DE102018001959A1 - Thermal separation process for the enrichment of cannabinoids - Google Patents

Abstract

Cannabinoids have hitherto been obtained mainly by filtration, extraction or chromatographic methods. Both the enrichment results and the economics of these methods are severely limited. It has long been known that distillation processes can be used to fortify cannabinoids, which generally results in better enrichment results. However, there are only a few publications to date. Due to the low thermal loading capacity of cannabinoids, challenges arise in operating a distillation apparatus efficiently and with high separation efficiency. The task was to find a method by which the efficiency and efficiency of the enrichment of cannabinoids compared to the known methods can be improved. The use of special internals, so-called structured or ordered packs, in a distillation apparatus, results in a distillation a particularly high ratio of separation efficiency and pressure loss. This relationship is particularly advantageous for the distillation of cannabinoids. It is thus possible to operate a distillation apparatus with a high separation efficiency at a relatively high throughput, so that the efficiency and economy of a distillation step is improved. Even further improved results can be achieved if, following a first distillation, at least one second distillation takes place. Likewise, further improvements can be achieved if at least two distillations are carried out at different pressures. The method described is suitable for the efficient enrichment of cannabinoids from meltable starting vegetable products. Even with low-concentration starting materials can thus achieve high enrichment results. Likewise, the method is suitable for isolating a cannabinoid in a particularly pure form (for example, crystalline cannabidiol) in high yield.

Description

The present invention describes a thermal separation process with which it is universally possible to efficiently and inexpensively enrich a cannabinoid-containing plant starting material for a high proportion of cannabinoid.

The provision of cannabinoids in high purities has become increasingly important in recent years. Cannabinoids are the subject of current research and development in many ways. In particular, the therapeutic applications of the cannabinoids cannabidiol (CBD) and tetrahydrocannabinol (THC) are in the focus. With the increasing use of THC and CBD in the medical field and the wide range of potential uses, the demand for these cannabinoids has been steadily increasing over time. The non-psychoactive, over-the-counter cannabinoid cannabidiol is now even used as a dietary supplement, as an ingredient in cosmetics, soaps, shower gels, or, for example, as an additive for liquids to evaporate in e-cigarettes.

In view of this development, it is becoming increasingly important that efficient and economical high-yielding processes can be provided for the enrichment, separation and isolation of these cannabinoids, and especially CBDs.

Numerous methods already exist for the fortification of cannabidiol from a vegetable product. Thus, methods are known in which an enrichment step based on an extraction with supercritical CO ₂ [1]. Likewise, in [2] a method is described in which an extraction with subcritical CO _{2 is} carried out. Further extraction methods with other solvents are presented in [3], [4] and [5]. Likewise, there are some methods in which an enrichment step occurs via a chromatographic step [6], [7], [8], [9]. Partly, these methods are also coupled.

The enrichment results via an extraction step strongly depend on the concentration in which the cannabinoid to be enriched is already present in the starting material. In order to obtain sufficiently high enrichments from a low-concentrated starting material, several extraction stages are usually necessary. Although very high purities can be achieved by means of a chromatographic separation, this is complicated and expensive. Also, the fact that both extraction and chromatography require the use of additional solvents which must be removed from the target product and recovered, which is costly, the inventors consider to be a disadvantage of these techniques.

It therefore appeared advantageous to the inventors to shift the considerations to a thermal separation process based on a distillative separation.

First steps were already described in 1940. According to [10], a vacuum distillation was carried out by means of a short-distance apparatus and then a column distillation in vacuo using a packed column in order to achieve an enrichment of cannabidiol for subsequent isolation of cannabidiol by compound formation.

Modern apparatus for distilling plant extracts are usually operated with thin-film evaporators with an external or internal condenser (short path evaporator). Thus, a vacuum distillation for the enrichment of cannabidiol by means of a thin-film evaporator or the vacuum distillation from a bottom flask is mentioned, for example, in [11].

In [12] an embodiment of a distillation process is shown in which two series-connected short-path evaporators are used.

Another method is known in which a thin-film evaporator or a short-range distillation is coupled to a column. The column is operated as a bottom or packed column, can have compartments and a minimum separation column height of 2.5 m is given [13].

The current methods have several disadvantages. The disadvantage of short-range distillation is that the number of equilibrium levels achievable is severely limited. For this reason, only moderate enrichment results can be achieved via an evaporation step via a short-range apparatus, which limits the economy.

With the aid of a bottom or packed column, theoretically, any number of equilibrium stages can be achieved, depending on the height and operation of the column. However, the number of equilibrium steps that can be achieved, the height of the column and the pressure loss (difference between top and bottom pressure) caused by the column are related to each other. The pressure loss caused within the column is approximately proportional to the height of the column. With increasing height of the column also increases the number of maximum achievable equilibrium levels. So if you limit the pressure loss, then the maximum separation efficiency of the column is limited as well with the height.

