LU102018B1 - Extraction process and mixture of substances - Google Patents

Abstract

The invention relates to an extraction method in which an extraction agent is used to separate at least one extraction material from a substance. According to the invention, the extractant contains fatty acid ethyl ester and/or fatty acid methyl ester. In one embodiment of the invention, the extractant is an omega-3 and/or omega-6 fatty acid, preferably EPA, DMA, DPA, ETA, 21:5n3 and/or SDA. In one embodiment of the invention, the extractant contains at least 500 mg/kg, preferably at least 700 mg/kg, of the fatty acid ethyl ester and/or the fatty acid methyl ester. The mixture of substances is expediently a plant material, preferably hemp, and the extraction material is a cannabinoid, preferably CBD and/or THC.

Description

- -1- LU102018 PATENT ATTORNEYS BERNHARDT | WOLFF Description: K.D. Pharma Bexbach GmbH, D-66450 Bexbach (Germany) Extraction process and substance mixture - ee. The invention relates to an extraction method in which an extraction agent is used to release at least one extraction material from a substance, in particular a plant material.

The invention also relates to a substance mixture that contains an extraction material extracted from a substance, in particular a plant material.

Various extraction methods are known through use, in which different extraction agents are used. Ethanol or supercritical CO2 is commonly used for extraction from plant material. The use of these extractants has also proven to be particularly suitable for the extraction of cannabinoids such as THC or CBD from hemp. Disadvantages of these processes are that they are energy-intensive and unwanted by-products are found in the products that are added.

Methods for extracting cannabinoids from hemp are known from US 2016/0213720 A1 and WO 2018/130682 A1.

The invention is based on the object of creating a method of the type mentioned at the outset, which enables a more efficient extraction in comparison to the known methods.

According to the invention, this object is achieved in that the extractant contains fatty sQure ethyl ester and/or fatty acid methyl ester.

_2- LU102018 Surprisingly, it has been found that, especially when the substance is a plant, the extraction material can be separated particularly well from the substance when using fatty ethyl ester and/or methyl ester. The process of extracting cannabinoids from hemp has proven to be particularly advantageous. Not only is a comparatively large extraction yield achieved, but the process can also be carried out efficiently in a comparatively large temperature range. In addition to the application to hemp, the method can also be used advantageously for the extraction of extraction material from other plants or components thereof, e.g.

- a-caryophyllene and/or B-caryophyllene from hops, - sesquiterpenes from valerian plants, - ginkgolide terpene lactones and/or flavone glycosides from Ginkgo biloba, - flavonoids from coca bush, - linoleic acid and/or linolenic acid from poppies, - thymol and/or sesquiterpene lactones from arnica, - cineol and/or cymen from eucalyptus, - catechins and/or theanines from tea plants (e.g. Camellia sinensis, Camellia assamica), - terminol and/or pinene from rosemary, - hydroxycinnamic acid and/or citronellal from lemon balm, - gingerol and /or zingiberol from ginger, - thymol and/or carvacrol from thyme, - cinnamaldehyde eugenol from cinnamon, - linalool, a-pinene and/or y-terpin from coriander, - menthol and/or menthone from mint, - linalyl acetate and/or Coumarins from lavender - thujane and/or borneol from sage - isoabienol, monoterpenes and/or careen from conifers.

The method is also suitable for producing the mixture of substances mentioned at the outset, which has fatty acid ethyl ester and/or fatty acid methyl ester and contains an extraction material extracted from a substance, in particular a plant material. It is conceivable to aromatize fatty acid ethyl ester and/or fatty acid methyl ester by means of the process.

