TW202137886A - Formulation of a turmeric extract comprising curcuminoids, method of production thereof, the use of the formulation and products comprising thereof - Google Patents

Abstract

The invention provides a formulation of a turmeric extract comprising curcuminoids, dispersible in water, and the method of production of the turmeric extract formulation dispersible in water, the use thereof in food products, feed products, medicinal products, beverage and beverage concentrate, dietary supplement, pharmaceutical composition, preferably activating the metabolism of acetaldehyde, acting as anti-inflammatory agent as well as relates to products comprising formulation, beverages and their concentrates, food products, feed products, dietary supplements, medicinal products, pharmaceutical composition and uses thereof.

Description

The formulation of curcumin-like turmeric extract, its production method, the use of the formulation and the products containing it

The present invention provides a turmeric extract formulation containing curcuminoids that can be dispersed in water; and a method for producing a turmeric extract formulation that can be dispersed in water; it is used in food products, feed products, dietary supplements, and pharmaceutical products , Beverages and beverage concentrates, dietary supplements, pharmaceutical compositions, the use of better activation of acetaldehyde metabolism; and products containing the same, beverages and their concentrates, food products, feed products, dietary supplements, pharmaceutical products, Pharmaceutical composition and its use.

Turmeric ( Curcuma longa ), commonly called turmeric (turmeric), is a tropical Zingiberaceae (Zingiberaceae) plant native to South Asia. Turmeric rhizomes are traditionally used not only as a coloring ingredient, but also as a spice. Turmeric is extremely common not only as a spice, but also as an additive in food or 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 types of curcumin can be present in different amounts and ratios with respect to each other, depending on the biological and environmental factors related to the cultivation of the rhizome itself, and in the case of oleoresin or extract, depending on the technology to obtain it. In addition to its coloring and spice properties, turmeric and especially the curcumin contained therein exhibit a variety of healing properties, which have been confirmed by pharmacological studies on various animals. Turmeric extract exhibits 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 for curcuminoids to work on living organisms (humans and animals), they must first be delivered to the body and then absorbed from the digestive tract to the bloodstream (Amalraj et al., 2017; Jäger et al., 2014).

Curcuminoids are compounds that are insoluble in water. In addition, their solubility in plant and animal fats is very limited and does not exceed 1 mg ml ^-1 , which obviously hinders the bioavailability of curcuminoids in the gastrointestinal tract. Curcuminoids are the easiest to dissolve in organic solvents (such as acetone), followed by ethyl acetate, methanol and ethanol (in the case of ethanol, in order to increase the solubility of curcuminoids, the solution must be heated to boiling temperature, that is, , About 78°C, which causes thermal decomposition of curcuminoids) (Amalraj et al., 2017; Anderson et al., 2000). Due to the toxicity of the solvent, the solution obtained in this form cannot be administered to living organisms. It is sought to dissolve or disperse curcuminoids in water so that they can be introduced into the body of humans or animals in this form. Research has shown that the physical or chemical forms of curcuminoids play a key role in their bioavailability. It has been shown that dispersions of curcuminoids in aqueous environments significantly improve their bioavailability (Jäger et al., 2014). In addition, the purpose of developing water-soluble or water-dispersible curcuminoids formulations is to promote their combination with appropriate fragrance compositions so that they can be easily consumed by humans and animals. Curcuminoids in concentrated form, such as turmeric powder itself, have a very strong characteristic and bitter taste, which actually denies the possibility of direct consumption. In this form, it can be encapsulated or used as a food additive. The development of curcuminoid formulations that can be dispersed in an aqueous environment is a major technical challenge, due to the low solubility of curcuminoids in fat (fat solubility <1 mg g ^-1 , and curcuminoids are completely insoluble in water ). In the case where the product is intended for use in food, the formation of the dispersion system must be carried out using organic solvents that have been approved for use in food production, and then the organic solvent must be removed from the final product. In addition, its content in the final product must meet the similar statutory requirements of the Member States on the extraction solvent used in the production of food and food ingredients (European Parliament and Council Directive 2009/32/WE, April 23, 2009).

Various methods have been described in the world literature for preparing curcumin formulations that can be dispersed in water. An extremely common way to obtain curcumin, which can be dispersed in water, is to dissolve it together with β-cyclodextrin in 70-80% ethanol, and then heat for a long time and mix at 70°C for at least 4 hours (Mangolim Et al., 2014; Marcolino et al., 2011). Solvents (ethanol and water) are usually removed by spray drying, but are also removed as a result of vacuum evaporation or freeze drying. There are several disadvantages to this method of obtaining curcumin such as dispersible in water. The first basic shortcoming is that curcuminoids undergo unfavorable chemical conversion in a water-ethanol environment, which is related to their thermal decomposition. The study by Wang et al. (1999) showed that curcuminoids undergo decomposition in an aqueous environment under the influence of high temperature, even at the most favorable environmental pH (curcuminoids exhibit the highest stability at a pH between 3 and 6 ). Wang et al. (1999) showed that heating curcumin at 37°C for 2 hours resulted in a loss of this compound as much as 10%. The formulation of curcuminoids that can be dispersed in water should be carried out at the lowest possible temperature, especially in the process of joining them with water. Another disadvantage of using β-cyclodextrin formulation is its limited use in food production. β-Cyclodextrin (E 459) can be used to produce, for example, beverages, but its content cannot exceed 1 g kg ^-1 (Commission Regulation (EU) No. 1129/2011). This limits the possibility of introducing any amount of curcuminoids into the final product.

Other formulations of curcumin that can be dispersed in water are these compounds that are adsorbed on silicates (such as silica) (Martins et al., 2013). The use of curcuminoids (E 551) adsorbed on silica for the production of, for example, beverages is greatly restricted because such formulations are thermodynamically unstable and such particles rapidly undergo sedimentation. This is due to the high density of silica and the combination of curcuminoids with itself.

Many different curcumin-like formulations are available on the world market, but not all of them are suitable for the production of beverages, that is, their aqueous dispersions. Meriva® produced by Indena SpA (Italy) is composed of 18-20% curcuminoids adsorbed on microcrystalline cellulose and added soy lecithin (Cuomo et al., 2011). This product is more suitable for preparing solid preparations or as food additives, but not suitable for beverages because the microcrystalline cellulose does not dissolve, drops from the solution and undergoes sedimentation. LongVida® produced by Verdure Sciences (USA) is a preparation supplemented with phospholipid choline, which contains about 20% curcuminoids suspended in fat particles, which are solid at room temperature (Gota et al. , 2010). This preparation is usually used to produce dietary supplements in the form of tablets or capsules, which can also be added to different foods, however, it is not suitable for the permanent dispersion of curcuminoids in water. CurQfen® produced by Akay Flavors & Aromatics Pvt. Ltd., MicroActive curcumin produced by BioActives LLC (USA) contains approximately 25% curcuminoids suspended in short-chain triglycerides and added with free fatty acids and polyglycerides. The formulation is stabilized by hydroxypropyl methylcellulose, sodium alginate and microcrystalline cellulose (Madhavi et al., 2014). This formulation was mainly developed for the production of tablets/capsules, which contain highly bioavailable curcumin in terms of their composition. The micronized curcumin preparation produced by Raps GmbH & Co., KG (Germany) contains approximately 25% curcumin powder dispersed in triacetin (glyceryl triacetate) in terms of its composition and is derived from soybeans, oil palms and rapeseeds. The lipid mixture obtained from the seed of the seed (Schiborr et al., 2014). The preparation is insoluble in water and is not suitable for obtaining stable curcuminoids that can be dispersed in water. NovaSOL® produced by Israel FRUTAROM is a micellar curcumin present in Tween-80 at a concentration of about 7% (Schiborr et al., 2014). Since many countries including the EU have not approved Tween-80 for food, the preparation cannot be used for food. CurcuWin® produced by OmniActive Health Technologies (India) contains 20-28% turmeric extract (a mixture of three types of curcumin) in terms of its composition, which is suspended in a composition of 63-75% polyvinylpyrrolidone ( E 1201), a mixture of 10-40% cellulose derivatives and 1-3% natural antioxidants added (Jager et al., 2014). The preparation can produce 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 composed of 45% aromatic turmeric and curcuminoids (Antony et al., 2008). CURCUGREEN® formulations are insoluble in water and not suitable for the production of beverages. The curcumin C3 Complex® + Bioperine® produced by Sabinsa USA is a mixture of piperine and curcuminoids, which has not been specially formulated (Shoba et al., 1998). This formulation is not suitable for water dispersion. CAVACURMIN® produced by Wacker Chemie AG (Germany) contains approximately 15% curcuminoids in combination with gamma-cyclodextrin (Puroura et al., 1998). This product is dispersed in water, but at high temperatures, curcuminoids and cyclodextrins form conjugates (described earlier), and this promotes thermal decomposition of curcuminoids. In addition, the EU prohibits the use of γ-cyclodextrin in food and the preparation cannot be used in the production of food including beverages. Theracurmin™ produced by Theravalues Corp. (Japan) is a colloidal nanoformulation that contains up to 30% curcuminoids in terms of composition. The preparation additionally contains glycerin and Indian gum (Sasaki et al., 2011). The product is fully dispersed in water and is suitable for the production of beverages. However, in the case of the present invention, it cannot be used for the production of food because the EU has not approved Indian gum as an additive for food production. In addition, due to the presence of maltose and maltodextrin, the Theracurmin™ preparation has a sweet taste, which limits its use in food products. The content of maltose and maltodextrin in Theracurmin™ preparations has high glycemic index and high calorific value, which hinders its use in the production of low-calorie or special beverages, such as diabetic patients or overweight people.