Since cannabinoids, as well as many of the byproducts contained in a plant extract, are substances that are very thermally sensitive, it is necessary that a column be operated at a low pressure drop. Exceeding the thermal load capacity of the material to be distilled occurs the formation of decomposition products, which is both detrimental to the operation of the column and adversely affect the quality of the product and makes it completely useless in the worst case. However, the condition of a low pressure loss leads to bottom or packed columns that a sufficiently high separation efficiency for a sufficiently high enrichment and efficient operation of the column due to the necessary low flow rates and thus low throughput can no longer be guaranteed.

Another disadvantage of currently known methods is that the enrichment results still strongly depend on the concentration of the starting product.

It was therefore the task of the inventors to find a simple, optimized and efficient method for the enrichment of cannabidiol or other cannabinoids to a high degree of purity with which the aforementioned disadvantages can be overcome.

The inventors have found that the key to solving this problem is that the accumulation of cannabidiol via a distillation by means of a so-called structured or even ordered pack.

Structured, or even ordered packs are built-in parts that can be used to produce surface in absorption, desorption or distillation columns. A high volume-specific surface portion of a flow-through packing is among other factors influencing a high separation efficiency of a column. In contrast to packed columns or random packings, which consist of disordered beds of packing, structured packings have an ordered, systematic structure of regularly arranged flat structures, which may consist of metal, sheet metal or plastic. Due to the advantageous ordered structure structured packings can be achieved in comparison to packed columns with the same volume-specific surface and the same operation, a much lower pressure loss. The decisive advantage of a distillation for the enrichment of cannabinoids using a structured packing is that so even at the low pressure losses required in the still high separation efficiency and yet high throughput can be achieved, which significantly increases the efficiency of the process.

Furthermore, the inventors found out that a particularly suitable process, which in a special way also permits the enrichment of any cannabinoids, consists in following a first, at least one, second distillation over a structured packing.

The distillations can be carried out successively, for example in the same distillation apparatus, or directly in series, using two or more distillation apparatuses.

A suitable distillation apparatus may consist of a distillation column, which is equipped with one, preferably two or more structured packing. Where, as is usual with packed columns, a renewed distribution of liquid through a liquid distributor is carried out above a structured packing.

The cannabinoid-containing plant starting material which is subjected to a first distillation via a structured packing is now always referred to in the further part of this document as a primary product or else simply as a starting material.

A suitable primary product for the process according to the invention is a product with a mass fraction of the cannabinoid to be enriched of at least 5%. Likewise, the primary product at ambient pressure is completely meltable at a temperature <95 ° C, preferably <85 ° C, more preferably <75 ° C.

In one embodiment of the present invention, the primary product is a product which has been obtained via extraction with supercritical CO ₂ or via a subcritical extraction with another solvent, preferably ethanol, from a vegetable raw material.

In a further preferred embodiment, the primary product is a product which has been obtained by extraction from a vegetable raw material and has already been distilled out by means of a conventional method, for example via a short-distance apparatus or from a bottom flask. The inventors found that the benefits of a structured packing can be used even better, so there is a possibility of one Plant extracts traditionally used but expensive to dispense thin-film evaporator and to use a cheaper sump evaporator.

In order to enable optimum operation under low thermal stress, embodiments of the invention are preferred in which a maximum total pressure drop within a separation apparatus of 75 mbar and a maximum height of a packing insert of 2.0 m is not exceeded. It is likewise preferred that the walls of a distillation column operated via a structured packing can be heated, which is exemplified in US Pat is shown. The heating not only has an advantageous effect on the operation, but also advantageously on the starting behavior of a distillation column.

Although in general the term "packed column" can be understood as meaning columns with packings of any type, including packed columns, the term "packed column" is used in the remainder of this document for reasons of clarity exclusively for distillation apparatus which are operated with structured packings.

In the following, an embodiment of the method according to the invention will be described in more detail using the example of cannabinoid cannabidiol. serves as an illustration.

Here, the cannabidiol-containing starting material is first subjected to a first distillation using a packed column. In this first distillation, those components are separated or depleted which boil at lower temperatures before the target product (in this example cannabidiol). The bottom product from the first distillation containing the target product is then fed to a second distillation step. In this case, those substances are removed which boil after the target product at higher temperatures. The thus enriched target product then leaves the second distillation step as an overhead product.

With the aid of the present invention it is possible to enrich even a primary product with a low mass fraction of cannabidiol from 5% to a mass fraction> 85%, or even> 90%, or even> 95%.

