Method and system for reducing volume of raw material liquid

Abstract

To provide a method for reducing the volume of a raw material liquid that allows the component composition of the raw material liquid to be adjusted to a predetermined value during volume reduction of the raw material liquid, thereby suppressing precipitation, aggregation and denaturation of valuable substances.SOLUTION: In a method for reducing the volume of a raw material liquid containing at least a valuable and a first solvent, the raw material liquid further contains an accessory component other than the valuable and the first solvent or contains as a solvent a mixed solvent containing the first solvent and a second solvent. and the method for reducing the volume of the raw material liquid is performed by combining a first process in which the first solvent is removed from the raw material liquid and a second process in which a concentration of the second solvent or the accessory component is adjusted from the raw material liquid using a dialysis method with a dialysis membrane.SELECTED DRAWING: Figure 6

Description

[Technical field]

[0001] The present invention relates to a method and system for reducing the volume of a feedstock liquid. [Background technology]

[0002] Volume reduction of raw material liquids containing valuable materials is carried out industrially on a large scale. For example, the raw material liquid in the purification process of peptides, DNA, RNA, enzymes, and derivative compounds thereof, as well as the raw materials thereof (hereinafter referred to as "peptides, etc.") may contain various organic solvents, organic acids, salts, etc., in addition to peptides, etc., and water. Such raw material liquids allow valuable substances to be present stably in the raw material liquid by adjusting the composition of the solvent and the concentrations of the organic acids, salts, etc., within respective predetermined ranges. Therefore, if the solvent composition changes or the concentrations of organic acids, salts, etc. fluctuate during the process of reducing the volume of the raw material liquid, the peptides, etc. may precipitate, aggregate, denature, etc., resulting in a poor yield of volume reduction. Since peptides, etc. are very expensive, a high yield is required for the volume reduction process of the raw material liquid containing them.

[0003] Furthermore, for example, in the case of a raw material liquid that is scheduled to be subjected to a reaction that does not tolerate the presence of moisture after volume reduction, it is desirable to reduce the water content as much as possible in the volume reduction step.

[0004] From the above viewpoints, there is a demand for a method for reducing the volume of a raw material liquid in which the component composition of the raw material liquid after volume reduction is adjusted to a desired value. As a method for reducing the volume of a raw material liquid while maintaining the concentration of an organic solvent, a membrane concentration method is known in which a solvent is added to the raw material liquid (Patent Document 1). In addition, dialysis is known as a method for transferring a specific component in a raw material solution through a membrane (Non-Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2020-196009 A [Non-patent literature]

[0006] [Non-Patent Document 1] Biotechnol. Prog., 2019, Vol. 35, No. 2, e2763 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to provide a method for reducing the volume of a raw material liquid, which can adjust the component composition of the raw material liquid to a desired value when reducing the volume of the raw material liquid, thereby suppressing precipitation, aggregation, and denaturation of valuable materials, and a raw material liquid volume reduction system for use in this method. [Means for solving the problem]