According to the World Health Organization, alcohol (ethanol) is at the top of the list of risk factors that endanger the health of the population. However, since its consumption is widely licensed, the level of medical problems mainly caused by the toxic effects of ethanol metabolites is constantly increasing. In terms of toxicology, one of the well-described substances produced during alcohol metabolism is acetaldehyde. Acetaldehyde is the first product of ethanol oxidation. It is a compound 30 times more toxic, mutagenic and carcinogenic than ethanol. It has been recorded to be active in multiple organs, especially in the liver and lungs. The conversion reaction of ethanol to acetaldehyde is catalyzed by alcohol dehydrogenase (ADH), and the main enzyme that catalyzes the oxidation of acetaldehyde to low-toxic acetic acid is aldehyde dehydrogenase (ALDH). So far, 19 ALDH isoenzymes that are encoded by different loci and show a variety of substrate specificities have been identified. Although ALDH exists in many molecular forms, only the enzymes encoded by ALDH1 and ALDH2 genes are involved in the degradation of acetaldehyde. The cytosolic ALDH1 exists in many tissues including the brain, but the catalytic efficiency of this enzyme is low (Km is about 50 µM). Mitochondrial ALDH2 shows a much higher affinity for acetaldehyde (Km<5 μM; pH 7.5). These mitochondrial ALDH2 not only exist in liver cells, but also in other types of cells, such as gastric epithelial cells, Glia and neurons. The single-point nonsense mutation in the gene at position 1510 changed the base G in exon 12 to A, resulting in the loss of ALDH2 enzyme activity. ALDH2 activity is closely related to ethnic affiliation: mutations that cause loss of enzyme activity mainly occur in Eastern populations (Japan, Taiwan, China, Korea, Hong Kong, Singapore, Vietnam, Malaysia, etc.) and affect up to 50% of the population, while in Caucasians In the case of, these values fluctuate in the range of 8-10%. The phenomenon of reduced ALDH2 activity also exists in patients with liver cirrhosis, regardless of the etiology of the disease and alcohol consumption. The concentration of acetaldehyde in the blood is used as a dependent variable of alcohol consumption and alcohol dehydrogenase activity that determines the rate of elimination of this compound. It is effective for various diseases of the liver and cardiovascular system, bronchial asthma, and Alzheimer's disease. As well as the occurrence and process of a variety of cancers in the respiratory system and gastrointestinal tract, it has a significant impact. Since acetaldehyde has extremely undesirable biological effects, reducing its level in the human body as quickly and effectively as possible is related to public health. In the market of dietary supplements and medical preparations, anti-inflammatory preparations and preparations used to compensate for vitamin, electrolyte and mineral deficiencies (symptomatic effects), alleviate the effects of alcohol and acetaldehyde poisoning, and functions to support liver work and accelerate alcohol Some preventive preparations for the metabolism of its metabolites, such as Morning Recovery (MoreLabs) or GETADAY (Drink6 Iberia SLU), which are based on herbal extracts with the active substance DHM (dihydromyricetin flavone) and herbs used in Ayurvedic medicine , That is, extracts of ginseng and opuntia fig. The active substance in ReadyQ (Handok) is DHM and curcumin, and the active substance in the alcorythm® preparation (Nomi Biotech Corporation) is curcumin. Although curcumin has a definite positive effect on activating acetaldehyde metabolism, the use of curcumin is limited due to the low natural bioavailability, and in preparations containing curcumin, it is necessary to use substances that support bioavailability, such as piperine , Piperine has a significant adverse effect on the taste of the preparation and irritates the mucosa of sensitive people. Enhanced bioavailability and high stability, based on ingredients that have been approved for use in the food and pharmaceutical industries, and lack of water-dispersible curcumin formulations characterized by neutral taste and odor is based on the use of curcuminoids to develop preventive properties The formulations (including those that activate the metabolism of acetaldehyde) have severe technical limitations.

All of the above-mentioned commercially available curcumin formulations were developed to maximize the bioavailability of curcuminoids, thereby bypassing the technical aspects necessary to develop formulations suitable for aqueous dispersions and therefore suitable for the production of beverages.

Technical problem The technical problem arising from the current state of the art is that it is not possible to obtain a powdered turmeric extract formulation that can be dispersed in water (it is assumed that the turmeric extract contains a high concentration of curcuminoids, preferably a minimum of 90% w/w). Curcumin, including curcumin, demethoxycurcumin and bisdemethoxycurcumin); its dispersion in water is stable without any observable and obvious long-term sedimentation or emulsification process. After the formulation is solubilized in water, the system should have a uniform coloration. Preferably, the content of turmeric extract in the final formulation should be at least 10%. All substances used in the production of formulations should have been approved for use in food, including in the EU that has been approved for use in food in accordance with the current regulations in this region. The emulsification process should preferably be carried out at the highest room temperature (20°C±2°C) to avoid thermal decomposition of curcuminoids. Higher temperatures lead to a decrease in viscosity and therefore an increase in particle size distribution, which adversely affects the stability of the dispersion system.

Object of the present invention The object of the present invention is to overcome the specified inconvenience caused by the current state of the art. This goal is achieved by the development of a formulation solution, its production method and the product obtained by this method, so as to obtain a turmeric extract formulation with enhanced stability and enhanced homogeneity that can be dispersed in water, in which an emulsified solution and In the dry form of curcumin formulation method, all substances used in the production process have been approved for food production.

The inventors have unexpectedly discovered that the use of an inconspicuous excipient system (preferably in the form of starch octenyl succinate and cellulose derivatives) as a carrier and the use of organic solvents approved for food production ( Preferably in the form of ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, especially ethyl acetate) allows the homogenization process to form emulsions with narrow and low particle distribution (most of them have a diameter of less than 1 μm) , Preferably in the range of 0.1 to 1 μm), so as to ensure the formation of a curcumin-like dispersible turmeric extract formulation with desired physicochemical properties and enhanced bioavailability in the spray drying process.

The essence of the present invention The novel research conducted by the inventors has shown that a combination of starch octenyl succinate and a cellulose derivative (specifically, hydroxypropyl cellulose or hydroxypropyl methyl cellulose) is used as a carrier Used for the extraction of turmeric containing curcuminoids dissolved in organic solvents approved for food production (which are ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, especially ethyl acetate) The material allows the homogenization process to obtain the emulsion. In addition, the inventors have discovered that the addition of a polysaccharide solution (preferably a high-viscosity cellulose derivative, particularly preferably carboxymethyl cellulose (CMC), and the solvent is preferably water) allows to stabilize the emulsion. The obtained emulsion is stable and has a narrow and low distribution of particles with a diameter of less than 1 μm, no visible sedimentation or emulsification process, and the maintenance period is preferably not less than 12 months.

The combination of starch octenyl succinate and modified cellulose is used as a carrier for the turmeric extract dissolved in an organic solvent. Even if only a turbo vortex is used for homogenization, it can produce a narrow and low particle size distribution in the form of an emulsion. The turmeric extract formulation of the present invention. In order to obtain the turmeric extract formulation of the present invention in a dry form, preferably in a powder form, the stabilization of the emulsion system during the drying of the curcumin formulation in the form of an emulsion consists of: It is preferably produced by diluting in an aqueous solution of carboxymethyl cellulose (CMC) with a concentration of 0.001 to 1%, preferably 0.01 to 0.5%, preferably 0.10 to 0.20%, preferably 0.1-1.4% in a ratio of about 1:8 And the emulsion stabilized in this way is dried (for example by spray drying) to obtain a powder. The resulting powder-curcumin formulation in powder form is still characterized by its narrow and low particle distribution, and after the resulting powder is solubilized, it has been stabilized by carboxymethyl cellulose, thus obtaining a stable dispersion system.

Surprisingly, the result is that dispersed phase particles containing curcumin-like turmeric extract with a dispersed phase particle size of less than 1 μm can be obtained, so that a stable system can be obtained from the thermodynamic point of view of the emulsion system. The lower diameter range of the obtained particles does not affect the stability of emulsion production, but most of the obtained particles are within a certain range (preferably in the particle size range of 0.1-1 μm), which facilitates the industrial processing of such homogeneous products in the later stage. In the case where the particle size of the dispersed phase of the extract prepared in this way is so small, the sedimentation velocity calculated according to the Stokes equation will be lower V =[(2r ² g(ρ _p -ρ _f ) ]/(9η) This is exactly what is obtained from the final curcumin formulation of the present invention.

More unexpectedly, the result is that the curcumin formulation of the present invention exhibits higher bioavailability, that is, its absorption by the body is better than that of known and available commercial preparations containing curcumin, and it has the ability to pass through the intestines. The higher permeability of the tract cell layer. Unexpectedly, the result is that the curcumin formulation of the present invention provides improved properties in the regulation of liver function, which better activates liver enzymes (especially the enzymes in the dehydrogenase group, including aldehyde dehydrogenase). It also exhibits greater anti-inflammatory, anti-tumor and anti-depressant activities than known and available curcumin preparations. The following explanations and general definitions relate to the following description of preferred embodiments of the present invention.

