Chromatography methods and chromatographic apparatus, particularly methods and apparatus for supercritical liquid chromatography.

Abstract

The present invention relates to a method for chromatography, in particular for supercritical fluid chromatography, in which a starting material to be separated is separated by chromatography into fractions, and at least one of said fractions, which contains at least one predefined target content of at least one target component of said starting material, is discharged as a target product fraction. According to the invention, the fraction that does not contain the predefined target content forms a remainder fraction, and at least a portion of at least one of said remainder fractions is added to the starting material to be separated therefrom. Preferably, at least a portion of at least one of the remainder fractions, whose target component content deviates from the predefined target content by less than the target component content of the starting material, is added to the starting material to be separated therefrom. In one embodiment of the invention, the remainder fraction, whose target component content deviates from the predefined target content by more than the target component content of the starting material, is discharged for further manipulation, in particular for further processing and / or disposal.

Description

Technical Field

[0001] The present invention relates to a chromatographic method, particularly a method for supercritical fluid chromatography, in which a starting material to be separated is separated into respective fractions by supercritical fluid chromatography, and at least one of the fractions contains at least one target component of the starting material at at least one predetermined target content rate, and at least one of the respective fractions is discharged as a target product fraction.

[0002] The present invention further relates to an apparatus for supercritical fluid chromatography.

Background Art

[0003] Chromatographic methods of the above type are known from use. A substance mixture to be separated is passed through a chromatography column having a stationary phase including, for example, a so-called packing made of a porous material. Different substances in the substance mixture are subjected to different retention when flowing through the stationary phase, that is, they flow through the stationary phase at different speeds due to different interactions of different strengths in the stationary phase. This enables separation.

[0004] Methods for performing supercritical fluid chromatography (SFC) are used, inter alia, for separating polyunsaturated fatty acids from fatty acid mixtures.

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present invention is based on the problem of creating a method of the type described at the beginning that provides a higher yield.

Means for Solving the Problems

[0006] According to the present invention, this problem is solved by the fact that a fraction that does not have a predetermined target content forms a residual fraction, and at least a portion of at least one of the residual fractions is added to the starting material to be separated from there.

[0007] Advantageously, the remaining fraction or at least a portion of it is recycled in the separation process. It is possible to subject the substance to the separation process multiple times in a single chromatography apparatus. Advantageously, the yield of the target product can be increased.

[0008] In a particularly preferred embodiment of the present invention, at least a portion of at least one of the remaining fractions in which the target component content is lower than the target component content of the starting material and deviates from a predetermined target component content is added to the starting material to be separated. It will be understood that the remaining fractions containing the last listed target component content can be optionally all added to the starting material to be separated. Preferably, only such remaining fractions, or at least a portion thereof, in which the target component content is lower than the target component content of the starting material and deviates from a predetermined target component content are added to the starting material to be separated.

[0009] If the target component content of the remaining fraction is lower than that of the starting material and deviates from a predetermined target component content, a portion of the remaining fraction is recycled directly in the method of the present invention by adding it to the starting material intended for separation. This, on the one hand, brings the target component content in the material to be processed by chromatography closer to the target component content, thereby enabling the achievement of a higher yield of the target product. On the other hand, the target component found in the remaining fraction to be recycled can be added to the target product fraction.

[0010] Preferably, any remaining fraction in which the target component content is greater than that of the starting material and deviates significantly from a predetermined target component content is discharged for further processing, in particular for further treatment and / or disposal.

[0011] In one embodiment of the present invention, the predetermined target content is the minimum and / or maximum content. When the content of each component in the target product is to be increased compared to the starting material, the predetermined target content is typically the minimum content. When the content of each component in the target product is to be decreased compared to the starting material, the predetermined target content is typically the maximum content.

[0012] Preferably, when the target content is at its minimum, only the remaining fraction in which the target component content is greater than the target component content of the starting material is added to the starting material to be separated.

[0013] Preferably, the remaining fraction in which the target component content is less than that of the starting material is discharged for further processing, in particular for further treatment and / or disposal.

[0014] Conversely, if the target content is the maximum content, preferably, only the remaining fraction in which the target component content is smaller than the target component content of the starting material is added to the starting material to be separated.

[0015] Preferably, the remaining fraction in which the target component content is greater than that of the starting material is then discharged for further operations, in particular for further processing and / or disposal.