[0008] The present invention has been made to achieve the above object. That is, one example of an embodiment of the present invention is as follows. Aspect 1: A method for reducing the volume of a raw material liquid that contains at least a valuable material and a first solvent, comprising: The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or As a solvent, a mixed solvent containing the first solvent and the second solvent is included, The method for reducing the volume of the raw material liquid comprises: a first process for removing the first solvent from the raw material liquid; a second process of adjusting a concentration of the second solvent or the subcomponent in the raw material solution by dialysis using a dialysis membrane; This is a method that combines Method for reducing raw material liquid volume. Aspect 2: The method for reducing the volume of a raw material liquid according to aspect 1, wherein the dialysis membrane used in the second treatment is a molecular sieve membrane. Aspect 3: A method for reducing the volume of a raw material liquid according to aspect 2, wherein the first treatment is a volume reduction treatment using a membrane, such as reverse osmosis, nanofiltration, or forward osmosis. Aspect 4: The method for reducing the volume of a raw material liquid according to aspect 2, wherein the first treatment is a forward osmosis method. <<Aspect 5>> The permeability of the membrane used in the first treatment to the second solvent or the subcomponent is higher than that of the membrane used in the first treatment. The molecular sieve membrane used in the second treatment has a higher permeability to the second solvent or the subcomponent; A method for reducing the volume of a raw material liquid according to aspect 3 or 4. Aspect 6: The method for reducing the volume of a raw material liquid according to any one of aspects 1 to 5, comprising carrying out the second treatment after carrying out the first treatment. Aspect 7: The method for reducing the volume of a raw material liquid according to any one of aspects 1 to 5, comprising carrying out the first treatment after carrying out the second treatment. Aspect 8: A method for reducing the volume of a raw material liquid according to any one of aspects 1 to 5, comprising carrying out the first treatment and the second treatment in parallel and mixing the raw material liquid after each treatment. Aspect 9: The method for reducing the volume of a raw material liquid according to any one of aspects 6 to 8, wherein the first treatment and the second treatment are cyclically performed on the raw material liquid. A method for reducing the volume of a raw material liquid described in Aspect 9, comprising measuring the concentration of at least one of the components in the raw material liquid being cyclically reduced in volume, and deciding to carry out or stop at least one of the first process and the second process, or to change the operating conditions, depending on the obtained measurement value. Aspect 11: The method for reducing the volume of a raw material liquid according to aspect 10, wherein the concentration measurement is performed using one or more measurement results selected from the group consisting of specific gravity measurement, pH measurement, electrical conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy, and weight measurement of the raw material liquid being circulatedly reduced in volume. Aspect 12: The method for reducing the volume of a raw material liquid according to any one of Aspects 1 to 11, wherein the valuable resource is a pharmaceutical raw material. Aspect 13: The method for reducing the volume of a raw material liquid according to any one of Aspects 1 to 12, wherein the valuable material has a number average molecular weight of 100 to 50,000. Aspect 14: The method for reducing the volume of a raw material liquid according to any one of Aspects 1 to 13, wherein the valuable substance is one or more selected from the group consisting of amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), and vitamins. Aspect 15: The second solvent is at least one selected from the group consisting of water, acetonitrile, methanol, ethanol, and isopropanol; The auxiliary component is at least one selected from the group consisting of an organic acid, a polymer (excluding the valuable substance), and a buffer salt. A method for reducing the volume of a raw material liquid according to any one of aspects 1 to 14. Aspect 16: The method for reducing the volume of a raw material liquid according to any one of aspects 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. Aspect 17: The method for reducing the volume of a feedstock liquid according to any one of aspects 3 to 5, wherein the draw solution used in the forward osmosis process is at least one selected from the group consisting of methanol, ethanol, isopropanol, and t-butanol. A system for reducing the volume of a raw material liquid that contains at least a valuable material and a first solvent, comprising: The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or As a solvent, a mixed solvent containing the first solvent and the second solvent is included, The raw material liquid volume reduction system includes: a first unit for removing the first solvent from the raw material liquid; a second unit for adjusting a concentration of the second solvent or the subcomponent in the raw material solution by dialysis using a dialysis membrane; It is a system that combines Raw material liquid volume reduction system. <Aspect 19> A raw liquid volume reduction system described in Aspect 18, wherein the dialysis membrane used in the second unit is a molecular sieve membrane. <Aspect 20> A raw material liquid volume reduction system as described in Aspect 19, wherein the first unit is a unit that performs a volume reduction process using a membrane, either reverse osmosis, nanofiltration, or forward osmosis. <Aspect 21> A raw material liquid volume reduction system as described in Aspect 20, wherein the first unit is a unit that performs forward osmosis. 22. The membrane contained in the first unit has a higher permeability to the second solvent or the auxiliary component than the membrane contained in the first unit, The molecular sieve membrane contained in the second unit has a higher permeability to the second solvent or the auxiliary component. 22. The raw material liquid volume reduction system according to claim 20 or 21. <<Aspect 23>> A raw material liquid volume reduction system described in any one of Aspects 18 to 22, wherein the first unit and the second unit are connected in series in this order in the flow direction of the raw material liquid. <<Aspect 24>> A raw material liquid volume reduction system described in any one of Aspects 18 to 22, wherein the second unit and the first unit are connected in series in this order in the flow direction of the raw material liquid. <<Aspect 25>> A raw material liquid volume reduction system described in any one of Aspects 18 to 22, wherein the first unit and the second unit are connected in parallel and include a mechanism for mixing the raw material liquid discharged from each unit. <<Aspect 26>> A raw material liquid volume reduction system described in any one of Aspects 23 to 25, including a mechanism for cyclically treating the raw material liquid by the first unit and the second unit. A concentration measuring mechanism for measuring the concentration of at least one of the components in the raw material liquid being circulated and reduced in volume; and a mechanism for determining whether to operate or stop, or to change an operating condition of, at least one of the first unit and the second unit, depending on a measurement value obtained from the concentration measuring mechanism; 27. The feedstock liquid volume reduction system of claim 26, comprising: <Aspect 28> A raw liquid volume reduction system as described in Aspect 27, wherein the concentration measurement mechanism is a mechanism that determines the concentration using one or more measurement results selected 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 of the raw liquid being circulatedly reduced in volume. <Aspect 29> A raw material liquid volume reduction system described in any one of Aspects 18 to 28, wherein the valuable material is a pharmaceutical raw material. <<Aspect 30>> A raw material liquid volume reduction system according to any one of Aspects 18 to 29, wherein the valuable material has a number average molecular weight of 100 to 50,000. Aspect 31: The system for reducing the volume of a raw material liquid according to any one of Aspects 18 to 30, wherein the valuable resource is one or more selected from the group consisting of amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), and vitamins. 32. The second solvent is at least one selected from the group consisting of water, acetonitrile, methanol, ethanol, and isopropanol; 32. The system for reducing a volume of a raw material liquid according to any one of aspects 18 to 31, wherein the accessory component is one or more selected from the group consisting of an organic acid, a polymer (excluding the valuable substance), and a buffer salt. <<Aspect 33>> A raw material liquid volume reduction system described in any one of Aspects 18 to 32, including a mechanism for adjusting the temperature of the raw material liquid to a range of 1°C or more and 50°C or less. Aspect 34: The system for reducing the volume of a raw material liquid according to any one of aspects 20 to 22, wherein an alcohol selected from methanol, ethanol, isopropanol, and t-butanol is used as a solute of the draw solution used in the forward osmosis method. Effect of the Invention