In a particularly preferred embodiment of the invention, the fatty acid ethyl ester comprises or is an omega-3 and/or omega-6 fatty acid. Beneficial can

) -3- LU102018 ’ an omega-3 and/or omega-6 fatty acid can be formed by the process, which is enriched with the extraction material. Omega-3 and/or omega-6 fatty acids are known to have particularly health-promoting effects as food and dietary supplements. The invention proves to be particularly advantageous if, after the extraction, the extraction material is present in the extraction agent, in particular the omega-3 and/or omega-6 fats, in particular dissolved. A fatty acid ethyl ester and/or fatty acid methyl ester enriched with the extraction material can then be produced directly with the method. Using the method according to the invention, combination preparations can be produced directly and therefore comparatively easily. It is therefore not necessary to first detach the extraction material from the substance, in particular the plant, by means of another method and then to add the extraction material to the fatty acid ethyl ester, in particular the omega-3 and/or omega-6 fatty acid. The invention has proven to be particularly advantageous if the extraction agent has or is EPA, DHA, DPA, ETA, 21:5n3 and/or SDA. These omega-3 fats, especially EPA and DHA, are particularly healthy foods or dietary supplements. Fatty acid methyl ester is used in many applications as a vegetable fuel. In addition to the use according to the invention as the extraction agent, the invention creates the possibility of enriching fatty acid methyl ester with the extraction material in a particularly simple manner. The advantages of using the fatty acid methyl ester as an extraction agent are that it can be produced sustainably from vegetable fats and is inexpensive and readily available. Furthermore, the extractant can be used particularly economically for short-path distillation. The use of the fatty acid methyl ester in the extraction from hemp has proven to be particularly advantageous. Cannabinoids and terpenes, which are also present in hemp, can be separated by short-path distillation using fatty acid methyl esters. In particular, the separation can take place via different boiling points. In one embodiment of the invention, the extractant is a mixture of substances, preferably an oil.

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| _4- LU102018 ; In a further embodiment of the invention, in addition to the fatty acid ethyl ester or the fatty acid methyl ester, another organic solvent is used as the extraction agent. While it would be conceivable to mix the fatty acid ethyl ester and/or the fatty acid methyl ester with the organic solvent as the extraction agent, at least two of the various extraction agents mentioned can be used in the process, fatty acid ethyl ester and/or fatty acid methyl ester and the organic solvent in succession, possibly in separate extraction steps, to extraction are used. The other organic solvent is expediently an alcohol, preferably ethanol, methanol, n-butanol and/or isopropanol. In one embodiment of the invention, the extractant has at least 90 mg/kg, preferably at least 120 mg/kg. Fatty acid ethyl ester, preferably EPA and/or DHA, and/or at least 175 mg/kg, preferably at least 190 mg/kg, of fatty acid methyl ester. However, it has proven particularly advantageous to use an extractant which contains at least 500 mg/kg, preferably at least 700 mg/kg, particularly preferably at least 900 mg/kg, of fatty acid ethyl ester, preferably EPA and/or DHA; and/or at least 500 mg/kg, preferably at least 700 mg/kg, particularly preferably at least 900 mg/kg of fatty acid methyl ester. As a result, not only can a particularly great extraction effect be achieved, but a product intended for consumption, in particular a food supplement to which the extraction material has been added, can optionally be formed directly using the fatty acid ethyl ester as the extraction agent. In a particularly preferred embodiment of the invention, the component to be released is a cannabinoid, preferably CBD and/or THC, and/or a terpene. The substance from which the extraction material is extracted is preferably hemp. Omega-3 and/or OMega-6 fatty acids are partially metabolized to epoxides in the human body. These epoxides can be converted to omega-3 and/or omega-6 fatty acid endocannabinoid epoxides by cytochrome P450. These endogenous endocannabinoid epoxides have proven to be particularly bioactive. They have an anti-inflammatory, vasodilating effect (vasodilatation) and can modulate platelet aggregation. In addition, the omega-3 and/or omega-6 fatty acids have been shown to be beneficial for the effectiveness of the cannabinoids. Omega-3 and/or omega-6 fatty acids act in the

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; -5- LU102018 | Cell membrane as an anchor for the endocannabinoids and for cannabinoids. They are involved in the synthesis of receptors of the endocannabinoid system, which forms part of the human or animal nervous system. The combination of cannabinoids with omega-3 and/or omega-6 fatty acids can thus contribute to improving the effects caused by both substances. The use of omega-3 and/or omega-6 fatty acids enriched with cannabinoids is considered to be particularly advantageous for use in pain therapy and/or chemotherapy, since they show a synergetic effect when administered together. While the omega-3 and/or omega-6 fatty acids in particular have an anti-inflammatory effect and this alone enables a reduction in painkillers, the cannabinoids can block the descending nerve tracts in particular and thus allow a reduction in the necessary dose of painkillers.

