HK40039601A - Solubilisate with curcuminin and at least the cannabinoidthc as a further active agent - Google Patents

Description

Solubilizates containing curcumin and at least cannabinoid THC as other active substances

Technical Field

The present invention relates to a solubilisate comprising curcumin and at least the cannabinoid THC. Furthermore, the invention relates to a liquid containing such a solubilisate, a capsule containing such a solubilisate or liquid, and a dietary supplement and/or a medicament containing such a solubilisate.

Background

Curcumin is considered an active substance based on various possible pharmacological properties. For example, there is evidence for the antioxidant and anti-inflammatory effects and antiviral and bacterial and anticancer efficacy of curcumin. Thus, the indication may be, for example, parkinson's disease, alzheimer's disease, diabetes, colorectal tumours, pancreatic cancer and liver dysfunction.

Cannabinoids are some of the transformation products and synthetic analogues of terpene phenols, mainly found in the Cannabis plant (Cannabis).

The term "Cannabis plant" ("Hanfpflanze" or "Cannabispflanze") includes wild-type Cannabis Sativa (Cannabis Sativa) and its varieties, including Cannabis chemical varieties naturally containing various cannabinoids in varying amounts (Cannabis-Chemovar), indian Cannabis subspecies, as well as plants which are the result of genetic crossing, selfing or hybrids thereof.

Cannabis plant contains at least 113 cannabinoids from the terpene phenolic group. One of these cannabinoids is Δ 9-Tetrahydrocannabinol (THC). Tetrahydrocannabinol (THC) is believed to be the major psychoactive substance responsible for the hallucinogenic effects of cannabis products. THC is naturally present in plants in the form of two THC acids which are converted to THC by heating the plant material.

In addition to hallucinogenic effects, THC has considerable medical properties, such as pain relief and relaxation, appetite stimulation, antioxidant and neuroprotective effects and relief of glaucoma (glaucoma).

Cannabis also contains a number of non-cannabinoids with different pharmacological properties. There are indications that cannabinoids such as Cannabinol (CBN), Cannabidiol (CBD) and others alter the effect of a 9-THC.

The artificial cannabinoids may be produced semi-synthetically, i.e. from natural cannabinoids, or completely synthetically from simple starting materials. Still other plants can produce active substances that are effective to the human body through the same mechanism as cannabinoids from cannabis plants.

In order to be able to enter the blood circulation after oral administration, the active substance must cross the blood barrier of the small intestine, then be metabolized in the liver and enter the hepatic vein as a bioavailable component. The remaining total active substance taken in and released in the body is degraded by microorganisms in the intestinal tract or eliminated through feces or bile.

The inventors have obtained a curcumin solublite having significantly improved bioavailability compared to natural curcumin. Such solubilizates are described in international patent application WO 2014094921 a 1. Surprisingly, it was found in several studies that this curcumin solublite, in its specific composition, also has an unexpectedly greater effect on alleviating the symptoms of diseases, in particular related to inflammation or cancer, due to high bioavailability.

The toxicity caused by the micellization of the active substance according to the invention, compared with the native form, can be ruled out by means of studies relating to the determination of cell viability (viatility) using the MTT assay. Cell viability was verified by MTT assay based on the reduction of the yellow water-soluble dye 3- (4, 5-dimethyl-2-thiazolyl) -2, 5-diphenyltetrazolium bromide (MTT) to blue-violet, water-insoluble formazan.

Disclosure of Invention

It is therefore an object of the inventors to provide a formulation which, in view of combination with at least the THC form of cannabinoid as another active substance, enables the human or animal organism to exploit the health promoting or therapeutic properties of curcumin. The object of the present invention is especially to achieve as high a bioavailability of curcumin as possible in combination with at least one cannabinoid.

It is another object of the invention to provide a THC which is nutritionally physiologically and/or pharmacologically acceptable. It is an object of the invention, inter alia, to provide THC in a form which, when mixed with water, gives a mixture which is haze-free to the human eye.

These objects are achieved in a surprisingly simple manner with the solubilizate of claim 1. The solubilizate consists of or comprises the following components: curcumin in a content equal to or less than 10% by weight, preferably less than or equal to 8% by weight, particularly preferably from 3% to 7% by weight, preferably from 1% to 3% by weight, and at least THC as at least one further active substance, and at least one emulsifier with an HLB value of less than 18, preferably between 13 and 18, in particular polysorbate 80 or polysorbate 20 or at least one sucrose ester of an edible fatty acid (approved as food additive E473 in the european union) or a mixture of at least two emulsifiers selected from polysorbate 20, polysorbate 80 and sucrose esters of edible fatty acids.

The invention also provides a solubilisate comprising, in particular consisting of: THC in an amount of less than or equal to 10% by weight, preferably less than or equal to 5% by weight, particularly preferably from 0.3% by weight to 3% by weight, and at least one emulsifier having an HLB value of less than 18, preferably from 13 to 18, in particular polysorbate 80 or polysorbate 20 or at least one sucrose ester of a dietary fatty acid or a mixture of at least two emulsifiers selected from polysorbate 20, polysorbate 80 and sucrose esters of a dietary fatty acid.

The solubilization substance can be mixed with curcumin solubilization substance for use. It may also contain other active substances. Furthermore, the THC solubilizate itself has the advantage of providing THC in an orally administrable form, for example in the form of a beverage or capsule filling. The solubilization of THC according to the invention provides an effective protection against oxidation of the active substance. The invention allows to provide products with a longer shelf life by improved oxidation protection of THC.

In an advantageous embodiment, the solubilizate is provided in a form which can be administered orally, in particular in a curcumin dose of 0.5mg/kg body weight to 1mg/kg body weight, preferably 0.81mg/kg body weight, in particular once daily.

Within the scope of the present application, the term "active substance" means a substance which is present in a pharmaceutically effective concentration and is preferably added for the purpose of having a pharmaceutical effect. The designation of the corresponding active substances is also understood here to mean substances which are converted in vivo into the respective corresponding active substances and/or their biologically active forms.

One active substance within the scope of the present application is THC. In the sense of the present application, "active substance" also includes secondary plant substances which are produced by plants in the form of compounds neither in the energy metabolism nor in the anabolic or catabolic metabolism. A group of secondary plant substances and thus active substances in the sense of the present invention are flavonoids. Natural polyphenols, such as resveratrol or polyphenols from licorice, as well as natural phenols, in particular chalcones, such as xanthohumol, also belong to the "active substances" in the sense of the present invention. It also includes plant extracts, i.e., substances extracted from plants or parts of plants using an extractant. These include extracts of hops. Even if the active substance is still dissolved in the extractant, it is also referred to as "extract". The term "extract" may also be used for extracts.

