Solubilizate with curcumin and optionally at least one other active substance

Abstract

In order to make available the health-promoting and healing properties of curcumin to the human or animal organism, also in combination with at least one further active substance, a solubilizate consists of or contains a content of curcumin equal to or smaller than 10 wt %, preferably equal to or smaller than 7.5 wt %, most preferably 6 wt %, and at least one emulsifier with an HLB value in a range below 18, preferably between 13 and 18, namely polysorbate 80 or polysorbate 20 or a mixture of polysorbate 20 and polysorbate 80, with an average diameter of the curcumin-loaded micelles ranging from 5 nm to 40 nm, preferably from 6 nm to 20 nm, most preferably from 7 nm to 10 nm, for use in particular as a dietary supplement and/or pharmaceutical drug for treating and/or preventing diseases involving inflammation, cancer and other diseases.

Claims

1. A solubilizate, comprising: a) an active substance that is curcumin in a content of 3 wt % o to 7 wt %; b) at least one second active substance selected from the group consisting of xanthohumol, plant extracts, resin of a frankincense tree, licorice, cannabinoids, enzymes, serrapeptase, coenzyme Q.sub.10, α-lipoic acid, and resveratrol; and c) at least one emulsifier having an HLB value below 18, wherein the emulsifier is polysorbate 80 or polysorbate 20 or a mixture of polysorbate 20 and polysorbate 80, and wherein the polysorbate content is at least 70 wt %.

2. The solubilizate as claimed in claim 1, wherein the solubilizate contains up to 20 wt % of ethanol.

3. The solubilizate as claimed in claim 1, wherein the solubilizate contains up to 25 wt % of glycerol.

4. The solubilizate as claimed in claim 1, wherein the solubilizate additionally contains u to 10 wt % of water.

5. The solubilizate as claimed in claim 1, wherein a diameter distribution of micelles in a dilution of the solubilizate with distilled water in a ratio of 1:500 under conditions of pH 1.1 and 37° C. is in a range from d.sub.10=6 nm to d.sub.90=20 nm.

6. The solubilizate as claimed in claim 1, wherein a turbidity of the solubilizate is less than 25 FNU, measured by scattered light measurement using infrared light according to the specifications of the ISO 7027 standard at a dilution of the solubilizate in a ratio of 1:50 or 1:500 in water under physiological conditions (pH 1.1 and 37° C.).

7. A capsule filled with the solubilizate as claimed in claim 1.

8. A fluid, containing a solubilizate as claimed in claim 1, wherein the fluid is selected from the group consisting of foods, dietary supplements, beverages, cosmetics, and pharmaceutical products.

9. The fluid of claim 8, wherein the fluid comprises an aqueous dilution of the solubilizate.

10. A method for treating diseases involving inflammation, cancer, Alzheimer's, Parkinson's, obesity, high cholesterol, elevated blood sugar, diabetes, metabolic syndrome, autoimmune diseases, and/or multiple sclerosis (MS), Q for reducing visceral fat, for thermogenesis, for lowering cholesterol, for lowering LDL cholesterol and/or glucose in the blood and/or triglycerides in the blood, for improving macular pigment density, for reducing oxidative stress, for reducing the accumulation of fat in the hepatocytes, or for treating fatty liver disease, Friedreich's ataxia, lysosomal diseases, Tay-Sachs disease, arteriosclerosis, heart diseases, r arthritis, comprising: administering to a dietary supplement consumer or patient in need thereof, a therapeutically effective amount of the solubilizate according to claim 1.

11. The method of claim 10, wherein the solubilizate is administered to the dietary supplement consumer or patient in a dose of curcumin ranging from 0.5 mg/kg body weight to 1 mg/kg body weight.

12. The method of claim 10, wherein the solubilizate is administered to the dietary supplement consumer or patient in a Boswellia dose ranging from 1 mg/kg body weight to 2 mg/kg body weight.

13. The method of claim 10, wherein the solubilizate is administered to the dietary supplement consumer or patient in a xanthohumol dose ranging from 0.5 mg/kg body weight to 1 mg/kg body weight.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The results will now be explained with reference to the accompanying figures, wherein:

(2) FIG. 1a illustrates the effect of curcumin in native and in solubilized form and of diclofenac on the serum CRP level (pg/L).

(3) FIG. 1b illustrates the effect of curcumin (5 mg/mL) in native and in solubilized form when administered together with either Boswellia or xanthohumol on the serum CRP level (pg/L), compared to diclofenac.