Particularly advantageous is the use of the inventive combination of omega-3 and / or omega-6 fatty acid and cannabinoids when used concomitantly to pain therapy with another painkiller, especially an opioid, considered because the additional intake of omega-3 and /or omega-6 fatty acid, which is mixed with the cannabinoid, allows a particularly large reduction in the necessary dose of the other analgesic, in particular the opioid.

It has proven advantageous to carry out the extraction at 15.degree. C. to 45.degree. C., preferably at .degree. C. to 40.degree.

Conveniently, the substance is incubated before extraction. When the substance is a plant material, the incubation is preferably between 80°C and 120°C, preferably between 90°C and 110°C.

The invention is explained in more detail below using examples and the attached graphics, which relate to the exemplary embodiments.

FIGS. 1 to 3 show substance contents after various processes or process steps have been carried out.

; -6- LU102018

1. Example Hemp of the Finola variety was incubated for two hours at 100° C. to decarboxylate CBD-A to CBD and THC-A to THC. Thereafter, 10 g of the incubated hemp, 20 g of an omega-3 fatty acid oil containing 96.5% EPA were mixed and allowed to stand at 23°C for 1 hour. It was then filtered, and the filtrate formed and the filter were washed with 30 g of ethanol to dissolve the omegoa-3 fatty acid oil from the filter and the filter cake. After evaporating the ethanol, the weight (total g) was determined and the concentration of cannabinoids measured. For comparison, 10 g of the incubated hemp were treated with 20 g of 100% ethanol in the same way. After filtration, the levels of CBD and THC shown in the table below could be determined: 109 [ethanol Jos |0.04 Joos | og fea Joe or Joss | Table 1 As can be seen from the results, using the EPA extracted both more CBD and more THC. Furthermore, the remaining CBD-A is lower when using the EPA.

Example 2 Hemp of the Finola variety was incubated for two hours at 100° C. to decarboxylate CBD-A to CBD and THC-A to THC. Thereafter, in a first extraction step, 10 g of the incubated hemp and 5 g of an omega-3 fatty acid oil containing 96.5% EPA were mixed and left to stand at 23°C for 1 hour. It was then filtered and the filtrate formed and the filter washed with 30 g of ethanol to dissolve the omega-3 fatty acid oil from the filter and the filter cake. After evaporation of the ethanol, the weight (total g) of cannabinoids in the extraction product formed was determined and their concentration in the extraction product formed was measured.

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"7- LU102018 The extraction product was used again as extraction agent in a second extraction step. In the second extraction step, 5 g of the extraction product of cannaboid-enriched omega-3 fatty acid oil obtained after the first extraction was again added to 10 g of the incubated hemp and left to stand at 23° C. for 1 hour. It was then filtered again and the filtrate formed and the filter washed with 30 g ethanol in order to remove the omega-3 fat sQuredl from the filter and the filter cake. After evaporation of the ethanol, the weight (total g) of cannabinoids in the extraction product formed was determined and their concentration in the extraction product formed was measured. The extraction product formed after the second extraction step was reused as an extractant in a third extraction step. In the third extraction step, 5 g of the extraction product of cannaboid-enriched omega-3 fatty acid oil obtained after the second extraction was again added to 10 g of the incubated hemp and allowed to stand at 23°C for 1 hour. It was then filtered again and the filtrate formed and the filter washed with 30 g of ethanol in order to dissolve the omega-3 fatty acid oil from the filter and the filter cake. After evaporation of the ethanol, the weight (total g) of cannabinoids in the extraction product formed was determined and their concentration in the extraction product formed was measured. The measurement results are shown in the table below. They are also shown graphically in Figures 1 and 2. arn | cn | omis [SA measurement by wt% wt% wt% g Table 2

3. Example Hemp of the Finola variety was incubated for two hours at 100° C. to decarboxylate CBD-A to CBD and THC-A to THC. Then, in nine series of experiments, each with a single extraction step | g of the incubated hemp and 5 g of an omega-3 fatty acid oil containing 96.5% EPA

; -8- LU102018, mixed and, as shown in Table 3, allowed to stand at different temperatures and for different periods of time.

