CHROMATOGRAMY METHOD AND DEVICE, IN PARTICULAR METHOD AND DEVICE FOR SUPERCRITICAL LIQUID CHROMATOGRAMY

Description

[0001] The invention relates to a chromatographic process, in particular a process for supercritical liquid chromatography, in which a starting material to be separated is separated into fractions by means of supercritical liquid chromatography and at least one of the fractions, which have at least a predetermined target content of at least one target component of the starting material, is derived as the target product fraction, wherein the fractions which do not have the predetermined target content form residual fractions and at least a part of at least one of the residual fractions is added to the starting material still to be separated.

[0002] The invention further relates to a device for supercritical liquid chromatography.

[0003] Chromatographic methods of the above-mentioned type are known from EP 1 982 752 A1 and the scientific publication KEßLER LC ET AL, "Improving performance of simulated moving bed chromatography by fractionation and feedback-back of outlet streams" (JOURNAL OF CHROMATOGRAPHY A, ELSEVIER, AMSTERDAM, NL, vol. 1207, no. 1-2, ISSN 0021-9673, (20081017), pages 55 - 71).

[0004] Another chromatography method is known from EP 3 173 782 A1.

[0005] Furthermore, it is known from practical experience to pass a mixture of substances to be separated through a chromatography column that has a stationary phase, which, for example, comprises a so-called packing of porous material. The different substances in the mixture are subject to different retentions as they flow 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.

[0006] Supercritical liquid chromatography (SFC) techniques are used, among other things, to separate polyunsaturated fatty acids from fatty acid mixtures.

[0007] The invention is based on the objective of creating a method of the type mentioned above that delivers a higher yield.

[0008] According to the invention, this problem is solved by adding at least a part of at least one of the residual fractions, whose content of the target component deviates less from the specified target content than the target component content of the starting material, to the starting material to be separated.

[0009] Advantageously, the residual fractions, or at least parts of them, are recycled in the separation process. This creates the possibility of subjecting a substance to the separation process multiple times in a single chromatography apparatus. Advantageously, the yield of a target product can be increased.

[0010] It is understood that the residual fractions with the aforementioned target component content can, if necessary, be added in their entirety to the starting material yet to be separated. However, it is more practical to add only those residual fractions whose target component content deviates less from the specified target content than the target component content of the starting material, or at least parts thereof, to the starting material yet to be separated.

[0011] The portion of the residual fractions whose target component content deviates less from the predetermined target content than the target component content of the starting material is directly recycled within the process according to the invention by being added to the starting material intended for separation. This brings the content of the target component in the separation material to be processed by chromatography closer to the target content, thus enabling a higher yield of the target product. Furthermore, the target component found in the residual fraction to be recycled can be added to the target product fraction.

[0012] It is expedient to derive the residual fractions whose target component content deviates more from the specified target content than that of the starting material for further handling, in particular further processing and / or disposal.

[0013] In one embodiment of the invention, the specified target content is a minimum content and / or a maximum content. The specified target content is typically a minimum content if the content of the respective component in the target product is to be increased compared to the starting material. The specified target content is typically a maximum content if the content of the respective component in the target product is to be decreased compared to the starting material.

[0014] In the case where the target content is a minimum content, it is expedient to add only the residual fractions to the starting material to be separated whose target component content is greater than that of the starting material.

[0015] Preferably, the residual fractions, whose target component content is lower than that of the starting material, are derived for further handling, in particular for further processing and / or disposal.

[0016] Conversely, if the target content is a maximum content, it is expedient to add only the residual fractions whose target component content is lower than that of the starting material to be separated.

[0017] Preferably, the residual fractions whose target component content is greater than that of the starting material are then derived for further handling, in particular for further processing and / or disposal.

[0018] In a further embodiment of the invention, the content of at least two, optionally several, different target components in the starting material and in the fractions is determined, and preferably the various target component contents of the residual fractions are compared with those of the starting material. Advantageously, the contents of several components can be taken into account. In particular, minimum contents can be specified for some of the target components and maximum contents for others.

[0019] In one embodiment of the invention, the levels of the target component in the starting material and in the fractions are determined, preferably by means of a suitable measuring device, wherein the determination of the target component levels is preferably carried out continuously.

