METHOD AND DEVICE FOR SEPARING A MIXTURE AND CORRESPONDING COMPUTER PROGRAM PRODUCT

Description

[0001] The invention relates to a method for separating a first substance from a mixture of substances by means of chromatography, wherein the mixture of substances comprises at least a second substance which is subject to greater retention during chromatography than the first substance, and a third substance which is subject to less retention during chromatography than the first substance, wherein the mixture of substances is fed to a chromatography apparatus comprising several interconnected chromatography columns, the mixture of substances and an eluent are fed to the apparatus, and the second substance is extracted and the first substance is removed as a raffinate.

[0002] WO 2017 / 194173 A1 relates to a process for the purification of cannabinoid compounds using simulated fluidized bed chromatography, wherein the cannabinoid compounds in the extract and / or the raffinate are obtained with a total amount of isomeric impurities below the limit of detection.

[0003] US 2012 / 0330043 A1 describes a chromatographic separation method for obtaining a polyunsaturated fatty acid (PUFA) product from a feed mixture, wherein the method comprises introducing the feed mixture into a simulated or actual fluidized bed chromatography apparatus with a plurality of interconnected chromatography columns containing an aqueous alcohol as an eluent.

[0004] Chromatography methods of the type described above are known through use. A mixture to be separated is passed through the chromatography column, which contains a stationary phase, for example, a packing of porous material. The different substances in the mixture are subject to different retentions as they pass through the stationary phase; that is, they flow through the stationary phase at different speeds due to varying degrees of interaction within it. This makes separation possible. While it is possible to perform chromatography in a batch process, where the separation always occurs in a single step, methods have been developed for continuous chromatography in which several chromatography columns are connected together.Chromatography methods that are carried out on an industrial scale include True Moving Bed Chromatography (TMB) and Simulated Moving Bed Chromatography (SMB).

[0005] In SMB chromatography, several chromatography columns are connected in series. The mixture and an eluent are introduced at different connection points between the columns. A raffinate and an extract are also taken from these connection points. The raffinate is the substance or substances that exhibit lower retention during chromatography, while the extract is the substance or substances that exhibit higher retention. Consequently, the mixtures can be separated into two distinct submixtures using known chromatographic methods, depending on the specific handling of the chromatography. The first submixture contains substances with lower retention, and the second submixture contains substances with higher retention.

[0006] The invention is based on the objective of making it possible to carry out substance separation using chromatography more flexibly.

[0007] According to the invention, this problem is solved by extracting the third substance.

[0008] The invention makes it possible to separate a substance from a mixture, even if the mixture contains other substances that are subject to varying degrees of retention during chromatography compared to the substance to be separated. Whereas previously it was necessary to perform several chromatographic processes sequentially to achieve a comparable result, the substance to be separated can now be separated using the inventive method by performing a single chromatographic process. The effort required to carry out the separation process is thus significantly reduced.

[0009] In one embodiment of the invention, the chromatography columns form zones, wherein a) a first zone between a device for supplying the eluent and a device for draining the extract, b) a second zone between a device for draining the extract and a device for supplying the mixture, c) a third zone between a device for supplying the mixture and a device for draining the raffinate, and d) a fourth zone between a drain of the raffinate and a device for supplying the eluent.

[0010] Advantageously, the material flows, in particular the inflows and / or outflows, are adjusted via the aforementioned inflow and / or outflow devices such that a sufficiently high flow rate exists in a zone between a device for the discharge of the raffinate and a device for the supply of the eluent to allow the third substance to be extracted. With such a setting of the chromatography apparatus, the third substance, unlike in known chromatography methods, is forced into zone I, from which the extract is taken. While the third substance would be extracted as raffinate in known chromatography methods due to its lower retention compared to the first substance, according to the invention it is extracted as an extract.

[0011] It has proven particularly advantageous to extract the third substance together with the second substance.