[0009] According to the method for reducing the volume of a raw material liquid of the present invention, when reducing the volume of the raw material liquid, the component composition of the reduced raw material liquid can be adjusted to a desired value. Therefore, the raw material liquid reduced in volume by the method of the present invention has precipitation, aggregation, and denaturation of valuables suppressed to the utmost, has an excellent yield of valuables, and has a composition that meets the requirements of the next process. By using the volume reduction system of the present invention, the feedstock liquid volume reduction method having the advantages described above can be efficiently carried out. [Brief description of the drawings]

[0010] [Figure 1]FIG. 1 is a conceptual diagram for explaining the mechanism of action of forward osmosis, which is an example of the first treatment in the method for reducing the volume of a raw material solution of the present invention. [Diagram 2] FIG. 2 is a schematic cross-sectional view illustrating an example of the structure of a forward osmosis membrane module used in the raw material solution volume reduction system of the present invention. [Diagram 3] FIG. 2 is a conceptual diagram for explaining the mechanism of action of dialysis, which is an example of the second treatment in the method for reducing the volume of a raw material solution of the present invention. [Figure 4] FIG. 2 is a schematic cross-sectional view illustrating an example of the structure of a dialysis membrane module used in the raw material solution volume reduction system of the present invention. [Diagram 5] FIG. 1 is a conceptual diagram for explaining an example of a raw material liquid volume reduction system of the present invention. [Figure 6] FIG. 2 is a conceptual diagram for explaining another example of the raw material solution volume reduction system of the present invention. [Figure 7] 1 is a conceptual diagram for explaining yet another example of the raw material solution volume reduction system of the present invention. FIG. [Figure 8] 1 is a conceptual diagram for explaining yet another example of the raw material solution volume reduction system of the present invention. FIG. [Figure 9] 1 is a conceptual diagram for explaining yet another example of the raw material solution volume reduction system of the present invention. FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] <Raw material liquid volume reduction system> The method for reducing the volume of a raw material liquid of the present invention is a method for reducing the volume of a raw material liquid containing at least a valuable material and a first solvent, The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or As a solvent, a mixed solvent containing the first solvent and the second solvent is included, The method for reducing the volume of the raw material liquid comprises: a first process for removing the first solvent from the raw material liquid; a second process of adjusting a concentration of the second solvent or the subcomponent in the raw material solution by dialysis using a dialysis membrane; This is a method that combines the above.

