Feedstock liquid reduction method and system

Abstract

A raw material liquid concentration reduction method is a raw material liquid concentration reduction method for reducing the concentration of a raw material liquid containing at least a valuable substance and a first solvent, wherein the raw material liquid further contains a by-product component other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and a second solvent as a solvent, and the raw material liquid concentration reduction method is a method in which a first treatment and a second treatment are combined, the first treatment removes the first solvent from the raw material liquid, and the second treatment adjusts the concentration of the second solvent or the by-product component from the raw material liquid by using a dialysis method using a dialysis membrane.

Description

TECHNICAL FIELD

[0001] The present application relates to a method and a system for reducing the volume of a raw material liquid. BACKGROUND

[0002] Reduction of the volume of a raw material liquid containing a valuable substance is carried out on an industrial scale.

[0003] For example, in a purification process of a raw material liquid of a peptide, DNA, RNA, and enzyme, and a derivative compound thereof, and a raw material thereof (hereinafter referred to as "peptide or the like"), the raw material liquid contains, in addition to the peptide or the like and water, various organic solvents, organic acids, salts, and the like, respectively. Such a raw material liquid is adjusted so that the composition of the solvent, the concentration of the organic acid, the salt, and the like are within a predetermined range, respectively, and the valuable substance can be stably present in the raw material liquid.

[0004] Therefore, in the process of reducing the volume of the raw material liquid, if the composition of the solvent changes or the concentration of the organic acid, the salt, and the like fluctuates, the peptide or the like is precipitated, aggregated, denatured, or the like, and the yield of the reduction of the volume is sometimes deteriorated. In this regard, since the peptide or the like is very expensive, a high yield is required for the reduction process of the raw material liquid containing the same.

[0005] In addition, for example, the raw material liquid is planned to be supplied to a reaction in which the presence of water is not desired after the reduction of the volume, and it is desirable to reduce the content of water as much as possible in the reduction process.

[0006] From the above aspect, there is a demand for a method for reducing the volume of a raw material liquid in which the composition of the raw material liquid after the reduction of the volume is adjusted to a desired value.

[0007] As a method for reducing the volume of a raw material liquid while maintaining the concentration of an organic solvent, a method in which membrane concentration is performed while adding a solvent to the raw material liquid is known (Patent Literature 1).

[0008] In addition, as a method for moving a specific component in a raw material liquid across a membrane, a dialysis method is known (Non-Patent Literature 1).

[0009] Prior Art Documents

[0010] Patent Literature

[0011] Patent Literature 1: Japanese Patent Application Publication No. 2020-196009

[0012] Non-Patent Literature

[0013] Non-Patent Literature 1: Biotechnol. Prog., 2019, Vol. 35, No. 2, e2763 SUMMARY

[0014] PROBLEMS TO BE SOLVED BY THE INVENTION

[0015] The present application provides a raw material liquid volume reduction method and a raw material liquid volume reduction system for the method, which can adjust the composition of a raw material liquid to a desired value when reducing the volume of the raw material liquid, thereby suppressing the precipitation, coagulation, and denaturation of valuable substances.

[0016] Means for solving the problem

[0017] The present application was made to achieve the above object.

[0018] That is, one example of the mode of the present application is as follows.

[0019] A raw material liquid volume reduction method for reducing the volume of a raw material liquid containing at least a valuable substance and a first solvent,

[0020] The raw material liquid further contains a by-product component other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and a second solvent as a solvent,

[0021] The raw material liquid volume reduction method is a method in which a first treatment and a second treatment are combined,

[0022] The first treatment removes the first solvent from the raw material liquid,

[0023] The second treatment adjusts the concentration of the second solvent or the by-product component in the raw material liquid by using a dialysis method using a dialysis membrane.

[0024] A raw material liquid volume reduction method according to Mode 1, wherein the dialysis membrane used for the second treatment is a molecular sieve membrane.

[0025] A raw material liquid volume reduction method according to Mode 2, wherein the first treatment is a volume reduction treatment using a membrane among reverse osmosis, nanofiltration, and forward osmosis.

[0026] A raw material liquid volume reduction method according to Mode 2, wherein the first treatment is forward osmosis.

[0027] A raw material liquid volume reduction method according to Mode 3 or 4, wherein the permeability of the second solvent or the by-product component of the molecular sieve membrane used for the second treatment is greater than the permeability of the second solvent or the by-product component of the membrane used for the first treatment.

[0028] A raw material liquid volume reduction method according to any one of Modes 1 to 5, which includes, after the first treatment, performing the second treatment.

[0029] The raw material liquid concentration reduction method according to any one of Modes 1 to 5, wherein the first treatment is performed after the second treatment.

[0030] The raw material liquid concentration reduction method according to any one of Modes 1 to 5, wherein the first treatment and the second treatment are performed in parallel, and the raw material liquids after the treatments are mixed.

[0031] The raw material liquid concentration reduction method according to any one of Modes 6 to 8, wherein the first treatment and the second treatment are performed on the raw material liquid in a cycle.

[0032] The raw material liquid concentration reduction method according to Mode 9, wherein a concentration measurement of at least one component in the raw material liquid subjected to the concentration reduction in a cycle is performed, and based on a measurement value obtained, the execution or stop of at least one of the first treatment and the second treatment, or a change in an operation condition is determined.

[0033] The raw material liquid concentration reduction method according to Mode 10, wherein the concentration measurement is performed using a measurement result of at least one selected from the group consisting of specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopic analysis, and weight measurement.

[0034] The raw material liquid concentration reduction method according to any one of Modes 1 to 11, wherein the valuable substance is a pharmaceutical raw material.

[0035] The raw material liquid concentration reduction method according to any one of Modes 1 to 12, wherein the number average molecular weight of the valuable substance is 100 to 50,000.

[0036] The raw material liquid concentration reduction method according to any one of Modes 1 to 13, wherein the valuable substance is at least one selected from the group consisting of an amino acid, a peptide, a protein, a sugar, a vaccine, a nucleic acid, an antibiotic, an antibody drug conjugate (ADC), and a vitamin.

[0037] The raw material liquid concentration reduction method according to any one of Modes 1 to 14, wherein the second solvent is at least one selected from the group consisting of water, acetonitrile, methanol, ethanol, and isopropanol,

[0038] The secondary component is at least one selected from the group consisting of an organic acid, a polymer (excluding the valuable substance), and a buffer salt.

[0039] The raw material liquid concentration reduction method according to any one of Modes 1 to 15, wherein the temperature of the raw material liquid is adjusted to a range of 1°C or higher and 50°C or lower.

[0040] Method 17: The feed liquid concentration reduction method according to any one of methods 3 to 5, wherein at least one kind of alcohol selected from the group consisting of methanol, ethanol, isopropanol and tert-butanol is used as a solute of a draw solution used in the forward osmosis method.

[0041] Method 18: A feed liquid concentration reduction system that reduces the concentration of a feed liquid containing at least a valuable substance and a first solvent, wherein

[0042] the feed liquid further contains a by-product component other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and a second solvent as a solvent,

[0043] the feed liquid concentration reduction system is a system in which a first unit and a second unit are combined,

[0044] the first unit removes the first solvent from the feed liquid,

[0045] the second unit adjusts the concentration of the second solvent or the by-product component in the feed liquid by using a dialysis method using a dialysis membrane.

[0046] Method 19: The feed liquid concentration reduction system according to method 18, wherein the dialysis membrane used in the second unit is a molecular sieve membrane.

[0047] Method 20: The feed liquid concentration reduction system according to method 19, wherein the first unit is a unit that performs concentration reduction treatment using a membrane in any one of a reverse osmosis method, a nanofiltration method and a forward osmosis method.

[0048] Method 21: The feed liquid concentration reduction system according to method 20, wherein the first unit is a unit that performs a forward osmosis method.

[0049] Method 22: The feed liquid concentration reduction system according to method 20 or 21, wherein the permeability of the second solvent or the by-product component of the molecular sieve membrane contained in the second unit is higher than the permeability of the second solvent or the by-product component of the membrane contained in the first unit.

[0050] Method 23: The feed liquid concentration reduction system according to any one of methods 18 to 22, wherein the first unit and the second unit are connected in series in this order in the flow direction of the feed liquid.

[0051] Method 24: The feed liquid concentration reduction system according to any one of methods 18 to 22, wherein the second unit and the first unit are connected in series in this order in the flow direction of the feed liquid.

[0052] The raw material liquid concentration reduction system according to any one of Modes 18 to 22, wherein the first unit and the second unit are connected in parallel, and the raw material liquid concentration reduction system includes a mechanism that mixes the raw material liquid discharged from each unit.

[0053] The raw material liquid concentration reduction system according to any one of Modes 23 to 25, including a mechanism that cyclically performs the processing of the raw material liquid using the first unit and the second unit.

[0054] The raw material liquid concentration reduction system according to Mode 26, including:

[0055] a concentration measurement mechanism that performs concentration measurement of at least one component in the raw material liquid that is cyclically concentrated; and

[0056] a mechanism that determines, based on a measurement value obtained by the concentration measurement mechanism, operation or stop of at least one of the first unit and the second unit, or a change in an operation condition.

[0057] The raw material liquid concentration reduction system according to Mode 27, wherein the concentration measurement mechanism is a mechanism that performs concentration determination using a measurement result of at least one selected from the group consisting of specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopic analysis, and weight measurement, of the raw material liquid that is cyclically concentrated.

[0058] The raw material liquid concentration reduction system according to any one of Modes 18 to 28, wherein the valuable material is a pharmaceutical raw material.

[0059] The raw material liquid concentration reduction system according to any one of Modes 18 to 29, wherein the number average molecular weight of the valuable material is 100 to 50,000.

[0060] The raw material liquid concentration reduction system according to any one of Modes 18 to 30, wherein the valuable material is at least one selected from the group consisting of an amino acid, a peptide, a protein, a sugar, a vaccine, a nucleic acid, an antibiotic, an antibody drug conjugate (ADC), and a vitamin.

[0061] The raw material liquid concentration reduction system according to any one of Modes 18 to 31, wherein the second solvent is at least one selected from the group consisting of water, acetonitrile, methanol, ethanol, and isopropanol,

[0062] the side component is at least one selected from the group consisting of an organic acid, a polymer (excluding the valuable material), and a buffer salt.

[0063] Method 33 The feed liquid concentration reducing system according to any one of methods 18 to 32, comprising a mechanism for adjusting the temperature of the feed liquid to a range of 1°C or more and 50°C or less.

[0064] Method 34 The feed liquid concentration reducing system according to any one of methods 20 to 22, wherein, as the solute of the draw solution used in the forward osmosis method, an alcohol selected from the group consisting of methanol, ethanol, isopropanol, and tert-butanol is used.

[0065] Effects of the Invention

[0066] The feed liquid concentration reducing method according to the present application enables adjustment of the composition of the feed liquid after concentration to a desired value when the feed liquid is concentrated. Therefore, the feed liquid concentrated by the method of the present application can suppress precipitation and denaturation of valuable substances to the limit, and has excellent yield of valuable substances, and has a composition that meets the requirements of the next process.

[0067] If the concentration system of the present application is used, the feed liquid concentration method having the above advantages can be efficiently performed. BRIEF DESCRIPTION OF DRAWINGS

[0068] Figure 1 is a schematic diagram for explaining the mechanism of action of the forward osmosis method as an example of the first process in the feed solution concentration method of the present application.

[0069] Figure 2 is a schematic cross-sectional view for explaining an example of the structure of a forward osmosis membrane module used in the feed solution concentration system of the present application.

[0070] Figure 3 is a schematic diagram for explaining the mechanism of action of the dialysis method as an example of the second process in the feed solution concentration method of the present application.

[0071] Figure 4 is a schematic cross-sectional view for explaining an example of the structure of a dialysis membrane module used in the feed solution concentration system of the present application.

[0072] Figure 5 is a schematic diagram for explaining an example of the feed liquid concentration system of the present application.

[0073] Figure 6 is a schematic diagram for explaining another example of the feed solution concentration system of the present application.

[0074] Figure 7 is a schematic diagram for explaining still another example of the feed solution concentration system of the present application.

[0075] Figure 8 is a schematic diagram for explaining still another example of the feed solution concentration system of the present application.