[0012] In one embodiment of the invention, the eluent supply device, the extract discharge device, the mixture supply device, and the raffinate discharge device each have multiple supply and discharge connections arranged between different chromatography columns. These supply and discharge connections are preferably equipped with valves by means of which the respective flow rates, in particular the inflows and / or outflows, of the mixture, the eluent, the extract, and / or the raffinate can be adjusted through the respective supply and discharge connections. According to the invention, the respective flow rates are adjusted such that the zones in the apparatus are formed alternately in different chromatography columns. In this way, it becomes possible to carry out the chromatography process according to the invention as a TMB or as an SMB process.

[0013] In a preferred embodiment of the invention, the content of the first substance in the raffinate is greater than the content of the first substance in the mixture, and preferably the content of the second and / or the third substance in the extract is greater than the content of the second or the third substance in the mixture. Advantageously, the content of the first substance in the raffinate is maximized, and in particular, the content of the second and / or the third substance in the extract is maximized.

[0014] Advantageously, the content of the first substance in the extract is lower than the content of the first substance in the mixture, and preferably the content of the second and / or the third substance in the raffinate is lower than the content of the second or third substance in the mixture.

[0015] Preferably, the content of the first substance in the extract is lower than the content of the first substance in the raffinate, and preferably the content of the second and / or the third substance in the raffinate is higher than the content of the second or third substance in the extract.

[0016] In a particularly preferred embodiment of the invention, the respective material flows are adjusted such that at least one of the aforementioned content ratios in the raffinate or extract is achieved. Preferably, the adjustment is carried out continuously, and particularly preferably by means of regulation and / or control.

[0017] Advantageously, the chromatography apparatus includes at least one device for determining a material property of the raffinate and / or the extract, and optionally also for determining a material property of the mixture and / or the eluent, wherein in particular the content of a component of the raffinate, the extract, the mixture and / or the eluent is determined.

[0018] Advantageously, the flows of the mixture, eluent, raffinate and / or extract in the device are adjusted, and particularly preferably controlled, depending on the result of a determination of the material properties by means of the sensor.

[0019] In one embodiment of the invention, the system is controlled and / or regulated in such a way that the content of the first substance in the raffinate is maximized and preferably the content of the second and / or the third substance in the raffinate is minimized.

[0020] In one embodiment of the invention, the mixture of substances is or comprises a fatty acid mixture, preferably a mixture of unsaturated, in particular polyunsaturated, fatty acids. The fatty acid mixture particularly preferably contains omega-3 fatty acids.

[0021] The first substance to be separated from the fatty acid mixture is advantageously a polyunsaturated fatty acid, preferably an omega-3 fatty acid, particularly preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA). If EPA is separated as the first substance from the mixture, DHA and / or arachidonic acid (ARA) can form the second substance, which is subject to greater retention during chromatography. The third substance, which is subject to greater retention than EPA during chromatography and is extracted, can be stearidonic acid (SDA). The aim of removing the omega-3 fatty acid, in particular eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA), can be to produce a product containing the respective omega-3 fatty acid in a particularly high concentration.

[0022] Furthermore, the process could be carried out with the aim of reducing the concentration of a specific substance in the mixture. For example, arachidonic acid could be extracted as the first substance, and thus as a refined form, from an omega-3 fatty acid using this process, in order to reduce the arachidonic acid content. The target product would then be obtained as an extract.

[0023] In a further embodiment of the invention, the mixture comprises a carboxylic acid mixture, preferably a mixture containing cannabinoids. The first substance is suitably cannabidiol (CBD). Alternatively, tetrahydrocannabinol (THC), in particular Δ9-THC and / or Δ8-THC, could constitute the first substance. This proves advantageous when the THC is to be removed from a carboxylic acid mixture, particularly from a cannabinoid.

[0024] When CBD is separated from the carboxylic acid as the first compound, cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), and / or cannabidivarin acid (CBDVA) can form the second compound. The third compound can be cannabigerol (CBG), tetrahydrocannabivarin acid (THCBA), Δ9- and / or Δ8-THC, and / or cannibigerolic acid (CBGA).

[0025] In a further embodiment of the invention, the mixture of substances is or comprises a mixture of pre-resolving mediators (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or specialized pre-resolving mediator (SPM), preferably lipoxins, resolvins, protectins and / or maresins.