[0012] In order to ensure the solubility and chemical stability of the valuables, raw material solutions containing valuables often use a mixed solvent of multiple solvents as the solvent, or contain secondary components such as salts and buffer salts. As a method for concentrating such a raw liquid containing valuable substances, distillation, reduced pressure distillation, membrane distillation, pervaporation, vapor permeation, reverse osmosis, nanofiltration, forward osmosis, etc. have been used. However, no matter what method is used, due to differences in the chemical and physical properties of multiple components contained in the raw liquid, certain components may be preferentially removed from the raw liquid, causing changes in the composition of the solvent or the concentration of the subcomponents. If this occurs, there is a concern that valuable substances may precipitate, coagulate, or denature during the volume reduction of the raw liquid. One method to solve this problem is to gradually add solvent and sub-components to the raw liquid during volume reduction so as to maintain the solvent composition and the concentration of the sub-components. However, this method does not solve the risk of precipitation, aggregation, and denaturation of valuable materials because the concentration of the solvent or sub-components changes rapidly near the place where the solvent or sub-components are added.

[0013] Therefore, the present inventors have focused on dialysis as a means for maintaining or gradually adjusting the solvent composition and the concentration of the minor component. In dialysis, the solvent composition or the minor component concentration in the feed solution gradually approaches the solvent composition or the minor component concentration in the dialysis solution over time. By combining such a dialysis method with the above-mentioned volume reduction means, it has become possible to reduce the volume of the raw material liquid while maintaining the solubility and chemical stability of the valuable substances. Due to the above-mentioned mechanism of action, the present invention can reduce the volume of the raw material liquid while minimizing the risk of precipitation, aggregation, and denaturation of valuable materials.

[0014] <Terminology> <Raw material liquid> The raw material liquid to be reduced in volume by the volume reduction method of the present invention is a solution or dispersion containing at least a valuable material and a first solvent. This raw material liquid is Further comprising secondary components other than the valuable substance and the first solvent, or The solvent includes a mixed solvent including a first solvent and a second solvent. Examples of raw material liquids that can be used in the volume reduction method of the present invention include food, pharmaceuticals, seawater, and produced water discharged from gas fields, oil fields, etc. However, considering the advantage of the present invention that volume reduction is possible without the need for heating, the volume reduction method of the present invention is effective when applied to raw material liquids that contain substances that are likely to decompose when heated, particularly pharmaceutical raw materials, functional chemical species, etc., as valuable resources.

[0015] The temperature of the raw material liquid to be subjected to the method for reducing the volume of a raw material liquid of the present invention is preferably adjusted to a range of 1°C or higher and 50°C or lower.

[0016] (valuable item) In this disclosure, valuables refer to pharmaceutical raw materials, functional chemical species, etc. Examples of pharmaceutical raw materials include amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), yeast, vitamins, and the like.

[0017] An amino acid is a compound having one amino acid backbone consisting of a carboxyl group, an amino group, and a moiety connecting them. In this specification, the term "amino acid" encompasses essential amino acids, non-essential amino acids, and unnatural amino acids. Examples of essential amino acids include tryptophan, lysine, methionine, phenylalanine, threonine, valine, leucine, isoleucine, etc. Examples of non-essential amino acids include arginine, glycine, alanine, serine, tyrosine, cysteine, asparagine, glutamine, proline, aspartic acid, glutamic acid, etc. The term "unnatural amino acid" refers to an artificial compound that does not exist in nature and has one amino acid skeleton in the molecule. In the present disclosure, unnatural amino acids as pharmaceutical raw materials include labeled amino acids, functionalized amino acids, etc. A labeled amino acid is a compound in which a desired labeling compound is bound to the amino acid backbone. Examples of the labeling compound include dyes, fluorescent substances, luminescent substances, enzyme substrates, coenzymes, antigenic substances, and protein-binding substances. Examples of functionalized amino acids include photoresponsive amino acids, photoswitch amino acids, fluorescent probe amino acids, and fluorescently labeled amino acids.