[0076] Figure 9 is a schematic view for explaining another example of the raw material solution concentration system of the present application. DETAILED DESCRIPTION

[0077] Raw material solution concentration system

[0078] The raw material solution concentration method of the present application is a raw material solution concentration method for concentrating a raw material solution containing at least a valuable substance and a first solvent, wherein

[0079] The raw material solution further contains a by-product component other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and a second solvent as a solvent,

[0080] The raw material solution concentration method is a method in which a first treatment and a second treatment are combined, the first treatment removes the first solvent from the raw material solution, and the second treatment adjusts the concentration of the second solvent or the by-product component in the raw material solution by using a dialysis method using a dialysis membrane.

[0081] In order to ensure the solubility and chemical stability of the valuable substance, the raw material solution containing the valuable substance mostly uses a mixed solvent of a plurality of solvents as a solvent, or contains a by-product component such as a salt or a buffer salt.

[0082] As a means for concentrating such a raw material solution containing a valuable substance, distillation, reduced pressure distillation, membrane distillation, gas permeation membrane method, vapor permeation membrane method, reverse osmosis membrane method, nanofiltration membrane method, and forward osmosis membrane method have been used. However, regardless of the means used, due to the difference in chemical / physical properties of the plurality of components contained in the raw material solution, sometimes a specific component is preferentially removed from the raw material solution, and the composition of the solvent or the concentration of the by-product component changes. If such a situation occurs, there is a concern that the valuable substance is precipitated, aggregated, or denatured in the concentration of the raw material solution.

[0083] As one of the methods to eliminate this problem, it is considered to add a solvent and a by-product component to the raw material solution sequentially in the concentration, in order to maintain the composition of the solvent and the concentration of the by-product component. However, in this method, near the place where the solvent or the by-product component is added, their concentrations change sharply, and therefore the risk of precipitation, aggregation, and denaturation of the valuable substance cannot be eliminated.

[0084] Therefore, the present inventors focused on a dialysis method as a means for maintaining or slowly adjusting the composition of the solvent and the concentration of the by-product component. In the dialysis method, the composition of the solvent or the concentration of the by-product component in the raw material solution slowly approaches the composition of the solvent or the concentration of the by-product component of the dialysate over time.

[0085] By combining such a dialysis method with the above-mentioned concentration means, it is possible to concentrate the raw material solution while maintaining the solubility and chemical stability of the valuable substance.

[0086] The present application can reduce the volume of the raw material liquid while reducing the risk of precipitation, aggregation, and denaturation of the valuable substance to the limit by the above-mentioned mechanism of action.

[0087] <Explanation of Terms>

[0088] <Raw Material Liquid>

[0089] The raw material liquid that becomes the object of the volume reduction method of the present application is a solution or dispersion liquid containing at least a valuable substance and a first solvent.

[0090] The raw material liquid further contains a by-product component other than the valuable substance and the first solvent, or

[0091] A mixed solvent containing the first solvent and a second solvent is contained as a solvent.

[0092] As the raw material liquid suitable for the volume reduction method of the present application, for example, food; pharmaceuticals; seawater; associated water discharged from a gas field, an oil field, or the like can be given. However, in view of the advantage of the present application that the volume can be reduced without heating, the volume reduction method of the present application is effectively applied to a raw material liquid containing a substance that is concerned about thermal decomposition, particularly a pharmaceutical raw material, a functional chemical species, or the like as a valuable substance.

[0093] The temperature of the raw material liquid for the volume reduction method of the raw material liquid of the present application is preferably adjusted to a range of 1°C or higher and 50°C or lower.

[0094] <Valuable Substance>

[0095] In the present application, the valuable substance refers to a pharmaceutical raw material, a functional chemical species, or the like.

[0096] As the pharmaceutical raw material, for example, an amino acid, a peptide, a protein, a sugar, a vaccine, a nucleic acid, an antibiotic, an antibody drug conjugate (ADC), a yeast, a vitamin, or the like can be given.

[0097] The amino acid is a compound having one amino acid skeleton composed of a carboxyl group and an amino group and a moiety connecting them. The amino acid in the present specification is a concept including an essential amino acid, a non-essential amino acid, and a non-natural amino acid.

[0098] As the essential amino acid, for example, tryptophan, lysine, methionine, phenylalanine, threonine, valine, leucine, isoleucine, or the like can be given. As the non-essential amino acid, for example, arginine, glycine, alanine, serine, tyrosine, cysteine, asparagine, glutamine, proline, aspartic acid, glutamic acid, or the like can be given.

[0099] The non-natural amino acid refers to an artificially synthesized compound that has one amino acid skeleton in the molecule and does not exist naturally. As the non-natural amino acid of the pharmaceutical raw material in the present application, a labeled amino acid, a functionalized amino acid, or the like can be given.

[0100] A labeled amino acid is a compound in which a desired labeling compound is bound to an amino acid skeleton. As the labeling compound, for example, a pigment, a fluorescent substance, a luminescent substance, an enzyme substrate, a coenzyme, an antigenic substance, a protein-binding substance, and the like can be given.

[0101] As the functionalized amino acid, for example, a light-responsive amino acid, a photoconversion amino acid, a fluorescent probe amino acid, a fluorescent labeling amino acid, and the like can be given.

[0102] A peptide refers to a compound in which 2 or more amino acid residues are bound, and is less than 70 residues. The peptide can be linear or cyclic. As the peptide in the present disclosure, for example, L-alanyl-L-glutamine, β-alanyl-L-histidine cyclosporine, glutathione, and the like can be given.

[0103] A protein generally refers to a substance in which amino acid residues are bound, and is longer than a peptide. As the protein in the present specification, for example, interferon α, interferon β, interleukin 1 to 12, growth hormone, erythropoietin, insulin, granulocyte colony-stimulating factor (G-CSF), tissue plasminogen activator (TPA), natriuretic peptide, coagulation factor VIII, somatomedin, glucagon, growth hormone-releasing factor, serum albumin, calcitonin, lipase Gando 50, and the like can be given.

[0104] As the sugar, for example, monosaccharides, disaccharides, sugar chains (except for disaccharides), sugar chain derivatives, and the like can be given.

[0105] As the monosaccharides, for example, glucose, fructose, galactose, mannose, ribose, deoxyribose, and the like can be given. As the disaccharides, for example, maltose, sucrose, lactose, and the like can be given.

[0106] The sugar chain in the present disclosure refers to a concept other than disaccharides, and for example, cellulose, glycosaminoglycan, starch, scytonin (SACRAN), dextran, dextrin, inulin, curdlan, fucoidan, levan, pullulan, pectin, polydextrose, maltodextrin, lignin, xylan, mannan, glucomannan, glucuronoxylan, xylose, and the like can be given. As the sugar chain derivative, for example, sugar derivatives such as N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, and the like can be given.

[0107] As the vaccine, for example, a hepatitis A vaccine, a hepatitis B vaccine, a hepatitis C vaccine, and the like can be given.

[0108] As the nucleic acid, for example, an oligonucleotide, RNA, an aptamer, a decoy nucleic acid, and the like can be given.

[0109] As antibiotics, for example, streptomycin, vancomycin, etc. can be given.

[0110] As antibody drug conjugates (ADCs), for example, brentuximab vedotin (Adcetris), emicymatuzumab (Kadcyla), gemtuzumab ozogamicin (Mylotarg), etc. can be given.

[0111] As yeasts, for example, Saccharomyces cerevisiae, Pichia stipitis, Candida shehatae, Pachysolentannophilus, etc. are given, and also their mutant strains are included.

[0112] As vitamins, for example, vitamin A, vitamin B, vitamin C, etc. are given, and also their derivatives, salts, etc. are included. Vitamin B includes, for example, vitamin B6, vitamin B12, etc.

[0113] Functional chemical species means various chemical species used as functional chemicals and their modifications, precursors, raw materials, etc.

[0114] As functional chemical species, for example, metal nanoparticles, semiconductor nanoparticles, metal colloid, nanodiamond, porous nanoclay, metal organic structure (MOFs), carbon nanotube, fullerene, graphene, graphene oxide, carbon nanohorn, cellulose nanofiber, etc. and their modifications, precursors, raw materials, etc. can be given.

[0115] As for the molecular weight of the valuable substance contained in the raw material liquid for the raw material liquid volume reduction method of the present application, the number average molecular weight calculated by the polyethylene oxide by gel permeation chromatography is preferably in the range of 100 to 500,000, more preferably in the range of 100 to 50,000, further preferably in the range of 100 to 30,000.

[0116] <Solvent>

[0117] In the present application, the solvent means a compound capable of dissolving or dispersing the valuable substance and, if present, the by-product component.

[0118] The solvent is typically 1 or 2 or more selected from water and organic solvents.

[0119] The organic solvent is an organic compound having 1 or more carbon atoms, and in one mode, is a compound existing in a liquid form at a temperature of 0°C or higher and less than 50°C under normal pressure.

[0120] However, the solvent in the present application does not include carboxylic acids.

[0121] As the organic solvent, for example, alcohol, ester, ether, aprotic polar compound, aromatic compound, aliphatic compound, chlorinated hydrocarbon, ketone, and the like can be given.

[0122] As the organic solvent, for example, alcohol, ester, ether, aprotic polar compound, aromatic compound, aliphatic compound, chlorinated hydrocarbon, ketone, and the like can be given.

[0123] As the alcohol, for example, methanol, ethanol, 1-propanol, isopropanol, n-butanol, sec-butanol, t-butanol, hexafluoroisopropanol, and the like can be given.

[0124] As the ester, for example, methyl formate, ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, and the like can be given.

[0125] As the ether, for example, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, cyclopentyl methyl ether, t-butyl methyl ether, anisole, 1,2-dimethoxyethane, and the like can be given.

[0126] As the aprotic polar compound, for example, acetonitrile, dimethylacetamide, N-methylpyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, sulfolane, and the like can be given.

[0127] As the aromatic compound, for example, benzene, toluene, xylene, cumene, pyridine, and the like can be given.

[0128] As the aliphatic compound, for example, heptane, hexane, cyclohexane, methylcyclohexane, tetralin, and the like can be given.

[0129] As the chlorinated hydrocarbon, for example, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2-dichloroethylene, 1,1,1-trichloroethane, 1,1,2-trichloroethylene, chlorobenzene, and the like can be given.

[0130] As the ketone, for example, acetone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, and the like can be given.

[0131] As the aldehyde, for example, formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, propylene aldehyde, benzaldehyde, furfural, vanillin, and the like can be given.

[0132] When the solvent of the raw material liquid contains a plurality of solvents, one of them can be the first solvent, and one or more other than the first solvent can be the second solvent.

[0133] When the solvent of the raw material liquid contains a plurality of solvents, one of them can be the first solvent, and one or more other than the first solvent can be the second solvent.

[0134] In this disclosure, the first solvent and the second solvent are not fixed concepts, but are variable depending on the types of valuable substances contained in the feed solution. That is, solvent A, which is the first solvent in a feed solution containing a certain valuable substance A, may sometimes be the second solvent in a feed solution containing other valuable substances B.

[0135] However, as a non-limiting example, the following examples can be cited regarding the feed liquid for which the feed liquid volume reduction method of the present invention is applicable.

[0136] The first solvent is water, and the second solvent is one or more selected from acetonitrile, methanol, ethanol, and isopropanol;

[0137] The first solvent is selected from one or more of methanol, ethanol, isopropanol and acetonitrile, and the second solvent is water;

[0138] The case where the first solvent is selected from one or more of methanol, ethanol and tetrahydrofuran, and the second solvent is hexane;

[0139] The first solvent is water, and the second solvent is one or more selected from dimethylacetamide, N-methylpyrrolidone, N,N-dimethylformamide, and dimethyl sulfoxide; etc.

[0140] The amount of the first solvent in the feed solution can be arbitrarily set according to the solubility and chemical stability of the valuable substances before and after volume reduction, as well as the planned reaction conditions after volume reduction.

[0141] When the solvent of the feed solution includes a first solvent and a second solvent, the mixing ratio of the first solvent and the second solvent can be arbitrarily set according to the solubility and chemical stability of the valuable substances before and after volume reduction, as well as the planned reaction situation after volume reduction.

