WO2019011414A1

WO2019011414A1 - Solubilisate with curcumin and boswellia

Info

Publication number: WO2019011414A1
Application number: PCT/EP2017/067381
Authority: WO
Inventors: Dariush Behnam
Original assignee: Aquanova Ag
Priority date: 2017-07-11
Filing date: 2017-07-11
Publication date: 2019-01-17

Abstract

The aim of the invention is to allow the best possible bioavailability of curcumin and boswellia. According to the invention, this is achieved by providing a solubilisate which contains curcumin with a content of less than or equal to 10 wt.%, preferably less than or equal to 8 wt.%, particularly preferably 3 wt.% to 7 wt.%, one or more boswellia acids and/or one or more boswellia acid derivatives with a total content of less than or equal to 10 wt.%, preferably less than or equal to 8 wt.%, particularly preferably 4.7 wt.% to 6.6 wt.%, and at least one emulsifier with an HLB value ranging between 13 and 18, in particular polysorbate 80 or polysorbate 20 or a mixture of polysorbate 20 and polysorbate 80.

Description

SOLUBILIZATION WITH CURCUMIN AND BOSWELLIA

The invention relates to a solubilizate with curcumin and boswellia according to claim 1

Invention, a fluid containing such a solubilizate, a capsule filled with such a solubilizate

or fluid and a drug or

Dietary supplement containing such

Solubilisate.

Curcumin is discussed as an active ingredient based on various potential pharmacological properties.

For example, there are indications for the antioxidant and also for the anti-inflammatory effect of curcumin as well as for the activity against viruses and bacteria as well as against cancer. Therefore, indications could be

for example Parkinson's, Alzheimer's, diabetes, colorectal tumors, pancreatic cancer and

Liver dysfunction.

In order to enter the bloodstream after oral intake, the drug must pass through the intestinal wall, is then metabolized in the liver and passes as

bioavailable fraction into the hepatic vein. The rest of the total ingested and released in the body

Active ingredient is either microbially degraded in the intestine or eliminated with the faeces or bile.

A toxicity due to the micellization of the active compound according to the invention in comparison to the native form could be demonstrated by investigations with MTT assays for cell viability The proof of cell vitality by MTT test is based on the

Reduction of the yellow, water-soluble dye 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) into a blue-violet, water-insoluble formazan.

The extract from the resin of the frankincense tree, Boswellia serrata extract contains in particular the boswellic acids "CCBA" CC-boswellic acid and "ßBA" ß-boswellic acid and its derivatives "KBA" 11-keto-ß-boswellic acid (CAS 17019-92-0) and "AKBA" 3-O-acetyl-l 1-keto-β-boswellic acid (CAS 67416-16-9) and "A BA" 3-O-acetyl-CC-boswellic acid and "AβBA" 3-O-acetyl ß-boswellic acid. Especially the derivative AKBA is said to have an anti-inflammatory effect.

In the context of the present application, the term "boswellia" is used, in particular in the term "boswellia solubilisate" in the sense that the term "boswellia" refers to the active ingredients from the resin of the

Frankincense tree refers, so at least one

Boswellic acid and / or at least one derivative of a

Boswellic acid refers. The term "boswellic acid solubilisate" refers to a micellar formulation of at least one boswellic acid, which may also contain at least one boswellic acid derivative.

The inventor therefore set himself the task of a

To provide formulation which the

health promoting to healing properties of

Curcumin and Boswellia makes the human or animal organism accessible. In particular, it is one Object of the invention to allow the best possible bioavailability of curcumin and boswellia.

These objects are achieved in a surprisingly simple manner with a solubilizate according to claim 1. This contains curcumin in a proportion of less than or equal to 10 wt .-%, preferably less than or equal to 8 wt .-%,

more preferably from 3% by weight to 7% by weight,

one or more boswellic acids and / or one or more boswellic acid derivatives in a proportion of less than or equal to 10 wt .-%, preferably less than or equal to 8 wt .-%, particularly preferably 4.7 wt .-% to 6, 6 wt. -% and

at least one emulsifier having an HLB value in the range between 13 and 18, in particular polysorbate 80 or

Polysorbate 20 or a mixture of polysorbate 20 and polysorbate 80.

In a preferred embodiment of the invention, the solubilizate consists of curcumin in an amount of less than or equal to 10% by weight, preferably less than or equal to

8 wt .-%, particularly preferably 3 wt .-% to 7 wt .-%, one or more boswellic acids and / or one or more boswellic acid derivatives with a proportion of less than or equal to 10 wt .-%, preferably less than or equal to 8 Wt .-%, particularly preferably 4.7 wt .-% to 6, 6 wt. -% and

Polysorbate 20 or a mixture of polysorbate 20 and polysorbate 80. Due to the high proportion of boswellia, the invention provides in an advantageous embodiment that the

Solubilisat as a source that the solubilizate as the source of the one or more boswellic acids and / or one or more boswellic acid derivatives obtained by extraction using acetic acid ethyl ester from the resin of the plant Boswellia serrata extract containing boswellic acids in this extract in a concentration of at least 85 Wt .-% present.

It turned out that depending on how much

Boswellia should be solubilized and, in particular, depending on the question of whether further active substances should be micellised in addition to boswellia, the

Mass ratio of emulsifier to boswellic acids and / or to boswellic acids and at least one of their derivatives in the range between 20: 1 and 3: 1, preferably in the range

between 16: 1 and 4: 1, preferably in the range between 14: 1 to 5: 1.

Depending on how much curcumin should be micellised in the solubilizate with curcumin and boswellia in addition to boswellia, in the context of the invention the ratio of

Emulsifier to curcumin in the range between 30: 1 and 3: 1, preferably in the range between 25: 1 and 9: 1, preferably in the range between 23: 1 to 12: 1 are selected.

For a stable micelling of curcumin and boswellia in the solubilizate according to the invention, it has proved favorable if the ratio of emulsifier to the total mass of curcumin and boswellic acids and / or of curcumin and boswellic acids and at least one of their derivatives in the

Range between 15: 1 and 3: 1, preferably in the range between 10: 1 and 4: 1, preferably in the range between 8.8: 1 to 5.7: 1.

The emulsifier content, in particular the polysorbate content, according to the invention is for this purpose at least 70% by weight, preferably in the range between 75% by weight and 95% by weight, more preferably in the range between 79% by weight and

88% by weight. Depending on how much emulsifier for a given

Purpose of the solubilizate can be used, the invention offers the possibility that the solubilizate contains up to 20 wt .-%, preferably up to 15 wt .-% ethanol. The addition of ethanol can reduce the proportion of polysorbate, which is an advantage in terms of the ADI value for polysorbate.