Within the meaning of the present application, "active substance" also includes enzymes. An example of an enzyme as "active substance" in the present application is serrapeptase. However, the present application is not limited to this enzyme.

An extract from the resin of the mastic tree, Boswellia Serrata (Boswellia serrrata), contains a variety of pentacyclic triterpenes, which together are commonly referred to as total boswellic acids ("total BAs"). The term "boswellic acids" refers to a group of chemical compounds naturally occurring in the aforementioned boswellia resin. The two basic structures are alpha-boswellic acid and beta-boswellic acid. Derivatives are also known from these boswellic acids, especially compounds carrying a keto group at the 11-position and/or being acetylated at the 3-position. Boswellic acids currently considered to be of particular importance in terms of pharmacological action include "α BA" α -boswellic acid and "β BA" β -boswellic acid and their derivatives "KBA" 11-keto- β -boswellic acid (CAS 17019-92-0) and "AKBA" 3-O-acetyl-11-keto- β -boswellic acid (CAS 67416-16-9) as well as "a α BA" 3-O-acetyl- α -boswellic acid and "a β BA" 3-O-acetyl- β -boswellic acid. In particular, the derivative AKBA is believed to have an anti-inflammatory effect.

Within the scope of the present application, the expression "boswellia", especially as used in the term "boswellia solubilisate", refers to the active substance from the resin of the boswellia serrata, i.e. to at least one boswellic acid and/or at least one boswellic acid derivative. The expression "boswellic acid solubilisate" refers to a micellar preparation of at least one boswellic acid. It may further comprise at least one boswellic acid derivative.

Xanthohumol is a flavonoid naturally present in hops. Here is an allylated plant polyphenol which belongs to chalcones and has only been identified so far in hops. The content of xanthohumol in the bitter hop variety is far higher than that in the aroma variety. In the tests, xanthohumol was found to be effective against the appearance and progression of cancer cells. In addition, it has been found in laboratory experiments that xanthohumol can protect nerve cells of the brain and thus may help slow the progression of diseases such as alzheimer's disease or parkinson's disease.

Serratia peptidase or serrapeptase is a proteolytic enzyme produced by Serratia bacteria living in the intestine of silkworms. Serratin peptidase is useful in relieving pain, inflammation, traumatic swelling and hypersecretion of mucus in organs and tissues. It has anti-inflammatory and analgesic effects in a manner similar to acetylsalicylic acid, ibuprofen, or other non-steroidal analgesics. In addition, it causes fibrinolytic anti-inflammatory and anti-edematous activity in the tissue. Like all enzymes, serrapeptase is sensitive to acid produced by the stomach. It is therefore an object of the present invention to provide a formulation which allows passage through the stomach.

The solubilizates according to the invention may comprise one or more boswellic acids and/or one or more boswellic acid derivatives in an amount of overall less than or equal to 10 wt.%, preferably less than or equal to 5 wt.%, particularly preferably from 2 to 4 wt.%.

Due to the high proportion of boswellia, the present invention sets in its advantageous embodiment that said solubilizate comprises an extract obtained from the resin of the plant boswellia serrata by extraction with ethyl acetate as source of one or more boswellic acids and/or one or more boswellic acid derivatives, wherein the concentration of boswellic acids in the extract is at least 85% by weight.

The solubilizates according to the invention can comprise xanthohumol in a fraction of less than or equal to 10% by weight, preferably less than or equal to 5% by weight, particularly preferably from 1% by weight to 3% by weight.

Due to the high fraction of xanthohumol, the invention therefore provides in an advantageous embodiment thereof that the solubilizate comprises an ethanolic extract of the hard resin of hops as a source of xanthohumol, the concentration of xanthohumol in the extract being in the range of 65% and 95% by weight, preferably in the range of 80% to 92% by weight. In particular, the products "Xantho-Flav pur" or "Xantho-Flav" which will be explained in more detail below, can be used as a source of xanthohumol within the scope of the present invention. The solubilizate according to the invention may comprise up to 3% by weight, preferably in the range between 0.1% and 2% by weight, particularly preferably in the range between 0.18% and 0.35% by weight, of serrapeptase.

Within the scope of the present invention, it may also be advantageous to set or use solubilizers consisting of or comprising curcumin and at least THC as further active substances for the treatment and/or prevention of diseases which are complicated by inflammation, cancer, alzheimer's disease, parkinson's disease, obesity, high cholesterol, elevated blood sugar, diabetes, metabolic syndrome and/or autoimmune diseases, Multiple Sclerosis (MS), for reducing visceral fat, for reducing heat development, for reducing cholesterol, in particular LDL cholesterol, and/or for reducing glucose in the blood and/or triglycerides in the blood, for improving macular pigment density, for reducing oxidative stress and/or reducing the accumulation of fat in liver cells, in particular as medicaments for the treatment and/or prevention of fatty liver, friedreich's ataxia, lysosomal diseases, especially Tay-Sachs disease, arteriosclerosis, heart disease, arthritis.

In particular, the present invention provides a solubilisate as described above for use as an anti-inflammatory agent and/or an antibiotic and/or a medicament having an effect against cancer, Alzheimer's disease, Parkinson's disease, obesity, high cholesterol, elevated blood glucose, diabetes, metabolic syndrome and/or autoimmune diseases, Multiple Sclerosis (MS), for reducing visceral fat, for reducing heat development, for reducing cholesterol, in particular LDL cholesterol, and/or as a medicament having an effect of reducing glucose in the blood and/or triglycerides in the blood, for improving macular pigment density, reducing oxidative stress and/or reducing the accumulation of fat in liver cells, in particular against fatty liver, Friedrei's ataxia, lysosomal diseases, in particular Tay-Sachs disease, arteriosclerosis, effective medicine for treating heart disease and arthritis.

In order to provide stable micelles of the active substance, the content of emulsifier, in particular polysorbate, may be at least 70% by weight, preferably between 75% and 95% by weight, particularly preferably within the range between 79% and 88% by weight, depending on which other components are included in the solubilizate, within the scope of the invention.