[0142] <Sub-components>

[0143] In this invention, by-products refer to components optionally included in the feed liquid, specifically components other than valuable substances and solvents. When the solvent of the feed liquid includes a first solvent and a second solvent, by-products refer to components in the feed liquid other than valuable substances, the first solvent, and the second solvent.

[0144] Byproducts include, for example, organic acids, polymers (excluding valuable substances), buffer salts, etc.

[0145] Examples of organic acids that can be used as byproducts in this invention include formic acid, acetic acid, propionic acid, citric acid, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, oxalic acid, gluconic acid, lactic acid, glycolic acid, and glyceric acid.

[0146] Substances that are valuable are excluded from the polymers that are secondary components. Examples of polymers that are secondary components in this invention include, for example, polyethylene oxide, polypropylene oxide, and copolymers of ethylene oxide and propylene oxide.

[0147] Examples of salts or buffer salts include sodium chloride, magnesium chloride, calcium chloride, sodium bicarbonate, potassium bicarbonate, sodium sulfate, sodium bisulfate, potassium bisulfate, magnesium sulfate, potassium sulfate, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium acetate, magnesium acetate, sodium citrate, magnesium citrate, and other organic acid salts, ammonium chloride, ammonium sulfate, ammonium carbonate, and ammonia.

[0148] The raw material liquid often contains a variety of by-products.

[0149] When the feed solution contains by-products, the amount of by-products in the feed solution can be arbitrarily set according to the solubility and chemical stability of the valuable substances, as well as the planned reaction conditions after volume reduction.

[0150] (Coexistence of the second solvent and byproducts)

[0151] The feed solution disclosed herein may contain a valuable substance, a first solvent, a second solvent, and byproducts. In this case, the feed solution volume reduction method of the present invention can yield a volume-reduced solution in which the concentrations of the second solvent and byproducts are respectively adjusted to desired values.

[0152] In a feed liquid containing a valuable substance, a first solvent, a second solvent, and byproducts, examples of feed liquid volume reduction methods preferably applicable to the present invention can be cited.

[0153] The first solvent is water.

[0154] The second solvent is selected from one or more of acetonitrile, methanol, ethanol, and isopropanol.

[0155] The by-component is selected from one or more of acetic acid and trifluoroacetic acid.

[0156] In particular, cases can be cited where the first solvent is water, the second solvent is acetonitrile, and the byproduct is acetic acid, typically in which these substances are contained in a weight ratio of 50 parts water to 49 parts acetonitrile to 1 part acetic acid.

[0157] <Transparency>

[0158] In this disclosure, permeability refers to the degree of ease with which a second solvent or byproduct permeates through the membrane.

[0159] The transmittance in this disclosure can be measured as follows.

[0160] A test solution is prepared in which a second solvent or byproduct is dissolved at a specified concentration in a first solvent. Meanwhile, a reference solution composed of the first solvent is prepared. When the test solution and the reference solution are brought into contact with each other through a membrane for a specified time, the amount of the second solvent or byproduct that migrates from the test solution to the reference solution through the membrane is quantified. Then, this amount of permeated component is allocated based on the concentration of the test solution, the membrane area, and the contact time, and the resulting value is used to evaluate permeability.

[0161] The specified concentration and contact time for the second solvent or byproduct in the test solution are typically 1 mol / L and 20 minutes. However, at a concentration of 1 mol / L, in the case of a membrane-damaging component (e.g., trifluoroacetic acid), the specified concentration and contact time for the second solvent or byproduct in the test solution can be 0.01 mol / L and 180 minutes.

[0162] Specifically, the determination can be performed, for example, by the method described in the embodiments described later.

[0163] <Rate of Goods>

[0164] In this disclosure, the yield of valuables refers to the percentage value obtained by dividing the total amount of valuables obtained by the feedstock volume reduction method by the total amount of valuables fed into the feedstock volume reduction process.

[0165] However, in the case of precipitation or agglomeration of valuable substances during the volume reduction method of the feed liquid, they are not considered the same valuable substance even if their chemical structure remains unchanged. Furthermore, of course, in the case of a change in the chemical structure of a valuable substance during the volume reduction method of the feed liquid, they are not considered the same valuable substance.

[0166] According to the method for reducing the volume of the raw material liquid of the present invention, the yield of valuable substances can be 70% or more, 80% or more, 90% or more, 95% or more, and even 99% or more.

[0167] <Volume Reduction Ratio>

[0168] In this disclosure, the volume reduction ratio refers to the value obtained by dividing the mass of the feed liquid before volume reduction by the mass of the feed liquid after volume reduction. According to the feed liquid volume reduction method of the present invention, the feed liquid can be reduced at a high volume reduction ratio without impairing the stability of the valuable substance.

[0169] According to the method for reducing the volume of the feed liquid of the present invention, the feed liquid can be reduced in volume by a factor of 3, 4, or 5 or more without impairing the stability of the valuable substances. The upper limit of the reduction factor also depends on the concentration and solubility of the valuable substances contained in the feed liquid, and is approximately 50 times.

[0170] Molecular sieve membranes

[0171] In this disclosure, a molecular sieve membrane refers to a membrane that retains molecular weights smaller than the pore size of an ultrafiltration membrane. The molecular weight cutoff of the molecular sieve membrane in this disclosure is defined as 5,000 or less, 4,000 or less, or 3,000 or less. The molecular weight cutoff of the molecular sieve membrane in this invention can, for example, be 2,000 or less, 1,500 or less, 1,000 or less, or 750 or less. The lower limit of the molecular weight cutoff of the molecular sieve membrane is approximately 100.

[0172] Therefore, in the first treatment of the feed liquid volume reduction method disclosed herein, molecular sieve membranes can be used as forward osmosis membranes, nanofiltration membranes, etc.

[0173] As described above, the feed liquid volume reduction method of the present invention is a feed liquid volume reduction method for at least a valuable substance and a first solvent, wherein,

[0174] The raw material liquid also contains by-products other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and the second solvent as the solvent.

[0175] The raw material liquid volume reduction method is a combination of the first treatment and the second treatment.

[0176] The first treatment removes the first solvent from the feed liquid.

[0177] The second treatment adjusts the concentration of the second solvent or the byproduct in the feed solution by using dialysis with a dialysis membrane.

[0178] The preferred embodiments of the present invention will be described in detail below as non-limiting examples.

[0179] <First Process>

[0180] The first treatment in the raw material liquid volume reduction method of the present invention is a treatment that mainly removes the first solvent from the raw material liquid.

[0181] Examples of such a first treatment include evaporation, thin-film distillation, evaporation method, membrane distillation method, pervaporation membrane method, vapor permeation membrane method, reverse osmosis membrane method, nanofiltration membrane method, and forward osmosis membrane method. The evaporation method mentioned above refers to a method in which gas is circulated in a container containing a feed liquid, causing the first solvent in the feed liquid to vaporize and be removed from the container.

[0182] Among these processes, evaporation, reverse osmosis, nanofiltration, and forward osmosis can remove the first solvent from the feed solution without heating, thus minimizing heat-induced denaturation of valuable substances and making them effective.

[0183] In addition, from the perspective of volume reduction efficiency, the first treatment is preferably a volume reduction treatment using membranes such as reverse osmosis, nanofiltration, or forward osmosis.

[0184] (Forward osmosis)

[0185] Of these processes, forward osmosis is particularly effective because it moves the first solvent with a high driving force by using a suitable driving solution, without the need for mechanical driving force.

[0186] The following description uses the forward osmosis method as an example of the first treatment in the feed liquid volume reduction method of the present invention.

[0187] Figure 1 This is a schematic diagram illustrating the mechanism of solvent movement using a forward osmosis membrane.

[0188] Figure 1 In this process, the feed solution (a) flows on one side of the forward osmosis membrane (520), while the driving solution (d), which has a higher osmotic pressure than the feed solution (a), flows on the opposite side. The two liquids are in contact through the forward osmosis membrane (520). Thus, driven by the osmotic pressure difference between the feed solution (a) and the driving solution (d), the first solvent (b) in the feed solution (a) passes through the forward osmosis membrane (520) and moves into the driving solution (d).

[0189] Figure 1 The forward osmosis membrane (520) has a substrate layer (521) and an active layer (522) formed on one side of the substrate layer (521). The active layer (522) has a very dense structure that allows small molecules to pass through but prevents valuable substances from passing through, and is formed on the side of the substrate layer (521) that is in contact with the feed liquid (a).

[0190] A porous membrane is typically used as the material for the substrate layer (521). In the forward osmosis membrane (520), a portion of the substrate layer (521) composed of a porous membrane permeates with the driving solution (d), and the feed solution (a) is in contact with the driving solution (d) through the active layer (522). At this time, the first solvent in the feed solution (a) moves towards the driving solution (d) side, which has a higher osmotic pressure, resulting in volume reduction.

[0191] The forward osmosis membrane can be any of the following structures: hollow fiber membrane, tubular membrane, or flat membrane. Hollow fiber membranes are preferred because they can form a flow path for the feed solution and the driving solution without the use of spacers, and can achieve uniform volume reduction.

[0192] The material used to form the porous membrane substrate can be selected from commercially available materials. However, raw materials that cannot maintain the pore shape of the membrane cannot be used if they dissolve or swell in organic solvents contained in the feed solution.

[0193] Specifically, materials used for the porous membrane constituting the substrate layer include, for example, polysulfone, polyethersulfone, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polypropylene, cellulose-based polymers, polyketone, polyamide, polyimide, polyetheretherketone, polybenzimidazole, and their crosslinks, with at least one selected from these preferred as the main component. For the porous membrane constituting the hollow fiber forward osmosis membrane, from the perspective of solvent resistance, at least one selected from polysulfone, polyethersulfone, polyketone, polyamide, and polyimide, and their crosslinks, is preferred as the main component.

[0194] Polyamides are primarily used as raw materials for the active layer. The active layer composed of polyamides can be formed by interfacial polymerization of polyfunctional acyl halides and / or polyfunctional amines on a substrate layer.

[0195] Multifunctional acyl halides refer to acyl halide compounds having two or more acyl halide groups in one molecule. Specifically, for example, they can be used...

[0196] Halides of fatty acids such as oxalic acid, malonic acid, maleic acid, fumaric acid, glutaric acid, 1,3,5-cyclohexanetricarboxylic acid, 1,3-cyclohexanedicarboxylic acid, and 1,4-cyclohexanedicarboxylic acid.

[0197] Acyl halide compounds of aromatic acids such as phthalic acid, isophthalic acid, 1,3,5-benzenetricarboxylic acid, 1,2,4-benzenetricarboxylic acid, 1,3-benzenedicarboxylic acid, and 1,4-benzenedicarboxylic acid; etc.

[0198] These acyl halide compounds can be used alone or in combination of two or more.

[0199] In this invention, from the perspectives of economy, ease of acquisition, ease of operation, and ease of reaction, it is particularly preferred to use pyromellitic chloride alone, or a mixture of pyromellitic chloride and isophthaloyl chloride, or a mixture of pyromellitic chloride and terephthaloyl chloride.

[0200] Polyfunctional amines are amino compounds that have two or more amino groups in one molecule, such as aromatic amino compounds and aliphatic amino compounds.

[0201] Examples of aromatic amino compounds include, specifically, m-phenylenediamine, p-phenylenediamine, 3,3'-diaminodiphenylmethane, 4,4'-diaminodiphenylamine, 4,4'-diaminodiphenyl ether, 3,4'-diaminodiphenyl ether, 3,3'-diaminodiphenylamine, 3,5-diaminobenzoic acid, 4,4'-diaminodiphenyl sulfone, 3,3'-diaminodiphenyl sulfone, 3,4'-diaminodiphenyl sulfone, 1,3,5-triaminobenzene, and 1,5-diaminonaphthalene. They can be used alone or in mixtures.

[0202] As the aromatic amino compound in this invention, from the perspectives of economy, ease of acquisition, ease of operation, and ease of reaction, it is particularly preferred to use one or more selected from m-phenylenediamine and p-phenylenediamine.

[0203] Examples of aliphatic amino compounds include, specifically, piperazine, 2,5-dimethylpiperazine, 2-methylpiperazine, 2,6-dimethylpiperazine, 2,3,5-trimethylpiperazine, 2-ethylpiperazine, 2,5-diethylpiperazine, 2,3,5-triethylpiperazine, 2-n-propylpiperazine, 2,5-di-n-butylpiperazine, ethylenediamine, and bispiperidinylpropane. They can be used alone or in mixtures.