(4) FIG. 2 illustrates the effect of curcumin in native and in solubilized form and of diclofenac on the serum MPO level (mU/mL).

(5) FIG. 3 illustrates the effect of curcumin in native and in solubilized form when administered together with either Boswellia or xanthohumol on the serum MPO level (mU/mL), compared to diclofenac.

DETAILED DESCRIPTION

(6) First, the effects on C-reactive protein (CRP) were studied. C-reactive protein is a specific marker for anti-inflammatory activity. Both the native and the solubilized forms of curcumin inhibited rat serum CRP levels in a dose-dependent manner, but the solubilized form was twice as effective as the native form and significantly more effective than diclofenac at the chosen dose (FIG. 1a).

(7) When Boswellia is administered together with curcumin in their native forms, the inhibitory effect on serum CRP does not change significantly (FIG. 1b). However, when curcumin and Boswellia are administered in solubilized form together and at an appropriate dose, the anti-inflammatory effect is enhanced. In this regard, Boswellia is superior to xanthohumol in potentiating the effect of curcumin at the considered doses.

(8) Myeloperoxidase (MPO) in plasma plays a central role as a pro-inflammatory mediator in rheumatoid arthritis and is an indicator of the invasion of neutrophil granulocytes into the affected tissue. Its concentration is elevated in patients with rheumatoid arthritis and causes oxidative stress. In the studies, the MPO concentration was effectively reduced by solubilized curcumin, at both dosages considered in the same way and not significantly different from diclofenac. However, native curcumin had no effect on the MPO levels (FIG. 2). The administration of Boswellia together with curcumin, both in the native and the solubilized forms, did not improve the effect of curcumin in reducing MPO levels.

(9) Oxidative stress is one of the major factors contributing to joint destruction in rheumatoid arthritis (RA). An increase in the production of so-called “reactive oxygen species (ROS)” leads to a reduced supply of endogenous antioxidants and ultimately results in the destruction of cells. The neutrophil granulocytes released in the rheumatoid joint produce free oxygen radicals which cause increased formation of lipid peroxides manifesting in an increase in serum TBARS. Therefore, an increase in antioxidant status represented by an increase in TAC can be used as an indication of protection against the development of degenerative inflammatory processes. There is an inverse relationship between the levels of TAC and TBARS, a high level of antioxidant capacity TAC corresponds to a low TBARS concentration.

(10) The studies that were performed showed that, at both dosages considered, the native form of curcumin had no significant effect on the levels of TBARS or TAC. Solubilized curcumin according to the disclosure reduced the TBARS level at both selected dosages and increased TAC, with hardly any differences to the effect of diclofenac.

(11) These data are summarized in the table below. The table contains data on the effect of curcumin and Boswellia in native and in solubilized form, administered either alone or in combination with diclofenac in a dose of 3 mg per kg body weight once daily for 21 days, on the antioxidant capacity TAC and the thiobarbituric acid reactive substances TBARS in the serum of arthritic rats (n=8). Indicated are mean values±standard error of the mean (SEM).

(12) TABLE-US-00001 TAC TBARS Group (nmol/microliter) (nmol/L) Arthritic control group 57.26 ± 3.36 13.10 ± 0.39  Diclofenac (3 mg/kg) 82.08 ± 2.96 7.93 ± 0.84 Native curcumin (5 mg/kg) 60.31 ± 3.25 11.64 ± 0.39  Solubilized curcumin (5 mg/kg) 77.01 ± 0.73 5.97 ± 0.47 Native curcumin (10 mg/kg) 68.41 ± 1.09 13.18 ± 0.46  Solubilized curcumin 87.15 ± 5.27 6.82 ± 0.56 (10 mg/kg) Native curcumin (5 mg/kg) + 64.56 ± 1.45 12.08 ± 0.52  Boswellia (10 mg/kg) Solubilized curcumin (5 mg/kg) + 76.94 ± 2.17 6.81 ± 0.19 Boswellia (10 mg/kg)

(13) According to the results presented in the table, the administration of Boswellia together with curcumin, each in native form, did not show any significant effect for reducing the oxidative stress. In solubilized form, however, these combinations were as effective as diclofenac in reducing TBARS and increasing TAC in arthritic rat's serum.

(14) First studies on the use of the curcumin solubilizate according to the present disclosure in combating cancer cells of the lines (MCF-7) and (T47D) for breast cancer, (Hepg-2) for liver cancer, (HCT-116) for colon cancer, and (PC3) for prostate cancer show very good results in terms of achieving the lowest possible proportion of cells that survive the treatment. The curcumin solubilizate permitted a reduction to a “surviving fraction” in the range from about 15% to about 25%.