The present invention as explained below can be suitably produced in the absence of any one or more elements, one or more restrictions not specifically disclosed herein.

As long as the term "include" or "include" is used in this specification and the scope of the patent application, it does not exclude other elements. For the purpose of the present invention, the term "consisting of" is regarded as a preferred embodiment of the terms "including" and "including". If a group containing at least a plurality of embodiments is defined below, it should also be understood to disclose a group composed of only these embodiments.

In the context of the present invention, the term "about" or "approximately" refers to the range of accuracy understood by those familiar with the art that is still sufficient to provide the technical effect of the specified feature. The term "typically" should be understood as a deviation of ±10%, preferably ±5%, relative to the specified value.

Technical terms are used according to their common meanings. If a specific meaning is used, the meaning will be described in detail in conjunction with the context in which the term is used.

Stability is understood to mean that the formed dispersion system has a dispersed phase particle size of <1 μm. The term "stability" should be understood to mean that the formed dispersion system has optical uniformity without visible emulsification or sedimentation process. If the amount of sediment at the bottom of the tube does not exceed 30% of the initial weight of the powder formulation dispersed in the water during the 20 minutes of centrifugation at 5000 rpm and at a temperature of 25°C, the system is considered stable.

Dispersion means that the system is composed of at least two immiscible phases, at least one of which is a fine powder system (dispersed phase), which is dispersed in a second phase with continuous characteristics (dispersible phase), called dispersion medium .

Solubility means the ability of a solid substance to dissolve in a liquid phase and create a dispersed system, thereby forming a heterogeneous mixture.

The present invention relates to the dry form of the curcumin formulation, preferably a water-soluble powder, so as to provide a dispersion system in which the dispersed phase has a particle size of <1 µm. Other characteristics of curcumin formulations are as follows: ● The formulation is produced without the use of ethanol or other alcohols or ketones (such as acetone) ● The taste of the blend is neutral, that is: no sweet, sour or bitter taste, that is, the unique turmeric flavor ● The formulation is produced at low temperature, which advantageously achieves the chemical stability of curcuminoids.

The present invention provides a dry form of a curcumin formulation, which comprises: -0.1-45% w/w, more preferably 25-35% w/w, especially preferably 28-32% w/w of starch octenyl succinate; -0.01-20% w/w of the cellulose derivative, which is in the form of hydroxypropyl methyl cellulose, hydroxypropyl cellulose or a mixture thereof, the amount of cellulose derivative is preferably 5-15% w /w, especially preferably 8-10% w/w; -0.01-20% w/w turmeric extract, wherein the turmeric extract contains at least 90% w/w curcuminoids, including curcumin, demethoxycurcumin and bisdemethoxycurcumin , The amount of the turmeric extract is preferably 5-15% w/w, and the amount of the turmeric extract is particularly preferably 8-10% w/w; -0.1-10% w/w, preferably 3-5% w/w, especially preferably 3.8-4.2% w/w β-glucan; -10-70% w/w amount, preferably 30-60% w/w amount, particularly preferably 48-52% w/w amount, cellulose derivatives with a viscosity of more than 5600 mPas, of which the viscosity is more than 5600 The cellulose derivative of mPas is selected from carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, ethyl methyl cellulose, cross-linked cellulose gum, cellulose with a viscosity of more than 5600 mPas The derivative is preferably carboxymethyl cellulose; Among them, at least 90%, more preferably at least 95%, and preferably at least 99% of the particles have a diameter of less than 1 µm.

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

The present invention also relates to a method for producing a curcumin formulation in a dry form, which comprises the following steps: a) Dissolve turmeric extract with a minimum content of 90% curcuminoids in organic solvents approved for food production, preferably in ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, especially Better dissolved in ethyl acetate; b) The dissolved turmeric extract obtained from step a) is added to a solution of a carrier, the solution of which contains starch octenyl succinate and a cellulose derivative (the cellulose derivative is preferably a hydroxy Propyl cellulose, hydroxypropyl methyl cellulose) polymer dissolved in a polar solvent, preferably a mixture of water, where cooling is preferably applied, wherein during the addition of the dissolved turmeric extract, the polymer mixture The temperature falls within the temperature range of about 5°C to about 10°C (the use of higher temperatures affects the viscosity of the continuous phase, thus causing the resulting emulsion system to have an unfavorable particle size distribution, that is, the diameter exceeds 1 μm); c) Homogenize the mixture obtained in step b) 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, thus resulting in an unfavorable particle size of the resulting emulsion system Distribution, that is, the diameter exceeds 1 μm); d) The emulsion obtained in step c) is diluted with an aqueous solution of β-glucan (which is a polymer that positively affects the stability of the dispersion system). Preferably, the concentration of β-glucan is 1-8% (preferably from Oats or barley), at low viscosity (preferably within the range of 40-200 mPas), further homogenize briefly; e) Stabilize the emulsion obtained in step d): by combining it with a high viscosity (>5600 mPas) cellulose derivative (preferably carboxymethyl cellulose, methyl cellulose, ethyl cellulose, 0.1 to 1.4% aqueous solution of hydroxypropyl cellulose, ethyl methyl cellulose, cross-linked cellulose gum, more preferably carboxymethyl cellulose with high viscosity) combined, by dilution, preferably not less than 1 : 6. It is better to dilute at a ratio of not less than 1:8, and stir it mechanically throughout; f) drying the stabilized emulsion obtained from step e) to provide a curcumin formulation in a dry form, wherein more than 90%, preferably more than 95%, preferably more than 99% of the resulting particles have a particle size of less than about 1 µm Diameter size, More preferably, at least 90%, more preferably at least 95%, and even more preferably at least 99% of the particles have a diameter in the range of 0.1 to about 1 µm.

In a preferred production method of curcumin formulations, the organic solvent used to dissolve the turmeric extract in step a) is ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, and more preferably ethyl acetate. In a preferred method, the polar solvent used to dissolve the carrier in step b) is water.

In a preferred production method of curcumin formulations, the cellulose derivative used to produce the carrier is hydroxypropyl cellulose, hydroxypropyl methyl cellulose or a mixture thereof, Among them, the preferred mixing ratio of hydroxypropyl cellulose to hydroxypropyl methyl cellulose falls within the range of a ratio as high as 10:1.

In a preferred production method of curcumin formulations, in step d), the emulsion is diluted with 1-8% β-glucan (preferably β-glucan derived from oats or barley, or a mixture thereof).

In a preferred production method of curcumin formulations, the cellulose derivative with high viscosity is 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 0.1 to 1.4% CMC at the concentration of w/w.

In the preferred production method of the curcumin formulation, the carrier solution is obtained by mechanically mixing the polymer, wherein the mixing is preferably carried out for not less than 10 hours, preferably about 12 hours.

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

In the preferred production method of curcumin formulations, the drying in step f) is carried out by spray drying, wherein the inlet temperature of the dryer is in the range of 110-160°C, more preferably about 150°C, and the outlet temperature does not exceed 65°C, preferably not more than about 55°C. It was unexpectedly found that a low temperature in the range of 2-20°C (preferably about 5°C to about 15°C, more preferably about 5°C to about 10°C, more preferably about 5°C to about 10°C is used in stages b) and c). 7°C, or in a water bath, preferably in an ice bath) can produce an emulsion with the desired particle size range. Higher temperature affects the viscosity of the continuous phase, thus resulting in an unfavorable particle size distribution with a diameter of more than 1 μm in the resulting emulsion system.

In a preferred embodiment of the method for producing a curcumin formulation in a dry form intended to provide a stabilized emulsion, a polymer carrier of starch octenyl succinate and cellulose derivatives is used, and the stabilized emulsion is It is characterized by a narrow and small distribution of particles in the diameter range of about 0.1 to about 1 µm, with no obvious sedimentation or emulsification process. The carrier system consists of a mixture of starch octenyl succinate and cellulose derivatives (preferably with a viscosity in the range of 40-200 mPas, especially hydroxypropyl cellulose, hydroxypropyl methyl cellulose) ( Preferably, the ratio of 0.1 to 30 g starch octenyl succinate (such as PURITY GUM 2000 ^® ) to 0.02 to 20 g hydroxypropyl cellulose or hydroxypropyl methyl cellulose or a mixture thereof is 0:0 To 10:1 ratio) made. After the polymer is mechanically mixed, it is dissolved in a polar solvent in a weight ratio of 1:5 to 1:25 (preferably 1:10), and the polar solvent is particularly preferably water. The resulting mixture is mechanically mixed to dissolve and combine the polymer. For proper solubilization and dissolution and combination of the polymer, it is preferably not less than 10 hours, preferably about 12 hours.