[0016] In further embodiments of the present invention, the content of at least two, optionally more, different target components in the starting material and in each fraction is determined, and preferably, the content of the different target components in the remaining fraction is compared with that of the starting material. Advantageously, the content of multiple components can be considered. In particular, a minimum content can be determined for some target components and a maximum content for others.

[0017] In one embodiment of the present invention, the content of the target component in the starting material and in the fraction is preferably determined by a suitable measuring device, where the determination of the target component content is preferably performed continuously.

[0018] Preferably, the target component content of the residual fraction is compared with the target component content of the starting material. Based on the results of the comparison, it is determined whether the fraction is treated as a target product fraction or a residual fraction, in particular whether the residual fraction is added to the starting material or discharged for further processing.

[0019] At least several residual fractions or all of the residual fractions may be mixed together, and the target component content of the residual fraction mixture may be measured. Based on the target component content of the residual fraction mixture, it is determined whether the residual fraction mixture is added to the starting material or discharged for further processing.

[0020] In preferred embodiments of the present invention, at least the determination and comparison of target component content, and the addition of the remaining fraction to the starting material to be separated, are performed automatically. Based on the determination of the target component content, it is identified how each fraction should be handled. If the target component content measurement reveals that each fraction has a target component content that allows it to be used as a target product fraction, each fraction is preferably automatically discharged as the target product. If a fraction has a target component content that is not suitable, each fraction is preferably automatically added to the starting material or disposed of.

[0021] In a further embodiment of the present invention, the residual fraction is added to the starting material to be separated, before its chromatographic separation. Preferably, a container is provided to which the residual fraction is added to the starting material. Preferably, the starting material and the residual fraction are mixed before separation.

[0022] In one embodiment of the present invention, the flow of the residual fraction added to the starting material to be separated before separation is adjusted and preferably controlled according to the content of the target component in the starting material and / or the target product fraction.

[0023] The chromatography method according to the present invention is found to be particularly advantageous for the implementation of methods for supercritical liquid chromatography. It can also be advantageously used for liquid chromatography, particularly 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).

[0024] The chromatography method according to the present invention can be carried out by a so-called batch method. In this case, separation is preferably carried out in steps. In particular, in the first separation step, separation into multiple fractions is carried out, and the fractions are handled as described above. The next step is carried out while optionally separating the starting material together with the remaining fraction or a portion thereof.

[0025] However, the method according to the present invention can also be used in chromatography methods that are performed continuously. Such chromatography methods, in which multiple chromatography columns are connected to one another, include, for example, true moving bed chromatography (TMB) and simulated moving bed chromatography (SMB).

[0026] In SMB chromatography, a plurality of chromatography columns are connected in series with each other. A substance mixture and an eluent are introduced at different connection sites between the chromatography columns. Similarly, the raffinate and the extract are taken out at another connection site, where one substance or optionally a plurality of substances that are subject to shorter retention in chromatography are taken out as the raffinate, and one substance or a plurality of substances that are subject to longer retention in chromatography are taken out as the extract. Therefore, a substance mixture can be separated into two different substance sub-mixtures according to the operation of chromatography when using a known chromatography method, where the first substance sub-mixture contains substances that are subject to shorter retention, and the second substance sub-mixture contains substances that are subject to longer retention.

[0027] Preferably, the method is carried out continuously. It has been found that the simulated moving bed (SMB) method is particularly suitable for the continuous implementation of the method.

[0028] For the treatment by the method of the present invention, starting materials that are soluble in the eluent for the chromatography method are suitable.

[0029] Particularly with respect to supercritical fluid chromatography, the starting material can be a mixture of at least one substance or a plurality of substances that are soluble in supercritical CO2 or in a mixture of supercritical CO2 and at least one additional solvent, such as methanol and / or ethanol.

[0030] It has been found that the method is particularly advantageous when the starting material is a mixture of fatty acids and / or their derivatives, preferably unsaturated, particularly polyunsaturated fatty acids and / or their derivatives, or contains them. In that case, the target component can be one of the polyunsaturated fatty acids and / or their derivatives. Particularly preferably, the target component is eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA).

[0031] Preferably, the minimum content of the target component of EPA is 900 mg / g, more preferably 970 mg / g.

[0032] The minimum target component content of DHA is preferably 850 mg / g, and more preferably 900 mg / g.