[0026] In a further embodiment of the invention, the first substance is a metabolite of a polyunsaturated fatty acid, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA) and / or docosapentaenoic acid (DPA), or has the same chemical composition as the metabolite.

[0027] In one embodiment of the invention, the method is expediently carried out in such a way that at least one pre-resolving mediator (PRM) and / or one specialized pre-resolving mediator (SPM), which is or are preferably derived from EPA, DHA and / or DPA, is separated from the mixture.

[0028] The pre-resolving mediator (PRM) is preferably at least one substance from the group of substances 18-HEPE, 17-HDHA, 14-HDHA.

[0029] The specialized pre-resolving mediator (SPM) is preferably at least one substance from the group of substances lipoxin, resolvin, protectin, maresin.

[0030] The lipoxin is preferably at least one substance from the group of substances LxA4 (5S,6R,15S-trihydroxy-7E,9E,11Z,13E-ETE), LxB4 (5S,14R,15S-trihydroxy-6E,8Z,10E,12E-ETE), 15-epi-LxA4 (5S,6R,15R-trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acid), 15-epi-LxB4 (5S,14R,15R-trihydroxy-6E,8Z,10E,1 2E-eicosatrienoic acid).

[0031] The resolvin is expediently derived from EPA, DHA, and / or DPA. The resolvin is preferably at least a substance from the group of substances RvE1 (5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA), 18S-RvE1 (5S,12R,18S-trihydroxy-6Z,8E,10E,14Z,16E-EPA), RvE2 (5S,18R-dihydroxy-6E,8Z,11Z,14Z,16E-EPA), RvE3 (17R,18R / S-dihydroxy-5Z,8Z,11Z,13E,15E-EPA), and / or a substance from the group of substances RvD1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-DHA), RvD2 (7S,16R,117S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-DHA), RvD3 (4S,11R,17S-trihydroxy-5Z,7E,9E,13Z,15E,19Z-DHA), RvD4 (4S,5R,17S-trihydroxy-6E,8E,10Z,13Z,15E,19Z-DHA), RvD5 (7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-DHA), RvD6 (4S,17S-dihydroxy-5E,7Z,10Z,13Z,15E,19Z-DHA), and / or a substance from the group of substances RvT1 (7,13R,20-trihydroxy-8E,10Z,14E,16Z,18E-DPA), RvT2 (7,8,13R-trihydroxy-9E,11E,14E,16Z,19Z-DPA), RvT3 (7,12,13R-trihydroxy-8Z,10E,14E,16Z,19Z-DPA), RvT4 (7,13R-dihydroxy-8E,10Z,14E,16Z,19Z-DPA).

[0032] The protectin is conveniently derived from DHA and / or DPA.

[0033] The protectin is preferred at least a substance from the group of substances PD1 or NPD1 (10R,17S-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-DHA), PDX (10S,17S-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-DHA), 22-hydroxy-PD1 (10R,17S,22-trihydroxy-4Z,7Z,11E,13E,15Z,19Z-DHA), 17-epi-PD1 or AT-PD1 (10R,17R-dihydroxy-4Z,7Z,11E,13E,15Z,19Z-DHA), 10-epi-PD1 or ent-AT-NPD1 (10S,17S-Dihydroxy-4Z,7Z,11E,13E,15Z,19Z-DHA) and / or a substance from the group of substances PD1n-3 (10,17-dihydroxy-7,11,13,15,19-DPA), PD2n-3 (16,17-dihydroxy-7,10,12,14,19-DPA).

[0034] Maresin is conveniently derived from DHA and / or DPA.