[0204] Interfacial polymerization of polyfunctional acyl halides and polyfunctional amines can be carried out using conventional methods.

[0205] The resulting active layer can be obtained by appropriate heat treatment. This heat treatment can be carried out using hot water or high-temperature, high-pressure steam in a pressure vessel such as an autoclave.

[0206] While the rationale for heating the active layer is still uncertain, it is expected to reduce the back diffusion of the driving solution.

[0207] When using hollow fiber forward osmosis membranes, the outer diameter of the hollow fiber membrane is, for example, 300 μm to 5,000 μm, preferably 350 μm to 4,000 μm, and the inner diameter of the hollow fiber membrane is, for example, 200 μm to 4,000 μm, preferably 250 μm to 1,500 μm. If the inner diameter of the hollow fiber is less than 200 μm, high back pressure may occur when the liquid flows through the space inside the hollow fiber. If the inner diameter of the hollow fiber exceeds 4,000 μm, the membrane area of ​​each module becomes too small when multiple forward osmosis membrane modules are used, sometimes making effective volume reduction impossible.

[0208] As the driving solution used in forward osmosis, a solution containing organic solvents, organic acids, buffer salts, etc., as solutes can be used.

[0209] As an organic solvent, the organic solvents listed above that are included as solvents in the feed liquid can be used. Specifically, for example, at least one selected from methanol, ethanol, isopropanol, and tert-butanol is preferred.

[0210] Examples of organic acids include formic acid, acetic acid, propionic acid, citric acid, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, oxalic acid, gluconic acid, lactic acid, glycolic acid, and glyceric acid.

[0211] As buffer salts, in addition to the metal salts of the organic acids mentioned above, examples include inorganic salts such as sodium chloride, magnesium chloride, calcium chloride, sodium sulfate, sodium bicarbonate, potassium bicarbonate, sodium bisulfate, potassium bisulfate, magnesium sulfate, potassium sulfate, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide; and organic acid salts such as sodium acetate, magnesium acetate, sodium citrate, and magnesium citrate.

[0212] The concentration of the solute in the driving solution can be appropriately set according to the composition of the feed solution and the type of solute in the driving solution, so that the first solvent can reliably move from the feed solution to the driving solution and generate an osmotic pressure differential that can produce a driving force within a range where the composition of the feed solution near the forward osmosis membrane does not change drastically.

[0213] In forward osmosis, the driving force for the first solvent (b) to move from the feed solution (a) to the driving solution (d) is the osmotic pressure difference between the feed solution (a) and the driving solution (b). Therefore, liquid renewal is required between the active layer (522) in the forward osmosis membrane (520) and the interface between the feed solution (a) or the driving solution. Therefore, it is necessary to ensure that the feed solution (a) and the driving solution (d) flow at appropriate rates across the forward osmosis membrane (520).

[0214] Figure 1 In this process, the two liquids are made to flow in a parallel manner, with the feed liquid (a) and the driving solution (d) flowing in parallel, but the flow of the two liquids can also be convective.

[0215] Figure 2 This is a schematic diagram showing an example of the structure of a forward osmosis membrane assembly preferably used as the first unit of the first process in the feed liquid volume reduction method for carrying out the present invention.

[0216] exist Figure 2 In the forward osmosis membrane module (500), multiple hollow fiber-shaped forward osmosis membranes (520) are housed within a housing (510). The two ends of each forward osmosis membrane (520) are bonded to the housing (510) using adhesive resin (530). Two housing side tubes are located on the side of the housing (510). One of these housing side tubes serves as a drive solution inlet (511), and the other as a drive solution outlet (512).

[0217] The outer shell (510) is divided into two parts by the outer wall of the forward osmosis membrane (520) and the adhesive resin (530): a space for the flow of raw material liquid (a) and a space for the flow of driving solution (d). The two spaces are separated by fluid, except that the first solvent can flow through the inner wall of the forward osmosis membrane (520).

[0218] If feed liquid (a) is introduced from one end of the forward osmosis membrane module (500), the feed liquid (a) flows inside the hollow fiber forward osmosis membrane (520) and flows out from the other end as reduced feed liquid (c).

[0219] Similarly, when the driving solution (d) flows into the driving solution from the driving solution inlet (511) in the side tube of the outer casing (510), the driving solution (d) flows in the space outside the hollow fiber-shaped forward osmosis membrane (520) and flows out from the driving solution outlet (512).

[0220] Thus, the feed solution (a) and the driving solution (d) can come into contact through the forward osmosis membrane (520). At this time, due to the difference in osmotic pressure between the two liquids, substances other than valuable substances move from the feed solution (a) to the driving solution (d). In the forward osmosis membrane process, volume reduction occurs through this mechanism.

[0221] In the case where the forward osmosis membrane (520) has a substrate layer and an active layer formed on one side of the substrate layer, as described above, the active layer is formed on the side of the substrate layer that is in contact with the feed liquid. Therefore, the feed liquid (a) flows inside the hollow fiber-shaped forward osmosis membrane. Figure 1 In the forward osmosis membrane module (500), it is preferable that an active layer is provided on the inner surface of the hollow fibrous substrate layer.

[0222] When the flow rates of the feed solution (a) and / or the driving solution (d) are high, the effect of the osmotic pressure difference across the active layer of the forward osmosis membrane (520) becomes greater, and thus the permeation of the first solvent per unit membrane area of ​​the forward osmosis membrane increases.

[0223] exist Figure 2 In the forward osmosis membrane module (500), the feed solution (a) and the drive solution (d) are flowed in a co-current manner, but the flow of the two liquids can also be convective.

[0224] about Figure 2 The material of the housing (510) in the forward osmosis membrane module (500) is selected based on factors such as chemical resistance, pressure resistance, heat resistance, impact resistance, and weather resistance, ensuring that its various properties are not degraded by the components contained in the feed solution (a) and drive solution (d). For example, resins and metals can be used as the material for the housing (510). Based on the above considerations, resins such as polypropylene, polysulfone, polyethersulfone, polyvinylidene fluoride, polytetrafluoroethylene, perfluoroalkoxyalkylene, ABS resin, fiber-reinforced plastics, and vinyl chloride resin are preferred; and metals such as stainless steel, brass, and titanium are also preferred.

[0225] As Figure 2The adhesive resin (530) in the forward osmosis membrane module (500) is desirable to have good mechanical strength and heat resistance up to 100°C. Examples of resins suitable for use as the adhesive resin (530) include, for example, thermosetting epoxy resins, thermosetting polyurethane resins, ceramic adhesives, and sealing materials obtained by melting polyethylene or low-melting-point metals. From the perspective of heat resistance, epoxy resin is preferred, while from the perspective of operability, polyurethane resin is preferred.

[0226] Regarding the method of bonding and fixing the forward osmosis membrane (520) to the housing (510), the known bonding methods related to the fabrication of hollow fiber membrane modules can be followed.

[0227] (Nanofiltration)

[0228] Nanofiltration will be described as another example of the first treatment.

[0229] In nanofiltration, the feed solution is supplied to one side of the nanofiltration membrane, and the feed solution supply side is pressurized. As a result, the primary solvent in the feed solution is removed through the nanofiltration membrane, reducing the volume of the feed solution. The secondary solvent or byproducts remain in the feed solution.

[0230] As a nanofiltration membrane, a known nanofiltration membrane can be used.

[0231] Nanofiltration membranes can be in the form of hollow fiber membranes, tubular membranes, or flat membranes. Hollow fiber nanofiltration membranes are preferred because they can form a flow path for the feed liquid and permeate (first solvent) without the use of spacers, and can achieve uniform volume reduction.

[0232] Nanofiltration is preferably performed using a nanofiltration membrane module that houses multiple hollow fibrous nanofiltration membranes in a suitable housing.

[0233] Examples of materials that can be used as nanofiltration membranes include polysulfone, polyethersulfone, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polypropylene, cellulose polymers, polyketone, polyamide, polyimide, polyether ether ketone, polybenzimidazole, and their crosslinks, and preferably at least one of these as the main component.

[0234] Regarding the housing and other component forms of nanofiltration membrane modules, the term "forward osmosis membrane" can be replaced with "nanofiltration membrane" and the above description of forward osmosis membrane modules can be referenced.

[0235] (Evaporation method)

[0236] The evaporation method will be described as another example of the first treatment.

[0237] In the evaporation method, gas is circulated in a container filled with raw material liquid, causing the component with the highest vapor pressure (the first solvent) in the raw material liquid to preferentially vaporize and be removed from the container, thereby reducing the volume of the raw material liquid. The component with the lowest vapor pressure (the second solvent or byproduct) remains in the raw material liquid.

[0238] Examples of gases that can flow through a container containing raw material liquid include air, nitrogen, and argon.

[0239] <Second Process>

[0240] The second treatment in the feed liquid concentration method of the present invention is used to adjust the concentration of the second solvent or byproduct in the feed liquid by using dialysis with a dialysis membrane, so as to maintain the composition of the reduced feed liquid within the range where valuable substances do not denature, coagulate or precipitate.

[0241] In the second treatment, dialysis is used. In particular, molecular sieve membranes are effective as dialysis membranes because they can effectively prevent valuable substances from being lost through the dialysis membrane.

[0242] The following describes a dialysis method using a molecular sieve membrane as a dialysis membrane, as an example of the second treatment in the feed liquid volume reduction system of the present invention.

[0243] Figure 3 This is a schematic diagram illustrating the mechanism of dialysis using a dialysis membrane.

[0244] exist Figure 3 In the process, the feed solution (a) flows on one side of the dialysis membrane (120), and the dialysate (e) flows on the opposite side, with the two liquids in contact through the dialysis membrane (120).

[0245] At this point, if there is a difference between the concentration of the second solvent or byproduct (g) in the feed solution (a) and the concentration of the second solvent or byproduct (g) in the dialysate (e), the second solvent or byproduct (g) will move from the concentrated solution to the dilute solution. This movement is driven by the concentration difference of the second solvent or byproduct (g) between the two liquids, and therefore movement in either direction is possible.

[0246] In the second process of the feed liquid volume reduction system of the present invention, through such movement, the concentration of the second solvent or byproduct (g) in the feed liquid (a) gradually approaches the concentration of the dialysate (d), and the composition of the feed liquid (a) is maintained within the desired range.

[0247] Furthermore, when forward osmosis is used as the first treatment, the driving solute in the driving solution sometimes mixes into the feed solution. The second treatment in the feed solution volume reduction method of the present invention also has the effect of removing the driving solute mixed into the feed solution from the feed solution. In this case, since the dialysate (e) does not contain the driving solute, the driving solute preferentially moves from the feed solution (a) to the dialysate (e), and the removal of the driving solute from the feed solution is effectively carried out.

[0248] Figure 3 The dialysis membrane (120) has a substrate layer (121) and an active layer (122) formed on one side of the substrate layer (121). The active layer (122) has a very dense structure that allows small molecules to pass through but prevents valuable substances from passing through, and is formed on the side of the substrate layer (121) that is in contact with the feed liquid (a).

[0249] Porous membranes are typically used as the material for the substrate layer (121). In the dialysis membrane (120), a portion of the substrate layer (121) composed of a porous membrane is impregnated with dialysate (d), and the feed solution (a) is in contact with the dialysate (d) through the active layer (122).

[0250] The material used to form the porous membrane substrate can be selected from commercially available materials. However, raw materials that cannot maintain the pore shape of the membrane cannot be used if they dissolve or swell in organic solvents contained in the feed solution.

[0251] In the case where the first treatment is a volume reduction treatment using a membrane,

[0252] Preferably, the permeability of the second solvent or byproduct of the dialysis membrane used for the second treatment is greater than that of the second solvent or byproduct of the membrane used for the first treatment.

[0253] The greater the permeability of the second solvent or byproduct of the dialysis membrane, the faster the movement of the second solvent or byproduct across the dialysis membrane, and the easier it is to achieve the effect of the concentration of the second solvent or byproduct gradually approaching the concentration of the dialysate. This can effectively correct the concentration of the second solvent or byproduct in the feed solution, and is therefore preferred.