It was then filtered and the filtrate formed and the filter washed with 30 g of ethanol to dissolve the omega-3 fatty acid oil from the filter and the filter cake.

After evaporation of the ethanol, the weight (total g) of cannabinoids in the extraction product formed was determined and their concentration in the extraction product formed was measured.

Table 3 Results of this measurement are that the highest yield was obtained at the highest temperature and the longest incubation.

Values identical to those at 30 °C were obtained at the highest temperature and the lowest incubation time.

The lowest temperature is not suitable for extraction due to low yield.

By doubling the temperature and quadrupling the incubation time, only a 17% increase was achieved compared to 30°C and 30 min incubation,

Claims (15)

_9- LU102018 patent claims: 1. Method for extraction, in which an extraction agent is used to release at least one component from a substance, in particular a plant material, characterized in that the extraction agent contains fatty acid ethyl ester and/or fatty acid methyl ester. 2. The method according to claim 1, characterized in that the extractant has or is omega-3 and/or omega-6 fatty acid(s). 3. The method according to claim 1 or 2, characterized in that the extraction agent has or is EPA, DHA, DPA, ETA, 21:5n3 and/or SDA. 4. The method according to any one of claims 1 to 3, characterized in that the extraction agent has a further organic solvent in addition to the fatty acid ethyl ester and/or the fatty acid methyl ester. 5. The method according to claim 4, characterized in that the further organic solvent is an alcohol, preferably ethanol, methanol, n-butanol and/or isopropanol. 6. The method according to any one of claims 1 to 5, characterized in that the extractant is a mixture of substances, preferably an oil. 7. The method according to any one of claims 1 to 6, characterized in that the extraction material is bound, preferably dissolved, in the fatty acid ethyl ester and/or fatty acid methyl ester during the extraction. ; -10- LU102018 8. The method according to any one of claims 1 to 6, characterized in that the extractant contains at least 90 mg/kg, preferably at least 120 mg/kg, fatty acid ethyl ester and/or at least 165 mg/kg. preferably at least 190 mg/kg fatty acid methyl ester. 9. The method according to any one of claims 1 to 8, characterized in that the extractant contains at least 500 mg / kg, preferably at least 700 mg / kg, particularly preferably at least 900 mg / kg, fatty acid ethyl ester and / or at least 500 mg / kg, preferably at least 700 mg/kg, particularly preferably at least 900 mg/kg, fatty acid methyl ester. 10. The method according to any one of claims 1 to 9, | characterized in that the component is a cannabinoid, preferably CBD, THC and/or CBD-A. 11. The method according to any one of claims 1 to 10, characterized in that the substance is hemp. 12. A substance mixture that contains an extraction material extracted from a substance, in particular a plant material, characterized in that the substance mixture has fatty acid ethyl ester and/or fatty acid methyl ester. 13. Substance mixture according to claim 12, characterized in that the fatty acid ethyl ester and/or fatty acid methyl ester is an extraction agent by means of which the extraction material has been extracted, the extraction material preferably being dissolved in the fatty acid ethyl ester and/or fatty acid methyl ester. 14. Substance mixture according to claim 12 or 13, _11- LU102018 characterized in that the extraction material is a cannabinoid, preferably CBD, THC and/or CBD-A. 15. Substance mixture according to one of claims 12 to 14, characterized in that the fatty acid ethyl ester contains omega-3 and/or omega-6 fatty acid(s), preferably EPA, DHA, DPA, ETA, 21:5n3 and/or SDA, comprises or is.