Separately prepare a solution of turmeric with a minimum curcuminoid content of 90% in an organic solvent. The organic solvent has been approved for food production, preferably ethyl acetate. The solution is obtained by dissolving turmeric extract (at least 90% curcuminoids) in a ratio of 0.01 to 3 g in an amount of 0.19 to 60 ml of organic solvent, which has been approved for food production, preferably Ethyl acetate. The dissolved curcuminoid extract is added to the polymer mixture (polymer ratio 2:3 w/w) and homogenized using, for example, a mechanical homogenizer. Homogenization can be performed continuously in a variety of ways, such as by gradually increasing the rotation speed, but it is best performed in two steps: first, a pre-emulsion is generated, and then a proper homogenization is performed. The two-step production of the emulsion is carried out at a rotation speed in the range of, for example, 5 000 rpm to 15 000 rpm, preferably at a rotation speed of 10,000 rpm of the operating element, until the pre-emulsion is formed. The entire mixture is cooled from the moment the curcuminoids are introduced into the polymer mixture, for example in an ice water bath. The temperature of the polymer mixture should preferably not exceed about 10°C and preferably should not be lower than about 5°C at the moment when the extract dissolved in ethyl acetate is introduced. After the pre-emulsion is produced, use a homogenizer (preferably a turbo vortex homogenizer) and process parameters in the range of 20 000-24 000 rpm (preferably 22,000 rpm) to properly homogenize it for 3 minutes, and then use 0.5 to Add water or a low viscosity (about 40-200 mPas) β-glucan aqueous solution in an amount of 210 ml (in a ratio of 1:0.25 w/w), preferably a 1-8% aqueous solution of β-glucan, Preferably, it is β-glucan derived from oats or barley, and is further homogenized, for example, for 1 minute. The emulsion prepared in this way is immediately combined with a polysaccharide solution (preferably a cellulose derivative with high viscosity, preferably a 0.1-1.4% aqueous solution of carboxymethyl cellulose (CMC) with high viscosity). This technical treatment can produce stable formulations, that is, a particle size distribution with a dispersed phase diameter of <1 µm (at least 90% particles, preferably 95%, and most preferably more than 99% particles in the dispersed phase). The emulsion is diluted with water in a ratio of not less than 1:6, more preferably not less than 1:8, and the whole process is mechanically stirred with a stirring rod or a better propeller stirring rod, and the stabilized emulsion is dried to provide a dry form and a relatively The best curcumin formulation in powder form. Drying can be carried out by various methods known in the current state of the art, but spray drying preferably uses a dryer inlet temperature within the range of 110-160°C (preferably 150°C) and an outlet temperature not exceeding 65°C (preferably 55°C) Temperature is carried out.

The present invention also provides a curcumin formulation in a dry form, which is obtained by the curcumin formulation production method of the present invention.

The formulations obtained as described above are only based on ingredients that have been approved for use in the food industry under EU law. At the same time, since only plant ingredients are used in the production process of the formulation and the use of ethanol as a solvent is completely eliminated, the formulation can be certified according to the HALAL program, so that the food product it is used for is expected to be used in the Muslim country market. , Because it does not use ethanol as a solvent in the production process of the formulation, its sales can be realized. The formulation is characterized by bright orange-yellow, which is the natural color of turmeric.

Different from the known turmeric formulations available on the market, the turmeric formulations, food products based on them, and emulsions made therefrom of the present invention are characterized by a completely neutral taste-they do not have the unique bitter taste of turmeric extracts and do not It has a sweet aftertaste unique to the use of maltodextrin and/or maltose, which obviously increases its use in the food and pharmaceutical industries and the production of dietary supplements. The dry form and aqueous solution form of the formulation exhibit stability, allowing it to be effectively used in a wide variety of food products.

The present invention relates to a beverage concentrate containing the curcumin formulation of the present invention.

The preferred beverage concentrate further comprises at least one of the following: -Stabilizers and thickeners with a concentration of 0-28% w/w, preferably 0-20% w/w, preferably glycerin and/or xanthan gum; -0-5% w/w antioxidant and acid regulator, preferably ascorbic acid; -0-5% w/w acid regulator, preferably citric acid; -0-80% w/w electrolytes and sweeteners, preferably glucose; -Vitamin B, preferably selected from thiamine, niacin, pyridoxine, folic acid and riboflavin; -Preservatives, preferably benzoic acid, sodium benzoate, potassium sorbate or mixtures thereof.

The present invention also relates to a beverage comprising the curcumin formulation of the present invention or obtained by diluting the beverage concentrate of the present invention.

Preferred beverages are juice-based beverages, water, milk beverages, and plant beverages that replace cow milk.

The preferred beverage is a functional beverage that supports liver function, wherein preferably, the concentration of curcumin in the beverage is 0.01-0.1% w/w.

The present invention relates to a dietary supplement comprising the curcumin formulation of the present invention, which is preferably in liquid form, and the supplement is preferably consumed at a dose corresponding to 0.2 to 2.0 g of curcuminoid per kilogram of an individual's body weight.

Preferably, the dietary supplement supports liver function, and preferably, it activates the action of liver enzymes (preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase).

Better dietary supplements support anti-inflammatory effects and are intended to be used for anti-inflammatory prevention and reduction of inflammation, including prevention of complications and severe disease course of viral infections, including coronavirus infections, including SARS-CoV-2, preferably when viral infections occur It is used during periods of increased rate, preferably in the form of capsules, which contain the curcumin formulation of the present invention in a dry form.

The preferred dietary supplement is in liquid form and contains the formulation of the present invention in an amount that can provide 0.01-0.1% w/v curcumin, 1-20% w/v juice concentrate, 2-10% w/v sweetness Flavoring agent, stabilizer and thickener with a concentration of 2-10% w/v.

The present invention also relates to a pharmaceutical composition comprising the curcumin formulation of the present invention and pharmaceutically acceptable additives.

The present invention also relates to the use of a pharmaceutical composition comprising the curcumin formulation of the present invention as a medicine.

Preferably, the composition is used as a medicine for regulating liver function, a medicine with anti-inflammatory, anti-cancer and anti-depressant effects.

Preferably, the composition is used as a medicine for regulating liver function and activating liver enzymes (preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase).

The present invention also relates to a pharmaceutical composition containing the curcumin formulation of the present invention, which is used as a stabilizer for liver function, a medicament for supporting the liver, and activating liver enzymes (preferably dehydrogenase enzymes, preferably aldehyde deoxidizers). Hydrogenase) acting as an agent.

The present invention also relates to a pharmaceutical composition comprising the curcumin formulation of the present invention, which is used as an anti-inflammatory agent for anti-inflammatory prevention and reduction of inflammation, and preferably prevents viral infections (including coronavirus infections, Including the complications and severe course of SARS-CoV-2), wherein it is preferably used in the time period when the incidence of viral infections is increasing.

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

Preferred dyes are food dyes used in medicine, cosmetics, food, and animal feed.

The present invention also relates to the use of the curcumin formulation according to the present invention, which is used as a functional additive in beverages, as a dye, as an active ingredient in a dietary supplement, as an active ingredient in a pharmaceutical composition, and as a food Additives, used as feed additives.

The present invention also relates to the use of the curcumin formulation according to the present invention, which is used as an anti-alcoholic agent, as an agent for preventing and/or alleviating hangover symptoms, or as an activating liver enzyme (preferably one of dehydrogenases) Enzymes, preferably aldehyde dehydrogenase) agents.

It is extremely important that due to the improved bioavailability, the beverage/emulsion or composition produced based on the turmeric formulation of the present invention does not need to add piperine, which is necessary for the improvement of the bioavailability of the turmeric formulation known in the current state of the art .

The inventors have found that the formulation of the present invention can be successfully used to produce a stable concentrate containing a 5 to 20% concentration of the formulation and preferably a final concentration of a 5 to 20 times concentrated concentrate ( 0.1 to 2.0% w/w) curcumin, used to produce beverages in which curcumin is an active substance, especially functional beverages, especially beverages that have an activating effect on the metabolism of acetaldehyde.

The formulation of the present invention can be used to produce functional dietary supplements or pharmaceutical preparations in which curcumin is one of the active substances due to its high stability, no change in the biological activity of curcuminoids and improved bioavailability. Preferably, such preparations include those that regulate liver function, activate liver enzymes (including dehydrogenase enzymes, including aldehyde dehydrogenase), and have anti-inflammatory, anti-cancer and anti-depressive effects.

In a preferred embodiment, the formulation is used to produce functional beverages in the form of dietary supplements, which support liver function, especially in activating acetaldehyde degrading enzymes and preventing alcohol consumption by reducing the concentration of acetaldehyde in the blood. The negative aspects of the field. In a preferred embodiment, the formulation is used at a concentration corresponding to the final concentration of curcumin such as 0.01-0.1% w/w level.

Due to the increased bioavailability of curcumin in the form of the formulation, the use of the formulation allows the functional drink concentrates and functional beverage formulations of the present invention to exclude the bioavailability-supporting substances used in commercially available formulations. For example, the following forms: black pepper in the form of piperine (ReadyQ, alcoholythm® preparations) that adversely affect the taste of the preparation due to strong and burning taste; substances that act as irritants; and additionally induce enzyme activity that accelerates the decomposition of acetaldehyde Such as DHM (dihydromyricetin flavone) (ReadyQ, Morning Recovery formulation).

The concentrate may also contain any combination of excipients, which includes at least one of the following substances, such as: -Stabilizers and thickeners with a concentration of 0-20% w/w, preferably 0-28% w/w, preferably glycerin and/or sanxian gum, -0-5% w/w antioxidant and acid regulator, preferably ascorbic acid, -0-5% w/w acid regulator, preferably citric acid, -0-80% w/w electrolytes and sweeteners, preferably glucose.