Depending on the particular application, the solubilizate according to the invention may comprise, for example, up to 20% by weight, preferably up to 15% by weight, of ethanol and/or up to 25% by weight, preferably between 12% and 20% by weight, particularly preferably up to 10% by weight, of glycerol and/or additionally up to 10% by weight, preferably up to 7% by weight, of water. The addition of ethanol may reduce the content of emulsifiers, in particular polysorbate, which is advantageous in view of the WHO recommended ADI value (25mg/kg body weight) for polysorbate. The content of emulsifiers, in particular of polysorbates, can also be reduced by the addition of glycerol.

The solubilizate of the invention has a narrow particle size distribution and a small average particle size even under physiological conditions of passage through the stomach, and the ratio of the particle size distribution of the solubilizate to the average particle size distribution of the solubilizate is 1: the micelle diameter distribution in the solubilizate diluted at a ratio of 500 ranged approximately d₁₀6nm to d₉₀20 nm. These values are determined by the volume distribution. Details of the particle size analysis of the micelles of the solubilizate will be explained below.

Determination of turbidity by measurement of the solubilizate, which is technically significantly simpler and feasible, gives an indication of the increased bioavailability compared with compositions which are not micellised according to the invention, in which at least THC, or curcumin and at least THC, are another active substance. The preparation according to the invention results in solubilizates having a turbidity of preferably less than 25FNU, more preferably less than 3FNU, measured by scattered light measurement with infrared light according to the specification according to ISO 7027 standard, in solubilizates diluted in water at a ratio of 1:50 under physiological conditions (pH 1.1 and 37 ℃).

In order to facilitate the oral administration of the solubilizate of the invention to the consumer or patient in a simpler and more convenient manner, the invention also provides a capsule filled with the above-mentioned solubilizate, wherein the capsule is formed as a soft or hard gelatin capsule, or as a soft or hard gelatin-free capsule, e.g. a cellulose capsule.

Furthermore, it is within the scope of the present invention that the solubilizate according to the invention can be incorporated into other fluids, in particular liquids. Where small micelles filled with active substance remain. Accordingly, the present invention also provides a fluid comprising a solubilisate as described above, wherein the fluid is selected from the group consisting of a food, a dietary supplement, a beverage, a cosmetic and a pharmaceutical product. Within the scope of the present invention, the fluid may in particular comprise an aqueous dilution of the solubilizate.

The invention also provides a method for the treatment and/or prevention of diseases which are complicated by inflammation, cancer, Alzheimer's disease, Parkinson's disease, obesity, high cholesterol, elevated blood glucose, diabetes, metabolic syndrome and/or autoimmune diseases, Multiple Sclerosis (MS), for the reduction of visceral fat, for the reduction of heat development, for the reduction of cholesterol, in particular LDL cholesterol, and/or for the reduction of glucose in the blood and/or triglycerides in the blood, for the improvement of macular pigment density, for the reduction of oxidative stress and/or for the reduction of fat accumulation in liver cells, in particular as a medicament for the treatment and/or prevention of fatty liver, Friedreich's ataxia, lysosomal diseases, in particular Tay-Sachs disease, arteriosclerosis, heart disease, arthritis, for improving the macular pigment density, in which method the solubilizate according to the invention is administered, in particular in capsules or in liquid form, in particular orally, to the dietary supplement consumer or patient, in particular once daily.

In order to produce the solubilizate comprising curcumin and at least THC as another active substance according to the invention, the respective separately prepared solubilizates can be mixed together or a solubilisate containing curcumin and at least one cannabinoid as another active substance can be prepared directly.

The present invention also provides a process for producing the solubilizate as described above. If co-micellization of curcumin and at least one cannabinoid as another active substance is desired, the present invention provides the following first variant of the production process, having the following steps

a) Providing a mixture of polysorbate 80 and/or polysorbate 20 and/or at least one sucrose ester of an edible fatty acid and/or an emulsifier selected from polysorbate 20, polysorbate 80 and sucrose esters of an edible fatty acid;

b) adding THC, especially THC oil;

c) adding curcumin powder;

wherein in step a) heating is carried out to a temperature in the range from 40 ℃ to 62 ℃, preferably to a temperature in the range from 45 ℃ to 57 ℃, particularly preferably to a temperature in the range from 48 ℃ and 52 ℃, and wherein in step b) heating is carried out to a temperature in the range from 82 ℃ to 97 ℃, preferably to a temperature in the range from 83 ℃ to 92 ℃, particularly preferably to a temperature in the range from 85 ℃ to 89 ℃, wherein the temperature is maintained in step c).

This preparation method allows the production of solubilizates which, in aqueous dilution, are capable of forming micelles loaded with curcumin and at least THC as further active substances. For this purpose, it is also possible to mix at least two active substances with one another in a preparatory step under appropriately matched temperature control and then to add them in the form of a mixture.

Within the scope of the invention, THC is used in particular in the form of oil. In principle, any formulation may be used as a source of THC within the scope of the invention. For example, THC oils, in particular so-called "full spectrum" THC oils, pastes, powders, crystalline forms and/or isolates, may be used, wherein all formulations mentioned contain THC. In principle, it is also possible to use an extract of THC to obtain the solubilizate according to the invention. The formulations mentioned may be those essentially comprising THC, for example in so-called "THC oils". However, it is also possible to use a mixture of essentially THC with at least one other cannabinoid as a THC formulation, which is used as "THC" within the scope of the invention.

In step b), further active substances, for example boswellia serrata extract and/or xanthohumol, can also be incorporated.

Additionally or alternatively, other active substances, such as serrapeptase, may be incorporated in step c). MCT oil may be added in step c) in addition to or instead of other active substances.

Here, it is possible in particular to carry out step b1) before step b) with the addition of water in the temperature range from 40 ℃ to 62 ℃, preferably in the temperature range from 45 ℃ to 57 ℃, particularly preferably in the temperature range from 48 ℃ to 52 ℃.

Additionally or alternatively, in step b1), ethanol may also be added at a temperature in the range of 40 ℃ to 62 ℃, preferably in the range of 45 ℃ to 57 ℃, particularly preferably in the range of 48 ℃ to 52 ℃.

The invention also relates to solubilizers which, at least immediately after preparation, exhibit micelles in an aqueous diluent both to which curcumin alone has been added and micelles which contain another active substance alone. The invention therefore also provides a pharmaceutical composition comprising a curcumin solublite and at least one THC solublite, in particular in a ratio of 1: 1 in a quantitative ratio to prepare the solubilizate as described above.