For the formation of stable micelles, it can be helpful, depending on which active ingredients are to be solubilized in which amount, that the solubilizate contains up to 25% by weight, preferably up to 10% by weight, of glycerol. By addition of glycerol, the proportion of polysorbate

be reduced. The solubilizates according to the invention also have a narrow particle size distribution with a small mean in the physiological conditions of a gastric passage

Particle sizes, preferably the diameter distribution of the micelles in a dilution of the solubilisate with distilled water in the ratio 1: 500 at pH 1.1 and 37 ° C of about

nm to about nm. These values were determined by volume distribution. Details of particle size analysis of the micelles of the solubilisates are discussed below.

The invention advantageously provides solubilisates having very good anti-inflammatory properties

Available. The anti-inflammatory activity measured as the concentration of C-reactive protein (CRP) in the blood serum of arthritic rats is after a single administration of the

Solubilisate at a dosage of 5 mg / kg body weight curcumin and 10 mg / kg body weight boswellic acids ranging from about 1200 pg / mL to about 1500 pg / mL im

Compared to about 3200 pg / mL to about 3500 pg / mL after administration of equal doses of native curcumin

or Boswellia. Reference is made to the attached figure lb and the description of this in the following.

The anti-inflammatory effect of a solubilizate according to the invention of curcumin and boswellia measured as

Concentration of myeloperoxidase (MPO) in the blood serum of arthritic rats is after a single dose of

Solubilisate at a dose of 5 mg / kg body weight curcumin and 10 mg / kg body weight boswellic acids in the range of about 750 mU / mL to about 815 mU / mL and thus significantly lower than about 1150 mU / mL to about 1250 mU / mL after a Administration of the same dose of native curcumin or boswellia. In this context, reference is made to the accompanying Figure 3 and the associated

Description below. The enzyme unit (U) is a unit which has since been replaced by the catalysis to indicate the enzyme activity. Since the numerical values change with the use of the catalysis, the enzyme unit (U) becomes in medicine and clinical chemistry still used. An enzyme unit U corresponds to a micro-mole substrate turnover per minute.

A reference to the compared to not according to the

Invention micellized compositions of boswellia with curcumin give improved bioavailability

Metrologically much easier to determine the turbidity of the solubilizate. The turbidity of the solubilizate is preferably less than 25 FNU, preferably less than 3 FNU, measured as a result of scattered light measurement with infrared light according to the invention

Standard ISO 7027 with dilution of the solubilisate 1:50 in water at pH 1.1 and 37 ° C.

In order to make oral administration of the solubilizate according to the invention easier and more convenient for the consumer or patient, the invention also provides a capsule filled with a boswellic acid solubilizate described above or a corresponding one

Available, wherein the capsule is formed as a soft gelatin capsule or hard gelatin capsule or as a soft, gelatin-free capsule or as a hard, gelatin-free capsule.

The solubilizate according to the invention can be used in the context of

Invention also in other fluids, in particular

Liquids are incorporated. The remain

Preserved drug-filled small micelles. Thus, the invention also provides a fluid containing the solubilizate described above, wherein the fluid is selected from the group consisting of foods, beverages, cosmetics and pharmaceutical products. In particular, that can Fluid in the context of the invention comprise an aqueous dilution of the solubilizate.

Thus, the invention also makes it possible in a particularly simple manner to use a solubilizate or fluid as medicaments for the treatment of inflammation-associated diseases, cancer, Alzheimer's, Parkinson's, obesity, high cholesterol, elevated blood sugar, metabolic syndrome and / or

Autoimmune diseases.

The invention also provides a method for

Treatment of associated with inflammation

Diseases, cancer, Alzheimer's, Parkinson's, obesity, high cholesterol, elevated blood sugar, metabolic

Syndrome and / or autoimmune diseases in which a solubilizate according to the invention, in particular in a capsule or as a fluid, is administered to the patient, in particular orally,

is administered. In a preferred embodiment of the method according to the invention, the solubilizate is the

Patients in a curcumin dose in the range of 0.5 mg / kg body weight to 1 mg / kg body weight, preferably at a dose of 0.81 mg / kg body weight, and in a boswellia dose in the range of 1 mg / kg body weight to 2 mg / kg body weight, preferably with a dose of

1.62 mg / kg body weight, especially once a day.

To produce a solubilizate according to the invention with the active ingredients curcumin and boswellia, either solubilisates prepared individually can be mixed with one another or a solubilizate containing curcumin and

Boswellia is made directly. The invention further provides methods of making a solubilizate as described above. If a co-micellization of boswellia with curcumin is desired, the invention sets the following variant

Manufacturing process ready with the steps

a) presentation of polysorbate 80 and / or polysorbate 20 and / or a mixture of polysorbate 20 and

Polysorbate 80

b) Addition of Boswellia serrata extract powder c) Addition of curcumin powder

wherein in step a) heating to a temperature in the range of 40 ° C to 62 ° C, preferably to a temperature in the range of 45 ° C to 57 ° C, more preferably to a temperature in the range of 48 ° C and 52 ° C, takes place

and wherein in step b) heating to a temperature in the range of 60 ° C to 75 ° C, preferably to a temperature in the range of 61 ° C to 70 ° C, more preferably to a temperature in the range of 63 ° C and 67 ° C takes place

and wherein in step c) heating to a temperature in the range of 82 ° C to 97 ° C, preferably to a temperature in the range of 83 ° C to 92 ° C, more preferably to a temperature in the range of 85 ° C and 89 ° C takes place. This method of production makes it possible to

Solubilisat produce, which can form in aqueous dilution micelles, which are loaded with both curcumin and boswellic acids. For this purpose, the two active ingredients, even with a correspondingly adapted temperature control in a preparatory step

mixed together and then added together as a mixture. In particular, before step b) a step

bl) adding water at a temperature in the range of 40 ° C to 62 ° C, preferably at a temperature in the range of 45 ° C to 57 ° C, more preferably at a temperature in the range of 48 ° C and 52 ° C, be performed.

The invention also relates to solubilizates which show micelles diluted in aqueous dilution both with curcumin and with boswellic acids alone, at least immediately after their preparation. Therefore, the

Invention also a method for producing a solubilizate described above by mixing a

Curcuminsolubilisats and a Boswellia solubilizate, in particular in the ratio 1: 1 available.