(15) The particle size analyzes of the micelles in aqueous dilutions of solubilizates according to the disclosure were measured according to the principle of dynamic light scattering using laser light of 780 nm wavelength, unless stated otherwise. The particle size measurements were performed using the ParticleMetrix NANO-flex backscatter particle analyzer. The measuring principle is based on dynamic light scattering (DLS) in a 180° heterodyne backscattering setup.

(16) For the experimental determination of turbidity of the solubilizates according to the disclosure, the turbidity meters are calibrated with a standard suspension. Thus, instead of measured light intensity, the concentration of the calibration suspension is indicated. So, when any arbitrary suspension is measured, the indication means that the respective liquid causes the same light scattering as the standard suspension at the indicated concentration. The internationally defined turbidity standard is formazine. The most common units include the indication FNU, i.e. Formazin Nephelometric Units. This is the unit used in water treatment, for example, for measuring at 90° in compliance with the requirements of the ISO 7072 standard.

(17) For preparing a solubilizate according to the disclosure including the active substances curcumin and at least one further active substance it is possible to either mix individually prepared solubilizates with one another or to directly prepare a solubilizate containing curcumin and at least one further active substance or several further active substances.

(18) Curcumin Solubilizates

(19) By way of example, a 7% curcumin solubilizate is prepared. To this end,

(20) TABLE-US-00002 925 g polysorbate 80 and 75 g curcumin powder 95% (= 71.2 g of curcumin)
are used. The polysorbate 80 is heated to 48 to 52° C. The curcumin powder is added to the polysorbate under stirring, while further heating to a temperature in the range from 95 to 97° C. The powder is added at an appropriate rate so as to be evenly drawn into the emulsifier during stirring. After cooling to a temperature below a maximum of 60° C., the curcumin solubilizate is bottled. This solubilizate was used for the preparation of a curcumin and Boswellia solubilizate.

(21) At a 1:500 dilution in water at pH 1.1 and a temperature of 37° C., the 7% curcumin solubilizate exhibits an average turbidity of 0.9 FNU.

(22) However, it should be noted that the curcumin content can be further increased without having to accept adverse consequences, for example in terms of stability of the micelles. A composition consisting of 100 g of 95% curcumin powder and 900 g of polysorbate 80 results in a stable product just like a composition consisting of 120 g of 95% curcumin powder and 880 g of polysorbate 80, or 70 g of 95% curcumin powder and 930 g of polysorbate 80.

(23) Moreover, the polysorbate 80 may be entirely or partially replaced by polysorbate 20. For example, for preparing a curcumin solubilizate with polysorbate 20 alone, 894 g of polysorbate 20 and 106 g of 95 curcumin powder can be used. The polysorbate 20 is heated to between about 63° C. and about 67° C. While stirring, the curcumin powder is slowly added to the polysorbate 20. While adding the curcumin powder, heating is continued to between about 83° C. and about 87° C. The resulting solubilizate is slowly cooled to below about 45° C. and is then ready for being bottled.

(24) Otherwise, the preparation of these variants corresponds to that described above. Solubilizates of up to about 11% can be produced in this way.

(25) 1.5% Serrapeptase Solubilizate

(26) The following is used:

(27) TABLE-US-00003 15 g serrapeptase: serratiopeptidase 20,000 U/mg = 300,000,000 U, 15 g water, 16.5 g MCT oil, 953.5 g polysorbate 80.

(28) At a temperature in the range between 18 and 22° C., water is mixed with serrapeptase, and the mixture is homogenized. This means that the serrapeptase is distributed as evenly as possible in the water. This creates the conditions for the serrapeptase to be largely completely dissolved in the water. While heating to a temperature in the range from 83 to 87° C., MCT oil is incorporated into the water-serrapeptase mixture under constant stirring. The stirring is performed intensely enough for the serrapeptase to dissolve evenly in the water. At unchanged temperature, polysorbate 80 is added under stirring and is homogenized. The stirring is performed intensely enough for the polysorbate 80 to be evenly distributed. The product is cooled to a temperature below 60° C. and bottled. It is then stored in the dark at not more than 25° C.

(29) 300,000 U/g corresponds to 15 mg/g of 1.5% serrapeptase in enzymatic units. At a dilution in water of 1:50, the turbidity of this solubilizate was determined under physiological conditions at pH 1.1 and 37° C. The resulting value was 1.8 FNU.