[0018] A peptide refers to a compound in which 2 to less than 70 amino acid residues are bound, and may be linear or cyclic. Examples of peptides in the present disclosure include L-alanyl-L-glutamine, β-alanyl-L-histidine cyclosporine, and glutathione. Protein generally refers to a compound having a longer chain than a peptide, among compounds in which amino acid residues are bound. Examples of proteins in this specification include interferon α, interferon β, interleukin 1 to 12, growth hormone, erythropoietin, insulin, granulocyte-colony stimulating factor (G-CSF), tissue plasminogen activator (TPA), natriuretic peptide, blood coagulation factor VIII, somatomedin, glucagon, growth hormone releasing factor, serum albumin, calcitonin, lipase G Amano 50, etc.

[0019] Examples of sugars include monosaccharides, disaccharides, sugar chains (excluding disaccharides), and sugar chain derivatives. Examples of monosaccharides include glucose, fructose, galactose, mannose, ribose, deoxyribose, etc. Examples of disaccharides include maltose, sucrose, lactose, etc. The sugar chain in the present disclosure is a concept excluding disaccharides, and examples thereof include cellulose, glycosaminoglycan, starch, sacran, dextran, dextrin, inulin, curdlan, fucoidan, fructan, pullulan, pectin, polydextrose, maltodextrin, lignin, xylan, mannan, glucomannan, glucuronoxylan, xylose, etc. Examples of sugar chain derivatives include saccharide derivatives such as N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, etc.

[0020] Vaccines include, for example, hepatitis A vaccine, hepatitis B vaccine, and hepatitis C vaccine; Examples of nucleic acids include oligonucleotides, RNA, aptamers, decoys, etc. Antibiotics include, for example, streptomycin and vancomycin; Antibody-drug conjugates (ADCs) include, for example, brentuximab vedotin (Adcetris), trastuzumab emtansine (Kadcyla), and gemtuzumab ozogamicin (Mylotarg); Each of them can be mentioned. Examples of yeast include Saccharomyces cerevisiae, Pichia stipitis, Candida shehatae, Pachysolen tannophilus, and the like, and mutant strains thereof are also included. Examples of vitamins include vitamin A, vitamin B, vitamin C, etc., including their derivatives, salts, etc. Examples of vitamin B include vitamin B6, vitamin B12, etc.

[0021] The functional chemical species refers to various chemical species used as functional chemical products, as well as their modifications, precursors, raw materials, etc. Examples of functional chemical species include metal nanoparticles, semiconductor nanoparticles, metal colloids, nanodiamonds, porous nanoclays, metal organic frameworks (MOFs), carbon nanotubes, fullerenes, graphene, graphene oxide, carbon nanohorns, cellulose nanofibers, and their modified forms, precursors, raw materials, etc.

[0022] The molecular weight of the valuable material contained in the raw material liquid subjected to the method for reducing the volume of a raw material liquid of the present invention is preferably in the range of 100 to 500,000, more preferably in the range of 100 to 50,000, and even more preferably in the range of 100 to 30,000, as a number average molecular weight calculated as polyethylene oxide, measured by gel permeation chromatography.

[0023] <solvent> In the present disclosure, a solvent is a compound capable of dissolving or dispersing the values ​​and, if present, minor ingredients. The solvent is typically one or more selected from water and organic solvents. The organic solvent is an organic compound having one or more carbon atoms, and in one embodiment, is a compound that exists in a liquid state at a temperature of 0° C. or higher and lower than 50° C. under normal pressure. However, the solvent in the present invention excludes carboxylic acids. Examples of the organic solvent include alcohols, esters, ethers, aprotic polar compounds, aromatic compounds, aliphatic compounds, chlorinated hydrocarbons, and ketones.