[0035] The Maresin is preferred at least a substance from the group of substances MaR1 (7R,14S-dihydroxy-4Z,8E,10E,12Z,16Z,19Z-DHA), MaR2 (13R,14S-dihydroxy-4Z,7Z,9E,11E,16Z,19Z-DHA), 7-epi-MaR1 (7S,14S-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-DHA), MaR-L1 (14S,22-dihydroxy-4Z,7Z,10Z,12E,16Z,19Z-DHA), MaR-L2 (14R,22-dihydroxy-4Z,7Z,10Z,12E,16Z,19Z-DHA), and / or a substance from the group of substances MaR1n-3 (7S,14S-dihydroxy-8E,10E,12Z,16Z,19Z-DPA), MaR2n-3 (13,14-dihydroxy-7,9,111,16,19-DPA), MaR3n-3 (13,14-dihydroxy-7,9,111,16,19-DPA).

[0036] The invention further relates to a device with which the described separation process can be carried out. In addition to the aforementioned chromatography columns and the aforementioned feed and / or discharge devices, the device preferably comprises a device for determining a material property of the raffinate and / or the extract, in particular for determining the content of a constituent. By means of the detection device, physical properties, in particular light absorption, fluorescence, light scattering and / or thermal conductivity, and / or chemical properties, for example color or the like, are preferably determined, and the substance content is thereby ascertained.

[0037] The device preferably further comprises a device for adjusting a material flow, in particular an inflow and / or outflow, of the mixture, the eluent, the raffinate and / or the extract.

[0038] In a particularly preferred embodiment of the invention, the device comprises a means for regulating and / or controlling material flows, in particular inflows and / or outflows, via the inflow and / or outflow devices depending on a result of the determination by means of the detection device. Preferably, the regulating and / or controlling device is provided for adjusting the respective material flows such that at least one of the aforementioned content ratios in the raffinate or extract is achieved.

[0039] The invention further relates to a computer program product by means of which the method according to the invention can be carried out. The computer program product can advantageously be loaded directly into the internal memory of a digital computer and comprises software sections with which, when the computer program is running on a computer, steps of the method according to the invention can be carried out. The computer program product preferably has interfaces for interacting with a device according to the invention. The computer program product can constitute or be part of the aforementioned control and / or regulation device. Preferably, the computer program product, particularly due to its interfaces, is designed to process the result of the determination by means of the detection device and to adjust the input and / or output devices.

[0040] The aforementioned computer program product is appropriately designed to execute one, several, or all of the process steps when running on the computer.

[0041] The computer program is preferably a computer program product stored on a volatile or non-volatile data carrier, preferably RAM, ROM, DRAM, SRAM, EPROM, EEPROM or the like, or on a device, in particular a personal computer, a device with an embedded processor, or a sequence of signals suitable for transmission over a computer network, in particular the Internet, representing data.

[0042] The invention further relates to a data carrier signal that is transmitted by the aforementioned computer product.

[0043] The invention is explained in more detail below with reference to exemplary embodiments and the accompanying drawings relating to these embodiments. The drawings show: Fig. 1 schematically shows a device according to the invention, Fig. 2 the device according to Fig. 1 in different positions and Fig. 3 a schematic graphic of retention times and Fig. 4 and 5 schematic graphics with retention times of substances of different mixtures.

[0044] In Fig. 1 A schematic representation of a chromatography apparatus 1 according to the invention is shown, comprising chromatography columns 2, 3, 4, 5 which are interconnected such that they are in flow communication with one another. Connections 11, 12, 13, 14 are arranged between the chromatography columns. Each of the connections 11, 12, 13, 14 is connected to a device 6 for supplying an eluent, a device 7 for discharging an extract, a device 8 for supplying a mixture, and a device 9 for discharging a raffinate. The aforementioned devices 6, 7, 8, 9 each have valves by means of which the flow rates, in particular the inflow and / or outflow of the eluent, the extract, the mixture, or the raffinate, can be adjusted, especially the magnitude of the respective flow rates.

[0045] The device comprises a sensor for determining the content of a first substance in the extract and a sensor for determining the content of the first substance in the raffinate.

[0046] Furthermore, the device 1 includes a device 16 for regulating and / or controlling the aforementioned inflows and / or outflows, in particular by adjusting the aforementioned valves. The regulating and / or controlling device 16 preferably comprises an embedded processor on which a computer program is stored, which is designed to perform the regulation and / or control by processing data provided by the sensors.