In particular for this variant of the production

The invention also relates to a method for producing a boswellia solubilizate with the following steps,

a) presentation of Boswellia serrata extract powder b) addition of polysorbate 80 and / or polysorbate 20 and / or a mixture of polysorbate 20 and

Polysorbate 80

wherein in step b) heating to a temperature in

Range of 82 ° C to 97 ° C, preferably to a temperature in the range of 84 ° C to 95 ° C, more preferably carried out at a temperature in the range of 87 ° C and 93 ° C. Optionally, before step b), a step

bl) adding water at a temperature in the range of 82 ° C to 97 ° C, preferably at a temperature in the range of 84 ° C to 95 ° C, more preferably at a temperature in the range of 87 ° C and 93 ° C, are performed.

The invention is described below with reference to

Embodiments explained in more detail. The following components were used.

Boswellia

The term "Boswellia" is used in the context of the present application, in particular an extract from the resin of

Frankincense plant. Specifically, an extract of the species boswellia serrata was used. This was an extract obtained by extraction with acetic acid ethyl ester from the resin of the plant with the botanical name boswellia serrata with the product code "HC22519" from the manufacturer Frutarom Belgium NV, Londerzeel, Belgium A solubilizate containing this extract is due to its content on boswellic acids also referred to as "boswellic acid solubilisate". In addition to extracts of the resin of the frankincense plant may also for the purpose of the solubilisate according to the invention

Boswellic acids and / or derivatives of boswellic acids are used. In particular, alpha-boswellic acid (CAS No. 471-66-9), beta-boswellic acid (CAS No. 631-69-6) and their derivatives are included

3-O-acetyl-alpha-boswellic acid (CAS No. 89913-60-0),

3-O-acetyl-beta-boswellic acid (CAS No. 5968-70-7),

11-keto-beta-boswellic acid (KBA, CAS # 17019-92-0) and 3-0-acetyl-ll-keto-beta-boswellic acid (AKBA, CAS-No.

67416-61-9) in question.

curcumin

The curcumin product used was the product "Turmeric Oleoresin Curcumin Powder 95%" having product code EP-5001 from Green Leaf Extraction Pvt Limited, Kerala, India The curcumin powder is CAS No. 458-37-7 is a natural product, which by

Solvent extraction of rhizomes of Curcuma Longa is obtained. The curcumin content of the powder is according to the manufacturer at least 95%. This curcumin content is determined by ASTA Method 18.0.

In the embodiments described below, alternatively to the mentioned "oleoresin turmeric 95%" - curcumin powder from Greenleaf as curcumin, for example, 95% curcumin extract from Neelam Phyto-extracts, Mumbai, India or curcumin BCM-95-SG or curcumin BCM-95- CG of eurochem GmbH, Gröbenzell,

Germany or Curcuma Oleoresin 95% of Henry Lamotte OILS GmbH, Bremen, Germany are used.

Polysorbate 80

The source of polysorbate 80 was the material "TEGO SMO 80 V FOOD" with the specification code "K04 EU-FOOD" from Evonik Nutrition & Care GmbH, Essen, Germany.

used. The product complies with the EU requirements of food additive E 433. In the following As an alternative to the mentioned TEGO SMO 80 V from Evonik as polysorbate 80, exemplary embodiments may also include TEGO SMO 80 V from InCoPA Gmbh, Illertissen, Germany or

Crillet 4 / Tween 80-LQ (SG) from CRODA GmbH, Nettetal, Germany or Lamesorb SMO 20 and Kotilen-O / 1 VL from Univar or Kolb Distributives AG, Hedingen, Switzerland.

Polysorbate 20

The source of polysorbate 20 was the material "TEGO SML 20 V FOOD" with the specification code "K09 EU-FOOD" from Evonik Nutrition & Care GmbH, Essen, Germany,

used. The product complies with the EU requirements of food additive E 432. Alternatively to

Evonik's TEGO SML 20 can be used as part of the

Invention as polysorbate 20 also Crillet 1 / Tween 20-LQ (SG) from CRODA GmbH, Nettetal, Germany.

If added in the preparation of a solubilizate, distilled water is used.

The particle size analysis of the micelles in aqueous

Dilutions of inventive solubilisates were measured according to the principle of dynamic light scattering

Laser light of wavelength 780 nm. The

Particle size measurements were made with the ParticleMetrix

NANOFLEX backscatter particle analyzer performed. The measuring principle is based on dynamic light scattering (DLS) in a 180 ° heterodyne backscatter arrangement. With this geometry, the scattered light becomes part of the Laser beam mixed (heterodyne technique). Because of the low light path from 200 microns to 300 microns in the sample, backscattering is beneficial for absorbing and highly concentrated samples. The heterodyne technique enhances the signal-to-noise ratio and the sensitivity of the sub-10 onm range.

The laser light gets into the Y-fork of an optical fiber

coupled. Come back in the same fiber on the

Saphir window of the sample chamber partially reflected laser light and the backward scattered from the sample light. The

Detector in the second branch of the Y-fork receives the interfering signals. A fast

Fourier transform evaluation breaks down the

Each frequency component represents a Brown ^' see diffusion constants and is thus attributable to a particle size

Particle size distribution uses the Stokes-Einstein formula:

In this equation are the diffusion constant D, the Bolt zmannkonstante k, the temperature T, the dynamic viscosity η of the medium and the diameter dp the

Particle. A temperature sensor is located in the meter near the sapphire window close to the sample. For the experimental determination of the turbidity of the

Solubilisates according to the invention are the

Turbidity meters calibrated with a standard suspension. The display is thus not in the form of the measured light intensity, but as a concentration of

Calibration suspension. When measuring any

Suspension thus means the indication that the liquid in question causes the same light scattering as the standard suspension of the indicated concentration. The internationally defined turbidity standard is Formazin. Among the most common units is the indication "FNU", ie "Formazine Nephelometry Units". this is the

For example, in the water treatment used unit for the measurement at 90 ° according to the provisions of the standard ISO 7072.

Boswellia is made directly. The following is an example of the preparation using two solubilisates prepared individually beforehand

described.

Embodiment 1

3% curcumin / 6% boswellic acid solubilisate

First, a 7% curcumin solubilizate is prepared. To do this

925 g polysorbate 80

75 g of curcumin powder 95 o

o (= 71.2 g curcumin) used. The polysorbate 80 is heated to 48 to 52 ° C. With stirring, the curcumin powder is added to the polysorbate and further heated to a temperature in the range of 95 to 97 ° C. The addition of the powder takes place at such a rate that it stirs

is fed evenly into the emulsifier. After cooling to a temperature below a maximum of 60 ° C, the curcumin solubilizate is filled. This solubilizate was used for the preparation of a curcumin and boswellia solubilizate.