Concentrates can also contain vitamin B (including thiamine, niacin, pyridoxine, folic acid and riboflavin). Considering the synergistic effect of excessive stability and the concentration value of the concentrate, the concentration of various vitamins does not exceed the highest reference diet Twice the intake.

The concentrate can contain any combination of preservatives, which contains at least one of the following substances (assuming that after the concentrate is diluted to the target concentration, the total concentration of preservatives will not exceed 0.2% w/w), the concentrate can Contains preservatives such as: 0-2% w/w concentration of benzoic acid, 0-2% w/w concentration of sodium benzoate, 0-2% w/w concentration of potassium sorbate, or mixtures thereof.

The formulation of the present invention has proven to be particularly preferred as a yellow dye for dyeing water-based food and medical and cosmetic products in the food, medicine, and cosmetic industries. Because the formulation of the present invention has a completely neutral taste, the use of excipients permitted in the food industry, the natural color produced by the unblocked chromophore group, and the high stability of the aqueous solution of the formulation of the present invention Therefore, the aqueous solution of the formulation of the present invention can be used with a sufficient amount of target concentration, for example, as a dye E100 for the production of beverages (including beverages based on natural or rehydrated fruit juices with a pH in the range of 3.0-7.0), for making cakes , Pastry dyeing, lozenges and syrups, and cosmetics (such as shampoos, creams, facial masks).

In non-traditional medicine and nutrition based on the Far Eastern medical tradition, "golden milk" (ie, a product obtained from the water extract of turmeric rhizome in cow's milk (ruminant milk)) or vegetable milk substitute (based on Beverages obtained from cereals, nuts, legume seeds) are used as beverages to enhance the body’s immunity and counteract inflammation. The peculiar turmeric bitter and burning taste of beverages hinders the use of this preparation as a preventive and therapeutic agent. Another disadvantage of the beverage is that the curcuminoid content in the water extract of turmeric rhizome is relatively low and the bioavailability is low.

Due to the completely neutral taste, the use of excipients allowed in the food industry, and bioavailability, the inventors have found that the use of the formulation of the present invention to produce beverages (especially dairy beverages) can overcome the technical status quo. Technical problems arising. The formulations of the present invention are used in animal milk (preferably ruminant milk, particularly preferably cow, buffalo, sheep or goat milk) and in vegetable milk substitutes in the form of beverages (obtained from cereal grains, nuts, legume seeds) (Preferably oats, millet, hemp, cashews, pecans, almonds, soybeans), including beverages containing additives and excipients, and supplements in the form of calcium salts, thickeners, stabilizers and sweeteners ) To form a stable suspension. In a preferred embodiment, the milk is dairy milk, almond, soybean or oatmeal beverage, and the concentration of the formulation in the final product is 0.01%-1.0%, particularly preferably 0.1%. After dissolving the formulation, the product is subjected to a pasteurization process.

The curcumin formulation in the form of the formulation of the present invention can be used as a food industry, dye industry, feed additives, and nutrition due to its completely neutral taste, excellent physical and physiological properties (including excellent bioavailability) Pharmaceuticals, functional foods, medicinal preparations (for example, for regulating liver function), excipients permitted in medicine with anti-inflammatory, anti-cancer and anti-depressant effects, and other uses where curcumin may be used. The inventors of the present invention have discovered that the formulation of the present invention avoids the technical problems arising from the current state of the art and works perfectly in the above-specified uses and examples.

Examples The following examples are presented only to illustrate the present invention and clarify its various aspects and are not intended to be limiting, and should not be equivalent to its full scope, which is defined in the scope of the appended application. In the following examples, unless otherwise specified, the standard materials and methods used in the field are used, or the manufacturer's instructions for specific materials and methods are used.

Example 1 Production of curcumin formulations in powder form 6 g starch octenyl succinate (e.g. PURITY GUM 2000 ^® ) and 2 g hydroxypropyl methylcellulose (cellulose with a viscosity in the range of 40-200 mPas derivative). After the polymer was mechanically mixed, it was dissolved in 100 ml of polar solvent water. The resulting mixture is mechanically mixed to dissolve and combine the polymers. The inventors unexpectedly found that this is done after not less than 10 hours (preferably 12 hours). At the boiling temperature of ethyl acetate, 1.6 g of turmeric extract (curcuminoid content of at least 90%) is dissolved in 30 ml of this solvent. Immediately after dissolution, the dissolved curcumin-like extract is added to the polymer mixture and homogenized using a mechanical homogenizer at a rotation speed of 10,000 rpm of the operating element until the moment when the pre-emulsion is formed, that is, the obtained Homogeneous mixture by visual assessment. The entire mixture is cooled in an ice-water bath from the moment the curcuminoids are introduced into the polymer mixture. The temperature is maintained in the range of 5-10°C, preferably about 7°C. After the pre-emulsion is produced, it is properly homogenized with a turbo vortex homogenizer and the following process parameters: 22,000 rpm for 3 minutes, and then 50 ml of water or 1.5% oats with low viscosity (40-200 mPas) are added Or an aqueous solution of barley β-glucan and further homogenize for 1 minute. The emulsion prepared in this way was immediately combined with a high viscosity (>5600 mPas) 1% carboxymethyl cellulose (CMC) aqueous solution. Using a propeller stir bar, the emulsion was diluted in 1 l of the solution prepared in this way by mechanical stirring. For emulsion solutions, determine the percentage distribution of the particle size of the sample within a specific size category. Results similar to those of Example 2 were obtained (more than 99% of the particles have a size in the range of about 0.1 to about 1 µm).

Using a dryer inlet temperature of about 150°C and an outlet temperature of about 55°C, the emulsion solution prepared in this way was subjected to classic spray drying.

For the obtained curcumin formulation in powder form, after its dissolution, the size of the obtained particles and their size distribution were measured ( Table 1 , Figure 2 ). Table 1. The percentage distribution of the particle size of the sample (the powder after dissolution) in a specific size category. serial number Lower limit of range (µm) Average particle size in the range (µm) Particle % serial number Lower limit of range (µm) Average particle size in the range (µm) Particle % serial number Lower limit of range (µm) Average particle size in the range (µm) Particle % 1 0 0.025 0 twenty three 1.24 1.34 0 45 35.56 38.495 0 2 0.05 0.055 0 twenty four 1.44 1.56 0.07 46 41.43 44.85 0 3 0.06 0.065 0 25 1.68 1.815 0.31 47 48.27 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 30 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 20 0.78 0.845 0 42 22.49 24.345 0 64 647.41 700.82 0 twenty one 0.91 0.985 0 43 26.2 28.365 0 65 754.23 816.45 0 twenty two 1.06 1.15 0 44 30.53 33.045 0 66 878.67 878.67 0

It was unexpectedly found that the formulation obtained according to the above description has a particularly preferred distribution of particle sizes in the diameter range of about 0.1 to about 1 µm (more than about 95% particles, preferably more than 97%, preferably 100% particles). ) Is a feature, in which the curcumin-like content is in the range of (0.01% to 15%), which enhances its dispersion characteristics in an aqueous environment, so that an emulsion with a high degree of homogeneity can be obtained.

The quantitative and qualitative composition of the dried (up to 5% humidity) formulation made according to the above example is as follows: 29.5% w/w starch octenyl succinate 9.8% w/w hydroxypropyl methylcellulose (as a cellulose derivative) 7.9% w/w turmeric extract (minimum 90% curcuminoids) 3.7% w/w β-glucan 49.1% w/w carboxymethyl cellulose; Among them, after dissolution, more than 97% of the particles have a size in the range of about 0.1 to about 1 µm.

The formulation is characterized by an intense orange-yellow color, has a neutral taste and is easily dissolved in water to form a homogeneous suspension.

Example 2 The production of the curcumin formulation in powder form is the same as the formulation of the mixture obtained in Example 1. The difference is:-After the polymer is mechanically mixed, it is dissolved in a polar solvent, 90 ml of water;-2 g Turmeric extract (minimum 90% curcuminoids content) is dissolved in 35 ml of a mixture of ethyl acetate and acetone at a ratio of 5:1 at the boiling temperature of the mixture.