[0033] The starting material may further be a mixture of carboxylic acids and / or derivatives thereof, preferably a mixture of cannabinoids and / or cannabinoid derivatives, or may contain them. The target component is preferably cannabidiol, preferably CBD, or tetrahydrocannibinol (THC) or its derivatives, particularly acids, preferably CBD / A, THC / A, CBG / A, CBN / A and / or CBC / A.

[0034] In one embodiment of the present invention, the starting material is a mixture comprising, or a mixture thereof, a mixture thereof, which comprises 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 said metabolite.

[0035] Preferably, 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 said metabolite.

[0036] In a further embodiment of the present invention, the starting material is a mixture comprising, or comprising, at least one pre-resolving mediator (PRM) and / or at least one specialized pre-resolving mediator (SPM), preferably derived from EPA, DHA and / or DPA.

[0037] Preferably, the target component is at least one inflammation-resolving mediator (PRM) and / or at least one specific inflammation-resolving mediator (SPM) derived from EPA, DHA and / or DPA, and is separated from the mixture of substances.

[0038] In a further embodiment of the present invention, the starting material is a mixture of or comprising a resolving inflammation mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or a specific resolving inflammation mediator (SPM), preferably lipoxins, resolvins, protectins and / or malecins.

[0039] Preferably, the target component is at least one anti-inflammatory mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or a specific anti-inflammatory mediator (SPM), preferably lipoxin, resolvin, protectin and / or malecin.

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

[0041] The specific anti-inflammatory mediator (SPM) is preferably at least one substance from the group of substances consisting of lipoxins, resolvins, protectins, and maresins.

[0042] 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), and 15-epi-LxB4 (5S,14R,15R-trihydroxy-6E,8Z,10E,12E-eicosatrienoic acid).

[0043] The resolvin is preferably derived from EPA, DHA, and / or DPA.

[0044] Resolvin is preferably at least Substances 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 -RvD1(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 Substances from the group of substances (4S,5R,17S-trihydroxy-6E,8E,10Z,13Z,15E,19Z-DHA), RvD5(7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-DHA), and RvD6(4S,17S-dihydroxy-5E,7Z,10Z,13Z,15E,19Z-DHA), and / or Substances 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), That is the case.

[0045] The protectin is preferably derived from DHA and / or DPA.

[0046] The protectin is preferably at least Substances from the group of substances including -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 Substances from the group of substances -PD1n-3 (10,17-dihydroxy-7,11,13,15,19-DPA) and PD2n-3 (16,17-dihydroxy-7,10,12,14,19-DPA), That is the case.

[0047] Malecin is preferably derived from DHA and / or DPA.

[0048] The malecin is preferably at least Substances 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 Substances 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), That is the case.

[0049] Preferably, supercritical carbon dioxide, propane, N-pentane, trifluoromethanomaxenon, water, or ammonia are used as eluents for supercritical liquid chromatography (SFC). The eluent may have a cosolvent, preferably ethanol, methanol, isopropanol, acetonitrile, tetrahydrofuran, dichloromethane, chloroform, ethyl acetate, and / or trifluoroacetic acid.

[0050] Preferably, the eluent for chromatography is used again for chromatography after separation, as is known from the prior art, for example, with respect to supercritical liquid chromatography (SFC). For this purpose, preferably, after separation following liquid chromatography, it is led to an eluent reservoir supplied with eluent for liquid chromatography.

[0051] The apparatus described first includes a typical configuration of a chromatography apparatus, particularly one for supercritical liquid chromatography, which is known in itself. In particular, the apparatus comprises a separation column, a separation material reservoir, an eluent reservoir, and a device for taking the aforementioned fractions. The separation material reservoir and the eluent reservoir are connected to the separation column so that the respective separation material and eluent can be added to the separation column in a controlled, preferably controlled and / or regulated manner. A fractionation device is connected to the separation column so that each fraction can be taken from the separation column, particularly in a regulated and / or regulated manner. Furthermore, the fractionation device is connected to the separation column so that the eluent or eluent mixture can be supplied back to the eluent reservoir after the separation has been performed. For the taking of various fractions, it is preferably provided with a plurality of fractionation columns, each capable of leading to a different fraction.

[0052] Preferably, the separation material reservoir is connected to the starting material reservoir, and the starting material is supplied, preferably continuously. Preferably, the separation material reservoir is further designed to add residual material fractions in which the target component content is greater than that of the starting material. To this end, a line can be provided between the fraction extraction device and the separation material reservoir, through which each residual material fraction can be added to the separation material reservoir.