It should be noted, however, that the curcumin content can be further increased without negative consequences,

For example, to accept the stability of the micelles. A composition of 100 g of 95% curcumin powder and 900 g of polysorbate 80 results in a stable product as well as a composition of 95 g of 95% curcumin powder and 880 polysorbate 80

Production of these two variants corresponds to that described above. In addition to a 7% so up to 11% solubilizates can be produced.

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

Next, a 6% boswellic acid solubilizate was prepared. In addition were

76 g Boswellia serrata extract 80%

(= 60.8 g boswellic acid)

24 g of water 400 g polysorbate 20 used. While heating to a temperature in the range of 87 to 93 ° C, the water is mixed with the Boswellia powder. While maintaining the temperature polysorbate 20 is incorporated. The addition of the emulsifier takes place at such a speed that the fluids homogenize stably with stirring to a solubilizate. In the production of strong foaming may occur. This can be ignored, as long as a clear solubilisate is visible on the bottom of the decanter during bottling. The control of this clarity, which suggests the complete micellization, takes place via

Laser measurements. Such a laser beam measurement, for example, by illuminating the sample using a commercial 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 illuminated solubilisate. The control is not carried out by sampling and thus outside the reaction vessel, but in the reaction vessel. The laser beam passes through a sight glass, 1 Q Ι Ή H T Ί H Q

ηΗρΙ "Y ΜΤΠ

R ai "! 1 Ί V" on S ^" t ^* 5uun inur ^* in cn ^" t umΙζ.t. e? -t sC-In mt. ^ s 1mci cj.ι

Particle structures formed in the

nn ^^ p] V 1 H ·] 1 1 1 H;

~ - f The filling of the product takes place at approx. 50 ° C.

Embodiment 2

Alternatively, a 7% boswellic acid solubilizate could be prepared. In addition were

82 g Boswellia serrata extract 80%

(= 65, 6 g boswellic acid)

70 g of water

350 g polysorbate 20

441 g of polysorbate 80 is used, which corresponds to a total of 943 g.

While heating to a temperature in the range of 48 to 52 ° C, polysorbate 20 and polysorbate 80 are homogenized with stirring with each other while dissolved in each other.

While maintaining the temperature, the

Emulsifier mixture mixed with the water. It is stirred so much that the water evenly in the

Emulsifier solution is released. At unchanged temperature, the Boswellia serrata extract is incorporated with stirring in the water-diluted emulsifier. The Boswellia serrata extract is added at such a slow rate that it is uniformly drawn into the dilute emulsifier solution with stirring. Embodiment 3

For the preparation of the 3% curcumin / 6% boswellic acid solubilizate

500 g of 3% curcumin solubilisate

500 g of 6% Boswellia solubilisate used.

Both solubilisates are optionally heated to a temperature in the range of 50 to 60 ° C to lower their viscosity, i. to improve the flowability. Both solubilizates are homogenized by stirring to a mixed solubilizate with curcumin and boswellia. The product is cooled to a maximum temperature of 60 ° C and filled. This product is particularly suitable for

Use as capsule filling.

With a dilution of water in the ratio 1: 500 turbidity measurements were made at a pH of 1.1 and a temperature of 37 ° C. These gave a value for the above mentioned solubilisate with curcumin and boswellia of 20.5 FNU.

Embodiment 4

5% boswellic acid solubilisate

This solubilizate can be used, in particular, as an intermediate for the preparation of a co-solubilizate comprising boswellic acid and curcumin according to exemplary embodiment 6 be used. For the preparation of this variant of the inventive Boswellia solubilizate be for an amount of 953.5 g

59 g Boswellia serrata extract 80%

(47.2 g boswellic acid)

60 g of water

381 g polysorbate 20

462.5 g polysorbate 80 is used.

While maintaining the temperature, the

Emulsifier solution is released. At unchanged temperature, the Boswellia serrata extract is incorporated with stirring in the water-diluted emulsifier. The Boswellia serrata extract is added at such a slow rate that it is uniformly drawn into the dilute emulsifier solution with stirring.

Subsequently, the temperature is increased to 63 to 67 ° C. The curcumin powder is then stirred into the

Intermediate incorporated. It is stirred so much that the powder is drawn evenly into the fluid. The temperature is further increased to a value in the range between 85 and 89 ° C. After cooling to one

Temperature below a maximum of 45 ° C, the product is filled and stored at a maximum of 25 ° C dark. This too Solubilisat is particularly suitable for filling capsules.

Also for this solubilizate the turbidity was determined under physiological conditions at a dilution in water of 1: 500. The result was 1.9 FNU as the average of two measurements (2.9 FNU, 0.8 FNU).

Embodiment 5

3% curcumin / 4, 7% boswellic acid solubilisate It will

59 g Boswellia serrata extract 80%

(47.2 g boswellic acid)

37.5 g of 95% curcumin powder (

35, 6 g curcumin)

60 g of water

381 g polysorbate 20

462.5 g polysorbate 80 is used.

While heating to a temperature in the range of 48 to 52 ° C, polysorbate 20 and polysorbate 80 are homogenized with stirring with each other while dissolved in each other. While maintaining the temperature, the

Emulsifier solution is dissolved. At unchanged temperature, the Boswellia serrata extract with stirring in the with Water diluted emulsifier incorporated. The Boswellia serrata extract is added at such a slow rate that it is uniformly drawn into the dilute emulsifier solution with stirring.

For a particle size analysis of this under

Example 5 described Solubilisats this Solubilisat this first in the ratio 1: 500 diluted with distilled water and brought under constant stirring with a magnetic stirrer and with the aid of a hot plate to 37 ° C. Subsequently, the pH was adjusted to 1.1 with 32% hydrochloric acid. The samples were in the

Measure the connection immediately. The results are summarized in the following table. The data of two measurements were averaged.

Embodiment 6

5.4% curcumin / 6, 6% boswellic acid solubilisate

This further embodiment of the solubilizate according to the invention was also prepared directly. Like in the case of the previously described curcumin-boswellic acid solubilis, co-micellization of the active ingredients was also carried out here. This was here

Boswellia serrata extract

(= 65, 6 g boswellic acid) Curcumin powder 95% (= 54.1 g curcumin)

70 g of water

350 g polysorbate 20

441 g polysorbate 80 used.

The production of the 5.4% curcumin / 6, 6% boswellic acid solubilizate was carried out in the same way as the preparation of the previously described 3, 6% curcumin / 4, 7% boswellic acid solubilisate.