The resulting mixture is mechanically mixed to dissolve and combine the polymers for not less than 10 hours, preferably 12 hours. Immediately after dissolution, the dissolved curcuminoid extract was added to the polymer mixture and homogenized using a mechanical homogenizer at a rotation speed of 10 000 rpm of the operating element until a pre-emulsion was formed, that is, a visual evaluation Homogeneous mixture. The entire mixture is cooled in an ice water bath when the curcuminoids are introduced into the polymer mixture. The temperature is maintained in the range of 5-10°C, preferably about 7°C. For the obtained curcumin formulation in the form of an emulsion, the size of the obtained particles and their size distribution were measured ( Table 2 , Figure 1) . The inventors have unexpectedly discovered that the formulation obtained according to the above description is characterized by a particularly preferred distribution of particle sizes in the diameter range of about 0.1 to about 1 µm (more than about 95% particles, preferably 100% particles) , The content of curcuminoids is in the range of (0.01% to 20%), which enhances its dispersion properties in water environments and can obtain emulsions with high homogeneity. Table 2. The percentage distribution of the particle size of the sample (emulsion) within a specific size category. serial number Lower limit of range (µm) Average particle size in the range (µm) Particle % serial number Average particle size in the range (µm) Average particle size in the range (µm) Particle % serial number Average particle size in the range (µm) Average particle size in the range (µm) Particle % 1 0 0.025 0 twenty three 1.24 1.34 0 45 35.56 38.495 0 2 0.05 0.055 0 twenty four 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 30 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 18 0.58 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 20 0.78 0.845 0 42 22.49 24.345 0 64 647.41 700.82 0 twenty one 0.91 0.985 0 43 26.2 28.365 0 65 754.23 816.45 0 twenty two 1.06 1.15 0 44 30.53 33.045 0 66 878.67 878.67 0

The quantitative and qualitative composition of the dried (up to 5% humidity) formulation made according to the above example is as follows: 28.9% w/w starch octenyl succinate; 9.6% w/w hydroxypropyl methylcellulose; 9.6% w/w turmeric extract (minimum 90% curcuminoids); 3.6% w/w β-glucan; 48.3% w/w carboxymethyl cellulose; Among them, in this composition in the form of an emulsion, 100% of the particles have a size in the range of about 0.1 to about 1 µm.

For the resulting curcumin formulation in powder form, the size of the resulting particles and their size distribution after dissolution are determined. After dissolution, more than 98% of the particles have a size in the range of about 0.1 to about 1 µm. Therefore, a distribution similar to that of Example 1 was obtained.

The formulation is characterized by a strong orange-yellow color, has a neutral taste and is easily dissolved in water to form a homogeneous suspension.

Example 3 Production of curcumin formulation in powder form. The formulation of the mixture was obtained as in Example 1. The difference is:-After the polymer is mechanically mixed, it is dissolved in 90 ml of polar solvent water;-The following process parameters are used for all The prepared emulsion solution is freeze-dried: drying pressure 0.5 mbar, storage temperature program: -20°C: 0 to 2 hours, 20°C: 2-3 hours, 20°C: 3-18 hours, 40°C: 18-19 hours, 0.2 mbar pressure: 18-19 hours, 40°C: 19-24 hours, until the end of the process. For the obtained curcumin formulation in the form of emulsion and powder, after dissolving the powder, the size and size distribution of the obtained particles are measured. Results with distributions similar to those in Examples 1 and 2 were obtained.

The inventors have unexpectedly discovered that the formulation obtained according to the above description has a particularly preferred distribution of particle sizes in the diameter range of about 0.1 to about 1 µm (more than about 95% particles, preferably 100% particles). Characteristic, the content of curcuminoid is in the range of (0.01% to 20%), which enhances its dispersion characteristics in water environment, so that an emulsion with high homogeneity can be obtained.

The quantitative and qualitative composition of the dried (up to 5% humidity) formulation made according to the above example is as follows: 26.5% w/w starch octenyl succinate 9.8% w/w hydroxypropyl methylcellulose 16.4% w/w turmeric extract (minimum 90% curcuminoids) 3.7% w/w β-glucan 43.6% w/w carboxymethyl cellulose Among them, after dissolution, more than 97% of the particles have a size in the range of about 0.1 to about 1 µm.

The formulation is characterized by a strong orange-yellow color, has a neutral taste and is easily dissolved in water to form a homogeneous suspension.

Example 4 Aqueous solution of curcumin formulation The curcumin formulation in powder form prepared according to Examples 1-3 was dissolved in water according to certain concentrations and its physicochemical properties were analyzed. Based on the results obtained, it is found that the formulation forms a stable suspension in a concentration range of 0.01% to 30% w/w in an aqueous environment. The concentration is preferably 0.05-10.00%, particularly preferably 0.5%-1.5% w/w. At the specified concentration, especially the preferred concentration, the formulation formed an optically homogeneous suspension at room temperature after 24 hours, and no visible precipitate formation was observed.

The aqueous solution of the formulation at a better concentration is characterized by chemical stability (based on the color change indicating the oxidation process of the active substance and the color change in the acidic environment within the pH range of equal to or higher than 3.0 and lower than 7.0 As a result, research has been conducted so that it can be used in food production.

In the aqueous solution of the formulation, the stable period of time under accelerated aging conditions is at least 12 months, as shown in the aging test (according to the guideline ICH Q1A (R2) Stability Testing of New Drug Substances and Drugs-EDQM Recommendations).

In order to verify the stability of the suspension and determine the degree of sedimentation, a test consisting of the following was performed: In the REF 11778 rotor of the MPW380R centrifuge manufactured by MPW, at a speed of 5000 rpm, 0.5% concentration of curcumin was added to 15 ml of distilled water. The suspension was centrifuged at 25°C for 20 minutes.

Compare the following suspensions: a) Test formulations of Examples 1 to 3 b) Turmeric extract containing 95% curcuminoids c) CAVACURMIN formulation (Wacker Chemie AG) and CurQfen formulation (Akay Group Ltd.)

The suspension was normalized to a total concentration of curcumin such as 0.5% w/w. Table 3. Stability results of the developed formulations and similar commercially available formulations. P1, P2, P3-formulations made according to Examples 1, 2, and 3, respectively. Test product Sample concentration (the sample volume for stability test is 15 ml) Concentration of curcuminoids in aqueous suspension (15 ml) After centrifugation at 50,000 rpm at 25°C and after 20 minutes, the substance in the form of a precipitate% The formulation of the present invention P1 (7.9% curcuminoids*) P2 (9.6% curcuminoids*) P3 (16.4% curcuminoids*) 949.33 mg/15 ml water 781.22 mg/15 ml water 457.3 mg/15 ml water 0.5% 0.5% 0.5% 20.4% 19.9% 19.5% CAVACURMIN ® (16.4% curcuminoids*) 457.3 mg/15 ml water 0.5% 100% CurQfen ® (47.1% curcuminoids*) 159.2 mg/15 ml water 0.5% 95% Turmeric extract (% curcuminoids*) 81.5 mg/15 ml water 0.5% The extract floats on the water surface *Under λ=420 nm, the content of curcuminoids is measured by spectrophotometry. The solution used to extract curcuminoids from the formulation and the spectrophotometric measurement is water:acetone 30:70 v/v.

The results clearly show that the suspension of the formulation of the present invention is more stable.

Example 5 Bioavailability of the aqueous suspension of the formulation The inventors conducted a bioavailability study on the suspension of the formulation of the present invention in water. Using the Caco-2 cell line, according to the protocol described in Frank, J., 2017, the cell model that absorbs and penetrates through the upper epithelial cell layer of the intestinal epithelial tissue was tested by an in vitro method. In the study, the bioavailability of turmeric extract (the test formulation of the present invention) was compared with the preparations CAVACURMIN® (Wacker Chemie AG) and CurQfen® (Akay Group Ltd.). The bioavailability of the suspension is tested, standardized to a concentration of-10 μg/ml relative to the final curcuminoids content. Table 4. Absorption and permeability of curcumin-like formulations through the Caco-2 cell monolayer within 60 minutes. P1, P2, P3-formulations made according to Examples 1, 2, and 3, respectively. Initial concentration of curcuminoids Time ( minutes ) % Of curcumin absorbed by cells % Curcumin that has penetrated through the cell monolayer CurQufen® 10 μg/ml 60 39.64% ± 0.22% 0.66% ± 0.04% CAVACURMIN® 10 μg/ml 60 21.61% ± 0.15% 0.00% ± 0.00% The formulation of the present invention P1 P2 P3 10 μg/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%

Studies clearly show that compared with CAVACURMIN® preparations and CurQufen® preparations, the bioavailability of the formulation of the present invention is enhanced. The level of absorption of the formulation of the present invention by cells is more than 2 times higher than that of CAVACURMIN® preparations and more than 10% higher than that of CurQfen® preparations (Research shows that the bioavailability of CurQfen® preparations is 45 to 270 times higher than that of natural turmeric extract-Kumar et al. , 2016). At the same time, the permeability of the formulation of the present invention through the cell monolayer is 1.5% higher than that of the CurQfen® formulation, as measured within 60 minutes.

Example 6 Concentrates for the production of functional beverages and dietary supplements , which use a formulation made according to one of the methods described in Examples 1 , 2 and 3 to prepare a 5-fold concentrated concentrate, which comprises: According to Example 1 The prepared formulation of the present invention: 5% w/w, Sanxian gum: 1.1% w/w; Glycerin: 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.

Confirmed by pH and microbiological tests, the concentrate exhibits high stability. During storage for up to 6 months, no changes in pH or growth of mesophilic bacteria, molds and yeasts were found. The color of the concentrate and other organoleptic properties are also unchanged. In order to prepare the final beverage, it is preferable to reconstitute juice with water or concentrate, preferably tropical juice, preferably mango, peach or orange juice or a mixture of these juices, and dilute the concentrate in a ratio of 1:4 (concentrate: liquid) . Similarly, the concentrates were prepared using the formulations prepared according to Example 2 (prepared formulation using 7% w/w) and Example 3 (prepared formulation using 10% w/w).