[0254] In this regard, from the perspective that the permeability of the second solvent or by-product can be arbitrarily controlled by the selection of monomers when forming the active layer on the substrate layer, polyamide is preferred as the raw material for the active layer.

[0255] The material of the porous membrane constituting the substrate layer and the method for forming the polyamide constituting the active layer can be found in the descriptions of the substrate layer and active layer of the aforementioned forward osmosis membrane.

[0256] It should be noted that, as part or all of the multifunctional acyl halide used to form the active layer of the dialysis membrane, multifunctional acyl halide compounds converted into acid anhydrides can be used. Specifically, examples include trimellitic anhydride chloride, 3,3',4,4'-biphenyltetracarboxylic dianhydride, pyromellitic dianhydride, benzophenone tetracarboxylic dianhydride, diphenyl ether tetracarboxylic dianhydride, etc.

[0257] Furthermore, if piperazines are used as part or all of the multifunctional amines used to form the active layer of the dialysis membrane, the permeability of the second solvent or byproduct is improved, which is therefore preferred.

[0258] In the case of the first treatment by forward osmosis, as described above, both the forward osmosis membrane used for forward osmosis and the dialysis membrane used for the second treatment have a substrate layer made of porous membrane and an active layer made of polyamide, and in this respect they have a common structure.

[0259] On the other hand, as mentioned above, regarding the permeability of the second solvent or byproduct contained in the feed solution, it is preferable that the permeability of the dialysis membrane is greater than that of the forward osmosis membrane.

[0260] In forward osmosis and dialysis membranes made of homogeneous materials, differences in the permeability of a second solvent or byproduct can be achieved, for example, by selecting monomers when forming the active layer on the substrate layer, adjusting the interfacial polymerization conditions, and performing post-treatment after interfacial polymerization.

[0261] For example, by using aliphatic amine compounds as multifunctional amines used in interfacial polymerization, the permeability of the second solvent or byproduct can be improved.

[0262] The morphology of dialysis membranes can be any of the following: hollow fiber membrane, tubular membrane, or flat membrane. Hollow fiber dialysis membranes are suitable because they can form a flow path for the feed solution and dialysate without the use of spacers, and can maintain uniform flow.

[0263] When using hollow fiber dialysis membranes, the outer diameter of the hollow fiber membrane is, for example, 300 μm to 5,000 μm, preferably 350 μm to 4,000 μm, and the inner diameter of the hollow fiber membrane is, for example, 200 μm to 4,000 μm, preferably 250 μm to 1,500 μm. The reasoning is not yet certain, but if the inner diameter of the hollow fiber is less than 200 μm, it may sometimes cause precipitation, aggregation, or denaturation of valuable substances. If the inner diameter of the hollow fiber exceeds 4,000 μm, when multiple dialysis membrane modules are used, the membrane area of ​​each module becomes too small, and sometimes the movement of the concentration of the second solvent or byproducts cannot be sufficiently achieved.

[0264] As the composition of the dialysate used in dialysis, a composition in which the valuable substances can be stably present is preferred. The appropriate composition of the dialysate should be determined based on the chemical / physical properties of the valuable substances contained in the feed solution. For example, using a dialysate with the same composition as the solution after the valuable substances have been removed from the feed solution is one candidate.

[0265] To avoid adverse effects on piping, analytical equipment, etc., the pH of the dialysate is preferably between pH 1 and 14, and more preferably between pH 2 and 13.

[0266] In dialysis, the driving force for the movement of a second solvent or byproduct between the feed solution and the dialysate is the concentration difference between the two solutions. Therefore, for effective component movement to occur, fluid renewal is required at the interface between the active layer of the dialysis membrane and the feed or dialysate.

[0267] Therefore, it is necessary to ensure that the feed solution and dialysate flow at an appropriate flow rate on both sides of the dialysis membrane (120).

[0268] Figure 3 In this process, the two liquids are made to flow in a parallel manner, with the feed liquid (a) and the driving solution (d) flowing in parallel, but the two liquids can also flow in a convective manner.

[0269] It should be noted that, depending on the composition of the feed solution, due to the osmotic pressure difference between the feed solution and the dialysate, the first solvent in the dialysate may move through the dialysis membrane into the feed solution, potentially causing volume increase in the feed solution. In this case, pressurizing the feed solution in contact with the dialysis membrane can suppress volume increase. The pressurization pressure of the feed solution is preferably 0.05 MPaG or more, more preferably 0.1 MPaG or more, and even more preferably 0.2 MPaG or more.

[0270] Figure 4 This is a schematic diagram showing an example of the structure of a dialysis membrane assembly preferably used as a second unit in the second process of the feed liquid volume reduction method for carrying out the present invention.

[0271] exist Figure 4 In the dialysis membrane assembly (100), multiple hollow fibrous dialysis membranes (120) are housed within a housing (110). The two ends of each dialysis membrane (120) are bonded to the housing (110) with adhesive resin (130). Two housing side tubes are located on the side of the housing (110). One of these housing side tubes serves as a dialysate inlet (111), and the other as a dialysate outlet (112).

[0272] The outer shell (110) is divided into two parts by the outer wall of the dialysis membrane (120) and the adhesive resin (130): a space for the flow of the feed liquid (a) and a space for the flow of the dialysate (d). The two spaces are fluid-separated except that the second solvent or byproduct can flow through the inner wall of the dialysis membrane (120).

[0273] If feed solution (a) is introduced from one end of the dialysis membrane assembly (100), the feed solution (a) flows inside the hollow fiber dialysis membrane (120) and flows out from the other end as feed solution (f) with adjusted component concentration.

[0274] Similarly, if the dialysate (d) flows from the dialysate inlet (111) in the side tube of the outer shell (110), the dialysate (e) flows in the space outside the hollow fibrous dialysis membrane (120) and flows out from the dialysate outlet (112).

[0275] Thus, the feed solution (a) and the dialysate (e) can come into contact through the dialysis membrane (120). At this time, depending on the concentration of the components contained in the feed solution (a) and the dialysate (d), the second solvent or byproduct (g) moves from the feed solution (a) to the dialysate (e) or from the dialysate (d) to the feed solution (a). In dialysis, the concentration of the second solvent or byproduct is adjusted through this mechanism.

[0276] When the flow rates of feed solution (a) and / or dialysate (e) are high, the effect of the concentration difference across the dialysis membrane (120), especially the active layer, becomes more significant, and thus the amount of movement of the second solvent or byproduct per unit membrane area of ​​the dialysis membrane increases.

[0277] exist Figure 4 In the dialysis membrane assembly (100), the feed solution (a) and the dialysate (e) are flowed in a co-current manner, but the flow of the two liquids can also be convective.

[0278] Figure 4 The materials of the housing (110) and adhesive resin (130) in the dialysis membrane assembly (100), and the method of bonding and fixing the dialysis membrane (120) to the housing (110), can be directly referenced from [the relevant sources]. Figure 2 The above description of the forward osmosis membrane module (500).

[0279] <Implementation methods for the first and second processes>

[0280] The order in which the first and second processes are performed is arbitrary. For example,

[0281] The second process can be performed after the first process.

[0282] The first process can be performed after the second process;

[0283] The first and second processes can also be performed simultaneously.

[0284] Simultaneous processing of the first and second treatments refers to, for example, performing the first and second treatments in parallel and mixing the resulting raw material solutions.

[0285] When the first and second processes are performed in any order, the piping for supplying the feed liquid to either process and the piping for supplying the processed feed liquid to the other process can be connected in series.

[0286] In the case where the first and second processes are carried out in parallel, for example, the piping for supplying the feed liquid to the first process and the piping for supplying the feed liquid to the second process can be connected in parallel.

[0287] The first and second processes are preferably performed cyclically. For example, the following methods are preferred:

[0288] Repeat the following operation: store the raw material liquid in the raw material liquid tank, take out a portion of the raw material liquid from the raw material liquid tank, and feed it to the first process and the second process in sequence, so that the raw material liquid after the first process and the second process is returned to the raw material liquid tank;

[0289] Repeat the following operation: store the raw material liquid in the raw material liquid tank, take out a portion of the raw material liquid from the raw material liquid tank, and feed it to the second process and the first process in sequence, so that the raw material liquid after the second process and the first process is returned to the raw material liquid tank;

[0290] The raw material liquid is stored in a raw material liquid tank, and the following operation is repeated, which is performed in parallel (simultaneously) with the following steps:

[0291] Repeat the following operations: Remove a portion of the feed liquid from the feed liquid tank for the first process, and return the feed liquid after the first process to the feed liquid tank; and

[0292] Repeat the following steps: Take out a portion of the raw material liquid from the raw material liquid tank for the second process, and return the raw material liquid after the second process to the raw material liquid tank.

[0293] When the first and second treatments are carried out in a cyclic manner, it is preferable to measure the concentration of at least one component in the feed liquid that is being cyclically reduced in volume, and based on the measured value, determine whether to implement or stop at least one of the first and second treatments, or to change the operating conditions.

[0294] For example, if the concentration of the first solvent in the feed solution is about to fall below the lower limit of an appropriate range based on the component analysis, it may be considered to temporarily stop the first treatment or stabilize the treatment conditions of the first treatment.

[0295] On the other hand, when the concentration of the first solvent in the feed solution is about to exceed the upper limit of an appropriate range, it may be considered to make the processing conditions of the first treatment more stringent.

[0296] Furthermore, when the concentration of the second solvent or byproduct in the feed solution is about to deviate from the appropriate range, it is advisable to consider changing the concentration of the second solvent or byproduct in the dialysate used for the second treatment. Specifically, the reduction rate tends to be faster in the latter half of the reduction process than in the initial stage. Therefore, it is believed that in the latter half of the reduction process, the concentration of the second solvent or byproduct in the recycled dialysate increases, and the efficiency of adjusting the concentration of the second solvent or byproduct in the feed solution decreases. In this case, it is advisable to consider, for example, discarding the recycled dialysate during the reduction process and replacing it with dialysate of the initial composition to improve the efficiency of adjusting the concentration of the second solvent or byproduct in the feed solution.

[0297] The concentration of at least one component in the feed solution can be determined, for example, by using the results of measurements such as specific gravity, pH, conductivity, liquid level, optical rotation, refractive index, near-infrared spectroscopy, and weight.

[0298] Furthermore, if the feed liquid is reduced to the desired reduction rate, both the first and second treatments are stopped, and the reduction of the feed liquid is completed.

[0299] The volume reduction rate can be obtained, for example, by measuring the weight of the raw material liquid or by measuring the liquid level.

[0300] The composition analysis of the final reduced feed solution (e) can be appropriately selected based on the types of components contained in the reduced feed solution.

[0301] For example, various well-known analytical methods can be used, such as ICP-MS (inductively coupled plasma mass spectrometry), nuclear magnetic resonance spectroscopy (NMR), gas chromatography-mass spectrometry (GC / MS), colorimetry, fluorescence spectroscopy, and high-performance liquid chromatography (HPLC).

[0302] In order to achieve a high volume reduction rate while suppressing the precipitation and denaturation of valuable substances contained in the feed solution, it should be noted that it is preferable to perform the first treatment and the second treatment in parallel. When the first treatment and the second treatment are performed in parallel, there is a tendency to easily maintain the composition of the feed solution within a specified range during volume reduction.

[0303] Feed Liquid Volume Reduction System

[0304] According to another aspect of the present invention, a raw material liquid volume reduction system is provided.

[0305] The raw material liquid volume reduction system of the present invention is a system for implementing the raw material liquid volume reduction method of the present invention.

[0306] Therefore, the feed liquid volume reduction system of the present invention is a feed liquid volume reduction system for reducing the volume of a feed liquid containing at least a valuable substance and a first solvent, wherein,

[0307] The raw material liquid also contains by-products other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and the second solvent as a solvent.

[0308] The raw material liquid volume reduction system is a system that combines Unit 1 and Unit 2.

[0309] The first unit removes the first solvent from the raw material solution.

[0310] The second unit adjusts the concentration of the second solvent or the byproduct in the feed solution by using dialysis with a dialysis membrane.

[0311] For details regarding the raw material liquid volume reduction system of the present invention, the above description of the raw material liquid volume reduction method of the present invention can be directly referenced, or it can be referenced after modification by those skilled in the art in a manner suitable for the invention of the "system".