[0047] Depending on the open or closed position of the various valves, the positions to which the eluent or mixture is fed and the extract or raffinate is discharged can be adjusted. Accordingly, zones I, II, III, and IV can be alternately formed in the various chromatography columns 2, 3, 4, and 5. a) a first zone I between a port through which the eluent is supplied and a port through which the extract is discharged, b) a second zone II between a port through which the extract is discharged and a port through which the mixture is supplied, c) a third zone III between a port through which the mixture is supplied and a port through which the raffinate is discharged, and d) a fourth zone IV between a port through which the raffinate is discharged and a port through which the eluent is supplied.

[0048] The control and / or regulating device 16 is configured to adjust the positions of the valves based on signals from the sensors 16 in order to regulate material flows, in particular inflows and / or outflows. By adjusting the various valves, zones I, II, III, and IV can be assigned differently in the chromatography columns 2, 3, 4, and 5. The valve positions are adjusted such that the first substance can be extracted as the raffinate. Fig. 2a shows the device 1 according to the invention in a valve switching position in which the chromatography column 2 forms zone I, the chromatography column 3 forms zone II, the chromatography column 4 forms zone III, and the chromatography column 5 forms zone IV.

[0049] By switching the valves, zones I, II, III, and IV can be formed in different chromatography columns 2, 3, 4, and 5, for example, with appropriate valve switching, as in Fig. 2b As shown, chromatography column 2 forms zone IV, chromatography column 3 zone I, chromatography column 4 zone II, and chromatography column 5 zone III. The switching of the valves is essentially the same as in known TMB or SMB chromatography methods, but taking into account the conditions explained below.

[0050] The implementation of the method according to the invention will be explained in more detail below. Fig. 3 The diagram explains the retention times of different substances A, B, C, D, and E in a mixture. Substance D is to be separated from the mixture. Substance D, as shown in the diagram, exhibits... Fig. 3 Substance D exhibits a longer retention time than substances A, B, and C, and a shorter retention time than substance E. To extract substance D as a raffinate, the inflows and outflows are adjusted such that substance D can be extracted as a raffinate after passing through Zone III. Substances A, B, and C, which have a shorter retention time than substance D, are extracted as an extract after passing through Zone I. Furthermore, according to the invention, the inflows and outflows are adjusted such that a flow is generated in Zone IV that substance E is forced into Zone I and can be extracted as an extract in Zone I together with substances A, B, and C.

[0051] In a first specific embodiment, the separation process according to the invention is carried out on a mixture of polyunsaturated fatty acids. The mixture, in particular an oil, for example a fish oil, an algal oil and / or a linseed oil, contains DHA, ARA, EPA and SDA. The corresponding retention times are shown in Fig. 4 As shown, EPA is to be extracted as a raffinate. DHA and ARA exhibit shorter retention times than EPA. SDA, on the other hand, exhibits a longer retention time. While conventional chromatography methods would require first separating substances into DHA and ARA on the one hand, and EPA and SDA on the other, and then performing a further separation of the already separated portion containing EPA and SDA to separate the two components, as explained above, the inventive method not only extracts DHA and ARA, but also extracts SDA, provided the inflows and outflows are appropriately adjusted. EPA is extracted exclusively as a raffinate. Table 1 Q I Q II Q III Q IV Q Eluent Q SG Q Raf Q Extr Gehalte im Raffinat mL / min mL / min mL / min mL / min mL / min mL / min mL / min mL / min %SDA % EPA % DHA 353 263,4 265 190 163 1,6 75 89,6 4,10% 91,7% 0,0% 353 263,4 265 200 153 1,6 65 89,6 4,40% 90,7% 0,0% 353 263,4 265 210 143 1,6 55 89,6 4,50% 91,2% 0,0% 353 263,4 265 220 133 1,6 45 89,6 3,70% 93,2% 0,0% 353 263,4 265 230 123 1,6 35 89,6 3,00% 93,0% 0,0%

[0052] Table 1 shows that different SDA and EPA concentrations can be achieved in the raffinate by adjusting the flow rates (Q IV) in Zone IV. The lowest SDA concentration is achieved by setting a comparatively high flow rate in Zone IV. As also shown in Table 1, the different flow rates in Zones I, II, III, and IV are achieved by adjusting the mass flows, particularly the inflows and / or outflows, of the eluent (Q Eluent), the mixture (Q SG), the raffinate (Q Raf), and the extract (Q Extr).