To this end, the present invention provides a method for producing a THC solubilisate having the steps of:

a) providing a mixture of polysorbate 80 and/or polysorbate 20 and/or at least one sucrose ester of an edible fatty acid and/or an emulsifier selected from polysorbate 20, polysorbate 80 and sucrose esters of an edible fatty acid;

b) adding THC, e.g. THC oil;

wherein in step a) heating is carried out to a temperature of at least 40 ℃ to 62 ℃, preferably to a temperature of 45 ℃ to 57 ℃, particularly preferably to a temperature of 48 ℃ to 52 ℃;

and wherein in step b) heating is carried out to a temperature in the range from 82 ℃ to 97 ℃, preferably to a temperature in the range from 83 ℃ to 92 ℃, particularly preferably to a temperature in the range from 85 ℃ to 89 ℃.

The temperature can also be increased in step a) to a value in the range from 82 ℃ to 97 ℃, preferably to a temperature in the range from 83 ℃ to 92 ℃, particularly preferably to a temperature in the range from 85 ℃ to 89 ℃. As a preparation, steps may be performed

a1) Mixing glycerol and THC, for example in the form of THC oil, to produce a solution; wherein in step a1) heating is carried out to a temperature of from 82 ℃ to 97 ℃, preferably to a temperature of from 83 ℃ to 92 ℃, particularly preferably to a temperature of from 85 ℃ to 89 ℃.

In the context of the present invention, the following steps may also be carried out as a preparation

a11) Mixing water and at least one sucrose ester of an edible fatty acid, wherein at least the heating to a temperature in the range of 40 ℃ to 62 ℃, preferably to a temperature in the range of 45 ℃ to 57 ℃, particularly preferably to a temperature in the range of 48 ℃ to 52 ℃ in step a11),

and carrying out the step

a12) Adding polysorbate 20 and/or polysorbate 80 to the mixture prepared in step a11), wherein in step a12) heating is carried out to a temperature of 82 ℃ to 97 ℃, preferably to a temperature of 83 ℃ to 92 ℃, particularly preferably to a temperature of 85 ℃ to 89 ℃.

After step a1) or after step a11) or after step a12) cannabinoids are added in step b).

Detailed Description

The invention will now be explained in more detail by way of examples. The following components were used herein.

Curcumin (curcumin)

Curcumin was obtained from Green Leaf extracts Pvt ltd, inc, of karalabang, under the name "95% curcumin powder in turmeric oil resin" product code EP-5001. The CAS number of the curcumin powder is 458-37-7. It is a natural product obtained by solvent extraction of turmeric (Curcuma Longa). The curcumin content of the powder is at least 95% according to the manufacturer's specifications. The curcumin content was determined by the ASTA method 18.0.

As an alternative to the "oleoresin turmeric 95%" curcumin powder from Green Leaf company, mentioned above, the examples described below use, for example, 95% curcumin Extracts from Neelam Phyto-Extracts from Meng of India, or curcumin BCM-95-SG or curcumin BCM-95-CG from eurochem GmbH from German George, or turmeric oil 95% oleoresin GmbH from Henry Lamotte OILS GmbH from Nelumbo, Germany, as curcumin.

THC

THC oil is used as a source of THC.

Olibanum (Boswellia carterii)

Within the scope of the present application, the term "mastic gum" especially refers to an extract of resin from mastic gum plants. Specifically, an extract of the species Boswellia serrata (Boswellia serrata) was used. It is an extract obtained by extraction with ethyl acetate from the resin of a plant of the botanical name Boswellia serrata (Boswellia serrata), product name "HC 22519", manufactured by frutam Belgium n.v. of lonerzeel, Belgium. The solubilizate containing the extract is also called "boswellic acid solubilization" due to its boswellic acid content.

In addition to the extract in the resin of the boswellia plant, boswellic acid and/or derivatives of boswellic acid may also be used for the purpose of the solubilizate according to the invention. Especially considered are α -boswellic acid (CAS No. 471-66-9), β -boswellic acid (CAS No. 631-69-6) and derivatives thereof, 3-O-acetyl- α -boswellic acid (CAS No. 89913-60-0), 3-O-acetyl- β -boswellic acid (CAS No. 5968-70-7), 11-keto- β -boswellic acid (KBA, CAS No. 17019-92-0) and 3-O-acetyl-11-keto- β -boswellic acid (AKBA, CAS No. 67416-61-9).

Xanthohumol

As a source of xanthohumol, the "hopstein" brand products "Xantho-flavor" or "Xantho-flavor pur" manufactured by Simon h. Both are natural products of hop production. The active content is the hop polyphenol xanthohumol. This is a yellow powder whose xanthohumol content, according to the manufacturer's specifications, is 65% to 85% in "Xantho-flavor" and at least 85% in "Xantho-flavor pur".

The manufacturer quantitated the concentration of xanthohumol and isoxanthohumol in "Xantho-flavor pur" according to UV spectrophotometry or according to HPLC EBC 7.8 using either pure XN (370nm) or IX (290nm) external calibration standards. "Xantho-Flav pur" contains a very high concentration of the prenylflavonoid xanthohumol. For examples within the scope of this application, "Xantho-Flav pur" of lot number 9432 was used.

Serrapeptase

A product from Shanxi Panier Biotech Co.Ltd (Shaanxi Pioneer Biotech Co. Ltd.) named Serratiopeptidase 20,000U/mg, batch No. PBD 20170708 was used as serrapeptase. It is an off-white to light brown powder. The enzyme unit (U) is the unit currently substituted by Katal for indicating enzyme activity. Since the values change when Katal is used, the enzyme units (U) continue to be used in medical and clinical chemistry. One enzyme unit U corresponds to 1 micromole substrate conversion per minute.

Polysorbate 80

As a source of polysorbate 80, a material "TEGO SMO 80V FOOD" having the specification code "K04 EU-FOOD" of Evonik Nutrition & Care GmbH of Esson, Germany was used. The product meets the requirement of European Union on for food additive E433. As an alternative to the TEGO SMO 80V of Evonik described above, TEGO SMO 80V of InCoPA Gmbh of Ill Di Send, or Crillet 4/Tween 80-LQ- (SG) of CRODA GmbH of Nettal, Germany, or Lamesorb SMO 20 and Kotilen-O/1VL from Univar or Kolb diagnostics AG of Hedingen, Switzerland, may also be used as polysorbate 80 in the examples described below.

Polysorbate 20

As a source of polysorbate 20, a "TEGO SML 20V FOOD" material having the specification code "K09 EU-FOOD" of Evonik Nutrition & Care GmbH, Germany was used. The product meets the requirement of European Union on for food additive E432. As an alternative to the TEGO SML 20 from Evonik, the use of Crillet 1/Tween 20-LQ- (SG) from Croda GmbH, Tetalr, Germany, as polysorbate 20 is also within the scope of the present invention.