[0053] In a particularly preferred embodiment of the present invention, the fractionation device is designed to deliver the target product fraction and the residual fraction in various ways, particularly depending on the respective target component content. Preferably, the fractionation device has a plurality of valved lines through which fractions can be delivered as desired. The target product fraction is preferably led to a target product container intended for that purpose. A suitable residual fraction is led to a separation material container. Another residual material fraction is led to a container for further processing.

[0054] The apparatus preferably includes a device for measuring the content of the target component in the starting material and a device for measuring the content of the target component in the fraction. Furthermore, a device for measuring the content of the target component in the separated material, which is located in a separation container into which the remaining fraction is added to the starting material, may be provided.

[0055] In one embodiment of the present invention, the apparatus is configured such that the fraction extraction device appropriately delivers fractions according to the measurement results from the measuring device. To this end, the apparatus may include a control and / or adjustment device that reads and evaluates the measured values ​​and adjusts the fraction extraction device, particularly under valve operation, according to the respective evaluation results, so that the intended material transfer occurs.

[0056] The present invention will be described in more detail below with reference to examples and accompanying drawings relating to those examples. [Brief explanation of the drawing]

[0057] [Figure 1] Figure 1 schematically shows the apparatus according to the present invention. [Figure 2] Figure 2 schematically shows a part of the apparatus according to the present invention as shown in Figure 1. [Figure 3] Figure 3 schematically shows a further apparatus according to the present invention.

[0058] A. Apparatus shown in Figures 1 and 2: Figure 1 schematically shows apparatus 1 according to the present invention for supercritical liquid chromatography. Apparatus 1 has known components of an SFC apparatus, such as those described in DE19934168A1. In particular, it comprises a separation column 5 that holds the starting material from a starting material reservoir 2 and the eluent from an eluent reservoir 4.

[0059] The fractions generated during separation by separation column 5 are guided to fractionation columns 7, 8, and 9 via fractionation device 6. Each of the fractionation columns 7, 8, and 9 is connected via lines to the target product container 13, the residual material container 14, and the separated material container 3, respectively.

[0060] Furthermore, each of the fractionation columns 7, 8, and 9 has a switchable valve device 10, 11, and 12, respectively, which allows adjustment of which container the fractions obtained from each fractionation column 7, 8, and 9 are directed to. Thus, the switchable valve devices 10, 11, and 12 allow the fractions from each of the fractionation columns 7, 8, and 9 to be directed to containers 3, 13, and 14 as desired.

[0061] The starting material from the starting material reservoir 2 is supplied to the separation material container 3. The material to be separated by the separation column 4 is supplied from the separation material container 3.

[0062] The starting material reservoir 2 and fractionation columns 7, 8, and 9, as well as optionally the separated material container 3, are each provided with measuring devices 15, 16, 17, 18, and 19, respectively, intended to determine the content of at least one component of the substance in each container.

[0063] Apparatus 1 includes a control unit 20, which, as schematically shown in Figure 2, is designed to receive measurement data from measuring devices 15, 16, 17, 18, and 19 and to adjust switchable valve devices 10, 11, and 12 based on said measurement data.

[0064] In supercritical liquid chromatography, the starting material is supplied to the separation vessel 3 from the starting material reservoir 2, and the material from the separation vessel is separated in the separation column 5 with the addition of the eluent 4. The various resulting fractions are separated into fractionation columns 7, 8, and 9 via the fractionation device 6, and the content of the target product in the fractions in each fractionation column 7, 8, and 9 is measured by measuring devices 15, 16, and 17. Furthermore, the content of the target product in the starting material reservoir 2 and optionally in the separation vessel 3 is measured by measuring devices 18 and 19.

[0065] The control unit 20 stores conditions (based on which the valves of valve devices 10, 11, and 12 are adjusted).

[0066] The first condition is the minimum content of the target product. In each measurement, if a fraction has a predetermined minimum content of the target product, the valve is switched so that these fractions are directed to the target product container 13.

[0067] Another condition is that the target product content measured by the measuring device 18 is less than the minimum target product content but greater than the target product content of the starting material. If a fraction from one of the fractionation columns 7, 8, or 9 satisfies this condition, that fraction is fed into the separation container 3 and separated together with the starting material that has not yet been processed in the separation column 5.