[0053] In a further embodiment, it is provided to use the same mixture of materials for which in Fig. 4 The retention times shown indicate the need to remove ARA as a raffinate to eliminate arachidonic acid from the mixture. In this case, the flow rates are adjusted so that the EPA and SDA are forced into Zone I, allowing them to be extracted along with the DHA. It is understood that this requires higher flow rates in Zone IV compared to conventional SMB chromatography.

[0054] In another embodiment, the separation process is carried out on a mixture of substances containing cannabidiol. Fig. 5 The diagram schematically shows the retention times of individual selected substances of the mixture, namely those of CBDVA, CBD, Δ9-THC, Δ8-THC and CBGA.

[0055] The intention is to extract CBD from the mixture. For this purpose, the flow rates during chromatography are adjusted so that CBD can be extracted as the sole refined compound. CBDVA, which has a shorter retention time than CBD, as well as Δ9-THC, Δ8-THC, and CBGA, which have longer retention times than CBD, are extracted together.

[0056] Furthermore, it is possible to remove THC from the aforementioned cannabidiol mixture using the inventive method by adjusting the material flows such that Δ9-THC and Δ8-THC are extracted together as a refined product. CBDVA and CBD, which have a shorter retention time than Δ9-THC and Δ8-THC, and CBGA, which has a longer retention time than Δ9-THC and Δ8-THC, are extracted together as a single extract.

Claims

1. Method for separating a first substance from a substance mixture by chromatography, wherein the substance mixture comprises at least one second substance which is subject to greater retention than the first substance in the chromatography, and comprises at least one third substance which is subject to lower retention than the first substance in the chromatography, wherein the substance mixture is fed to an apparatus (1) for chromatography comprising a plurality of interconnected chromatography columns (2, 3, 4, 5), the substance mixture and an eluent are fed to the apparatus (1), and the second substance is withdrawn as an extract and the first substance is withdrawn as a raffinate, characterized in that the third substance is withdrawn as an extract.

2. Method according to Claim 1, characterized in that the third substance and the second substance are withdrawn together as an extract.

3. Method according to Claim 1 or 2, characterized in that the chromatography columns (2, 3, 4, 5) form zones (I, II, III, IV), wherein a) a first zone (I) is formed between a device (6) for supplying the eluent and a device (7) for discharging the extract, b) a second zone (II) is formed between a device (7) for discharging the extract and a device (8) for supplying the substance mixture, c) a third zone (III) is formed between a device (8) for supplying the substance mixture and a device (9) for discharging the raffinate and d) a fourth zone (IV) is formed between a device (9) for discharging the raffinate and a device (6) for supplying the eluent.

4. Method according to Claim 3, characterized in that substance flows, in particular inflows and / or outflows, are adjusted via the supply and / or discharge devices (6, 7, 8, 9) in such a way that in a zone (IV) between a device (9) for discharging the raffinate and a device (6) for supplying the eluent there is such a large flow that the third substance can be withdrawn as an extract.

5. Method according to any of Claims 1 to 4, characterized in that the device (6) for supplying the eluent, the device (7) for discharging the extract, the device (8) for supplying the substance mixture and the device (9) for discharging the raffinate comprise a plurality of supply and discharge connections (10, 11, 12, 13) between different chromatography columns (2, 3, 4, 5) and respective substance flows through the supply and discharge connections (10, 11, 12, 13) are adjusted in such a way that the zones (I, II, III, IV) in the apparatus (1) are formed alternately in different chromatography columns (2, 3, 4, 5).