Sucrose esters of edible fatty acids

As sucrose esters of edible fatty acids, sucrose esters with the product name "DUB SE 15P" manufactured by the manufacturer Stiarine Dubois are used. It is approved in the european union as food additive E473.

Ethanol

Within the scope of the present applicationEthanol from BerkelSpritfabrik GmbH&Kg. The ethanol content of the product was about 92.6 to 95.2% by weight, according to the specification "taxation on unmodified neutral alcohol 1411U".

Glycerol

The product used as glycerol in the context of the present application is "Glycamed 99.7%" from Glaconchemie GmbH, Muserburg, Germany. The glycerol content of the product is at least 99.5% according to the manufacturer's instructions.

Medium chain triglycerides

Medium-chain triglycerides (MCTs) are triglycerides containing medium-chain fatty acids. Medium chain fatty acids include caproic acid, caprylic acid, capric acid and lauric acid. Here are saturated fatty acids, which are naturally present in tropical vegetable fats, such as coconut oil and palm kernel oil. It is also included in small amounts in milk fat. Pure MCT oil is not found in nature, however, pure MCT oil can be obtained synthetically. Within the scope of the present invention, MCTs alone or mixtures of different MCTs may be used as medium chain triglycerides. The medium chain triglycerides were used in the form of MCT oil Delios VK Kosher, manufactured by Cognis GmbH, Mongham, Germany, or in the form of MCT oil (70/30) Rofetan GTCC 70/30, manufactured by DHW Dessatte Hydrierwerke Rodleben GmbH, Dessau-Ro beta lau, Germany, with CAS numbers 73-398-61-5.

In addition, medium chain triglycerides may be used in the form of the product ROFETAN DTCC 70/30(ph. This is a caprylic/capric triglyceride, CAS number 73398-61-5. This product corresponds to the monograph "medium chain triglycerides" of the european pharmacopoeia available at the date of filing. The manufacturer is Ecogreen Oleochemicals DHW, Deutsche Hydrierwerke GmbH, Rodband, Germany.

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

Unless otherwise stated, the analysis of the particle size of the micelles in the aqueous dilution of the solubilizate according to the invention is measured according to the principle of dynamic light scattering using a laser with a wavelength of 780 nm. Particle size measurements were performed using a particle metric NANOFLEX backscatter particle analyzer. The measurement principle is based on Dynamic Light Scattering (DLS) in a 180 deg. heterodyne backscatter setup.

To determine the turbidity of the solubilizate according to the invention experimentally, the turbidimeter was calibrated with a standard suspension. Thus, the indicating data is given as the concentration of the calibration suspension rather than the measured light intensity. Thus, when measuring any suspension, the indicating data indicates that the respective liquid causes the same light scattering as the standard suspension at the indicated concentration. The internationally defined turbidity standard is formalin. The most common Units include "FNU", i.e., "formalzine Nephelometric Units", formalin turbidimetric Units ". This is the unit measured at 90 ° according to the requirements of the ISO 7072 standard, for example for water treatment.

In order to prepare the solubilizates according to the invention comprising curcumin active substance and at least THC as other active substances, the solubilizates prepared separately may be mixed with each other or directly prepared as solubilizates containing curcumin and at least THC or a plurality of other active substances.

Curcumin solubilizate

For example, prepare7% curcumin solublization. For this purpose use

925 g polysorbate 80

75 g curcumin powder 95% (═ 71.2 g curcumin).

Polysorbate 80 was heated to between 48 and 52 ℃. Curcumin powder was added to polysorbate with stirring while further heating to a temperature of 95 to 97 ℃. The powder is added at a suitable rate to be uniformly absorbed into the emulsifier during stirring. Cooling to below 60 deg.C, and bottling. The solubilization substance is used for preparing curcumin and Olibanum solubilization substance.

1 at pH 1.1 and 37 ℃ in water: the average turbidity of 7% curcumin solublite was 0.9FNU at a dilution ratio of 500.

It should be noted, however, that the curcumin content can be further increased without having to face adverse consequences, for example in terms of stability of the micelles.

Furthermore, polysorbate 80 may be replaced, in whole or in part, by polysorbate 20 or sucrose esters of edible fatty acids. For example, for the preparation of a curcumin solublite with only polysorbate 20, 894g polysorbate 80 and 106g 95% curcumin powder may be used. Polysorbate 20 is heated to between about 63 ℃ to about 67 ℃. While stirring, curcumin powder was slowly added to polysorbate 80. While curcumin powder was added, heating was continued to about 83 ℃ to about 87 ℃. The resulting solubilizate was slowly cooled to below about 45 ℃ and then ready for bottling.

Furthermore, the preparation of these variants corresponds to the above. In this way, up to about 11% of the solubilizate can be produced.

To prepare

10% THC oil solubilisate (water free)，

Use of

900g Polysorbate 80, and

100g of THC oil.

Polysorbate 80 was heated to between 48 ℃ and 52 ℃. The THC oil was added to the polysorbate with stirring while the temperature was further raised to between 85 ℃ and 89 ℃. After cooling to a temperature below 60 ℃ at most, the solubilized THC oil is bottled.

The turbidity of the anhydrous 2.4% THC oil solublite was 2.9FNU when diluted in water at a ratio of 1:50 at pH 1.1 and a temperature of 37 ℃.

The anhydrous THC solubilizate according to the invention, in particular according to one of the above embodiments, is particularly suitable as a filling for capsules.

Another example of a cannabinoid solubilizer according to the invention is

10% THC oil solubilization，

It uses

100g THC oil

27g sucrose ester of edible fatty acid

54g of water

22.5g of glycerol, and

796.5g Polysorbate 80.

Water and glycerol were mixed and heated to a temperature of 48 ℃ to 52 ℃. Sucrose ester was added with vigorous stirring. Stirring was performed sufficiently vigorously to dissolve the sucrose ester in water and glycerol. Polysorbate 80 is added with stirring and homogenized at a temperature of heating to 85 ℃ to 89 ℃. Stirring was performed vigorously enough to evenly distribute polysorbate 80. After cooling to a temperature below 60 ℃ with stirring, the THC oil is added with vigorous stirring and thoroughly homogenized again at a temperature of 85 ℃ to 89 ℃. The THC oil is distributed homogeneously by vigorous stirring. The product is then cooled to a temperature below 60 ℃ and bottled. It is then stored in a dark environment not exceeding 25 ℃.