[0020] It is advisable to compare the target component content of the residual fractions with that of the starting material. Based on the results of these comparisons, a decision is made as to whether the fractions are treated as target product fractions or residual fractions, and in particular whether the residual fractions are added to the starting material or diverted for further processing.

[0021] It may be planned to mix at least some or all of the residual fractions together and determine the target component content of the mixture. Based on this target component content, a decision is made as to whether the mixture is added to the starting material or separated for further processing.

[0022] In the preferred embodiment of the invention, at least the determination and comparison of the target component contents, as well as the addition of the residual fraction to the starting material to be separated, are performed automatically. The determination of the target component contents dictates how the respective fractions are to be handled. If the determination shows that the respective fraction has a target component content suitable for use as the target product fraction, the respective fraction is expediently automatically derived as the target product. If the fraction has a different target component content, the respective fraction is preferably automatically added to the starting material or disposed of.

[0023] In a further embodiment of the invention, the residual fraction is added to the starting material to be separated before its separation by chromatography. Preferably, a container is provided in which the residual fraction is added to the starting material. Advantageously, the starting material and the residual fraction are mixed before separation.

[0024] In one embodiment of the invention, the flow of the residual fraction, which is fed to the starting material to be separated before its separation, is adjusted, preferably controlled, depending on the content of the target component in the starting material and / or in the target product fraction.

[0025] The chromatography method according to the invention proves to be particularly advantageous for carrying out supercritical liquid chromatography. It can also be advantageously applied to liquid chromatography, in particular to thin-layer chromatography or column chromatography, especially low-pressure liquid chromatography, high-performance liquid chromatography (HPLC), gel permeation chromatography (GPC) or ion exchange chromatography (IC), or field-flow fractionation (FFF).

[0026] The chromatography process according to the invention can be carried out in a so-called batch process. The separation is then expediently carried out stepwise. In particular, in a first separation step, a separation into several fractions is carried out and the fractions are handled as described above. A next step may involve separating the starting material together with a residual fraction or a part thereof.

[0027] However, the inventive method can also be applied to continuously performed chromatography processes. Such chromatography processes, in which several chromatography columns are connected to one another, include, for example, True Moving Bed Chromatography (TMB) and Simulated Moving Bed Chromatography (SMB).

[0028] 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.

[0029] The process is expediently carried out continuously. The Simulated Moving Bed (SMB) method has proven particularly suitable for continuous execution.

[0030] Starting materials that are soluble in an eluent for chromatography processes are suitable for processing using the method according to the invention.

[0031] In particular for supercritical liquid chromatography, the starting material can be at least one substance or a mixture of substances that are soluble in supercritical CO2 or in a mixture of supercritical CO2 and at least one additional solvent, e.g. methanol and / or ethanol.

[0032] The process has proven particularly advantageous when the starting material is or comprises a mixture of fatty acids and / or derivatives thereof, preferably a mixture of unsaturated, especially polyunsaturated, fatty acids and / or derivatives thereof. The target component can then be one of the polyunsaturated fatty acids and / or derivatives thereof. Eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA) are particularly preferred as the target component.

[0033] It is advantageous for the target component minimum content of EPA to be 900 mg / g, preferably 970 mg / g.

[0034] The minimum target component content of DHA is expediently 850 mg / g, preferably 900 mg / g.

[0035] The starting material may further be or comprise a mixture of carboxylic acids and / or derivatives thereof, preferably a mixture of cannabinoids and / or cannabinoid derivatives. The target component is preferably cannabidiol, preferably CBD, or tetrahydrocannabinol (THC) or derivatives, in particular acids, thereof, preferably CBD / A, THC / A, CBG / A, CBN / A or / and CBC / A.

[0036] In one embodiment of the invention, the starting material is or comprises a mixture comprising at least one metabolite of a polyunsaturated fatty acid, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA) and / or docosapentaenoic acid (DPA), or a substance having the same composition as the metabolite. Advantageously, the target component is a metabolite of a polyunsaturated fatty acid, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA) and / or docosapentaenoic acid (DPA), or a substance having the same composition as the metabolite.

[0037] In a further embodiment of the invention, the starting material is or comprises a mixture containing 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.

[0038] Advantageously, the target component is at least a pre-resolving mediator (PRM) and / or a specialized pre-resolving mediator (SPM), which is / are preferably derived from EPA, DHA and / or DPA, and is separated from the mixture.