(30) For a particle size analysis of the serrapeptase solubilizate, this solubilizate was first diluted with distilled water in a ratio of 1:500 and heated to 37° C. under constant stirring using a magnetic stirrer and a hotplate. Subsequently, the pH was adjusted to 1.1 using 32% hydrochloric acid. The samples were then measured immediately. The results are summarized in the table below, for which the data of two measurements were averaged.

(31) TABLE-US-00004 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 9.23 10.47 12.23 13.56 Volume distribution 9.10 10.18 11.82 13.12
10% Resveratrol Solubilizate

(32) The following is used:

(33) TABLE-US-00005 100 g resveratrol, 45 g MCT oil, 600 g polysorbate 80, 180 g polysorbate 20, and 75 g mixed tocopherol.

(34) At a temperature in the range between 18 and 22° C., the polysorbates, the mixed tocopherol and the MCT oil are mixed and homogenized while stirring sufficiently so that the components are evenly distributed. The resveratrol is added to the mixture or solution of polysorbate, MCT oil and mixed tocopherol while heating to a temperature in the range from 83 to 87° C., while stirring sufficiently so that the resveratrol is evenly drawn into the emulsifier-containing preparation. Once a homogeneous and transparent product is obtained, it is cooled to a temperature below 30° C. and bottled. The product is yellowish, transparent and viscous and is stored in the dark at a temperature of 25° C.

(35) If, for therapeutic purposes, the administration of 3,500 mg of the native form of the resveratrol raw material is taken as a basis, the following calculation applies to the equivalent amount of solubilizate:

(36) 3 capsule fillings, each with 675 mg of solubilizate, correspond to an amount of 2,025 mg per day or 200 mg of the active substance resveratrol and 100 mg of mixed tocopherol. With a DV factor of 1:17 the following applies: 200 mg×17=3,400 mg of resveratrol pure substance.

(37) Turbidity of this solubilizate was also determined under physiological conditions (pH 1.1; 37° C.) at a dilution in water of 1:50. The resulting value was 16.1 FNU.

(38) 5% Coenzyme Q.sub.10 Solubilizate

(39) The following is used:

(40) TABLE-US-00006 57.5 g coenzyme Q.sub.10, 160 g MCT oil, and 782.5 g polysorbate 80.

(41) The polysorbate is heated to a temperature in the range between 83° C. and 87° C. Then the coenzyme Q.sub.10 powder is incorporated under stirring. Stirring is performed intensely enough so that the components are evenly distributed. While maintaining the temperature or reheating to a temperature in the range from 83 to 87° C., the coenzyme Q.sub.10 is dissolved in the polysorbate 80. Then, the MCT oil is incorporated while maintaining the temperature. Once a homogeneous and transparent product is obtained, it is cooled to a temperature below 60° C. and bottled. The product is orange-red, transparent and partially solid at room temperature. It is stored in the dark at a temperature of 25° C.

(42) The measurement of turbidity under physiological conditions (pH 1.1; 37° C.) at a dilution in water of 1:50 gave a value of 11.9 FNU as the mean value of three measurements (11.4 FNU; 10.5 FNU; 13.9 FNU).

(43) A particle size analysis of a sample of 20 microliters in a dilution ratio of 1:50 in a solution of table salt (50 mmol/L) and sodium azide (200 mg/L) by Wyatt Technology Europe GmbH in the Eclipse program, i.e. by field flow fractionation, gave a peak with a radius of 16.5 nm for the micelles of this solubilizate. Accordingly, the diameter of the micelles is 33 nm.

(44) 10% α-Liponic Acid Solubilizate

(45) The following is used:

(46) TABLE-US-00007 896.7 g polysorbate 80, 103.3 g α-lipoic acid.

(47) The polysorbate 80 is heated to between 28 and 32° C. Under stirring, the α-lipoic acid powder is added to the polysorbate and incorporated. The powder is added at such a rate that it is evenly drawn into the emulsifier during stirring. This is followed by heating up to a temperature in the range between 83° C. and 87° C. Once a homogeneous and transparent product is obtained, it is cooled to a temperature below 60° C. and bottled. The product is yellow and viscous and is stored in the dark at a temperature of 25° C.

(48) The product can also be produced using polysorbate 20 or a mixture of polysorbate 80 and polysorbate 20.

(49) At a dilution ration of 1:50 in water at pH 1.1 and a temperature of 37° C., the solubilizate exhibits an averaged turbidity of 2.9 FNU.