Example 7 Use of the formulation of the present invention as a dye The formulation of the present invention is used as the food dye E-100 (curcumin) according to the concentration allowed in the food law, that is, 100 in juice-based beverages mg/l (kg), 150 mg/l (kg) in milk-based products. a) Mix 5 times concentrated juice concentrate (preferably orange, peach, pineapple, especially orange) with the formulation made according to Example 1 , so that the final concentration of the formulation in the final product is 0.01% w /v, replenish the mixture with water to obtain a juice of 1 times the final concentration. b) Add the formulation of the present invention to fruit yogurt (preferably peach or mango flavored) to obtain a final concentration of 0.015% w/w. The resulting mixture is stirred and homogenized.

Example 8 formulations for the production of invention) A 10-fold concentrated mixture of milk cows based on the curcumin-containing milk beverage or milk beverage substituted plant with the use of a formulation according to Example 1 was prepared such that the final product The final concentration of the formulation is 0.015%. Replenish the mixture with water to obtain 1 times the final concentration of milk.

The 10-fold concentrated plant beverage concentrate (preferably soybean, almond or oatmeal beverage) that replaces cow's milk is mixed with the formulation made according to Example 1 , so that the final concentration of the formulation in the final product is 0.01%. Replenish the mixture with water to obtain a beverage of 1 times the final strength.

Example 9 Functional Drink A functional drink is produced, which supports liver function by activating liver enzymes (preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase) before or during drinking. a) Mix 5 times concentrated juice concentrate (preferably lemon, grapefruit, mango, passion fruit, orange, peach, pineapple, especially orange) with the formulation made according to Example 1 to make the final product The final concentration of the formulation in is 0.01% w/v, and the mixture is supplemented with water to obtain a juice of 1 times the final concentration. b) Mix 5 times concentrated fruit juice concentrate (preferably lemon, grapefruit, mango, passion fruit, orange, peach, pineapple) with the formulation prepared according to Example 1 , so that the final formulation concentration in the final product is 0.01% w/v, supplement the mixture with water to obtain a juice of 1 times the final concentration, then add sweetener (glucose) to the mixture until the concentration in the final product is 4% and add citric acid until the concentration in the final product is 0.4 %, and then make up enough to obtain a double-diluted juice.

Fruit juice-like functional drinks can be consumed in the form of (not limited to) equivalent to dilute alcohol-based mixtures or sipped alcohol juices to activate acetaldehyde metabolism, preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase, And to reduce the effects of drinking caused by acetaldehyde poisoning.

Example 10 Dietary supplements in the form of capsules. Dietary supplements in the form of capsules that are intended to be ingested before or during drinking were developed to activate liver enzymes (including dehydrogenase enzymes, especially aldehyde dehydrogenase). Function to support the liver. The formulation prepared according to Example 1 was encapsulated in a pharmaceutically acceptable gel capsule at a dose of 500 mg according to the formula. In an optional variation, in addition to the formulation, the gel capsule is also added with an adjuvant and a filler. Preferably, the adjuvant is β-glucan at a dose of at most 100 mg, and the filler is Cellulose. Preferably, the capsule is made of a gel material that dissolves in the small intestine, and the material is preferably a polymer of plant, microbial, or synthetic origin that meets HALAL and vegetarian certification criteria. For adults weighing up to 85 kg, a single gel capsule is a single-dose supplement that is taken during the 60-minute period before the start of drinking or during drinking. Ingesting these capsules (especially before drinking alcohol) activates the action of liver enzymes (including enzymes such as dehydrogenases), so that the ingester of curcumin formulations with enhanced bioavailability will affect the individual's consumption of ethanol Increased tolerance.

Example 11 Preparation of dietary supplements in liquid form can support liver function, activate liver enzymes (preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase), and liquid dietary supplements taken before or during drinking Agent.

In a container, preserve the mango juice concentrate with water, glucose, glycerin, three gum, citric acid, vitamin B, thiamine, niacin, pyridoxine, folic acid, riboflavin, and sodium benzoate via a vortex mixer. Mixture with potassium sorbate and the formulation according to Example 1 (curcuminoid final concentration is 0.1% w/v) and natural passion fruit flavor. For adults weighing up to 85 kg, after thoroughly mixing the ingredients, ^{pour the prepared liquid dietary supplement with a density of 1.02 g*cm 3-1} into a 100 ml bottle to form a single-dose supplement. It is ingested within 60 minutes before the start of drinking or during drinking.

The final concentrations of the ingredients in the ready-to-use liquid dietary supplement are: -6% w/v mango juice concentrate -0.001% w/v natural passion fruit flavor -8% w/v glucose -0.226% w/v Sanxian Gum -5.333% w/v glycerin (99.5%) -0.5% w/v citric acid -0.1% w/v potassium sorbate -0.1% w/v sodium benzoate -0.0165% w/v niacin -0.00296% w/v Thiamine -0.00132% w/v riboflavin -0.023% w/v pyridoxine -0.000352% w/v folic acid -The formulation of the invention according to Example 1 with a final concentration of curcuminoids of 0.1% w/v

For adults weighing up to 85 kg, the dietary supplement in liquid form is scheduled to be consumed immediately before or during drinking in a single dose of 100 ml, which is used before or during drinking to support the liver and activate liver enzymes (Preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase). Ingestion of dietary supplements in liquid form (especially ingestion before drinking) activates the action of liver enzymes (including dehydrogenase enzymes), so that the curcumin formulation of the present invention contained therein has enhanced bioavailability The intake of the individual has an increased tolerance for the ethanol consumed by the individual.

Example 12 Dietary supplement in capsule form - as an anti-inflammatory agent to produce a dietary supplement in capsule form with anti-inflammatory effect, which is intended for anti-inflammatory prevention, including the prevention of viral infections (including coronavirus infections, including SARS- Complications and severe course of CoV-2 virus), which are ingested during the time period when the incidence of viral infection increases.

The formulation prepared according to Example 1 was encapsulated in a pharmaceutically acceptable water-soluble biopolymer (gelatin gel capsule, hard capsule containing powdered hypromellose) at a dose of 450 mg capsule according to the formula.

Preferably, the capsule is made of a gel material that dissolves in the small intestine, and the material is preferably a polymer of plant, microbial, or synthetic origin that meets HALAL and vegetarian certification criteria. A single gel capsule is a single-dose supplement that is taken every day during the time period when the incidence of viral infections is increasing. Ingesting these capsules, especially those belonging to groups with increased disease risk, especially those with proven disease risk (such as hypertension, obesity, type 2 diabetes, hypercholesterolemia) at least one Human intake reduces the inflammation caused by the above-mentioned diseases, and thereby reduces the post-infection complications and severe viral diseases during the period of viral infections (especially coronavirus infections, especially SARS-CoV-2 virus infections). .

Document Amalraj, A., Pius, A. Gopi , S. 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, AM Mitchell, MS Mohan, RS Isolation of curcumin from turmeric. J Chem Educ. 2000, 77, 359-360. Antony, B. Merina, B. Iyer, VS 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. Dern, AS Schneider, E. McKinnon, TP Brown, MJ 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-Z silavecz, 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. Gota, VS Maru, GB Soni, TG Gandhi , TR Kochar, N. Agarwal, MG 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, VS Turmericschemistry, technology and quality. CRC Crit. Rev. Food Sci. Nutr. 1980, 12, 199-501. Jäger, R. Lowery, RP Calvanese, AV Joy, JM Purpura, M. Wilson, JM Comparative absorption of curcumin formulations. Nutrition Journal 2014 , 13:11, 1-8. Krishnakumar, IM Ravi, A. Kumar, D. Kuttan, R. Maliakel, B. An enhanced bioavailable formulation of curcumin using fenugreek-derived soluble dietary fibre. 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, CS Moriwaki, C. Nogueira, AC Sato, F. Baesso, LM Neto, AM Matioli, G. Curcumin-β-cyclodextrin inclusion complex: Stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chemistry 2014, 153, 361-370. Marcolino,VA Zanin,GM Durrant, LR Benassi, MT Matioli, G. Interaction of Curcumin and Bixin with β-Cyclodextrin: Complexation Methods, Stability, and Applications in Food. J. Agric. Food Chem. 2011, 59, 3348-3357. Martins, RM Pereira, SV Siqueira, S. Salomão, WF Freitas, LAP Curcuminoid content and antioxidant activity in spray dried microparticles containing turmeric extract. Food Research International 2013 , 50, 657-663. Purpura, M., Lowery, RP Wilson, JM Mannan, H. Münch, G. Razmovski-Naumovski, V. Analysis of different innovative formulations of curcumin for improved relative oral bioavailability in human subjects. Eur. J. Nutr. 2018, 57(3), 929-938. Ruby, AJ; Kuttan, G.; Baby, KD; Rajasekharan, KN; Kuttan , R. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995, 94, 79-83. Salzer, DU; Haarne, G.; Reimer, G. Analytical evaluation of seasoning extracts (oleoresins) and essential oils from seasonings . Flavours 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. Pharm. 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. Mol. Nutr. Food Res. 2014, 58(3), 516-527. Shoba, G. Joy, D. Joseph, T. Majeed, M. Rajendran, R. Srinivas, PS Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta. Med. 1998, 64(4), 353-356. Yamamoto, H.; Hanada, K.; Kawasaki, K.; Nishijima, M. Inhibitory effect on curcumin on mammali an phospholipase D activity. FEBS Lett. 1997, 417, 196-198.