[0312] The composition of the raw material liquid volume reduction system of the present invention will be described in more detail below with reference to the accompanying drawings.

[0313] Figures 5 to 8 The diagram shows an example of the configuration of the feed liquid volume reduction system of the present invention.

[0314] Figure 5 The feed liquid volume reduction system is an example of one that uses an evaporation unit as the first unit, which allows gas to flow within a container holding the feed liquid, causing the first solvent in the feed liquid to evaporate and move out of the container.

[0315] Figure 5 The feed liquid volume reduction system (1) has an evaporation unit (900), a dialysis membrane assembly (100), a feed liquid tank (200), a dialysis liquid tank (300), and a trap (400).

[0316] The evaporation unit (900) has a blower (BL) for flowing gas in the raw material tank (200) and piping for conveying the evaporated first solvent (b) to the collector (400).

[0317] exist Figure 5 In the raw material liquid volume reduction system (1), a gas (e.g., air) is supplied to the raw material liquid tank (200) by a blower (BL) provided in the evaporation unit (900). Then, the introduced gas and the first solvent (b) evaporated by the gas are discharged out of the raw material liquid tank (200), thereby reducing the volume of the raw material liquid.

[0318] The vapor of the first solvent (b) discharged from the raw material tank (200) can be liquefied again and recovered by the trap (400).

[0319] According to the method of using an evaporation unit (900) as the first unit and supplying gas into the raw material tank (200), volume reduction occurs at and around the surface of the raw material liquid (a), which may cause the composition of the raw material liquid (a) to vary depending on its position in the raw material tank (200). In this regard, by providing a stirring device (not shown) in the raw material tank (200), the composition of the raw material liquid (a) in the raw material tank (200) can be maintained uniformly, and volume reduction can be achieved while suppressing the precipitation, coagulation, and denaturation of valuable substances.

[0320] exist Figure 5 In the feed liquid volume reduction system (1), the component with high vapor pressure (the first solvent) is preferentially removed using the evaporation unit (900). Therefore, in the feed liquid (a) after volume reduction by the evaporation unit (900), the concentration of components with low vapor pressure (e.g., valuable substances and the second solvent or byproducts) is generally higher.

[0321] exist Figure 5 The feed liquid volume reduction system (1) includes an evaporation unit (900) and a dialysis membrane assembly (100) for performing dialysis as a second unit.

[0322] exist Figure 5 In the feed liquid reduction system (1), feed liquid (a) is pumped (P) from the lower part of the feed liquid tank (200) filled with feed liquid (a) to one side of the dialysis membrane assembly (100) (e.g., the space inside the hollow fiber membrane) at an appropriate flow rate. At this time, the flow rate of feed liquid (a) is adjusted manually or automatically using a flow meter or the like (not shown). On the other hand, dialysate (d) is supplied from the dialysate tank (300) filled with dialysate (d) to the other side of the dialysis membrane assembly (100) (e.g., the space outside the hollow fiber membrane) using a pump (P). Furthermore, the concentration difference between feed liquid (a) and dialysate (d) is used to correct the concentration of the second solvent or byproduct in feed liquid (a) to be close to the concentration of the second solvent or byproduct in dialysate (d). The concentration-corrected feed liquid (a) flows out of the dialysis membrane assembly (100) and returns to the feed liquid tank (200) for circulation.

[0323] As the concentration of the second solvent or byproduct in the feed solution (a) is adjusted using the function of the dialysis membrane module (100), the concentration of the second solvent or byproduct in the dialysate (d) changes. Therefore, in order to perform appropriate concentration adjustments of the second solvent or byproduct during continuous operation, the dialysate (d) needs to be replaced sequentially, or the dialysate needs to be regenerated in a device that has the function of restoring the concentration of the second solvent or byproduct in the dialysate (d) to a specified value. Figure 5 The regeneration device is not shown in the figure.

[0324] Figure 6 The feed liquid volume reduction system is an example of a forward osmosis membrane module used for forward osmosis as the first unit.

[0325] Figure 6 The feed liquid volume reduction system (2) has a forward osmosis membrane module (500), a feed liquid tank (200), a drive solution tank (600), a dialysis membrane module (100), and a dialysate tank (300).

[0326] exist Figure 6 In the feed liquid reduction system (2), the forward osmosis membrane module (500) and the dialysis membrane module (100) are connected in parallel to the feed liquid tank (200).

[0327] The concentration of the second solvent or byproduct of the dialysis membrane assembly (100) is adjusted by means of... Figure 5 The same method is used for the raw material liquid volume reduction system (1).

[0328] In the volume reduction process using the forward osmosis membrane module (500), a pump (P) supplies feed solution (a) at an appropriate flow rate from the bottom of the feed solution tank (200) to a space on one side of the forward osmosis membrane module (500) (e.g., the space inside the hollow fiber membrane). After passing through the hollow fiber membrane, the feed solution (a) returns to the feed solution tank (200) for circulation. This return position is preferably located away from the collection position used to supply the feed to the forward osmosis membrane module (500), and is the bottom of the feed solution tank (200). Returning to a position away from the collection position can prevent the concentration of the second solvent or byproduct in the feed solution (a) from increasing excessively due to the short path. In addition, returning to the bottom of the feed solution tank can prevent valuable substances in the feed solution (a) from precipitating and being lost on the walls of the feed solution tank (200).

[0329] On the other hand, a driving solution (d) with a higher osmotic pressure than the feed solution (a) is introduced into the space on the other side of the forward osmosis membrane module (500) using a pump (P) (e.g., the outer space of the membrane for hollow fiber membrane distillation).

[0330] Therefore, due to the osmotic pressure difference between the feed solution (a) and the driving solution (d), the first solvent moves from the feed solution (a) to the driving solution (d), and the feed solution (a) is reduced in volume. The reduced-volume feed solution (a) flows out of the forward osmosis membrane module (500) and returns to the feed solution tank (200). The driving solution (d) increases in volume due to the first solvent mixing into it from the feed solution (a). Therefore, it is necessary to make the capacity of the driving solution tank (600) sufficiently large, or to take measures such as overflowing to discharge a portion outside the driving solution tank (600). Figure 6 The device for discharging the driving solution (d) to the driving solution tank (600) is not shown in the figure.

[0331] Figure 7 The feed liquid volume reduction system is an example of a nanofiltration module used for nanofiltration membrane processes, which is taken as the first unit.

[0332] Figure 7 The feed liquid volume reduction system (3) has a nanofiltration membrane module (700), a feed liquid tank (200), a permeate tank (800), a dialysis membrane module (100), and a dialysis liquid tank (300).

[0333] exist Figure 7 In the feed liquid volume reduction system (3), the nanofiltration membrane module (700) and the dialysis membrane module (100) are connected in parallel to the feed liquid tank (200).

[0334] The concentration of the second solvent or byproduct of the dialysis membrane assembly (100) is adjusted by means of... Figure 5 The same method is used for the raw material liquid volume reduction system (1).

[0335] In the volume reduction process using the nanofiltration membrane module (700), a pump (P) supplies feed liquid (a) at an appropriate flow rate from the bottom of the feed liquid tank (200) to a space on one side of the nanofiltration membrane module (700) (e.g., the space inside the hollow fiber membrane). After passing through the hollow fiber membrane, the flow rate of the feed liquid (a) is reduced by a valve (V), thereby applying pressure to the nanofiltration membrane module (700). Under this pressure, the permeate (first solvent) that has passed through the nanofiltration membrane is collected in the permeate tank (800). The feed liquid (a) that has passed through the valve (V) returns to the feed liquid tank (200) for circulation. This return position is preferably located away from the collection position used to supply the nanofiltration membrane module (700) and is at the bottom of the feed liquid tank (200). By returning to a position away from the collection position, it is possible to prevent the concentration of the second solution or byproducts in the feed liquid (a) from increasing excessively due to the short path. In addition, if the liquid is returned to the bottom of the raw material tank, valuable substances in the raw material liquid (a) can be prevented from precipitating out and being lost from the walls of the raw material tank (200).

[0336] The first solvent permeates through the pressurized nanofiltration membrane, thereby reducing the volume of the feed solution (a). The reduced-volume feed solution (a) flows out of the nanofiltration membrane module (700) and returns to the feed solution tank (200) via valve (V).

[0337] Figure 8 The feed liquid volume reduction system (4) is another embodiment using a forward osmosis membrane module (500) as the first volume reduction unit. It is a system in which a dialysis membrane module (100) as the second unit and a forward osmosis membrane module (500) as the first unit are sequentially connected in series in the flow direction of the feed liquid (a). Figure 8 In the feed liquid reduction system (4), the feed liquid (a) taken from the bottom of the feed liquid tank (200) first passes through the dialysis membrane module (100) and then through the forward osmosis membrane module (500). However, it can also be configured to first pass through the forward osmosis membrane module (500) and then through the dialysis membrane module (100).

[0338] Figure 9 The feed liquid volume reduction system (5) is another embodiment where a nanofiltration membrane module (700) is used as the first volume reduction unit. It is a system in which a dialysis membrane module (100) as the second unit and a nanofiltration membrane module (700) as the first unit are arranged in series in the flow direction of the feed liquid (a). Figure 9 In the feed liquid volume reduction system (5), the feed liquid (a) taken from the bottom of the feed liquid tank (200) first passes through the dialysis membrane module (100) and then through the nanofiltration membrane module (700). However, it can also be configured to first pass through the nanofiltration membrane module (700) and then through the dialysis membrane module (100).

[0339] exist Figures 5 to 9 In any of the feed liquid volume reduction systems, the feed liquid (a) is taken out from the bottom of the feed liquid tank (200) and returned to the bottom of the feed liquid tank (200). This is effective in preventing valuable substances in the feed liquid (a) from adhering to the tank wall and being lost. In addition, the installation of a stirring device inside the feed liquid tank (200) is also effective for stable volume reduction.

[0340] exist Figures 5 to 9 In the feed liquid volume reduction system, a hydrometer (HM) can be used to track the specific gravity of the feed liquid (a). This allows for monitoring of the concentration of the second component or byproduct in the feed liquid (a). Furthermore, as needed, the first or second unit can be operated or stopped, or the operating conditions can be changed, to reduce the volume while adjusting the composition of the feed liquid (a) within a range where valuable substances do not precipitate, agglomerate, or denature.

[0341] The degree of volume reduction of feed liquid (a) can be determined by measuring the volume of feed liquid (a) using a liquid level gauge (LG). Furthermore, the volume reduction can be completed at the moment when the target volume reduction ratio is achieved.

[0342] As a method for monitoring the properties of the feed liquid (a) (e.g., the concentration of at least one component in the feed liquid), in addition to the exemplified specific gravity measurement, pH measurement, conductivity measurement, optical rotation measurement, refractive index measurement, ultraviolet light analysis, visible light analysis, infrared light analysis, near-infrared light analysis, etc., can also be used. Using the results of one or more measurements selected from these analyses, for example, the concentration of at least one component in the feed liquid can be determined. By simultaneously monitoring this result and the measured value of the liquid level gauge, the weight of the liquid, etc., and by operating or stopping the first or second unit as needed, or changing the operating conditions, it is possible to reduce the volume while maintaining the concentration of the second solvent or byproduct in the feed liquid (a).

[0343] Furthermore, if known AI technologies such as regression analysis, category classification, clustering, deep learning using neural networks, or a combination thereof are used to estimate the concentration of the second solvent or byproduct in the feed solution (a), a higher accuracy concentration estimation can be achieved, which is therefore preferred.

[0344] By using this method, the concentration of the second solvent or byproduct in the feed solution (a) can be monitored with high precision, and the operating conditions can be appropriately controlled. This allows the concentration of the second solvent or byproduct to be maintained within an appropriate range with higher precision, while simultaneously reducing volume. Therefore, it is preferable to further reduce the risk of valuable substances precipitating, agglomerating, or denaturing.

[0345] Example

[0346] Hereinafter, embodiments that specifically illustrate the structure and effects of the present invention will be further described, but the present invention is not limited to any of the following embodiments.