[0039] In a further embodiment of the invention, the starting material is or comprises 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. Advantageously, the target component is at least one pre-resolving mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or one specialized pre-resolving mediator (SPM), preferably lipoxin, resolvin, protectin and / or maresin.

[0040] The pre-resolving mediator (PRM) is preferably at least one substance from the group of substances 18-HEPE, 17-HDHA, 14-HDHA.

[0041] The specialized pre-resolving mediator (SPM) is preferably at least one substance from the group of substances lipoxin, resolvin, protectin, maresin.

[0042] The lipoxin is preferably at least one substance from the group of substances LxA4 (5S,6R, 1 5S-trihydroxy-7E,9E,111Z,13E-ETE), LxB4 (5S,14R,15S-trihydroxy-6E,8Z,10E,12E-ETE), 15-epi-LxA4 (5S,6R,15R-trihydroxy-7E,9E,11I, 13E-eicosatetraenoic acid), 15-epi-LxB4 (5S,14R,15R-trihydroxy-6E,8Z,10E,12E-eicosatrienoic acid).

[0043] 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 RvD 1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-DHA), RvD2 (7S,16R,17S-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).

[0044] The protectin is conveniently derived from DHA and / or DPA.

[0045] 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-PD 1 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).

[0046] Maresin is conveniently derived from DHA and / or DPA.

[0047] 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,2Z,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).

[0048] The eluent used for supercritical liquid chromatography (SFC) is preferably supercritical carbon dioxide, propane, n-pentane, trifluoromethanomaxenone, water, or ammonia. The eluent may contain a solvent as a co-solvent, preferably ethanol, methanol, isopropanol, acetonitrile, tetrahydrofuran, dichloromethane, chloroform, ethyl acetate, and / or trifluoroacetic acid.

[0049] Advantageously, an eluent from the chromatography process is reused for further chromatography after separation, as is known in the prior art, for example, for supercritical liquid chromatography (SFC). For this purpose, it is preferably fed into an eluent reservoir after separation following liquid chromatography, from which the eluent for the liquid chromatography is supplied.

[0050] The apparatus mentioned above comprises a typical structure of a chromatography apparatus, in particular a supercritical liquid chromatography apparatus, which is known per se. Specifically, the apparatus includes a separation column, a separating agent reservoir, an eluent reservoir, and a device for withdrawing the aforementioned fractions. The separating agent reservoir and the eluent reservoir are connected to the separation column in such a way that the respective separating agent and the eluent can be fed to the separation column in a controlled, preferably regulated, manner. The fraction withdrawal device is connected to the separation column in such a way that the respective fractions can be withdrawn from the separation column, in particular in a regulated and / or controlled manner. Furthermore, the fraction withdrawal device is connected to the separation column in such a way that the eluent or eluent mixture can be fed back into the eluent reservoir after the separation has been carried out.For the extraction of the various fractions, it is preferably equipped with several fractionation columns into which the respective fractions can be fed. Preferably, the separation agent reservoir is connected to a feedstock reservoir and is, preferably, continuously fed with the feedstock. Advantageously, the separation agent reservoir is also designed to supply the residual fractions whose target component content is higher than that of the feedstock. For this purpose, a line can be provided between the fraction extraction device and the separation agent reservoir, through which the respective residual fraction can be fed into the separation agent reservoir.

[0051] In a particularly preferred embodiment of the invention, the fraction extraction device is configured to route the target product fraction and the residual fractions differently, particularly depending on the respective target component content. Advantageously, the fraction extraction device has several lines equipped with valves through which the fractions can be selectively routed. The target product fractions are preferably routed into a designated target product container. The appropriate residual fractions are routed into the separation material container. The remaining residual material fractions are routed into a container for further handling.

[0052] The device expediently comprises a device for measuring the target component content in the starting material and a device for measuring the target component content in the fractions. Furthermore, a device for measuring the target component content in the separating agent located in the separation vessel, into which the residual fraction is added to the starting material, may be provided.

[0053] In one embodiment of the invention, the device is configured such that the fraction extraction unit forwards the fractions accordingly, depending on the measurement results obtained by the measuring devices. For this purpose, the device can be equipped with a control and / or regulation unit that reads and evaluates the measured values ​​and, based on the respective evaluation results, adjusts the fraction extraction unit, in particular by manipulating the valves, so that the intended material transfer takes place.