In order to better understand the present invention, the present invention has been illustrated in non-limiting examples and drawings, in which: Figure 1 shows the particle size distribution of the emulsion before spray drying; Figure 2 shows that the composition contains 15% The particle size distribution of curcumin-like soluble powder.

Claims (24)

A curcumin formulation in dry form, characterized in that it contains 0.1-45% w/w of starch octenyl succinate, 0.01-20% w/w cellulose derivative, in the form of hydroxypropyl methyl cellulose, hydroxypropyl cellulose or a mixture thereof; A turmeric extract in an amount of 0.01-20% w/w, wherein the turmeric extract contains at least 90% w/w curcuminoids, including curcumin, demethoxycurcumin and bisdemethoxycurcumin, 0.1-10% w/w of β-glucan, 10-70% w/w of a cellulose derivative with a viscosity> 5600 mPas, which is selected from carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, ethyl methyl Cellulose, cross-linked cellulose gum, preferably, the cellulose derivative having a viscosity of >5600 mPas is carboxymethyl cellulose; Among them, at least 90%, more preferably at least 95%, and preferably at least 99% of the particles have a diameter of less than 1 µm. Such as the curcumin formulation in dry form of claim 1, which comprises 25-35% w/w, more preferably 28-32% w/w of starch octenyl succinate; A cellulose derivative in an amount of 5-15% w/w, preferably 8-10% w/w, in the form of hydroxypropyl methylcellulose, hydroxypropyl cellulose or a mixture thereof; Turmeric extract in an amount of 5-15% w/w, preferably 8-10% w/w, wherein the turmeric extract contains at least 90% w/w curcumin, including curcumin, demethoxy Curcumin and bisdemethoxy curcumin, Β-glucan in an amount of 3-5% w/w, preferably 3.8-4.2% w/w; 30-60% w/w, preferably 48-52% w/w, a cellulose derivative with a viscosity exceeding 5600 mPas, preferably, the cellulose derivative with a viscosity> 5600 mPas is carboxymethyl Cellulose. The curcumin formulation in dry form according to any one of claims 1 to 2, wherein in the curcumin formulation in dry form, at least 90%, more preferably at least 95% of the particles, preferably at least 99% of these particles have a diameter in the range of 0.1 to about 1 µm. A method for producing a curcumin formulation in a dry form, which comprises the following steps: a) Dissolve turmeric extract with a minimum content of 90% curcumin in an organic solvent approved for food production; Wherein in step a), the preferred organic solvent for dissolving the turmeric extract is ethyl acetate, methyl acetate, butyl acetate, ethanol, butanol, and more preferably ethyl acetate; b) The dissolved turmeric extract obtained from step a) is added to a carrier solution, which is a mixture of polymers containing starch octenyl succinate and cellulose derivatives dissolved in a polar solvent, wherein the The cellulose derivative is hydroxypropyl cellulose, hydroxypropyl methyl cellulose or a mixture thereof; wherein the preferred polar solvent for dissolving the carrier is water; wherein during the addition of the dissolved turmeric extract, the carrier solution is The temperature falls within a temperature range of about 5°C to about 10°C, wherein cooling is preferably applied to maintain this temperature of the resulting mixture; Among them, preferably, the mixture of hydroxypropyl cellulose and hydroxypropyl methyl cellulose has a ratio of 10:1; Among them, preferably, the carrier solution is obtained by mechanically mixing the polymers, wherein the mixing is preferably carried out for not less than 10 hours, preferably about 12 hours; Preferably, the carrier solution is dissolved in a polar solvent at a weight ratio of 1:5 to 1:25, preferably 1:10; c) homogenizing the mixture obtained in step b) to obtain an emulsion, the homogenization being at a temperature of about 5°C to about 10°C; d) The emulsion obtained in step c) is diluted with a low-viscosity β-glucan aqueous solution and further homogenized briefly; preferably, the viscosity is in the range of 40-200 mPas, The emulsion is preferably diluted with 1-8% β-glucan, preferably with β-glucan derived from oats or barley or a mixture thereof; e) The emulsion obtained in step d) is diluted with an aqueous solution of high-viscosity cellulose derivative higher than 5600 mPas, the dilution ratio is not less than 1:6, preferably not less than 1:8, and it is stabilized by mechanical stirring throughout the process. Among them, preferably, the cellulose derivative with high viscosity is carboxymethyl cellulose (CMC), the concentration is preferably 0.01 to 0.5%, the concentration is more preferably 0.10 to 0.20%, and the concentration is more preferably 0.1 to 1.4% w/w, and f) drying the stabilized emulsion of step e) to obtain the curcumin formulation in a dry form, Among them, more than 90%, preferably more than 95%, and more preferably more than 99% of the resulting particles have a diameter size of less than about 1 µm, 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 µm, The drying is preferably carried out by spray drying, wherein the temperature at the inlet of the dryer is in the range of 110-160°C, more preferably about 150°C, and the temperature at the outlet does not exceed 65°C, preferably does not exceed about 55°C. A curcumin formulation in a dry form, which is produced by the method of claim 4. A beverage concentrate comprising the formulation according to any one of claims 1 to 3 and/or 5. Such as the beverage concentrate of claim 6, wherein it further comprises at least one of the following: Stabilizers and thickeners with a concentration of 0-28% w/w, preferably 0-20% w/w, preferably glycerin and/or sanxian gum; 0-5% w/w antioxidant and acid regulator, preferably ascorbic acid; 0-5% w/w acid regulator, preferably citric acid; 0-80% w/w electrolyte and sweetener, preferably glucose; Vitamin B, preferably selected from thiamine, niacin, pyridoxine, folic acid and riboflavin; The preservative is preferably benzoic acid, sodium benzoate, potassium sorbate or a mixture thereof. A beverage comprising a formulation as in any one of claims 1 to 3 and/or 5 or obtained by diluting a concentrate as in any one of claims 6 to 7. Such as the beverage of claim 8, wherein it is a beverage based on fruit juice and water, a milk beverage, and a plant beverage that replaces cow milk. The beverage according to any one of claims 8 to 9, wherein it is a functional beverage supporting liver function, wherein preferably, the concentration of curcuminoids in the beverage is 0.01-0.1% w/w. A dietary supplement comprising the formulation of any one of claims 1 to 3 and/or 5, preferably in liquid form, capsule, lozenge, or oral approved form. The dietary supplement according to claim 11, wherein it supports liver function, and preferably, it activates the action of liver enzymes, preferably dehydrogenase-like enzymes, and preferably aldehyde dehydrogenase. Such as the dietary supplement of claim 12, where it supports anti-inflammatory effects and aims to prevent and reduce inflammation, including the prevention of viral infections, coronavirus infections, SARS-CoV-2 infection complications and severe disease course, preferably During the time period when the incidence of viral infections increased. The dietary supplement according to any one of claims 11 to 13, wherein it is in liquid form and contains A formulation such as any one of Claims 1 to 3 and/or 5 that provides curcumin such as 0.01-0.1% w/v concentration, 1-20% w/v juice concentrate, 2-10% w/v sweetener, Stabilizer and thickener with a concentration of 2-10% w/v. A pharmaceutical composition comprising the formulation according to any one of claims 1 to 3 and/or 5 and pharmaceutically acceptable additives. A pharmaceutical composition comprising the formulation according to any one of claims 1 to 3 and/or 5, which is used as a medicine. The composition of claim 16, which is used as a medicine for regulating liver function, and a medicine with anti-inflammatory, anti-cancer and anti-depressant activities. The composition according to any one of claims 15 to 17, which is used as a medicine for regulating liver function and activating the action of liver enzymes. The liver enzymes are preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase. A pharmaceutical composition comprising the formulation according to any one of claims 1 to 3 and/or 5, which is used as a stabilizer of liver function, a drug for supporting the liver, a drug for activating the action of liver enzymes, and the liver enzymes are more It is preferably an enzyme of the dehydrogenase type, and more preferably an aldehyde dehydrogenase. A pharmaceutical composition comprising the formulation according to any one of claims 1 to 3 and/or 5, which is used as a medicament supporting an anti-inflammatory effect, aimed at preventing and reducing inflammation, preferably preventing viruses Complications and severe course of infection. Such viral infections include coronavirus infections, including SARS-CoV-2 virus infections, and it is preferably used in a period of time when the incidence of viral infections increases. A dye containing the formulation according to any one of claims 1 to 3 and/or 5. Such as the dye of claim 21, wherein it is a food dye used in medicine, cosmetics, food, and animal feed. A use of the curcumin formulation according to any one of claims 1 to 3 and/or 5, which is used as a functional additive in beverages, as a dye, as an active ingredient in a dietary supplement, and as a pharmaceutical composition The active ingredient in the product is used as a food additive and as a feed additive. A use of the curcumin formulation according to any one of claims 1 to 3 and/or 5, which is used as an anti-hangover agent, an agent for preventing and/or relieving hangover symptoms, or Used as a medicament for activating liver enzymes, the liver enzymes are preferably dehydrogenase enzymes, preferably aldehyde dehydrogenase.

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