[0068] If a fraction from any of the fractionation columns 7, 8, or 9 does not meet the last specified condition, it is directed to the residual material container 14. [Examples]

[0069] Example 1: In the apparatus 1 described above, an oil containing 20% ​​by weight of EPA and 70% by weight of DHA is processed as a starting material. Here, it may be an oil produced from fish oil or algenoel.

[0070] The purpose of processing with apparatus 1 is to obtain oil having a DHA content of at least 90% by weight.

[0071] The oil to be processed is located in the starting material reservoir 2.

[0072] A mixture of CO2 and ethanol as a cosolvent is used as the eluent supplied to the eluent reservoir 4. After supercritical liquid chromatography, a fraction containing 68% by weight of DHA is generated in fractionation column 7, a fraction containing 83% by weight of DHA is generated in fractionation column 8, and a fraction containing 93% by weight of DHA is generated in fractionation column 9.

[0073] Depending on the measurement results, valve devices 10, 11, and 12 are switched to guide the fraction from fractionation column 7, which has a lower DHA content than the starting material, to the residual material container 14. Valve device 11 is switched to guide the fraction from fractionation column 8, which has a DHA content of 83 wt%, which is lower than the target product content but higher than the starting material content, to the separated material container. The fraction from fractionation column 9 has a DHA content of 93 wt% DHA, which is higher than the minimum target product content of 90 wt% DHA, and is therefore guided to the target product container 3.

[0074] Example 2: Departure data as described in Example 1 above.

[0075] However, fractions from the fractionation column that do not meet the minimum target product content of 90 wt% DHA are mixed together to form a residual mixture, and the DHA content of this mixture is measured. If the residual mixture has a DHA content greater than that of the starting material, it is added to the separation material container 3 and mixed with the starting material there. If the DHA content of the residual mixture is less than that of the starting material, it is led to the residual material container 14.

[0076] Example 3: The apparatus 1 described above processes an oil containing 20% ​​by weight of EPA, 70% by weight of DHA, and 4% by weight of arachidonic acid (ARA) as a starting material. Here, it may be an oil produced from fish oil or algal oil.

[0077] The purpose of processing with apparatus 1 is to obtain oil having a DHA content of at least 90% by weight and an ARA content of <0.5%.

[0078] The oil to be processed is located in the starting material reservoir 2.

[0079] A mixture of CO2 and ethanol as a cosolvent is used as the eluent supplied to the eluent reservoir 4. After supercritical liquid chromatography, a fraction containing 66% by weight of DHA and 3.8% by weight of ARA is produced in fractionation column 7, a fraction containing 83% by weight of DHA and 1.7% by weight of ARA is produced in fractionation column 8, and a fraction containing 93% by weight of DHA and 0.3% by weight of ARA is produced in fractionation column 9.

[0080] Depending on the measurement results, valve devices 10, 11, and 12 are switched to guide the fraction from fractionation column 7, which has a lower DHA content and a higher ARA content than the starting material, to the residual material container 14. Valve device 11 is switched to guide 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, and an ARA content of 1.7 wt% (higher than the target product content) but lower than the starting material content, to the separated material container. The fraction from fractionation column 9 has a DHA content of 93 wt% DHA, which is higher than the minimum DHA target product content of 90 wt% DHA, and an ARA content of 0.3 wt% ARA, which is lower than the maximum ARA target product content, and is therefore guided to the target product container 3.

[0081] Example 4: In the apparatus 1 described above, an oil containing 72% by weight of EPA, 12% by weight of DHA, and 16% by weight of SDA is provided as the starting material in the starting material reservoir. Here, it may be an oil produced from fish oil or algal oil.

[0082] A mixture of CO2 and ethanol as a cosolvent is used as the eluent supplied to the eluent reservoir 4. The EPA, DHA, and SDA content is determined by measuring devices 15, 16, 17, 18, and 19 and switched accordingly as described above.

[0083] The purpose of processing with apparatus 1 is to obtain oil having an EPA content of at least 96% by weight. The fraction having such an EPA content is placed in the target product container 13.

[0084] Furthermore, fractions containing ≤96% by weight of EPA, but also containing ≥75% by weight of EPA, <3% by weight of DHA, and <6% by weight of SDA, are introduced into the separation material container 3.

[0085] Fractions that do not have the above-mentioned content are placed in the residual substance container 14.