[0347] <Dialysis Membrane Module 1>

[0348] As the substrate layer, a hollow fiber ultrafiltration membrane made of polyethersulfone with an inner diameter of 0.7 mm and an outer diameter of 1.0 mm was used. 130 of these hollow fiber ultrafiltration membranes were packed into a cylindrical plastic shell with a diameter of 2 cm and a length of 10 cm, and the two ends were fixed with adhesive, thereby creating an effective membrane with an inner surface area of ​​approximately 0.02 m². 2 The substrate layer assembly.

[0349] Add 2.5 g of piperazine and 0.8 g of sodium lauryl sulfate to a 0.5 L container, and then add 489.2 g of pure water to dissolve them, thus preparing 0.5 kg of the first solution for interfacial polymerization.

[0350] Add 0.8 g of trimesoyl chloride to another 0.5 L container, add 399.2 g of n-hexane and dissolve to prepare a second solution of 0.4 kg for interfacial polymerization.

[0351] These solutions are introduced into the support layer assembly in the order of solution 1 and solution 2 through the inside of the hollow fiber ultrafiltration membrane. Interfacial polymerization occurs on the inside surface of the hollow fiber ultrafiltration membrane, forming an active layer on the support layer, thus producing a hollow fiber dialysis membrane.

[0352] Then, a dialysis membrane assembly 1 containing 130 hollow fiber dialysis membranes is fabricated. The dialysis membranes are obtained by washing the inner side of the hollow fiber dialysis membrane with pure water, and have an active layer made of polyamide on the inner surface of the support layer made of hollow fiber ultrafiltration membrane made of polyethersulfone.

[0353] <Forward Osmosis Membrane Module 1>

[0354] In the preparation of the first solution, 10g of m-phenylenediamine was used instead of 2.5g of piperazine. Otherwise, the same as the dialysis membrane module was fabricated, with an active layer of polyamide on the inner surface of the support layer made of a hollow fiber ultrafiltration membrane of polyethersulfone. Next, hot water at 85°C was flowed into the inner space of the hollow fibers for 30 minutes, followed by water at 20°C for 30 minutes. Then, the module was placed in an autoclave (manufactured by Tomy Seiko Co., Ltd., ES-315), and heated with high-temperature steam at 125°C for 4 hours. Afterward, water at 20°C was flowed through the inner space of the hollow fibers for at least 30 minutes for washing, thereby fabricating a forward osmosis membrane module 1 containing 130 hollow fiber forward osmosis membranes.

[0355] <Dialysis Membrane Module 2>

[0356] The same component manufactured in the same manner as the "forward osmosis membrane component 1" described above is used as the "dialysis membrane component 2".

[0357] <Nanofiltration Membrane Module 1>

[0358] The same component manufactured in the same manner as the aforementioned "forward osmosis membrane component 1" is used as "nanofiltration membrane component 1".

[0359] <Evaporation Unit>

[0360] Using a blower (BL) for supplying air into the raw material tank (200), piping for discharging the introduced gas and the first solvent (b) evaporated by the gas to the outside of the raw material tank (200), and a collector (400) for storing the first solvent (b) supplied through the aforementioned piping, a system is constructed that is compatible with... Figure 5 Evaporation unit 1 is constructed in the same way as the evaporation unit (900) shown.

[0361] <Membrane Distillation Module 1>

[0362] Porous hollow fiber membranes made of PVDF with an inner diameter of 0.7 mm, an outer diameter of 1.3 mm, an average pore size of 0.21 μm, a maximum pore size of 0.29 μm, and a porosity of 72% as determined by ASTM-F316-86, were cut into 15 cm lengths.

[0363] Using the obtained hollow fiber membranes, membrane module 1 for membrane distillation was fabricated.

[0364] The membrane module was fabricated as follows: Using thermosetting epoxy resin as the adhesive, the hollow fiber membrane was centrifugally bonded and fixed inside the outer shell. At this point, the length of the portion of the hollow fiber membrane not embedded in the adhesive resin was adjusted to approximately 10 cm, and the total membrane area of ​​the inner surface of the hollow fiber membrane was approximately 0.02 m². 2 .

[0365] Fabricate two membrane modules of the same specifications.

[0366] In these membrane modules, the outer space of the hollow fiber membrane is filled with FS-392B manufactured by Fluoro Technology at a concentration of 3 times. After coating the outer side of the hollow fiber membrane, it is dried to obtain membrane module 1 for membrane distillation.

[0367] One component of membrane module 1 for membrane distillation obtained by the above method was disassembled, and the contact angle was measured without analyzing the porous hollow fiber membrane. The water contact angle of the porous hollow fiber membrane was calculated as follows: 2 μL of pure water was added dropwise at 23°C and 50% relative humidity, and the angle formed between the droplet and the outer surface of the hollow fiber membrane was calculated through image analysis. The measurement was performed 5 times, and the mean value was calculated. The resulting contact angle of the outer surface of the hollow fiber membrane was 132°, confirming its extremely strong hydrophobicity.

[0368] The remaining membrane distillation membrane module 1 was used in Comparative Example 3.

[0369] <Determination of molecular weight cutoff>

[0370] A 0.002% by weight aqueous solution of Rhodamine B (molecular weight 479) was used as the test supply solution to determine the molecular weight cutoff of the obtained dialysis membrane module 1 and forward osmosis membrane module 1.

[0371] Filtration was initiated under conditions where the test solution was supplied at an average linear velocity of 4 cm / s and a pressure of 0.2 MPaG within the inner space of the hollow fibers in each component. Filtration was continued for 20 minutes to allow the condition to stabilize, after which the filtrate was collected.

[0372] The absorbance of the collected filtrate was measured at a wavelength of 552 nm, and the concentration of Rhodamine B in the filtrate was investigated. The results showed that for both dialysis membrane module 1 and forward osmosis membrane module 1, the concentration of Rhodamine B in the test supply solution was less than 1 / 10.

[0373] This result means that the molecular weight cutoff for both dialysis membrane module 1 and forward osmosis membrane module 1 is below 479.

[0374] Based on the results, it was confirmed that both dialysis membrane module 1 and forward osmosis membrane module 1 are molecular sieve membrane modules.

[0375] <Measurement of Transparency>

[0376] For the obtained dialysis membrane assembly 1 and forward osmosis membrane assembly 1, water was used as the first solvent, and the permeability of acetonitrile as the second solvent and acetic acid as a by-product was measured respectively.

[0377] The permeability of acetonitrile was evaluated using water as a reference solution and a 1 mol / L acetonitrile 1M aqueous solution as the test solution. The test solution was circulated within the hollow fiber space of each module at an average linear velocity of 0.04 m / s, while the reference solution was circulated within the hollow fiber space at an average linear velocity of 0.025 m / s, ensuring co-current flow. Twenty minutes after the start of circulation, the acetonitrile concentration in the reference solution was measured to quantify the amount of acetonitrile that moved from the test solution through the hollow fiber membrane into the reference solution. The obtained value (g) was expressed using the initial concentration of the test solution (M = mol / L) and the membrane area of ​​each module (m²). 2 The product of ) and cycle time (h) (m) 2 The value obtained is used as the transparency.

[0378] An aqueous solution of acetic acid with a concentration of 1 mol / L was used as the test solution. Otherwise, the permeability of acetic acid was evaluated in the same manner as described above.

[0379] The results are shown in Table 1.

[0380] [Table 1]

[0381] Table 1.

[0382]

[0383] [Example 1]

[0384] In Example 1, the first treatment was performed using forward osmosis. Figure 6 The feed liquid reduction system (2) shown is used as a forward osmosis membrane module (500) and the forward osmosis membrane module 1 manufactured above is used.

[0385] As the feedstock solution (a), a solution containing 0.2% by weight glutathione disulfide as a valuable component, 298.2 g of water as the first solvent, 298.2 g of acetonitrile as the second solvent, and 3.6 g of acetic acid as a byproduct is used. The initial concentration of acetonitrile in the solvent of the feedstock solution (a) is 50% by weight.

[0386] 600g of the feed solution (a) was filled into a feed solution tank (200) with a capacity of 1,000mL. On the other hand, as the driving solution (d), 1,200g of a 50% by weight aqueous solution of isopropanol was filled into a driving solution tank (600).

[0387] Then, 1,200g of water, which is used as dialysate (e), is filled into the dialysate tank (300).

[0388] To perform forward osmosis as the first treatment, the feed solution (a) and the drive solution (d) are circulated in the forward osmosis membrane module (500) which is the first unit. The flow rate of the feed solution (a) is set to 120 mL / min, and the flow rate of the drive solution (d) is set to 240 mL / min, with the two liquids flowing in parallel.

[0389] To perform dialysis as a second process, the above-mentioned feed solution (a) and dialysate (e) are circulated in the dialysis membrane assembly (100), which is the second unit. The flow rate of feed solution (a) is set to 120 mL / min, and the flow rate of dialysate (e) is set to 240 mL / min, with the two liquids flowing in parallel.

[0390] 4.7 hours after the start of operation, the dialysate is replaced. That is, all the dialysate in the dialysate tank (300) is discarded and replaced with 1,200g of water.

[0391] After replacing the dialysate, the system continued to operate for a total of 8 hours. As a result, the mass of the feed solution (a) became 46.2g, representing a volume reduction of 13 times. The system was then stopped.

[0392] The concentration of glutathione disulfide in the feed solution (a) was analyzed by ICP-MS, and the yield was calculated. The yield of glutathione disulfide was over 99%.

[0393] In addition, a small amount of feed solution (a) was taken out every hour from the start of operation and the concentration of acetonitrile was tracked by gas chromatography. As a result, the concentration of acetonitrile in the solvent of feed solution (a) decreased from 50% by weight of the initial concentration to 31% by weight 120 minutes after the start of operation, and thereafter maintained a water-rich composition.

[0394] This verifies that the method of the present invention enables the reduction of the volume of the raw material liquid while maintaining the solvent composition of the raw material liquid within the desired range; and that the reduction of the volume of the raw material liquid is achieved without impairing the valuable components.

[0395] [Examples 2-6]

[0396] As described in Table 2, the composition of the feed solution and the dialysate (e) flowing in the dialysis membrane assembly (100) which is the second unit were changed respectively, but otherwise the operation was carried out in the same manner as in Example 1.

[0397] [Example 7]

[0398] The dialysis membrane assembly 2 is used as the second unit of the dialysis membrane assembly (100), and otherwise it is operated in the same manner as in Example 1.

[0399] [Example 8]

[0400] In Example 8, the first treatment was performed using nanofiltration. Figure 7 The feed liquid volume reduction system (3) shown is used as a nanofiltration membrane module (700) and operates in the same manner as in Example 1, except that it uses the nanofiltration membrane module 1 prepared above.

[0401] [Example 9]

[0402] In Example 9, the first treatment was performed using an evaporation method. Figure 5 The feed liquid volume reduction system (1) shown is used as an evaporation unit (900). The evaporation unit 1 manufactured above is used, and the composition of the feed liquid and the dialysate (e) flowing in the dialysis membrane assembly (100) which is the second unit are changed as described in Table 2. Otherwise, it is operated in the same way as in Example 1.

[0403] [Comparative Example 1]

[0404] Except that the dialysis membrane assembly (100) is not used, it is operated in the same manner as in Example 1.

[0405] Four hours after the start of operation, when the volume reduction ratio reached 2.6 times, turbidity was detected in the raw material liquid, so operation was stopped.

[0406] The cloudy feed solution was filtered to remove the precipitated solids, and the concentration of glutathione disulfide in the filtrate was analyzed to calculate the yield of the valuable compound. The yield of the valuable compound in Comparative Example 1 was 59.9%.

[0407] In addition, a small amount of raw material liquid was taken out every hour from the start of operation and the concentration of acetonitrile was tracked by gas chromatography analysis. The results confirmed that the concentration of acetonitrile increased over time, from 50% by weight at the initial concentration to 61% by weight at the time of operation stop.

[0408] [Comparative Example 2]

[0409] Except for not using the forward osmosis membrane module (500), the operation was performed in the same manner as in Example 1. The weight of the feed solution in the feed solution tank (200) was tracked during operation, and as a result, even after one hour from the start of operation, no reduction in the mass of the feed solution was detected. Therefore, in this comparative example, it was determined that volume reduction had not occurred, and operation was stopped.