6. Method according to any of Claims 1 to 5, characterized in that the substance mixture is or comprises a fatty acid mixture, preferably a mixture of unsaturated, in particular polyunsaturated, fatty acids, and / or a carboxylic acid mixture, preferably a mixture of cannabinoids, and / or a mixture of pre-resolving mediators (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or of specialized pre-resolving mediators (SPM), preferably lipoxins, resolvins, protectins and / or maresins.

7. Method according to any of Claims 1 to 6, characterized in that the first substance is a polyunsaturated fatty acid, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA), or cannabidiol (CBD) or tetrahydrocannabinol (THC).

8. Method according to any of Claims 1 to 7, characterized in that a) the third substance is stearidonic acid (SDA) and / or the second substance is arachidonic acid (ARA) and / or docosahexaenoic acid (DHA), b) the third substance is stearidonic acid (SDA) and / or eicosapentaenoic acid (EPA) and / or the second substance is arachidonic acid (ARA) or c) the third substance is tetrahydrocannabinol (THC), CBGA and / or CBG and / or the second substance is CBDVA, THCV and / or CBDV.

9. Method according to any of Claims 1 to 8, characterized in that the first substance is a metabolite of a polyunsaturated fatty acid, preferably of eicosapentaenoic acid (EPA) and / or of docosahexaenoic acid (DHA) and / or of docosapentaenoic acid (DPA), or has the same composition as the metabolite.

10. Method according to any of Claims 1 to 9, characterized in that at least one pre-resolving mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or at least one specialized pre-resolving mediator (SPM), preferably lipoxins, resolvins, protectins and / or maresins, is withdrawn from the substance mixture.

11. Method according to any of Claims 1 to 10, characterized in that the first substance is a pre-resolving mediator (PRM) and / or a specialized pre-resolving mediator (SPM).

12. Method according to any of Claims 1 to 11, characterized in that a) the third substance is a pre-resolving mediator (PRM) and / or a specialized pre-resolving mediator (SPM) and / or the second substance is arachidonic acid (ARA) and / or docosahexaenoic acid (DHA), b) the third substance is a pre-resolving mediator (PRM) and / or a specialized pre-resolving mediator (SPM) and / or the second substance is eicosapentaenoic acid (EPA) and / or arachidonic acid (ARA) or c) the third substance is a pre-resolving mediator (PRM) and / or a specialized pre-resolving mediator (SPM) and / or the second substance is docosapentaenoic acid (DPA).

13. Apparatus for separating a first substance from a substance mixture by chromatography, comprising a plurality of interconnected chromatography columns (2, 3, 4, 5) and comprising a device for supplying the substance mixture, a device for supplying an eluent, a device for discharging an extract, and a device for discharging a raffinate, wherein the substance mixture comprises at least one second substance which is subject to greater retention than the first substance in the chromatography, and comprises at least one third substance which is subject to lower retention than the first substance in the chromatography, wherein the apparatus is configured to withdraw the second substance as an extract and the first substance as a raffinate, characterized in that the apparatus is configured to withdraw the third substance as an extract.

14. Apparatus according to Claim 13, characterized by a device for adjusting an inflow and / or outflow of the substance mixture, of the eluent, of the raffinate and / or of the extract in such a way that the third substance can be withdrawn together with the second substance as an extract.

15. Computer program product which can be loaded directly into the internal memory of a digital computer and which comprises software sections by means of which, when the computer program product runs on a computer, steps of a method for controlling and / or regulating a substance separation apparatus are carried out, wherein the substance separation apparatus comprises a plurality of interconnected chromatography columns (2, 3, 4, 5) and is provided for separating a first substance from a substance mixture, wherein the substance mixture comprises at least one second substance which is subject to greater retention than the first substance when chromatography is carried out, and comprises a third substance which is subject to lower retention than the first substance in the chromatography, wherein the substance mixture and an eluent are fed to the apparatus (1), and the second substance is withdrawn as an extract and the first substance is withdrawn as a raffinate, characterized in that substance flows, in particular inflows and / or outflows, of the substance mixture, of the eluent, of the raffinate and / or of the extract in the apparatus (1) are adjusted in such a way that the third substance is withdrawn as an extract.