(50) A particle size analysis of a sample of 20 microliters in a dilution ratio of 1:50 in a solution of table salt (50 mmol/L) and sodium azide (200 mg/L) by Wyatt Technology Europe GmbH in the Eclipse program, i.e. by field flow fractionation, gave a peak with a radius below 10 nm for the micelles of this solubilizate. Accordingly, the diameter of the micelles is not more than 20 nm.

(51) 10% Xantho-Flav Pure Solubilizate (Corresp. To 9.2% Xanthohumol) with Ethanol

(52) For this variant of a xanthohumol solubilizate according to the disclosure, the following was used:

(53) TABLE-US-00008 100 g Xantho-Flav Pure ({circumflex over (=)} 92 g of xanthohumol), 150 g ethanol (96%) of neutral alcohol grade 1411U, and 750 g polysorbate 80.

(54) First, the Xantho-Flav Pure powder is dissolved in ethanol while being heated to a temperature in the range between 48 and 52° C. A homogeneous solution is created. Polysorbate 80 is then added into the solution of Xantho-Flav Pure in ethanol while heating to between 83 and 87° C. The adding is done at a rate such that the two fluids homogenize well under stirring. The resulting solubilizate is cooled to below 60° C. and is bottled and stored in the dark and cool, i.e. at temperatures below 25° C.

(55) 15% Glavonoid Solubilizate (=0.45% Glabridin) with Glycerol

(56) The following was used:

(57) TABLE-US-00009 150 g glavoniod (= 4.5 g glabridin), 100 g 99% glycerol, 750 g polysorbate 80.

(58) First, glycerol and glavonoid were mixed and homogenized at a temperature in the range from 18 to 22° C. While heating up to 83-87° C., polysorbate 80 was added to the fluid consisting of glycerol and glavonoid, under stirring. The stirring was performed intensely enough so that a homogeneous solubilizate was obtained, which was allowed to cool to a maximum of 30° C. and bottled and then stored in the dark at a temperature below 25° C.

(59) The solubilizates described above can be used to prepare the solubilizate according to the disclosure comprising curcumin and at least one further active substance by mixing. This will be described below with reference to exemplary embodiments 3, 5, 6, and 7.

Exemplary Embodiment 1

(60) Solubilizate of 5.4% Curcumin/6.6% Boswellic Acid

(61) This exemplary embodiment of the solubilizate according to the disclosure was prepared directly. The active substances were co-micellized. To this end, the following was used here:

(62) TABLE-US-00010 82 g 80% Boswellia serrata extract (= 65.6 g boswellic acid), 57 g 95% curcumin powder (= 54.1 g of curcumin), 70 g water, 350 g polysorbate 20, 441 g polysorbate 80.

(63) While heating to a temperature in the range from 48 to 52° C., polysorbate 20 and polysorbate 80 are homogenized with each other and thereby dissolved in each other under stirring. While maintaining the temperature, the emulsifier mixture is mixed with the water while stirring intensely enough so that the water and the ethanol are dissolved evenly in the emulsifier solution. At unchanged temperature, the Boswellia serrata extract is incorporated into the water-diluted emulsifier under stirring. The Boswellia serrata extract is added at a rate slow enough to be evenly drawn into the dilute emulsifier solution under stirring. Subsequently, the temperature is increased to a range between 63° C. and 67° C. under vigorous stirring. The curcumin powder is incorporated under stirring. The temperature is further increased to a value in the range between 85° C. and 89° C. while stirring intensely enough for the curcumin to be evenly distributed in the preparation and homogenized.

(64) At a dilution ration of 1:500 in water at pH 1.1 and a temperature of 37° C., the solubilizate exhibits an averaged turbidity of 1.9 FNU.

(65) In the context of the present application, a verification about whether the homogenization of the components to form a solubilizate according to the disclosure has been sufficiently completed in the preparation of any solubilizates is obtained by measurements of the clarity of the product, which indicates complete micellization, using a laser beam. Such a laser beam measurement may be performed, for example, by illuminating the sample using a commercially available laser pointer, in particular with a wavelength in the range between 650 nm and 1700 nm (spectral color red), and subsequent visual inspection of the illuminated or irradiated solubilizate. The verification is not achieved by sampling and thus outside the reaction vessel, but in the reaction vessel. The laser beam is directed through a sight glass which is located on the front of the reaction vessel, perpendicularly to the reaction vessel. If merely a point of light appears on the rear inner surface of the reaction vessel, completely free of scattering, the resulting particle structures in the reaction vessel are smaller than the wavelength of the visible light, which is thus a visual confirmation that the process of micellization has been completed.