[0054] 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 schematically shows a part of a device according to the invention. Fig. 1 , and Fig. 3 schematically shows another device according to the invention

[0055] A. Device according to Figs. 1 and 2 : Fig. 1 Figure 1 schematically shows a device 1 according to the invention for supercritical liquid chromatography. The device 1 comprises the components of an SFC apparatus known per se, as described, for example, in DE 199 34 168 A1. In particular, it comprises a separation column 5, which is charged with a starting material from a starting material reservoir 2 and an eluent from an eluent reservoir 4.

[0056] Fractions produced during separation using the separation column 5 are conveyed via a fractionation unit 6 to fractionation columns 7, 8, 9. Each of the fractionation columns 7, 8, 9 is connected via lines to a target product container 13, a residual material container 14, and a separation material container 3.

[0057] Furthermore, each of the fractionation columns 7, 8, 9 has a switchable valve assembly 10, 11, 12, by means of which it is possible to select into which container the fractions obtained in the respective fractionation columns 7, 8, 9 are directed. Consequently, by means of the switchable valve assemblies 10, 11, 12, the respective fractions from the fractionation columns 7, 8, 9 can be selectively directed into any of the containers 3, 13, 14.

[0058] The separation tank 3 is fed with the feed material from the feed material reservoir 2. The material to be separated in the separation column 5 is fed from the separation tank 3.

[0059] The starting material reservoir 2 and the fractionation columns 7, 8, 9 and optionally the separation material container 3 are each equipped with a measuring device 15, 16, 17, 18, 19, which is intended to determine the content of at least one component of a substance in the respective container.

[0060] The device 1 comprises a control 20 which, as Fig. 2 schematically shows that it is set up to receive measurement data from the measuring devices 15, 16, 17, 18, 19 and to use the measurement data to adjust the switchable valve devices 10, 11, 12.

[0061] In supercritical liquid chromatography, the separation vessel 3 is fed with starting material from the starting material reservoir 2, and the substance is separated in the separation column 5 by adding the eluent 4. The various fractions produced are separated into fractionation columns 7, 8, and 9 via the fractionation unit 6, and the concentration of a target product in the fractions in the respective fractionation columns 7, 8, and 9 is measured using the measuring devices 15, 16, and 17. Furthermore, the concentration of the target product in the starting material reservoir 2 and, if applicable, in the separation vessel 3 is measured using the measuring devices 18 and 19.

[0062] Regulation 20 contains conditions according to which the valves of the valve devices 10, 11, 12 are set.

[0063] A first condition is a minimum target product content. For fractions that exhibit a specified minimum target product content according to the respective measurement, the valves are switched in such a way that these fractions are directed into the target product container 13.

[0064] Another condition is that the target product content is lower than the minimum target product content but higher than the target product content of the starting material, which is measured by measuring device 18. If a fraction from one of the fractionation columns 7, 8, 9 meets this condition, the fraction is fed into the separation vessel 3 and separated together with the unprocessed starting material in the separation column 5.

[0065] If one of the fractions from one of the fractionation columns 7, 8, 9 does not meet any of the aforementioned conditions, it is directed into the residual waste container 14. Example 1:

[0066] In the device 1 described above, an oil containing 20 wt% EPA and 70 wt% DHA is processed as a starting material. This oil can be produced from fish oil or algae oil.

[0067] The aim of the processing using device 1 is to obtain an oil that has a DHA content of at least 90 wt.%.

[0068] The oil to be processed is located in the feedstock reservoir 2.

[0069] The eluent, which is provided in eluent reservoir 4, is a mixture of CO₂ with ethanol as a co-solvent. After supercritical liquid chromatography, a fraction is formed in fractionation column 7, which 68 wt% DHA, fraction formed in fractionation column 8 which contains 83 wt% DHA and fraction formed in fractionation column 9 which contains 93 wt% DHA.

[0070] Based on the measurement results, valve devices 10, 11, and 12 are switched such that the fraction from fractionation column 7, which has a lower DHA content than the starting material, is directed into the residual material container 14. Valve device 11 is switched such that the fraction from fractionation column 8, which has a DHA content of 83 wt% (lower than the target product content but higher than the starting material content), is directed into the separation material container. The fraction from fractionation column 9 has a DHA content of 93 wt%, which is higher than the minimum target product content of 90 wt% DHA, and is therefore directed into the target product container 13. Example 2:

[0071] Initial data as described above for Example 1.

