least 95% of the particles, more preferably at least 99% of the particles have a diameter in the range of 0.1 to 1 Pm. 5. A method for producing a curcumin formulation according to claim The method of claim 4, wherein the organic solvent used to dissolve the turmeric extract in step a) is ethyl acetate. 6. A method for producing a curcumin formulation according to claim 4-5, wherein the cellulose derivative used to make the carrier is a 10:1 mixture of hydroxypropyl cellulose to hydroxypropyl methylcellulose. PL 241 417 B1 7. A method for producing a curcumin formulation according to claim 4-6, characterized in that in step d) the emulsion is diluted with 1-8% β-glucan, preferably oat or barley β-glucan, or a mixture thereof. 8. A method for producing a curcumin formulation according to claim 4-7, wherein the high viscosity cellulose derivative is carboxymethyl cellulose (CMC), preferably at a concentration of 0.01 to 0.5%, more preferably at a concentration of 0.10 to 0.20%, more preferably at a concentration of 0.01 to 0.20%. .1 to 1.4% (w/w). 9. A method for producing a curcumin formulation according to claim 4-8, characterized in that the carrier solution is obtained by mechanical mixing of polymers, the mixing being carried out for not less than 10 hours, preferably 12 hours. 10. A method for producing a curcumin formulation according to claim 4-9, characterized in that the carrier solution is dissolved in water in a weight ratio of 1:5 to 1:25, preferably 1:10. 11. A method for producing a curcumin formulation according to claim 4-10, characterized in that the drying in step f) is carried out using spray drying with an inlet temperature to the dryer in the range of 110-160°C, more preferably 150°C, and an outlet temperature of not more than 65°C, preferably not more than than 55°C. 12. A beverage concentrate comprising a formulation according to claim 1. 1-3. 13. A beverage concentrate according to claim 1. The method of claim 12, further comprising at least one of: - 0-20% w/w glycerol and/or xanthan gum; - 0-5% w/w ascorbic acid; - 0-5% w/w citric acid; - 0-80% w/w glucose; - B vitamins selected from thiamine, niacin, pyridoxine, folic acid and riboflavin, or a mixture thereof; - preservatives selected from benzoic acid, sodium benzoate, potassium sorbate, or a mixture thereof. 14. A dye comprising the formulation of claims 1-3. 15. The dye according to claim 14, characterized in that it is a food dye, used in medicine, cosmetics, food, animal feed. 16. A beverage comprising the formulation according to claims 1-3. 17. A beverage according to claim A beverage based on fruit juices, water, a milk beverage, a vegetable milk substitute beverage. 18. A beverage according to claims 16-17, characterized in that it is a functional beverage, wherein the concentration of curcuminoids in the beverage is 0.01-0.1% w/w. 19. A dietary supplement comprising the formulation according to claims 1-3.