12% boswellic acid solubilizate

Use of

76g 80% boswellia serrata extract (═ 60.8g boswellic acid)

24g of water

400g polysorbate 20.

Mixing water with Olibanum powder at 87-93 deg.C. Polysorbate 20 was added while maintaining the temperature. The emulsifier is added at such a rate that the fluid is stably homogenized with stirring to form a solubilized mass. A large amount of foam may be generated during the preparation process. This can be ignored if a clear solubilisate is visible at the bottom of the collection container during bottling.

1.5% serrapeptase solubilized product

Use of

15g of serrapeptase:

Serratiopeptidase 20,000U/mg＝300,000,000U

15g of water

16.5g MCT oil

953.5g polysorbate 80.

Water is mixed with serrapeptase at a temperature in the range of 18 to 22 ℃ and the mixture is then homogenized. This means that serrapeptase is distributed as homogeneously as possible in water. This creates a precondition for substantially complete dissolution of serrapeptase in water. MCT oil was blended into the water-serrapeptase mixture with constant stirring while heating to a temperature of 83 to 87 ℃. Stirring was vigorously carried out here to dissolve serrapeptase uniformly in water. Polysorbate 80 was added with stirring and homogenized at constant temperature. Stirring was intense here to distribute polysorbate 80 evenly. The product is cooled to a temperature below 60 ℃ and bottled. It is then stored in a dark environment not exceeding 25 ℃.

300,000U/g corresponds to an enzyme unit of 15mg/g 1.5% serrapeptase. The turbidity of the solubilizate was determined at physiological conditions of pH 1.1 and 37 ℃ upon 1:50 dilution in water. The obtained value was 1.8 FNU.

10% Xantho-Flav solubilisate with ethanol ( 7.5% xanthohumol)

For this variant of the xanthohumol solubilizate according to the invention, use is made of

100g Xantho-Flav(75 g xanthohumol)

150g ethanol (96%) neutral alcohol, grade 1411U, and

750g polysorbate 80.

First, Xantho-Flav powder was dissolved in ethanol, where it was heated to a temperature of 48 to 52 ℃. A homogeneous solution was produced. Polysorbate 80 was then added to the solution of Xantho-Flav in ethanol heated to 83 to 87 ℃. The rate of addition homogenizes the two fluids by stirring. The resulting solubilizate is cooled to below 60 ℃ and bottled and stored in the dark and in the shade, i.e. at a temperature below 25 ℃.

The above solubilizates can be used for preparing the solubilizates according to the invention comprising curcumin and at least THC as another active substance by mixing. This is illustrated below with reference to example 1.

Within the scope of the present application, it is checked whether the components have been sufficiently completely homogenized to the solubilizate according to the invention by measuring the clarity of the product, which can be inferred from complete micellization, with a laser beam when preparing all solubilizates. Such laser beam measurements can be performed, for example, by irradiating the sample with a commercially available laser pointer, in particular at a wavelength between 650nm and 1700nm (spectral red), and then performing a visual inspection of the irradiated sample. The validation is not done by sampling and therefore is not performed outside the reaction vessel but in the reaction vessel. The laser beam is directed in the vertical direction of the reaction vessel by a sight glass, which is located at the front side of the reaction vessel. If only one spot of light appears on the rear inner surface of the reaction vessel, with no scattering at all, the resulting particle structure in the reaction vessel is smaller than the wavelength of visible light, so that it can be confirmed optically that the micellization process is complete.

Example 1

1.4% curcumin/2.4% boswellic acid/1.5% xanthohumol/0.2% THC oil/0.3% serrapeptase solublizer

Respectively used according to the above formula

200g of 7% curcumin solublite

200g of 12% boswellia solubilisate

200g of a 7.5% solubilization of xanthohumol, and

200g 10% solubilisate of anhydrous THC oil

200g of 1.5% serrapeptase solubilized.

All five solubilizates can be heated to a temperature of 50 ℃ to 60 ℃ to reduce their viscosity and thus increase flowability. Then, they were mixed together by stirring. Once a homogeneous complete product is obtained, it can be cooled to a temperature below 60 ℃ and bottled, if possible.

Before further processing, for example filling into capsules, it is advantageous to stir the product again to homogenize it and, if possible, to heat it moderately for this purpose, i.e. to a temperature of about 40 ℃ to 50 ℃.

Example 2

Directly prepared 1.4% turmeric2.4% boswellic acid/1.5% xanthohumol/0.2% THC oil/3% serrapeptase Solubilized product of

Use of

15g of 95% curcumin powder

30.4g boswellia serrata extract (24.3 boswellic acid)

20g Xantho-Flav powder (at least 70% xanthohumol ═ 15g xanthohumol)

20g of THC oil

3g Serrapeptase (60,000,000U)

12.6g of water

20g of ethanol

3.3g MCT oil

160g polysorbate 20, and

715.7g polysorbate 80.

Polysorbate 80 and polysorbate 20 are mixed at a temperature in the range of 48 ℃ to 52 ℃. Stirring is effected intensively here, so that a homogeneous mixture results. Water and ethanol were added. Stirring vigorously at a temperature of 48 ℃ to 52 ℃ to produce a homogeneous mixture. The xanthohumol and boswellia were slowly mixed with constant stirring. The temperature was then increased to 63 ℃ to 67 ℃ with vigorous stirring. Subsequently curcumin, serrapeptase, and THC oil and MCT oil were incorporated into the mixture. Care was taken for good mixing and homogeneity of the product. There may be a slight pause between the addition of one substance and the addition of the next. Here, the addition and the stirring are slowly performed so that the raw materials added respectively are uniformly incorporated into the substrate.

The temperature is further raised to a value between 85 ℃ and 89 ℃. The heating is carried out with continuous stirring and is slow enough that the heated mixture remains homogeneous and a clear product is obtained. Cooling to below 60 deg.C, and bottling. It is dark viscous and stored in the dark at a temperature not exceeding 25 ℃. Before further processing, for example filling into capsules, it is advantageous to stir the product again to homogenize it and, if possible, to heat it to this end moderately, i.e. to about 40 to 50 ℃.

Example 3

Solubilizate of 3% curcumin/3.2% boswellic acid/1.6% xanthohumol/1% THC oil

Use of

40.5g 80% boswellia serrata extract (32.4% boswellic acid)

31.5g 95% curcumin powder (29.925 g curcumin)

20.7g Xantho Flav powder containing at least 80% xanthohumol (16.5 g xanthohumol)

54g of water

45g of ethanol

315g Polysorbate 20

483g Polysorbate 80

10g of THC oil.