[0072] However, the fractions from the fractionation columns that do not meet the minimum target product content of 90 wt% DHA are mixed together to form a residue mixture, and the DHA content of the mixture is measured. If the residue mixture has a DHA content higher than that of the starting material, it is transferred to separation container 3 and mixed with the starting material. If the DHA content of the residue mixture is lower than that of the starting material, it is directed to residue container 14. Example 3:

[0073] The device 1 described above uses as a starting material an oil containing 20 wt% EPA, 70 wt% DHA and 4 wt% arachidonic acid (ARA). This oil can be derived from fish oil or algae oil.

[0074] The aim of the processing using device 1 is to obtain an oil that has a DHA content of at least 90 wt.% and an ARA content of < 0.5%.

[0075] The oil to be processed is located in the feedstock reservoir 2.

[0076] The eluent, which is provided in eluent reservoir 4, is a mixture of CO₂ with ethanol as a co-solvent. After supercritical liquid chromatography, a fraction containing 66 wt% DHA and 3.8 wt% ARA is formed in fractionation column 7, a fraction containing 83 wt% DHA and 1.7 wt% ARA is formed in fractionation column 8, and a fraction containing 93 wt% DHA and 0.3 wt% ARA is formed in fractionation column 9.

[0077] Based on the measurement results, the valve devices 10, 11, and 12 are switched such that the fraction from fractionation column 7, which has a lower DHA content and a higher ARA content than the starting material, is directed into the residual material container 14. Valve device 11 is switched such that the fraction from fractionation column 8, which has 83 wt% DHA (a lower DHA content than the target product content but a higher content than the starting material) and 1.7 wt% ARA (a higher ARA content than the target product content but a lower content than the starting material), is directed into the separation material container. The fraction from fractionation column 9 has 93 wt% DHA, which is higher than the minimum target product DHA content of 90 wt% DHA, and 0.3 wt% ARA.-% ARA has an ARA content that is smaller than the ARA target product maximum content and is therefore directed into the target product container 13. Example 4:

[0078] In the device 1 described above, the starting material reservoir contains an oil comprising 72 wt% EPA, 12 wt% DHA, and 16 wt% SDA. This oil may be derived from fish oil or algae oil.

[0079] The eluent, which is provided in eluent reservoir 4, is a mixture of CO₂ with ethanol as a co-solvent. The concentrations of EPA, DHA, and SDA are determined using measuring devices 15, 16, 17, 18, and 19, and the circuit is switched accordingly as described above.

[0080] The purpose of the processing using device 1 is to obtain an oil with an EPA content of at least 96 wt.%. A fraction with such an EPA content is placed in target product container 13.

[0081] Furthermore, fractions containing ≤ 96 wt% EPA but ≥75 wt% EPA, < 3 wt% DHA and < 6 wt% SDA are directed to the separating agent container 3.

[0082] Fractions that do not contain any of the aforementioned levels are placed in the residual waste container 14. Example 5:

[0083] The device 1 described above uses as a starting material an oil containing 70% CBD by weight. This can be an extract made from hemp.

[0084] The aim of the processing using device 1 is to obtain an oil that has a CBD content of at least 90% by weight.

[0085] The oil to be processed is located in the feedstock reservoir 2.

[0086] The eluent, which is provided in eluent reservoir 4, is a mixture of CO₂ with ethanol as a co-solvent. After supercritical liquid chromatography, a fraction is formed in fractionation column 7, which 63 wt% CBD, a fraction containing 87 wt% CBD was formed in fractionation column 8 and a fraction containing 95 wt% CBD was formed in fractionation column 9.