The inventors also found that there are dependencies between the enrichment results and the composition that can be described as follows: In some cases, unfavorable compositions of the primary product exist that cause azeotropic behavior to occur during distillation. This means that a sufficiently high enrichment can no longer be achieved. The problem associated with the occurrence of azeotropy is well known to those skilled in the art, therefore, further explanation is not given here. Instead, the inventors also describe a solution to this problem.

The location of azeotropic points is pressure dependent. By varying the pressure, azeotropic points can be displaced or even eliminated altogether, with the result that improved enrichment results can be achieved.

In a further embodiment of the present invention, at least two distillations are carried out at respectively different pressures in succession or in series. The pressures are chosen so that compared to the operation at the same pressure improved enrichment results are obtained. Thus, in an exemplary embodiment, a first distillation or a first packed column may be operated at a head pressure of 0.01 mbar to improve the depletion of the low boilers and a second distillation or a second packed column at a top pressure of 5 mbar to improve the depletion of the high boilers.

The inventors have found that a product enriched with the method according to the invention with a proportion by mass of a respective cannabinoid> 85% is ideally suited for a further step in a cannabinoid in a particularly pure form with a mass fraction> 98.0%,> 99.0 % and> 99.9% with high yield.

Further embodiments of the present invention thus consist in that, from a product enriched with a cannabinoid by the distillation method described, a target product, which in this case represents the particular enriched cannabinoid which is to be further purified, by an extraction method, a crystallization method or a chromatographic method Process with a purity> 97.0% is isolated. In order to minimize losses in yield, it is preferred that a product is used which has a cannabinoid mass fraction> 85% and particularly preferably> 90% after application of the described distillation process.

If the target product is cannabidiol, it is preferred that a crystallization process be carried out following the described distillation process. In this case, a cooling crystallization is particularly preferably carried out. In this way, highly purified crystalline cannabidiol with a mass fraction>98.0%,> 99.0% or> 99.9% can be obtained become. In For this purpose, an exemplary embodiment is illustrated as an overall process.

sites

1. [1] EP1326598B1
2. [2] EP1536810B1
3. [3] US20060167283A1
4. [4] EP1542952A1
5. [5] EP1385595B1
6. [6] US6403126B1
7. [7] EP3061510A1
8. [8th] WO2016187679A1
9. [9] US20050266108A1
10. [10] ADAMS, Roger; PEASE, D.C .; CLARK, J.H .: Isolation of Cannabinol, Cannabidiol and Quebrachitol from Red Oil of Minnesota Wild Hemp. In: Journal of the American Chemical Society 62 (8) (1940), 8, pp. 2194-2196
11. [11] EP2314580B1
12. [12] US20160002133A1
13. [13] W02017055619A1

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• EP 1326598 B1 [0035]
• EP 1536810 B1 [0035]
• US 20060167283 A1 [0035]
• EP 1542952 A1 [0035]
• EP 1385595 B1 [0035]
• US 6403126 B1 [0035]
• EP 3061510 A1 [0035]
• WO 2016187679 A1 [0035]
• US 20050266108 A1 [0035]
• EP 2314580 B1 [0035]
• US 20160002133 A1 [0035]
• WO 2017055619 A1 [0035]

Claims (10)

Process for the enrichment of a cannabinoid, characterized in that a distillation is carried out by means of a structured packing in a vacuum. Method according to Claim 1 , characterized in that subsequent to a first still at least a second distillation via a structured packing. Wherein the distillations can be done sequentially or directly in series. Method according to one of the preceding claims, characterized in that the primary product is a below 95 ° C, preferably below 85 ° C and more preferably a below 75 ° C meltable product in which the mass fraction of the cannabinoid to be enriched is at least 5%. Method according to one of the preceding claims, characterized in that it is the primary product to an already distilled product which has been distilled through a short path evaporator or a thin-film evaporator or from a bottom flask out. Method according to one of the preceding claims, characterized in that a maximum total pressure loss within a separation apparatus of 75 mbar and a maximum height of a package insert of 2.0 m is not exceeded. Method according to one of the preceding claims, characterized in that the walls of a operated via a structured packing distillation column can be heated. Method according to one of the preceding claims, characterized in that at least two distillations are carried out at different pressures in succession or directly connected in series. Method according to one of the preceding claims, characterized in that an enriched product with a mass fraction of a respective Cannabinoides> 85%, preferably> 90%, by an extraction process, a crystallization process, preferably a cooling crystallization, or a chromatographic process is further purified, so the mass fraction of the respective cannabinoid is>97.0%,>98.0%,> 99.0% or> 99.9%. Method according to one of the preceding claims, when the cannabinoid to be enriched is cannabidiol. Method according to one of Claims 1 - 8th if the cannabinoid to be enriched is tetrahydrocannabinol.

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