Whether a sufficiently complete homogenization of the

Components for a solubilizate according to the invention

is completed, the clarity of the product is checked with the aid of a laser beam during production via measurements. In the context of the invention, the contents of curcumin and boswellia extract in the individual solubilisates, depending on the application, also significantly higher than shown

Example to be set. If higher loadings are set with active ingredient, this is limited by the fact that, when an individual active ingredient content that is individual for the respective composition is exceeded, no solubilisate is produced, but rather an emulsion. If the active ingredient content is increased, necessarily the corresponding proportions of the other components (in

Wt .-%). Above a specific limit one obtains a disperse system, which does not however like that

solubilisates according to the invention irreversible in water is soluble and for these solubilisate under

physiological conditions of the gastric passage, ie at pH 1.1 and 37 ° C, measured very low turbidity. Such dispersions may be (nano) emulsions, but they are not solubilizates in which the active ingredient or agents are included in the very small micelles. However, only the solubilizates allow according to the experience of the inventor significantly increased

Bioavailability of the active ingredient (s) according to the invention, even if an emulsion has a higher

Drug loading allowed.

Scientific studies have investigated the improved bioavailability of the solubilizates according to the invention.

N. Gray published below

"http://nutraingredients.com/Research/" his article "Curcumin touted for metabolic benefits in people with fatty liver disease: RCT data", which is the results of a randomized controlled trial (RCT), in which phytosomal curcumin was administered A phytosome is a complex of a natural active substance and

Phospholipids. These suggest that an eight-week dose of curcumin may affect several health factors, including BMI (body mass index) and liver fat, and transaminase levels in people with non-alcoholic fatty liver (NAFLD). In addition, curcumin has been associated with the lowering of serum total cholesterol, LDL cholesterol,

Triglycerides, non-HDL cholesterol and uric acid. In the publication of Ch. Schiborr et al. : "The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes", Molecular Nutrition & Food Research, 2014, 0, pages 1 to 12

Studies on the bioavailability of native curcumin and a curcumin micronisate compared to one

Curcuminsolubilisat the applicant described. The low systemic bioavailability has hitherto hindered the clinical application of curcumin. Due to the rapid conversion into the liver and intestinal wall, the concentrations of curcumin in the blood are low and the distribution in the tissue is limited after oral intake. Even after taking up to 12 g of curcumin, the maximum moves

Plasma concentration in humans in the area below

160 nmol / L.

The investigations used native curcumin powder (Jupiter Leys, Cochin, Kerala State, India). It contained 82% by weight of curcumin. The curcumin micronisate was manufactured by RAPS GmbH & Co. KG, Kulmbach, Germany with the so-called "concentrated powder form technology"

(concentrated powder form technology) by mixing 25 wt .-% curcumin powder with 58.3 wt .-% triacetin

(Glycerol triacetate) and 16.7% by weight of Panodan®, a

Diacetyltartaric acid glyceride, which in the EU as

Food additive of the designation E 472e without

Quantitative limit (quantum satis) is generally permitted for food. The resulting solution is sprayed onto a porous support of silicon dioxide. The resulting curcumin micronisate contains 17.2% by weight. Curcumin powder, which corresponds to 14.1 wt .-% curcumin. Applicant's curcumin isolate consisted of 7% by weight of curcumin powder, which corresponds to 6% by weight of curcumin, and

93% by weight Tween 80.

The study involved 23 healthy individuals, 13 women aged 19 to 28 and 10 men aged 20 to 28 years. They got sober in the morning

Single dose of 500 mg curcuminoids containing 410 mg

Curcumin, administered in 50 g of woodruff syrup. Before intake of curcumin and after 0.5; 1; 1.5; 2; 4; Blood samples were taken 8 and 24 hours.

The measured data thus obtained became statistical

and AUC (area under the curve) is calculated using the GraphPad Prism 6 software. The AUC value is the most reliable measure of bioavailability, as this is the total response of the organism over time. In part, the maximum total concentration in the plasma Cmax is used as a value, x times

Increase in bioavailability. The

maximum total concentration in plasma Cmax, however, only indicates the condition at a specific time and is therefore less meaningful than the AUC value.

Curcumin was never detected in the blank samples. The maximum total concentration in plasma Cmax and the associated AUC value was significantly higher for the

Curcumin micronisate and the curcumin solubilisate as for the native curcumin. Averaged over all subjects, a 185-fold higher AUC value after taking the

Curcuminsolubilisats compared to the native form

measured. Based on native curcumin was after the Ingestion of curcumin solubilized averaged over all

Subjects measured a 453-fold higher maximum total plasma concentration C _ma x. The time T _ma x, after which this higher maximum total concentration was detected in the plasma C _ma x, clearly after taking the micellized curcumin from the solubilisate, namely about 7 times, shorter than the native form.

With the 185-fold higher AUC value is the

Curcuminsolubilisat the applicant according to their knowledge the formulation of curcumin, which of all hitherto

tested formulations have the highest bioavailability.

The Central Laboratory Deutscher Apotheker e. V.,

Eschborn, Germany, determined the main boswellic acids

(BAs) after oral administration in rats of blood plasma for determination of bioavailability in a 10%

Solubilisate of Applicant's Boswellia serrata extract compared to native dry extract of Boswellia serrata

(BSE, 80%). The data relate to wt .-%. The animal experiments were conducted at the Institute of Pharmacy and

Molecular Biotechnology in the Department of Pharmaceutical Technology and Pharmacology, Heidelberg, Germany.

The most relevant boswellic acids are according to U.

Siemoneit et al. "Inhibition of microsomal prostaglandin E2 synthase I as a molecular base for the anti-inflammatory actions of boswellic acids from frankincense", British Journal of Pharmacology 162 (1), pages 147-162, KBA, AKBA and beta-BA greatest availability for the Organism of the experimental animals of these Boswelliasauren in blood plasma was achieved with the 10% solubilizate of Boswellia serrata extract of the applicant in comparison with native dry extract of Boswellia serrata (BSE, 80%). The formulation as a solubilizate led to a

Significant increase in values for AUC and C _ma x im

Comparison to the pure extract.

For these investigations, 12 female albino-Wistar rats weighing 250 g were taken orally

Dry extract of Boswellia serrata (BSE, 80%) or

10% solubilisate from Applicant's Boswellia serrata extract. For this purpose, initially 300 mg BSE were mixed with 15 ml water. From the resulting suspension, 2 ml were administered to the rats. This corresponds to a dose of 128 mg BSE / kg body weight. Based on a total content of boswellic acid (KBA, AKBA, beta-BA, A-beta-BA, alpha-BA and A-alpha-BA) in the Boswellia serrata extract of 33.21%, one animal thus had 57.67 mg BSE / kg body weight given orally.