(66) In the context of the disclosure, the contents of curcumin and Boswellia extract in the individual solubilizates may also be adjusted so as to be significantly higher than in the example shown, depending on the application case.

Exemplary Embodiment 2

(67) Solubilizate of 3.3% Curcumin/3.6% Boswellic Acid with 1.8% Xanthohumol

(68) The following is used:

(69) TABLE-US-00011 45 g 80% Boswellia serrata extract (36 g boswellic acid), 35 g 95% curcumin powder (33.25 g of curcumin), 23 g Xantho-Flav with at least 80% xanthohumol (18.4 g xanthohumol), 60 g water, 50 g ethanol (96%) neutral alcohol, grade 1411U, 350 g polysorbate 20, 437 g polysorbate 80.

(70) While heating to a temperature in the range from 48 to 52° C., polysorbate 20 and polysorbate 80 are homogenized with each other while being dissolved in each other, under stirring. While maintaining the temperature, the emulsifier mixture is mixed with the water and ethanol. Stirring is performed intensely enough so that the water and the ethanol are dissolved evenly in the emulsifier solution. At unchanged temperature, the Boswellia serrata extract and the xanthohumol are incorporated into the water-diluted emulsifier mixture while stirring. The adding occurs at a rate slow enough so that the Boswellia serrata extract and the xanthohumol are evenly drawn into the dilute emulsifier solution, under stirring. Subsequently, the temperature is increased to a range between 63° C. and 67° C. under vigorous stirring. The curcumin powder is incorporated while stirring. The temperature is further increased to a value in the range between 85° C. and 89° C. while stirring intensely enough so that the curcumin is evenly distributed in the preparation and homogenized.

(71) This is followed by cooling to a temperature of less than or equal to 45° C. The dark yellow, viscous preparation comprising a solubilizate of curcumin and boswellic acid and xanthohumol is then bottled and stored in the dark and cool, i.e. below 25° C.

(72) At a dilution ratio of 1:500 in water at pH 1.1 and a temperature of 37° C., the solubilizate exhibits an averaged turbidity of 1.9 FNU.

(73) For particle size analysis of a solubilizate according to the disclosure, unless stated otherwise, this solubilizate was first diluted with distilled water in a ratio of 1:500 and brought to 37° C. under constant stirring with a magnetic stirrer and using a hot plate. Subsequently, the pH was adjusted to 1.1 using 32% hydrochloric acid. The samples were then measured immediately. The results are summarized in the table below.

(74) TABLE-US-00012 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 10.18 15.70 533.0 3080 Volume distribution 7.90 10.96 15.21 20.37

Exemplary Embodiment 3

(75) Solubilizate of 1.5% Curcumin/3% Boswellic Acid/2% Xanthohumol/0.35% Serrapeptase

(76) The following is used according to the formulations described above:

(77) TABLE-US-00013 250 g 7% curcumin solubilizate, 250 g 12% Bowellia solubilizate, 250 g 9.2% xanthohumol solubilizate, and 250 g 1.5% serrapeptase solubilizate.

(78) All four solubilizates can be heated to a temperature in the range from 50° C. to 60° C. to lower viscosity and thus enhancing flowability. Subsequently, they are mixed together by stirring. As soon as a homogeneous complete product is obtained, it is optionally cooled to a temperature below 60° C. and bottled.

(79) Prior to further processing such as filling into capsules, it is favorable to again stir the product to homogenize it, and if necessary to heat it moderately, that is to a temperature of about 40° C. to 50° C. At a dilution ratio of 1:500 in water at a pH of 1.1 and a temperature of 37° C., the solubilizate exhibits an averaged turbidity of 1.0 FNU. The results of particle size analysis are summarized in the table below.

(80) TABLE-US-00014 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 9.08 15.64 292.7 615 Volume distribution 6.35 9.36 14.10 20.16

Exemplary Embodiment 4

(81) Solubilizate of 5% Glavonoid (=1.8% Glabridin)/3% Curcumin/3.5% Xanthohumol

(82) The following is used:

(83) TABLE-US-00015 32 g 95% curcumin powder (= 30.4 g of curcumin), 44 g Xantho-Flav Pure powder (= 35.2 g of xanthohumol), 60 g Kaneka glavonoid (= 1.8 g glabridin), 60 g 96% ethanol, neutral alcohol grade 1411U, 44 g 99.5% glycerol, 760 g  polysorbate 80.