[0087] Based on the measurement results, valve devices 10, 11, and 12 are switched such that the fraction from fractionation column 7, which has a lower CBD content than the starting material, is directed into the residual material container 14. Valve device 11 is switched such that the fraction from fractionation column 8, which has a CBD content of 87 wt% (lower than the target product content but higher than the starting material content), is directed into the separation material container. The fraction from fractionation column 9 has a CBD content of 95 wt%, which is higher than the minimum target product content of 90 wt% CBD, and is therefore directed into the target product container 13. B. Device according to Fig. 3:

[0088] In Fig. 3A further apparatus 1a according to the invention is shown schematically. For separating a mixture of substances, the apparatus 1a comprises a chromatography unit 5a, which is suitable for performing simulated moving bed chromatography (SMB). The chromatography unit 5a has several interconnected separation columns, which together form zones I, II, III, and IV. As is known per se for SMB processes, the mixture of substances to be separated and an eluent are supplied to the chromatography unit 5a at alternating locations, and a raffinate and an extract are withdrawn from it at similarly alternating locations.

[0089] For this purpose, a piping system 27 is provided, comprising suitable pipes and valves and, if necessary, connections, as well as a device for adjusting the valves. The piping system 27 can further comprise at least one pump, preferably several pumps, to enable the control of material flows in the pipes.

[0090] The device 1a has a separating agent container 3a for supplying the chromatography unit 5a with the mixture to be separated. This separating agent container is connected to a starting material reservoir 2a in which the starting material to be separated is located. Raffinate extracted by the chromatography unit 5a is directed into a raffinate container 21, and extract extracted into an extract container 22. Before the raffinate and extract are directed into their respective containers 21 and 22, the eluent can be separated from the raffinate and extract, respectively, in separation units 23 and 24, in particular by evaporation. The separation units 23 and 24 can, for example, be formed by a falling film evaporator. The eluent from the separation units 23 and 24 can be returned to an eluent reservoir.

[0091] Depending on the target product content(s), the raffinate is directed to a target product container 13a or, for recycling purposes, to the separating material container 3a. The extract, also depending on the target product content, is placed in the separating material container 3a or in a residual material container 14a.

[0092] The mixture from the separation vessel 3a, which consists of the starting material supplied via the starting material reservoir 2a and, if applicable, raffinate and / or extract, is now given to the chromatography unit 5a. Continuous separation of the substances takes place there.

[0093] How Fig. 3 As shown, the chromatography device 5a is connected via the conduit device 27 to the raffinate container 21, the extract container 22, the residue container 14a and the separation material container 3a.

[0094] How Fig. 3As can be seen, a measuring device 19a is provided for the separating agent container 3a, a measuring device 25 for the raffinate container 21, and a measuring device 26 for the extract container, by means of which the target product content(s) of the substances arranged therein can be measured. Furthermore, the starting material reservoir 2a can be equipped with a measuring device 18a for determining the product content(s).

[0095] In a similar manner to above, using the Figs. 1 and 2As explained above, the device 1a may include a control and / or regulating device 20a which, taking into account the measured values ​​determined by the measuring devices 19a, 25, 26 and, if applicable, 18a, adjusts how the mixture of substances in the separation vessel 3a is mixed from the starting material, the raffinate and the extract and / or how much of the mixture is supplied to the chromatography device 5a. It is understood that the control and / or regulating device 20a is configured to adjust the piping device 27, in particular its valves and, if applicable, pumps. Example 6:

[0096] In the device 1a described above, the starting material processed is an oil containing 60 wt% EPA, 15 wt% DHA, and 10 wt% ARA. This oil can be derived from fish oil or algae oil.

[0097] The aim of the processing using device 1a is to obtain an oil that has a DHA content of at least 90 wt.%.

[0098] The oil to be processed is located in the starting material reservoir 2a.

[0099] Ethanol is used as the eluent, which is provided in eluent reservoir 4.

[0100] During the continuous separation of substances using the chromatography unit 5a in the SMB process, a mixture of substances is extracted as raffinate, the EPA content of which varies between 86 wt.% and 97.5 wt.%.

[0101] The control and / or regulation device 20a is programmed such that the raffinate is directed into the target product container 13a if the EPA content is > 90 wt.%, and into the separation material container if the EPA content is ≤ 90 wt.%.

[0102] Furthermore, the control and / or regulating device 20a is programmed such that the extract is directed into the separation container if the EPA content is > 70 wt.% and the ARA content is < 10 wt.%, and otherwise into the residual material container 14a.

[0103] The control and / or regulation device 20a may further be provided such that the quantity of each substance supplied from the feedstock reservoir 2a, the raffinate tank 21 and the extract tank to the separation tank 3a is adjusted so that the respective contents of EPA, DHA and ARA are within a certain predetermined range.