In the case of solubilisate with a total content

Boswellia acids of 3.12% were added to 20 g of solubilisate with 80 mL of water. From the resulting solution was added 2 mL corresponding to a dose of 128 mg BSE / kg

Body weight equivalent to the dose of BSE administered orally to the rats.

Blood plasma samples were taken at defined times

after oral administration ("0") and after 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h and after 8 h, the samples were centrifuged and stored at -20 ° C. The content of boswellia acids in the samples was determined by a sensitive LC-MS / MS method based on

Liquid chromatography determined in K. Gerbeth et al. "Determination of major boswelic acids in plasma by high-pressure liquid chromatography / mass spectrometry", Journal of Pharmaceutical and Biomedical Analysis 56 (5), pages 998 - 1005. The following compositions were prepared in the native dry extract of Boswellia serrata ( BSE, 80%) or in solubilisate

found.

Table 1: Determination of boswellic acids in the dry extract of Boswellia serrata (BSE, 80%), data in% by weight

Table 2: Determination of boswellic acids in a 10% solubilisate of Boswellia serrata of the Applicant, data in% by weight

The absolute total amount of 128 mg Boswellia serrata dry extract (100%) per kg of body weight

contained the found boswellic acids in

following dose Table 3: Administered dose of the individual

Boswellia acids, data in mg / kg body weight

The determined ratio was used to determine a consistent level of values for the dry extract and for the solubilizate for the determination of the Cmax, Tmax and AUC values. In the evaluation in

Table 4 shows the values calculated with this correction. For each of the boswellia acids mentioned, the value of the blood plasma content in ng / mL, averaged over the respective number of animals, was investigated over a period of 8 hours.

The evaluation of the measured data for 6 rats leads to the following result.

Table 4: AUC, Cmax and T _ma x for each

Boswellia acids after a single dose of the dry extract of Boswellia serrata (BSE, 80%) or 10%

Solubilisate of Boswellia serrata of the Applicant

Cmax / ng / mL Tmax / h AUC / ng / mL * h

KBA dry extract 0 0 0

Solubilisate 440, 09 0, 92 1187.74

AKBA dry extract 38.44 2.00 97, 66

Solubilisate 890, 06 2, 67 5142.44

CC-BA dry extract 282, 60 7, 33 1260.43

Solubilizate 1480, 87 7, 33 8590.25 ß-BA dry extract 447.33 7, 67 1983, 15

Solubilisate 2511,23 6, 33 14875,20

A-CC-BA dry extract 184.48 7.00 745.26

Solubilisate 841, 64 7, 67 3808, 67

A-β-BA dry extract 766, 13 7, 67 3081.89

Solubilisate 1760, 32 7, 67 10833.70

While the oral administration of BSE did not lead to a detectable in blood plasma concentrate ion of KBA, was transported with the Boswellia solubilizate KBA in the bloodstream and thus by the Applicant in bioavailable form to

Provided.

The Boswellia Solubilisat the Applicant to the

The dry extract equivalent level of AKBA resulted in a 23-fold increase in Cmax and a 53-fold increase in AUC compared to the dry extract.

The Boswellia Solubilisat the Applicant to the

Dry extract equivalent content of CC-BA or ß-BA led to a 5-fold or almost 6-fold increase in Cmax and a nearly 7-fold

or 7.5 times higher AUC value compared to the dry extract.

The Boswellia Solubilisat the Applicant to the

Dry extract equivalent content of A-CC-BA

or A-ß-BA led to a nearly 5-fold

or 2 times increased value for Cmax and a 5-fold or 3.5-fold increased AUC value in

Comparison to the dry extract.

In summary, it can be stated that the formulation of the Boswellia serrata dry extract as Solubilizate according to the invention to a clear

Increasing the values for C _ma x and AUC for the investigated boswellia acids. That means the

Bioavailability of these boswellia acids by the

inventive formulation is significantly increased over the dry extract.

The dosages for humans corresponding to the doses determined in rats in animal experiments were calculated as described below. The conversion of the dosage for rats into the dosage for humans, in mg pr kg body weight and day, takes place according to the equation

Dosage _Rat

Dosage _human = - ° 6

5 mg curcumin / kg body weight rat 0.81 mg curcumin / kg body weight human. 10 mg boswellia / kg body weight rat 1.62 mg boswellia / kg body weight human.

Based on a body weight of 70 kg, a daily dose for humans results from:

Curcumin:

((5 37) x 6) x 70 = 56, 76 mg curcumin / human / day

Boswellia: ((10 37) x6) x 70 = 113.51 mg boswellia / human / day

For the daily dose of a human results in the following solubilisate amount:

The following calculation was done for a

6% curcumin solubilizate according to the invention. Curcumin: 56.76 mg x 16.67 = 946.19 mg solubilisate

Polysorbate:

946.19 mg solubilisate x 0.925 = 870.49 mg polysorbate

Curcumin solubilisate. The following calculation was made for a 12% Boswellia solubilizate according to the invention.

Boswellia: 113.51 mg x 8.33 = 945.54 mg solubilisate

Polysorbate: 945.54 mg x 0.80 = 756.43 mg polysorbate in Boswellia solubilisate.

The total amount of polysorbate in solubilisate with 5 mg

Curcumin and 10 mg Boswellia is thus 1,626.92 mg. Based on a body weight of 70 kg and the WHO recommendation of a daily intake of 25 mg polysorbate (= 1750 mg polysorbate / day), the solubilisates described above are all within the recommended daily limits

Intake of WHO.

At the University of Cairo in the Faculty of Pharmacy at the Institute for Pharmacology, Prof. Dr. Ing. MT Khayyal Investigations on the anti-inflammatory effect of combinations of curcumin with boswellia in each case in native or in solubilized according to the invention form.

There were anti-inflammatory markers and the

antioxidant capacity determined. Female Wistar rats weighing between 150 and 200 g were prepared according to "Pearson et al. (1956) "the" adjuvant induced arthritis "exposed. The animals were subplanted

Injection of 0.1 ml of Freund s ^e administered adjuvant (FCA) on day 0 into the right hind paw. The animals were randomly divided into 12 groups of 8 animals each

divided up .

Group 1 formed the control group.

Group 2 received diclofenac as a reference drug at a dose of 3 mg / kg body weight.

Group 3 received native curcumin at a dosage of 5 mg / kg body weight.

Group 4 was solubilized according to the invention

Curcumin at a dosage of 5 mg / kg body weight.