While heating to a temperature of 48 to 52 ℃, polysorbate 20 and polysorbate 80 are homogenized with one another and dissolved in one another here with stirring. While maintaining the temperature, the emulsifier mixture was mixed with water and ethanol. Stirring is carried out intensively here to dissolve water and ethanol homogeneously in the emulsifier solution. The boswellia serrata extract and xanthohumol are incorporated into the emulsifier mixture diluted with water with stirring at constant temperature. The addition is carried out at a rate sufficiently slow so that boswellia serrata extract and xanthohumol are introduced uniformly into the diluted emulsifier solution with stirring. Subsequently, the temperature was increased to a range between 63 ℃ and 67 ℃ under vigorous stirring. Curcumin powder was added with stirring. The temperature is further raised to a value between 85 ℃ and 89 ℃. Here, stirring is intense to allow the curcumin to be evenly distributed and homogenized in the substrate. Subsequently, THC oil was added to the mixture. Here, stirring is intense to disperse the THC oil evenly in the substrate and homogenize.

Cooling to a temperature of less than or equal to 45 ℃. The dark yellow viscous formulation comprising the solubilisate of curcumin and boswellic acid and xanthohumol and THC was then bottled and stored in the dark, cool place, i.e. below 25 ℃. The solubilizate and the aqueous solution thereof are stably, uniformly, clear and transparently soluble.

It is obvious to the person skilled in the art that the invention is not limited to the examples described above, but that it can be varied in various ways. In particular, features of the individual illustrative embodiments may be combined with or substituted for one another. This applies in particular to the emulsifier and active substance combination of the solubilizer according to the invention.

Claims (30)

1. A solubilisate comprising, in particular consisting of:

curcumin in an amount of less than or equal to 10% by weight, preferably less than or equal to 8% by weight, particularly preferably from 3% to 7% by weight, preferably from 1% to 3% by weight,

at least THC as at least one further active substance, and

at least one emulsifier having an HLB value of less than 18, preferably between 13 and 18, in particular polysorbate 80 or polysorbate 20 or at least one sucrose ester of an edible fatty acid or a mixture of at least two emulsifiers selected from polysorbate 20, polysorbate 80 and sucrose esters of edible fatty acids.

2. The solubilizate of claim 1, wherein the solubility-increasing agent is a surfactant,

it is characterized in that the preparation method is characterized in that,

the solubilizate comprises, as at least one further active substance, one or more substances selected from the group consisting of:

secondary plant matter, especially flavonoids, natural phenols, especially chalcones, such as xanthohumol, plant extracts, especially resins from boswellia serrata, and enzymes, especially serrapeptases.

3. A solubilisate comprising, in particular consisting of:

THC in an amount of less than or equal to 10% by weight, preferably less than or equal to 5% by weight, particularly preferably from 0.3% to 3% by weight, and

at least one emulsifier having an HLB value of less than 18, preferably from 13 to 18, in particular polysorbate 80 or polysorbate 20 or at least one sucrose ester of an edible fatty acid or a mixture of at least two emulsifiers selected from polysorbate 20, polysorbate 80 and sucrose esters of edible fatty acids.

4. The solubilizate according to any of the preceding claims,

for the treatment and/or prevention of diseases which are complicated by inflammation, cancer, alzheimer's disease, parkinson's disease, obesity, high cholesterol, elevated blood sugar, diabetes, metabolic syndrome and/or autoimmune diseases, Multiple Sclerosis (MS), for reducing visceral fat, for reducing heat development, for reducing cholesterol, in particular LDL cholesterol and/or glucose in the blood and/or triglycerides in the blood, for improving macular pigment density, for reducing oxidative stress and/or for reducing the accumulation of fat in liver cells, in particular as a medicament for the treatment and/or prevention of fatty liver, Friedreich's ataxia, lysosomal diseases, in particular tay-saxophone disease, arteriosclerosis, heart disease, arthritis.

5. The solubilizate according to any of the preceding claims,

as an anti-inflammatory dietary supplement and/or as a medicament with an effect against cancer, alzheimer's disease, parkinson's disease, obesity, high cholesterol, elevated blood glucose, diabetes, metabolic syndrome and/or autoimmune diseases, Multiple Sclerosis (MS), for reducing visceral fat, for reducing heat development, for reducing cholesterol, especially LDL cholesterol and/or as a medicament with a lowering of glucose in the blood and/or triglycerides in the blood, for improving macular pigment density, reducing oxidative stress and/or reducing the accumulation of fat in liver cells, especially as a medicament with an effect on fatty liver, Friedreich's ataxia, lysosomal diseases, especially tay-saxophone, arteriosclerosis, heart disease, arthritis.

6. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

a total curcumin concentration in human plasma measured one hour after oral administration of 500mg curcumin in the solubilized form of any one of the preceding claims is about 500ng curcumin per ml plasma ± 100ng curcumin per ml plasma.

7. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

the content of emulsifier, in particular polysorbate, is at least 70 wt.%, preferably between 75 wt.% and 95 wt.%, particularly preferably in the range between 79 wt.% and 88 wt.%.

8. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

the solubilizate comprises at most 20% by weight, preferably at most 15% by weight, of ethanol.

9. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

the solubilizate comprises at most 25% by weight, preferably between 12% and 20% by weight, particularly preferably at most 10% by weight, of glycerol.

10. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

the solubilizate comprises additionally up to 10% by weight, preferably up to 7% by weight, of water.

11. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

under physiological conditions (pH 1.1 and 37 ℃) with distilled water at a molar ratio of 1: the micelle diameter distribution in solubilizate diluted at a ratio of 500 is about d₁₀6nm to d₉₀＝20nm。

12. The solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

the solubilizate has a turbidity of less than 25FNU, preferably less than 5FNU, particularly preferably less than 3FNU, measured by scattered light measurement with infrared light according to the specification of ISO 7027 standard, in solubilizate diluted in water at a ratio of 1:50 or 1:500 under physiological conditions (pH 1.1 and 37 ℃).

13. Capsule filled with the solubilizate according to any of the preceding claims,

it is characterized in that the preparation method is characterized in that,

the capsules are formed as soft or hard gelatin capsules, or as soft or hard gelatin-free capsules, such as cellulose capsules.