(84) Polysorbate 80 and glycerol are mixed together under stirring while being heated to a temperature in the range from 48 to 52° C. to homogenize the mixture adequately. Ethanol is incorporated into the polysorbate-glycerol mixture while stirring intensely enough to form a homogeneous solution, while the temperature is kept constant. Then, xanthohumol is incorporated into the solution of polysorbate, glycerol, and ethanol, while the temperature is raised to a value between 63 and 67° C. under stirring intensely enough for the xanthohumol to combine homogeneously with the prepared solution.

(85) Subsequently, curcumin powder is incorporated into the xanthohumol solubilizate, while the temperature is raised to a value in the range between 78 and 82° C. As with the xanthohumol and also with the incorporation of glavonoid described below, stirring is performed intensely enough so that the newly added component of the solubilizate combines homogeneously with the solubilized product in the prepared fluid. For the addition of glavonoid, the temperature is further increased to a value in the range between 85 and 98° C.

(86) The product is a solubilizate with co-micellated curcumin, xanthohumol, and glavonoid. It is allowed to cool to a maximum value of 45° C. while stirring and is then bottled.

Exemplary Embodiment 5

(87) Solubilizate of 1.5% Curcumin/2% Xanthohumol/3.5% Glavonoid (0.1% Glabridin)/1.2% Coenzyme Q.sub.10

(88) The following is used according to the formulations described above:

(89) TABLE-US-00016 250 g 7% curcumin solubilizate, 250 g 9.2% xanthohumol solubilizate, 250 g 15% glavonoid solubilizate, and 250 g 5% coenzyme Q10 solubilizate.

(90) All four solubilizates can be heated to a temperature in the range from 50° C. to 60° C. to lower viscosity and thus enhance flowability. Then, they are mixed together by stirring. Once a homogeneous complete product is obtained, it is optionally cooled to a temperature below 60° C. and bottled.

(91) Prior to further processing such as filling into capsules, it is favorable to again stir the product to homogenize it, and if necessary to this end to heat it moderately, that is to a temperature of about 40° C. to 50° C.

(92) The results of particle size analysis are summarized in the following table.

(93) TABLE-US-00017 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 8.22 10.88 14.80 450 Volume distribution 7.78 10.06 13.10 16.39

Exemplary Embodiment 6

(94) Solubilizate of 1.3% Curcumin/1.6% Xanthohumol/3% Glavonoid (0.09% Glabridin)/1% Coenzyme Q.sub.10/2% α-Liponic Acid

(95) The following is used according to the formulations described above:

(96) TABLE-US-00018 200 g 7% curcumin solubilizate, 200 g 9.2% xanthohumol solubilizate, 200 g 15% glavonoid solubilizate, 200 g 5% coenzyme Q.sub.10 solubilizate, and 200 g 10% α-lipoic acid solubilizate.

(97) All five solubilizates can be heated to a temperature in the range from 50° C. to 60° C. to lower viscosity and thus enhance flowability. Then, they are mixed together by stirring. Once a homogeneous complete product is obtained, it is optionally cooled to a temperature below 60° C. and bottled.

(98) Prior to further processing such as filling into capsules, it is favorable to again stir the product to homogenize it, and if necessary to this end to heat it moderately, i.e. to a temperature of about 40° C. to 50° C.

(99) The results of particle size analysis are summarized in the following table.

(100) TABLE-US-00019 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 8.85 11.64 17.05 981 Volume distribution 7.16 9.41 12.36 15.43

Exemplary Embodiment 7

(101) Solubilizate of 0.8% Curcumin/1.5% Boswellic Acid/1% Xanthohumol/1.8% Glavonoid (0.05% Glabridin)/0.18% Serrapeptase/1.2% Resveratrol/0.6% Coenzyme Q10/1.2% α-Liponic Acid

(102) The following is used according to the formulations described above:

(103) TABLE-US-00020 125 g 7% curcumin solubilizate, 125 g 12% Boswellia solubilizate, 125 g 9.2% xanthohumol solubilizate, 125 g 15% glavonoid solubilizate, 125 g 1.5% serrapeptase solubilizate, 125 g 10% resveratrol solubilizate, 125 g 5% coenzyme Q.sub.10 solubilizate, and 125 g 10% α-lipoic acid solubilizate.

(104) All eight solubilizates can be heated to a temperature in the range from 50° C. to 60° C. to lower viscosity and thus enhance flowability. Then, they are mixed together by stirring. Once a homogeneous complete product is obtained, it is optionally cooled to a temperature below 60° C. and bottled.