[0410] [Comparative Example 3]

[0411] In Unit 2, membrane distillation module 1 was used instead of dialysis membrane module (100). Membrane distillation was performed while circulating cooling water at 10°C to replace dialysis, and otherwise, the operation was the same as in Example 1. Four hours after the start of operation, a change in the appearance of the membrane wettability of the membrane distillation module was observed, and operation was stopped. The concentration of glutathione disulfide in the feed solution (a) was analyzed by ICP-MS, and the yield at the time of operation stoppage was calculated. The yield of glutathione disulfide was 45%.

[0412] [Comparative Example 4]

[0413] Except that the dialysis membrane assembly (100) is not used, it is operated in the same manner as in Example 9.

[0414] The results of Examples 1-9 and Comparative Examples 1-4 are shown in Table 2.

[0415]

[0416] [Table 3]

[0417] Table 2. (Continued)

[0418]

[0419] (End of Table 2)

[0420] The results of Comparative Examples 1 and 4 above show that, in the case of only performing the first treatment, although the volume reduction of the feed solution was carried out, precipitates were generated in the feed solution as the volume reduction proceeded, resulting in a low yield of valuable substances. It is believed that the precipitates in the feed solution are due to the fact that the concentration of valuable substances increases as the volume reduction proceeds, and on the other hand, the concentration of the solvent composition or by-products was not adjusted to a region where the valuable substances can exist stably, thus causing the valuable substances to precipitate.

[0421] Furthermore, according to the results of Comparative Example 2, when only the second treatment is performed, the volume of the raw material liquid is not reduced.

[0422] Furthermore, based on the results of Comparative Example 3, in the case of the second treatment using membrane distillation, although the volume of the feed liquid was reduced, the yield of valuable substances contained in the feed liquid remained at a low value.

[0423] In contrast, the method of the present invention, which combines volume reduction based on the first treatment with dialysis as the second treatment, has demonstrated the ability to perform high-rate volume reduction without the formation of precipitates in the feed solution. This is believed to be because, according to the method of the present invention, volume reduction of the feed solution is performed while maintaining the solvent composition and concentration of byproducts within the desired range.

[0424] The above results verify that the method of the present invention can achieve a high rate of volume reduction with a high yield of valuable materials.

[0425] Symbol Explanation

[0426] 1, 2, 3, 4 Raw material liquid volume reduction system

[0427] 100 Dialysis Membrane Modules

[0428] 110 Outer shell

[0429] 111 Dialysate inlet

[0430] 112 Dialysis fluid outlet

[0431] 120 dialysis membrane

[0432] 121 Substrate layer

[0433] 122 Active layer

[0434] 130 and 530 adhesive resins

[0435] 200 Raw material liquid tank

[0436] 300 dialysis fluid tank

[0437] 400 trap

[0438] 500 Forward Osmosis Membrane Module

[0439] 510 casing

[0440] 511 Drive solution inlet

[0441] 512 Drive solution outlet

[0442] 520 Forward Osmosis Membrane

[0443] 521 Substrate Layer

[0444] 522 active layer

[0445] 600 Driven Solution Tank

[0446] 700 nanofiltration membrane module

[0447] 800 through the liquid tank

[0448] 900 Evaporation Unit

[0449] a raw material liquid

[0450] b. Solvent 1

[0451] c. Reduced volume of the feed liquid

[0452] d driving solution

[0453] e Dialysate

[0454] f. Raw material liquid with adjusted component concentration

[0455] g Second solvent or by-product

[0456] BL blower

[0457] HM hydrometer

[0458] LG Liquid Level Gauge

[0459] P pump

[0460] V valve

Claims

1. A method for reducing the volume of a feed liquid, comprising reducing the volume of a feed liquid containing at least a valuable substance and a first solvent, wherein, The raw material liquid also contains by-products other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and the second solvent as a solvent. The raw material liquid volume reduction method is a combination of the first treatment and the second treatment. The first treatment removes the first solvent from the feed solution, and the first treatment is a volume reduction treatment using a membrane, which is any one of reverse osmosis, nanofiltration, and forward osmosis. The second treatment adjusts the concentration of the second solvent or the byproduct in the feed solution by using dialysis with a dialysis membrane.

2. The method for reducing the volume of the raw material liquid as described in claim 1, wherein, The dialysis membrane used in the second treatment is a molecular sieve membrane.

3. The method for reducing the volume of the raw material liquid as described in claim 2, wherein, The first treatment is a forward osmosis method.

4. The method for reducing the volume of raw material liquid as described in claim 2, wherein, The permeability of the second solvent or the byproduct of the molecular sieve membrane used in the second treatment is greater than the permeability of the second solvent or the byproduct of the membrane used in the first treatment.

5. The method for reducing the volume of the raw material liquid as described in any one of claims 1 to 4, comprising: After the first process is performed, the second process is performed.

6. The method for reducing the volume of the raw material liquid as described in any one of claims 1 to 4, comprising: After the second process is performed, the first process is performed.

7. The method for reducing the volume of the raw material liquid as described in any one of claims 1 to 4, comprising: Parallel Perform the first and second treatments, and mix the raw material liquids after each treatment.

8. The method for reducing the volume of the raw material liquid as described in claim 5, wherein, The raw material liquid is circulated and subjected to the first and second treatments.

9. The method for reducing the volume of raw material liquid as described in claim 8, wherein, The concentration of at least one component in the recycled liquid is measured, and based on the measured value, the implementation or cessation of at least one of the first and second treatments, or the change of operating conditions, is determined.

10. The method for reducing the volume of raw material liquid as described in claim 9, wherein, The concentration determination is performed using one or more of the following measurements of the cyclically reduced feed solution: specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy analysis, and weight measurement.

11. The method for reducing the volume of the raw material liquid as described in any one of claims 1-4 and 8-10, wherein, The valuable item is a pharmaceutical raw material.

12. The method for reducing the volume of the raw material liquid as described in any one of claims 1-4 and 8-10, wherein, The number-average molecular weight of the valuable substance is 100 to 50,000.

13. The method for reducing the volume of the raw material liquid as described in any one of claims 1-4 and 8-10, wherein, The valuable substance is selected from one or more of the following groups: amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), and vitamins.

14. The method for reducing the volume of the raw material liquid as described in any one of claims 1-4 and 8-10, wherein, The second solvent is selected from one or more of water, acetonitrile, methanol, ethanol, and isopropanol. The by-product is one or more selected from the group consisting of organic acids, polymers and buffer salts, wherein the polymer does not include the valuable substance.

15. The method for reducing the volume of the raw material liquid as described in any one of claims 1-4 and 8-10, wherein, The temperature of the raw material liquid is adjusted to a range of 1°C to 50°C.

16. The method for reducing the volume of the raw material liquid according to any one of claims 1 to 4, wherein, The solute used as the driving solution in the forward osmosis method is selected from at least one of methanol, ethanol, isopropanol and tert-butanol.

17. The method for reducing the volume of the raw material liquid as described in claim 1, wherein, The first solvent is selected from one or more of water and organic solvents.

18. The method for reducing the volume of raw material liquid as described in claim 1, wherein, The dialysis membrane used for the second treatment is a hollow fiber membrane.

19. The method for reducing the volume of raw material liquid as described in claim 1, wherein, The membrane used in the first treatment is a molecular sieve membrane.

20. The method for reducing the volume of the raw material liquid as described in claim 2 or 19, wherein, The molecular sieve membrane has a molecular weight cutoff of 100 or higher and 5,000 or lower.

21. The method for reducing the volume of raw material liquid as described in claim 1, wherein, The membrane used in the first treatment is a hollow fiber membrane.

22. The method for reducing the volume of the raw material liquid as described in claim 14, wherein, The first solvent is water, the second solvent is acetonitrile, and the byproduct is acetic acid.

23. The method for reducing the volume of the raw material liquid as described in claim 18 or 21, wherein, The hollow fiber membrane has an inner diameter of 200 μm or more and 4,000 μm or less.

24. A feed liquid volume reduction system, which is a feed liquid volume reduction system for reducing the volume of a feed liquid containing at least a valuable substance and a first solvent, wherein, The raw material liquid also contains by-products other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and the second solvent as a solvent. The raw material liquid volume reduction system is a system that combines Unit 1 and Unit 2. The first unit removes the first solvent from the feed solution. The first unit is a unit that performs a membrane-based volume reduction process using any of the following methods: reverse osmosis, nanofiltration, and forward osmosis. The second unit adjusts the concentration of the second solvent or the byproduct in the feed solution by using dialysis with a dialysis membrane.

25. The feed liquid volume reduction system as described in claim 24, wherein, The dialysis membrane used in the second unit is a molecular sieve membrane.

26. The feed liquid volume reduction system as described in claim 24, wherein, The first unit is the unit for performing forward osmosis.

27. The feed liquid volume reduction system as described in claim 25, wherein, The permeability of the second solvent or the byproduct of the molecular sieve membrane contained in the second unit is greater than the permeability of the second solvent or the byproduct of the membrane contained in the first unit.

28. The feed liquid volume reduction system according to any one of claims 24 to 27, wherein, In the flow direction of the raw material liquid, the first unit and the second unit are connected in series.

29. The feed liquid volume reduction system according to any one of claims 24 to 27, wherein, In the flow direction of the raw material liquid, the second unit and the first unit are connected in series.

30. The feed liquid volume reduction system according to any one of claims 24 to 27, wherein, The first unit and the second unit are connected in parallel, and the raw material liquid volume reduction system includes a mechanism for mixing the raw material liquid discharged from each unit.

31. The feed liquid volume reduction system of claim 28, comprising a mechanism for cyclically processing the feed liquid using the first unit and the second unit.

32. The feed liquid volume reduction system as described in claim 31, comprising: A concentration measuring apparatus for measuring the concentration of at least one component in a feed liquid that is being circulated and reduced in volume; as well as An apparatus for determining the operation or shutdown, or the change of operating conditions, of at least one of the first unit and the second unit based on the measured values ​​obtained by the concentration measuring apparatus.

33. The feed liquid volume reduction system as described in claim 32, wherein, The concentration determination mechanism is an institution that uses one or more of the following measurement results from the group consisting of specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy analysis, and weight measurement to determine the concentration of the raw material liquid that has been circulated and reduced in volume.

34. The feed liquid volume reduction system according to any one of claims 24-27 and 31-33, wherein, The valuable item is a pharmaceutical raw material.

35. The feed liquid volume reduction system according to any one of claims 24-27 and 31-33, wherein, The number-average molecular weight of the valuable substance is 100 to 50,000.

36. The feed liquid volume reduction system according to any one of claims 24-27 and 31-33, wherein, The valuable substance is selected from one or more of the following groups: amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), and vitamins.

37. The feed liquid volume reduction system according to any one of claims 24-27 and 31-33, wherein, The second solvent is selected from one or more of water, acetonitrile, methanol, ethanol, and isopropanol. The by-product is one or more selected from the group consisting of organic acids, polymers and buffer salts, wherein the polymer does not include the valuable substance.

38. The raw material liquid volume reduction system according to any one of claims 24-27 and 31-33, comprising a mechanism for adjusting the temperature of the raw material liquid to a range of 1°C to 50°C.

39. The feed liquid volume reduction system according to any one of claims 24 to 27, wherein, The solute used as the driving solution in the forward osmosis process is an alcohol selected from methanol, ethanol, isopropanol and tert-butanol.

40. The feed liquid volume reduction system as described in claim 24, wherein, The first solvent is selected from one or more of water and organic solvents.

41. The feed liquid volume reduction system as described in claim 24, wherein, The dialysis membrane used in the second unit is a hollow fiber membrane.

42. The raw material liquid volume reduction system as described in claim 24, wherein, The membrane used in the first unit is a molecular sieve membrane.

43. The feed liquid volume reduction system as described in claim 25 or 42, wherein, The molecular sieve membrane has a molecular weight cutoff of 100 or higher and 5,000 or lower.

44. The feed liquid volume reduction system as described in claim 24, wherein, The membrane used in the first unit is a hollow fiber membrane.

45. The feed liquid volume reduction system as described in claim 37, wherein, The first solvent is water, the second solvent is acetonitrile, and the byproduct is acetic acid.

46. ​​The feed liquid volume reduction system as described in claim 41 or 44, wherein, The hollow fiber membrane has an inner diameter of 200 μm or more and 4,000 μm or less.

Images