14. Fluid comprising the solubilizate according to any one of claims 1 to 12,

it is characterized in that the preparation method is characterized in that,

the fluid is selected from the group consisting of food, dietary supplements, beverages, cosmetics and pharmaceutical products.

15. The fluid of claim 14 wherein the fluid is selected from the group consisting of,

it is characterized in that the preparation method is characterized in that,

the fluid comprises an aqueous dilution of the solubilizate.

16. A method for the treatment and/or prevention of diseases which are complicated by inflammation, cancer, Alzheimer's disease, Parkinson's disease, obesity, high cholesterol, elevated blood glucose, diabetes, metabolic syndrome and/or autoimmune diseases, Multiple Sclerosis (MS), for the reduction of visceral fat, for heat development, for the reduction of cholesterol, in particular LDL cholesterol and/or glucose in the blood and/or triglycerides in the blood, for improving macular pigment density, for reducing oxidative stress and/or reducing the accumulation of fat in liver cells, in particular as a medicament for the treatment and/or prevention of fatty liver, Friedreich's ataxia, lysosomal diseases, in particular Tay-saxose, arteriosclerosis, heart disease, arthritis,

it is characterized in that the preparation method is characterized in that,

the solubilizate according to any one of claims 1 to 12, in particular in a capsule according to claim 13 or in the form of a fluid according to claim 14 or 15, in particular orally, to a dietary supplement consumer or patient.

17. The method of claim 16, wherein the first and second light sources are selected from the group consisting of,

it is characterized in that the preparation method is characterized in that,

the solubilizate is administered to the dietary supplement consumer or patient in a metered curcumin dose of 0.5mg/kg body weight to 1mg/kg body weight, preferably 0.81mg/kg body weight, especially once daily.

18. The method according to claim 16 or 17,

it is characterized in that the preparation method is characterized in that,

the solubilizate is administered to the dietary supplement consumer or patient in a metered dose of boswellia from 1mg/kg body weight to 2mg/kg body weight, preferably 1.62mg/kg body weight, especially once daily.

19. The method according to claim 16 and/or 17 and/or 18,

it is characterized in that the preparation method is characterized in that,

the solubilizate is administered to the dietary supplement consumer or patient in a metered xanthohumol dose of 0.5mg/kg body weight to 1mg/kg body weight, preferably 0.81mg/kg body weight.

20. Method for producing the solubilizate according to any one of claims 1 or 2 or 4 to 12, having the following steps

a) Providing a mixture of polysorbate 80 and/or polysorbate 20 and/or at least one sucrose ester of an edible fatty acid and/or an emulsifier selected from polysorbate 20, polysorbate 80 and sucrose esters of an edible fatty acid;

b) adding THC;

c) adding curcumin powder;

wherein

Heating in step a) to a temperature in the range from 40 ℃ to 62 ℃, preferably to a temperature in the range from 45 ℃ to 57 ℃, particularly preferably to a temperature between 48 ℃ and 52 ℃, and wherein

Heating to a temperature of from 82 ℃ to 97 ℃, preferably to a temperature of from 83 ℃ to 92 ℃, particularly preferably to a temperature of from 85 ℃ to 89 ℃ in step b),

wherein the temperature is maintained in step c).

21. The method of claim 20, wherein the first and second portions are selected from the group consisting of,

wherein at least one further active substance, in particular boswellia serrata extract and/or xanthohumol, is incorporated in step b).

22. The method according to claim 20 or 21,

wherein in step c) further active substances, in particular serrapeptase, are incorporated.

23. The method according to any one of claims 20 to 22,

wherein MCT oil is added in step c).

24. The method of any one of claims 20 to 23,

wherein step b) is preceded by a step b1) for adding water in the temperature range from 40 ℃ to 62 ℃, preferably in the temperature range from 45 ℃ to 57 ℃, particularly preferably in the temperature range from 48 ℃ to 52 ℃.

25. The method of any one of claims 20 to 24,

wherein in step b1) ethanol is added at a temperature in the range of 40 ℃ to 62 ℃, preferably in the range of 45 ℃ to 57 ℃, particularly preferably in the range of 48 ℃ to 52 ℃.

26. Process for the preparation of a solubilisate according to any one of claims 1 or 2 or 4 to 12, wherein curcumin solubilisate is mixed with at least one THC solubilisate according to claim 3, in particular each solubilisate is present in a ratio of 1: 1 in a quantitative ratio.

27. A method of producing a THC solubilisate having the steps of:

a) providing a mixture of polysorbate 80 and/or polysorbate 20 and/or at least one sucrose ester of an edible fatty acid and/or an emulsifier selected from polysorbate 20, polysorbate 80 and sucrose esters of an edible fatty acid;

b) the THC is added into the mixture, and the mixture is stirred,

wherein in step a) heating is carried out to a temperature of at least 40 ℃ to 62 ℃, preferably to a temperature of 45 ℃ to 57 ℃, particularly preferably to a temperature of 48 ℃ to 52 ℃;

and wherein in step b) heating is carried out to a temperature in the range from 82 ℃ to 97 ℃, preferably to a temperature in the range from 83 ℃ to 92 ℃, particularly preferably to a temperature in the range from 85 ℃ to 89 ℃.

28. The method of claim 27, wherein the first and second light sources are selected from the group consisting of,

wherein in step a) the temperature is increased to a value in the range of 82 ℃ to 97 ℃, preferably to a temperature in the range of 83 ℃ to 92 ℃, particularly preferably to a temperature in the range of 85 ℃ to 89 ℃.

29. The method according to claim 27 or 28,

wherein step a1) is performed before step a), mixing glycerol and THC to produce a solution;

wherein in step a1) heating is carried out to a temperature of from 82 ℃ to 97 ℃, preferably to a temperature of from 83 ℃ to 92 ℃, particularly preferably to a temperature of from 85 ℃ to 89 ℃.

30. The method of any one of claims 27 to 29,

wherein the following steps are carried out before step a)

a11) Mixing water and at least one sucrose ester of an edible fatty acid, wherein heating in step a11) is carried out to a temperature in the range of at least 40 ℃ to 62 ℃, preferably to a temperature in the range of 45 ℃ to 57 ℃, particularly preferably to a temperature in the range of 48 ℃ to 52 ℃,

and carrying out the step

a12) Adding polysorbate 20 and/or polysorbate 80 to the mixture prepared in step a11), wherein in step a12) heating is carried out to a temperature of 82 ℃ to 97 ℃, preferably to a temperature of 83 ℃ to 92 ℃, particularly preferably to a temperature of 85 ℃ to 89 ℃.