(105) Prior to further processing such as filling into capsules, it is favorable to again stir the product to homogenize it, and if necessary to this end to heat it moderately, i.e. to a temperature of about 40° C. to 50° C.

(106) At a dilution ratio of 1:50 in water at a pH of 1.1 and a temperature of 37° C., the solubilizate exhibits an averaged turbidity of 12.5 FNU.

(107) The results of particle size analysis are summarized in the following table.

(108) TABLE-US-00021 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 8.09 10.91 15.19 425 Volume distribution 6.90 9.26 12.37 15.71

Exemplary Embodiment 8

(109) Solubilizate of 0.8% Curcumin/1.5% Boswellic Acids/1% Xanthohumol/1.8% Glavonoid (0.05% Glabridin)/0.18% Serrapeptase/1.2% Resveratrol/0.6% Coenzyme Q.sub.10/1.2% α-Liponic Acid in Direct Preparation

(110) The following is used:

(111) TABLE-US-00022 9.375 g 95% curcumin powder, 19 g Boswellia Serrata extract (15.2 boswellic acid), 12.5 g Xantho-Flav powder (at least 80% xanthohumol = 10 g xanthohumol), 18.75 glavonoid (0.56 g glabridin), 1.875 g serrapeptase (37,500,000 U), 12.5 g resveratrol, 7.19 g coenzyme Q.sub.10, 12.5 g α-lipoic acid, 7.875 g water, 18.75 g ethanol, 12.5 g glycerol, 9.375 g mixed tocopherol, 27.685 g MCT oil, 122.5 g polysorbate 20, and 707.225 g polysorbate 80.

(112) Polysorbate 80 is mixed with α-lipoic acid at a temperature in the range between 18 and 22° C. while stirring intensely enough so that a homogeneous mixture is created. Separately, the serrapeptase is dissolved in water in the same manner, at a temperature in the range from 18 to 22° C. The further ingredients ethanol, xanthohumol, curcumin, Boswellia, glavonoid, resveratrol, coenzyme Q.sub.10, mixed tocopherol, glycerol, MCT oil, and polysorbate 20 are slowly and successively added to the mixture or solution of serrapeptase and water under constant stirring while the temperature is still in the range between 18 and 22° C. Care is taken to ensure good mixing and homogeneity of the product. If appropriate, pauses are taken between the addition of a substance and the addition of the next substance. The adding and stirring is performed slowly enough so that the particular ingredient to be added is evenly incorporated into the preparation.

(113) Next, both mixtures, i.e. the polysorbate 80 and the α-liponic acid preparations, and the remaining mixture of all other ingredients are mixed together and further stirred at a temperature in the range from 18 to 22° C. This creates a homogeneous pasty mass similar to a slurry, which is heated to a temperature in the range from 85° C. to 89° C. The heating is performed under constant stirring and slowly enough so that the heated slurry always remains mixed as homogeneously as possible. After cooling to a temperature below 60° C., the product is bottled. It is dark and viscous and is stored in the dark at temperatures of not more than 25° C. Prior to further processing such as filling into capsules, it is favorable to again stir the product to homogenize it and, if necessary to this end, to heat it moderately, i.e. to a temperature of about 40° C. to 50° C.

(114) At a dilution ratio of 1:50 in water at a pH of 1.1 and a temperature of 37° C., the solubilizate exhibits a turbidity of 1.0 FNU.

(115) The results of the particle size analysis are summarized in the following table.

(116) TABLE-US-00023 d.sub.10 (nm) d.sub.50 (nm) d.sub.90 (nm) d.sub.99 (nm) Intensity distribution 8.66 11.01 14.58 220.4 Volume distribution 7.96 9.87 12.59 15.52

Exemplary Embodiment 9

(117) Solubilizate of 3% Curcumin/3.2% Boswellic Acid/1.6% Xanthohumol/1% CBD Oil

(118) The following is used:

(119) TABLE-US-00024 40.5 g 80% Boswellia serrata extract (32.4% boswellic acid), 31.5 g 95% curcumin powder (29.925 g of curcumin), 20.7 g Xantho-Flav powder containing at least 80% of xanthohumol (16.5 g xanthohumol), 54 g water, 45 g ethanol, 315 g polysorbate 20, 483 g polysorbate 80, 10 g CBD oil: 30% cannabidiol.

(120) Cannabidiol (CBD) is a barely psychoactive cannabinoid derived from the female hemp Cannabis sativa or Cannabis indica. A non-THC-free CBD oil was used,