Group 5 received native curcumin at a dose of 10 mg / kg body weight and

Group 6 curcumin solubilized in the same dosage. Group 7 received native xanthohumol at a dose of 5 m / kg body weight and

Group 8 solubilized xanthohumol in the same

Dosage.

Group 9 received a mixture of native curcumin at a dosage of 5 mg / kg body weight and native

Boswellia extract in a dosage of 10 mg / kg

Body weight . Group 10 received a mixture of solubilized

Curcumin and solubilized Boswellia in the same dosage.

Group 11 received a mixture of native curcumin at a dosage of 5 mg / kg body weight and native

Xanthohumol in a dosage of 5 mg / kg body weight and

Group 12 received a mixture of solubilized

Curcumin and solubilized xanthohumol in each case the same dosage.

All extracts or solubilisates were orally administered once daily from day 0 to day 21 post vaccination with the adjuvant. After day 21, the animals were killed and

Serum samples prepared and stored at - 80 ° C. Measured were myeloperoxidase (MPO), C-reactive protein (CRP), total antioxidant capacity (TAC) and

(thiobarbituratic acid reactive substances) (TBARS).

The results are explained below with reference to the accompanying figures. Show it

Figure la effect of curcumin in native and

solubilized form and diclofenac on serum CRP (pg / L),

Figure lb Effect of curcumin (5mg / mL) in native and

solubilized form given together with

either boswellia or xanthohumol compared to diclofenac on serum CRP (pg / L), FIG. 2 effect of curcumin in native and solubilized form and of diclofenac on the serum content of MPO (mU / ml), and

Figure 3 Effect of curcumin in native and

solubilized form given together with

either boswellia or xanthohumol compared to diclofenac on the serum content of MPO (mU / mL)

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

If boswellia is co-administered with curcumin in their native form, the inhibitory effect on serum CRP will not change significantly (Figure lb). However, when curcumin and boswellia are administered in solubilized form together and at the appropriate dosage, the anti-inflammatory effect is enhanced. In this

Relationship, Boswellia xanthohumol is superior in potentiating the effect of curcumin at the doses considered.

Myeloperoxidase (MPO) in plasma plays a central role as a pro-inflammatory mediator in rheumatoid Arthritis and is an indicator of immigration

neutrophilic granulocytes in the affected tissue. Its concentration is elevated in patients with rheumatoid arthritis and causes oxidative stress. In the

Investigations were the concentration of MPO by

solubilized curcumin was efficiently reduced at both considered dosages in the same way and not significantly different from diclofenac. However, native curcumin did not affect MPO levels (Figure 2). The use of boswellia with curcumin in both native and solubilized forms did not improve the effect of curcumin in reducing MPO levels.

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 oxigen species (ROS)" leads to a reduced intake of endogenous antioxidants and ultimately results in the destruction of cells .The neutrophilic granulocytes released in the rheumatoid joint

produce oxygen free radicals which result in increased formation of lipid peroxides which show an increase in serum TBARS. Therefore, the increase in antioxidant status, which is 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 level of the TAC and that of the TBARS, a high level of

antioxidant capacity TAC corresponds to a low concentration of TBARS. The investigations carried out showed that the native form of curcumin had no significant effect on the levels of TBARS or TAC at both dosages considered. Solubilized curcumin according to the invention reduced the level of TBARS at both selected dosages and increased TAC, with little difference to the effect of diclofenac.

These data are summarized in the following table. The table contains data on the effect of curcumin and

Boswellia in native and solubilized form either alone or in combination with diclofenac at a dosage of 3 mg / 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 SEM.

Group TAC TBARS

(nmol / microliter) (nmol / L)

arthritic

57, 26 ± 3.36 13, 10 ± 0.39 control group

diclofenac

82, 08 ± 2, 96 7, 93 ± 0.84 (3 mg / kg)

Native curcumin

60.31 ± 3.25 11.64 ± 0.39 (5 mg / kg)

solubilized

77.01 ± 0.73 5, 97 ± 0.47 curcumin (5 mg / kg)

Native curcumin

68.41 ± 1.09 13.18 ± 0.46 (10 mg / kg)

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)

The administration of boswellia together with curcumin, each in native form, did not show any significant effect of reducing the oxidative stress according to the results presented in the table. In solubilized

However, these combinations were as effective as diclofenac in reducing TBARS and increasing serum TAC in the arthritic rats.

By the measured small particle sizes becomes

advantageously the formation of a particular for the perception with the human eye clear

Liquid reached.

The clarity of the solubilizate can also be represented by its low turbidity. This is the following

Working hypothesis applied: the clearer a watery

Dilution of a solubilizate or another

Formulation of curcumin and boswellia, especially under physiological conditions of a gastric passage, ie at a pH of 1.1 and a temperature of 37 ° C, the better is its solubilization. The better the better

Solubilization, the better the bioavailability of the active ingredients or of the product containing them.

This bioavailability can already be deduced from the particularly low turbidity of the solubilizate, which can be understood as a type of parameter for bioavailability. The inventive transparent and completely stable water-soluble formulation has, without excipients as in soft and hard gelatin capsules, in gelatin-free capsules (hard and / or soft) and in liquid on water

based on pH-independent stable products

Transparency. Products with such transparency and water solubility are urgently needed by the relevant industry for innovative products as capsule filling. A formulation of curcumin with boswellia, that is to say with at least one boswellic acid and / or at least one derivative of a boswellic acid which meets these requirements, does not yet exist to the knowledge of the inventor.

As a result of the formulation according to the invention in one

Solubilisate with very small, stable and

enteric micelles, the invention provides a solubilisate of curcumin with boswellia for use as a medicament, in particular for use as a medicament having an antiinflammatory effect.

It will be apparent to those skilled in the art that the invention is not limited to the examples described above, but rather can be varied in many ways. In particular, the features of the individual

Examples shown also combined or replaced with each other.

Claims

claims

Containing solubilisate, in particular consisting of

Curcumin having a content of less than or equal to 10% by weight, preferably less than or equal to 8% by weight, particularly preferably 3% by weight to 7% by weight,

one or more boswellic acids and / or one or more boswellic acid derivatives in a proportion of less than or equal to 10 wt .-%, preferably less than or equal to 8 wt .-%, particularly preferably 4.7 wt .-% to 6.6 wt. -% and

at least one emulsifier having an HLB value in the range between 13 and 18, in particular polysorbate 80 or polysorbate 20 or a mixture of polysorbate 20 and polysorbate 80.