Claims

1. Chromatography method, especially method of supercritical fluid chromatography, in which a starting material to be separated is separated into fractions by means of chromatography and at least one of the fractions having at least a defined target content of at least one target component from the starting material is diverted off as target product fraction, where the fractions that do not have the defined target content form residual fractions and at least a portion of at least one of the residual fractions is added to the starting material yet to be separated, characterized in that at least a portion of at least one of the residual fractions wherein the content of the target component deviates less from the defined target content than the target component content of the starting material is added to the starting material yet to be separated.

2. Method according to Claim 1, characterized in that the residual fractions wherein the target component content deviates more from the defined target content than that in the starting material are diverted off for further handling, especially further processing or / and disposal, where the defined target content is preferably a minimum content or / and a maximum content.

3. Method according to Claim 2, characterized in that a content of the target component in the starting material and in the fractions is determined, and the target component contents of the residual fractions are preferably compared with those of the starting material.

4. Method according to any of Claims 1 to 3, characterized in that a content of at least two, and optionally more than two, different target components in the starting material and in the fractions is determined and the different target component contents of the residual fractions are preferably compared with those of the starting material.

5. Method according to any of Claims 1 to 4, characterized in that the method is conducted continuously.

6. Method according to any of Claims 1 to 5, characterized in that at least the determination and the comparisons of the target component contents and a feeding of the residual fraction to the starting material to be separated are conducted automatically.

7. Method according to any of Claims 1 to 6, characterized in that the residual fraction is fed to the starting material yet to be separated before separation thereof by means of chromatography, where the starting material and the residual fraction are preferably mixed before the separation.

8. Method according to Claim 7, characterized in that the flow rate of the residual fraction which is fed to the starting material yet to be separated before separation thereof is controlled as a function of the content of the target component in the starting material and / or in the target product fraction.

9. Method according to any of Claims 1 to 8, characterized in that the starting material is or comprises - a mixture of fatty acids and / or derivatives thereof, preferably a mixture of unsaturated, especially polyunsaturated, fatty acids and / or derivatives thereof, and / or - a mixture, preferably a mixture of carboxylic acids and / or derivatives thereof, preferably a mixture of cannabinoids and / or derivatives thereof, and / or - a mixture containing 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 a substance having the same composition as the metabolite, and / or - a mixture containing at least one pre-resolving mediator (PRM) and / or a specialized pre-resolving mediator (SPM) which is / are preferably derived from EPA, DHA or / and from DPA, and / or - a mixture containing at least one pre-resolving mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or specialized pre-resolving mediator (SPM), preferably lipoxins, resolvins, protectins and / or maresins.

10. Method according to any of Claims 1 to 9, characterized in that the target component is a polyunsaturated fatty acid, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA), or is cannabidiol (CBD) or tetrahydrocannabinol (THC).

11. Method according to any of Claims 1 to 10, characterized in that the target component 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 is a substance having the same composition as the metabolite.

12. Method according to any of Claims 1 to 11, characterized in that the target component is a pre-resolving mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or at least one specialized pre-resolving mediator (SPM), preferably lipoxin, resolvin, protectin and / or maresin.

13. Chromatography apparatus, especially apparatus for supercritical fluid chromatography, having at least one separating column (5) for separating a starting material into fractions, a device for removing the fractions, a device for diverting off at least one of the fractions that have a defined target content of at least one target component of the starting material, and a device for conduction of at least a portion of the fractions that do not have the defined target content to the starting material yet to be separated, characterized in that the conduction device is set up to conduct at least a portion of the fractions wherein the content of the target component deviates less from the defined target content than the target component content of the starting material to the starting material yet to be separated.

14. Apparatus according to Claim 13, characterized by a device for diverting off at least the fractions wherein the target component content deviates more from the defined target content than that of the starting material, preferably for further handling, especially further processing or / and disposal.

15. Apparatus according to either of Claims 13 and 14, characterized by a device (15, 16, 17) for measuring the content of the target component in the fractions and preferably by a device for closed-loop and / or open-loop control of the fraction removal device, which is intended to use measured values determined by the measurement devices as controlled variable and / or manipulated variable for closed-loop and / or open-loop control.