[0086] Example 5: The apparatus 1 described above processes an oil containing 70% by weight of CBD as the starting material. Here, it may be an extract produced from hemp (Hanf).

[0087] The purpose of processing with apparatus 1 is to obtain oil having a CBD content of at least 90% by weight.

[0088] The oil to be processed is located in the starting material reservoir 2.

[0089] A mixture of CO2 and ethanol as a cosolvent is used as the eluent supplied to the eluent reservoir 4. After supercritical liquid chromatography, a fraction containing 63% by weight of CBD is produced in fractionation column 7, a fraction containing 87% by weight of CBD is produced in fractionation column 8, and a fraction containing 95% by weight of CBD is produced in fractionation column 9.

[0090] Depending on the measurement results, valve devices 10, 11, and 12 are switched to direct the fraction from fractionation column 7, which has a CBD content lower than that of the starting material, to the residual material container 14. Valve device 11 is switched to direct the fraction from fractionation column 8, which has a CBD content of 87 wt% (lower than the target product content) but higher than that of the starting material, to the separated material container. The fraction from fractionation column 9 has a CBD content of 95 wt% CBD, which is higher than the minimum target product content of 90 wt% CBD, and is therefore directed to the target product container 3.

[0091] B. Apparatus according to Figure 3: Figure 3 schematically shows a further apparatus 1a of the present invention. For the separation of a mixture of substances, apparatus 1a has a chromatography device 5a suitable for performing pseudo-moving bed chromatography (SMB). The chromatography device 5a has multiple interconnected separation columns that together form zones I, II, III, and IV. As is known with respect to the SMB method, the mixture of substances to be separated and the eluent are added to the chromatography device 5a at fluctuating positions, and similarly, the raffinate and extract are removed at fluctuating positions.

[0092] For this purpose, a line device 27 is provided, which includes appropriate lines and valves, and optionally connectors, as well as devices for adjusting the valves. The line device 27 may further have at least one pump, preferably more pumps, so as to influence the flow of material in the line.

[0093] Apparatus 1a has a separation material container 3a connected to a starting material reservoir 2a containing the starting materials to be separated, for supplying a mixture of materials to be separated to a chromatography device 5a. The raffinate extracted by the chromatography device 5a is led to a raffinate container 21, and the extracted extract is led to an extract container 22. Before leading the raffinate and extract to their respective containers 21 and 22, the eluent can be separated from the raffinate or extract, respectively, in separation devices 23 and 24, particularly by evaporation. Separation devices 23 and 24 can be formed, for example, by a drip-film evaporator. The eluent from separation devices 23 and 24 can be returned to the eluent reservoir.

[0094] Depending on the target product content(s), the raffinate is introduced into the target product container 13a, or, for recycling purposes, into the separated material container 3a. The extract is similarly introduced into the separated material container 3a or the residual material container 14a, depending on the target product content.

[0095] A mixture of substances from the starting material added via the starting material reservoir 2a and optionally from the raffinate and / or extract, is then placed into the chromatography device 5a. There, continuous substance separation is performed.

[0096] As shown in Figure 3, the chromatography device 5a is connected to the raffinate container 21, the extract container 22, the residual material container 14a, and the separated material container 3a via the line device 27.

[0097] As can be seen in Figure 3, a measuring device 19a is provided for the separation material container 3a, a measuring device 25 for the raffinate container 21, and a measuring device 26 for the extract container, allowing for the measurement of the target product content (multiple products) of the substances placed in each container. Furthermore, a measuring device 18a for determining the product content (multiple products) can be provided in the starting material reservoir 2a.

[0098] As described above with reference to Figures 1 and 2, the apparatus 1a has a control-and / or adjustment device 20a that adjusts how the mixture of materials in the separated material container 3a from the starting material, raffinate, and extract is mixed, and / or how much of the mixture of materials is added to the chromatography device 5a, taking into account the measurements taken by the measuring devices 19a, 25, 26 and optionally 18a. Naturally, for this purpose, the control-and / or adjustment device 20a is designed to adjust the line device 27, in particular its valve and optionally the pump.

[0099] Example 6: In the apparatus 1 described above, an oil containing 60% by weight of EPA, 15% by weight of DHA, and 10% by weight of ARA is processed as a starting material. Here, it may be an oil produced from fish oil or algal oil.

[0100] The purpose of processing with apparatus 1 is to obtain oil having a DHA content of at least 90% by weight.

[0101] The oil to be processed is located in the starting material reservoir 2.