Solubilisate according to claim 1,

characterized in that the solubilizate as

A source of the one or more boswellic acids and / or one or more boswellic acid derivatives containing an extract obtained by extraction with acetic acid ethyl ester from the resin of the plant Boswellia serrata, boswellic acids being present in this extract in a concentration of at least 85% by weight.

present.

Solubilizate according to one of the preceding claims, characterized in that

the ratio of emulsifier to boswellic acids and / or to boswellic acids and at least one of their derivatives in the range between 20: 1 and 3: 1, preferably in the range between 16: 1 and 4: 1, preferably in the range between 14: 1 to 5: 1 lies. Solubilizate according to one of the preceding claims, characterized in that

the ratio of emulsifier to curcumin in the

Range between 30: 1 and 3: 1, preferably in the range between 25: 1 and 9: 1, preferably in the range between 23: 1 to 12: 1.

Solubilizate according to one of the preceding claims, characterized in that

the ratio of emulsifier to the total mass of curcumin and boswellic acids and / or curcumin and boswellic acids and at least one of their derivatives in the range between 15: 1 and 3: 1, preferably in the range between 10: 1 and 4: 1, preferably in the range between 8 , 8: 1 to 5.7: 1.

Solubilizate according to one of the preceding claims, characterized in that

the emulsifier content, in particular the

Polysorbate content, at least 70% by weight, preferably in the range between 75% by weight and 95% by weight, particularly preferably in the range between 79% by weight and 88% by weight.

Solubilizate according to one of the preceding claims, characterized in that

the solubilizate contains up to 20% by weight, preferably up to 15% by weight of ethanol.

Solubilizate according to one of the preceding claims, characterized in that the solubilisate contains up to 25% by weight, preferably up to 10% by weight, of glycerol.

9. Solubilisat according to one of the preceding claims, characterized in that

the diameter distribution of the micelles in a dilution of the solubilisate with distilled water in the ratio 1: 500 at pH 1.1 and 37 ° C of about

nm to about nm is sufficient.

10. Solubilisate according to one of the preceding claims 1 to 9,

characterized in that

the anti-inflammatory activity measured as the concentration of C-reactive protein (CRP) in the

Blood serum of arthritic rats after single administration of the solubilisate in a dosage of 5 mg / kg

Body weight of curcumin and 10 mg / kg body weight of boswellic acids ranges from about 1200 pg / mL to about 1500 pg / mL.

11. Solubilizate according to one of the preceding claims 1 to 10,

characterized in that

the antiinflammatory effect measured as the concentration of myeloperoxidase (MPO) in the blood serum of arthritic rats after a single dose of

Solubilisats in a dosage of 5 mg / kg

Body weight curcumin and 10 mg / kg body weight boswellic acids ranges from about 750 mU / mL to about 815 mU / mL.

12. Solubilisat according to any one of the preceding claims, characterized in that

the turbidity of the solubilizate is less than 25 FNU, preferably less than 3 FNU is measured by

Scattered light measurement with infrared light after the

13. capsule filled with a solubilizate according to any one of the preceding claims,

characterized in that

the capsule as a soft gelatin capsule or hard gelatin capsule or as a soft, gelatin-free capsule or as a hard, gelatin-free capsule

is trained.

14. Fluid containing a solubilizate according to one of

Claims 1 to 12,

characterized in that

the fluid is selected from the group comprising foods, beverages, cosmetics and pharmaceutical products.

15. Fluid according to claim 14,

characterized in that

the fluid comprises an aqueous dilution of the solubilizate.

16. Use of a solubilizate according to one of

Claims 1 to 12 or a fluid according to any one of claims 14 or 15 as medicaments for the treatment of inflammatory diseases, cancer, Alzheimer's, Parkinson's, obesity, high Cholesterol levels, elevated blood sugar, metabolic syndrome and / or autoimmune diseases.

Method of treating inflammatory diseases, cancer, Alzheimer's,

Parkinson's, obesity, high cholesterol, elevated blood sugar, metabolic syndrome and / or autoimmune diseases,

characterized in that

a solubilizate according to any one of claims 1 to 12, in particular in a capsule according to claim 13 or as a fluid according to any one of claims 14 or 15, the patient, in particular orally, is administered.

Method according to claim 21,

characterized in that

the solubilisate is administered to the patient at a dose of curcumin ranging from 0.5 mg / kg body weight to 1 mg / kg body weight, preferably at a dose of

0.81 mg / kg body weight, and in a boswellia dose in the range of 1 mg / kg body weight to 2 mg / kg

Body weight, preferably with a dose of

1.62 mg / kg body weight,

especially once daily.

A process for producing a solubilizate according to any one of claims 1 to 16,

with the following steps

Polysorbate 80

b) Addition of Boswellia serrata extract powder c) Addition of curcumin powder in which

in step a) heating to a temperature in the range of 40 ° C to 62 ° C, preferably to a

Temperature in the range of 45 ° C to 57 ° C, particularly preferably to a temperature in the range of 48 ° C and 52 ° C, takes place

and where

in step b) heating to a temperature in the range of 60 ° C to 75 ° C, preferably to a

Temperature in the range of 61 ° C to 70 ° C, more preferably at a temperature in the range of 63 ° C and 67 ° C,

and where

in step c) heating to a temperature in the range of 82 ° C to 97 ° C, preferably to a

Temperature in the range of 83 ° C to 92 ° C, more preferably to a temperature in the range of 85 ° C and 89 ° C.

Method according to claim 19,

wherein before step b) a step

bl) adding water at a temperature in the range of 40 ° C to 62 ° C, preferably at a temperature in the range of 45 ° C to 57 ° C, more preferably at a temperature in the range of 48 ° C and 52 ° C, is carried out.

A process for producing a solubilizate according to any one of claims 1 to 16,

by mixing a Curcuminsolubilisats and a Boswellia solubilizate, in particular in

Quantity ratio 1: 1.

22. A method for producing a Boswellia solubilizate, in particular for use in a method according to claim 21, comprising the following steps,

a) Presentation of Boswellia serrata extract powder b) Addition of polysobate 80 and / or polysorbate 20

and / or a mixture of polysorbate 20 and

Polysorbate 80

in which

in step b) heating to a temperature in the range of 82 ° C to 97 ° C, preferably to a

Temperature in the range of 84 ° C to 95 ° C, more preferably at a temperature in the range of 87 ° C and 93 ° C.

23. The method according to claim 22,

wherein before step b) a step

bl) adding water at a temperature in the range of 82 ° C to 97 ° C, preferably at a temperature in the range of 84 ° C to 95 ° C, more preferably at a temperature in the range of 87 ° C and 93 ° C, is carried out.