[0102] Ethanol is used as the eluent supplied to the eluent reservoir 4.

[0103] In the continuous substance separation process using chromatography device 5a in the SMB method, a mixture of substances with an EPA content varying between 86% and 97.5% by weight is extracted as raffinate.

[0104] The control-and / or adjustment device 20a is programmed to direct the raffinate to the target product container 13a if the EPA content is >90 wt%, and to the separation material container if the EPA content is ≤90 wt%.

[0105] Furthermore, the control-and / or adjustment device 20a is programmed so that if the EPA content is >70 wt% and the ARA content is <10 wt%, the extract is directed to the separated material container, otherwise it is directed to the residual material container 14.

[0106] The control device and / or adjustment device 20a may further be configured to adjust the amounts of substances from the starting material reservoir 2a, the raffinate container 21, and the extract container, respectively, in the amount of substance placed in the separation material container 3a, so that the respective contents of EPA, DHA, and ARA are within a specific predetermined range. While this application relates to the invention described in the claims, it may also encompass the following other embodiments. 1. A chromatography method, more particularly a method for supercritical liquid chromatography, wherein a starting material to be separated is separated into fractions by chromatography, and at least one of the fractions, each containing at least one target component of the starting material at at least one predetermined target content, is discharged as a target product fraction. The method is characterized in that a fraction not containing the predetermined target content forms a residual fraction, and at least a portion of at least one of the residual fractions is added to the starting material to be separated from there. 2. The method according to claim 1, characterized in that at least a portion of at least one of the remaining fractions, whose target component content is smaller than that of the starting material and deviates from the predetermined target component content, is added to the starting material to be separated. 3. The method according to 1 or 2 above, wherein the remaining fraction in which the target component content deviates significantly from the predetermined target component content of the starting material is discharged for further operations, in particular further processing and / or disposal, wherein the predetermined target component content is preferably a minimum and / or maximum content. 4. The method according to 3 above, characterized in that the content of the target component in the starting material and in each of the fractions is determined, and preferably the content of the target component in the remaining fraction is compared with the content of the target component in the starting material. 5. The method according to any one of 1 to 4 above, characterized in that the content of at least two, optionally more, different target components in the starting material and in each of the fractions is determined, and preferably the content of the different target components in the remaining fraction is compared with the content of the target components in the starting material. 6. The method according to any one of items 1 to 5 above, characterized in that it is carried out continuously. 7. The method according to any one of 1 to 6 above, characterized in that at least the determination and comparison of the target component content, and the addition of the remaining fraction to the starting material to be separated are carried out automatically. 8. The method according to any one of 1 to 7 above, characterized in that the remaining fraction is added to the starting material to be separated by chromatography before the separation of the starting material, and the starting material and the remaining fraction are preferably mixed before the separation. 9. The method according to 8, characterized in that the flow of the residual fraction added to the starting material to be separated before separation is controlled according to the content of the target component in the starting material and / or the target product fraction. 10. The starting material is - Mixtures of fatty acids and / or derivatives thereof, preferably unsaturated, especially polyunsaturated fatty acids and / or derivatives thereof, and / or - A mixture, preferably a mixture of carboxylic acids and / or their derivatives, preferably a mixture of cannabinoids and / or their derivatives, and / or - Metabolites of polyunsaturated fatty acids, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA) and / or docosapentaenoic acid (DPA), or mixtures containing substances having the same composition as said metabolites, and / or - Preferably a mixture containing at least one inflammation-resolving mediator (PRM) and / or specific inflammation-resolving mediator (SPM) derived from EPA, DHA and / or DPA, and / or - A mixture containing at least one anti-inflammatory mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or a specific anti-inflammatory mediator (SPM), preferably lipoxins, resolvins, protectins and / or malecins. A method according to any one of the above 1 to 9, characterized by being or including these. 11. The method according to any one of 1 to 10 above, characterized in that the target component is a polyunsaturated fatty acid, preferably eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA), or cannabidiol (CBD) or tetrahydrocannabinol (THC). 12. The method according to any one of 1 to 11 above, characterized in that 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. 13. The method according to any one of 1 to 12 above, characterized in that the target component is an inflammation-resolving mediator (PRM), preferably 18-HEPE, 17-HDHA and / or 14-HDHA, and / or at least one specific inflammation-resolving mediator (SPM), preferably lipoxin, resolvin, protectin and / or malecin. 14. A chromatography apparatus, particularly for supercritical liquid chromatography, comprising at least one separation column (5) for separating a starting material into fractions, a device for taking out each of the fractions, and a device for discharging at least one of the fractions containing at least one target component of the starting material at a predetermined target content, The apparatus is characterized by a device for guiding at least a portion of a fraction that does not contain the predetermined target content to a starting material to be separated from there. 15. The apparatus according to 14, characterized in that the device for guiding to the starting material to be separated is designed to guide at least a portion of a fraction in which the content of the target component is smaller than the content of the target component in the starting material and deviates from the predetermined target content to the starting material to be separated. 16. The apparatus according to 14 or 15, preferably comprising a device for discharging at least fractions in which the target component content deviates significantly from the predetermined target component content, more so than the target component content of the starting material, for further operations, particularly further processing and / or disposal. 17. The apparatus according to any one of 14 to 16, comprising a device for controlling and / or adjusting a fraction extraction device, provided to use as a control and / or manipulated variable a measurement value obtained by a device (15, 16, 17) for measuring the content of the target component in each of the fractions, and preferably by a measuring device for control and / or adjustment.

Claims

1. A chromatography method comprising separating a starting material to be separated into fractions by chromatography, and discharging at least one of the fractions, which contains at least one target component of the starting material at at least one predetermined target content, as a target product fraction, A fraction that does not contain the predetermined target content forms a remaining fraction, and at least a portion of at least one of the remaining fractions is added to the starting material to be separated from it. The method is characterized in that at least a portion of at least one of the remaining fractions, in which the content of the target component is smaller than the content of the target component of the starting material and deviates from the predetermined target content, is added to the starting material from which separation is to be performed.

2. The method according to claim 1, characterized in that the remaining fraction in which the target component content is greater than that of the starting material and deviates from the predetermined target component content is discharged for further processing.

3. The method according to claim 2, characterized in that the content of the target component in the starting material and in each of the fractions is determined.

4. The method according to claim 3, characterized in that the target component content of the remaining fraction is compared with the target component content of the starting material.

5. The method according to any one of claims 1 to 4, characterized in that the content of at least two, and optionally more, different target components in the starting material and in each of the fractions is determined.

6. The method according to claim 5, characterized in that the different target component content of the remaining fraction is compared with the target component content of the starting material.

7. The method according to any one of claims 1 to 6, characterized in that it is carried out continuously.

8. The method according to any one of claims 1 to 7, characterized in that at least the determination and comparison of the target component content, and the addition of the remaining fraction to the starting material to be separated are carried out automatically.

9. The method according to any one of claims 1 to 8, characterized in that the remaining fraction is added to the starting material to be separated by chromatography before the separation of the starting material, and the starting material and the remaining fraction are mixed.

10. The method according to claim 9, characterized in that the flow of the residual fraction added to the starting material to be separated before separation is controlled according to the content of the target component in the starting material and / or the target product fraction.

11. The method according to any one of claims 1 to 10, characterized in that the target component is eicosapentaenoic acid (EPA) and / or docosahexaenoic acid (DHA), or cannabidiol (CBD).

12. A chromatography apparatus comprising at least one separation column (5) for separating a starting material into fractions, a device for extracting each fraction, and a device for discharging at least one of the fractions containing at least one target component of the starting material at a predetermined target content, The device includes a device for guiding at least a portion of the fraction that does not contain the predetermined target content to the starting material to be separated from there, The apparatus is characterized in that the device for guiding a starting material to be separated is designed to guide at least a portion of a fraction in which the content of the target component is smaller than the content of the target component in the starting material and deviates from the predetermined target content, to the starting material to be separated.

13. The apparatus according to claim 12, further comprising a device for discharging at least fractions in which the target component content is greater than the target component content of the starting material and deviates from the predetermined target content.

14. The apparatus according to claim 13, further comprising a device for discharging at least fractions in which the target component content deviates from the predetermined target component content by a larger amount than the target component content of the starting material, for further operation.

15. The apparatus according to any one of claims 12 to 14, characterized by devices (15, 16, 17) for measuring the content of the target component in each of the aforementioned fractions.

16. The apparatus according to claim 15, further comprising a device for controlling and / or adjusting a fraction extraction device, provided to use a measured value, measured by a measuring device for control and / or adjustment, as a controlled and / or manipulated variable.

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