[0024] Specific examples of the organic solvent include: Examples of alcohols include methanol, ethanol, 1-propyl alcohol, isopropanol, normal butanol, sec-butanol, t-butanol, and hexafluoroisopropyl alcohol; Esters include, for example, methyl formate, ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, and the like; Ethers such as tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, cyclopentyl methyl ether, t-butyl methyl ether, anisole, 1,2-dimethoxyethane, etc.; Aprotic polar compounds include, for example, acetonitrile, dimethylacetamide, N-methylpyrrolidone, N,N-dimethylformamide, dimethylsulfoxide, nitromethane, sulfolane, and the like; Aromatic compounds include, for example, benzene, toluene, xylene, cumene, pyridine, etc.; Aliphatic compounds, for example, heptane, hexane, cyclohexane, methylcyclohexane, tetralin, etc.; Chlorinated hydrocarbons include, for example, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2-dichloroethene, 1,1,1-trichloroethane, 1,1,2-trichloroethene, chlorobenzene, etc.; Ketones, for example, acetone, methyl butyl ketone, methyl ethyl ketone, methyl isobutyl ketone, etc.; Aldehydes include, for example, formaldehyde, acetaldehyde, propionaldehyde, butanal, acrolein, benzaldehyde, furfural, vanillin, etc.; Each of them can be mentioned.

[0025] When the solvent of the raw material liquid contains only one type of solvent, the one type of solvent is the first solvent. When the solvent of the raw material liquid contains a plurality of solvents, one of these may be a first solvent, and one or more solvents other than the first solvent may be a second solvent. In the present disclosure, the first solvent and the second solvent are not fixed concepts, but are variable depending on the type of valuable material contained in the raw material liquid. That is, the solvent A that is the first solvent in a raw material liquid containing a valuable material A may be the second solvent in a raw material liquid containing another valuable material B. However, typical non-limiting examples of raw material liquid to which the method for reducing the volume of the raw material liquid of the present invention can be applied include the following examples. The first solvent is water, and the second solvent is one or more selected from acetonitrile, methanol, ethanol, and isopropanol; The first solvent is at least one selected from methanol, ethanol, isopropanol, and acetonitrile, and the second solvent is water; The first solvent is at least one selected from methanol, ethanol, and tetrahydrofuran, and the second solvent is hexane; The first solvent is water, and the second solvent is at least one selected from dimethylacetamide, N-methylpyrrolidone, N,N-dimethylformamide, and dimethylsulfoxide; etc.

[0026] The amount of the first solvent in the raw material liquid may be set arbitrarily depending on the solubility and chemical stability of the valuable material before and after the volume reduction, as well as the convenience of the reaction planned after the volume reduction. When the solvent of the raw material liquid contains the first solvent and the second solvent, the blending ratio of the first solvent and the second solvent may be arbitrarily set depending on the solubility and chemical stability of the valuable material before and after the volume reduction, as well as the convenience of the reaction planned after the volume reduction.

[0027] <Secondary ingredients> In the present disclosure, the subcomponent is a component optionally contained in the raw material liquid, and refers to components other than the valuable substance and the solvent among the components contained in the raw material liquid. When the solvent of the raw material liquid includes a first solvent and a second solvent, the subcomponent refers to components other than the valuable substance, the first solvent, and the second solvent among the components contained in the raw material liquid. The accessory components are, for example, organic acids, polymers (excluding valuable substances), buffer salts, and the like. Examples of the organic acid as a secondary component in the present 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.

[0028] The polymers as the secondary components exclude those that are considered to be valuable substances. Examples of the polymers as the secondary components in the present invention include polyethylene oxide, polypropylene oxide, and copolymers of ethylene oxide and propylene oxide. Examples of the salt or buffer salt include organic acid salts such as sodium chloride, magnesium chloride, calcium chloride, sodium bicarbonate, potassium bicarbonate, sodium sulfate, sodium hydrogen sulfate, potassium hydrogen sulfate, 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, and magnesium citrate, ammonium chloride, ammonium sulfate, ammonium carbonate, and ammonia. In many cases, the raw material solution contains multiple subcomponents. When the raw material liquid contains a subcomponent, the amount of the subcomponent in the raw material liquid may be set arbitrarily depending on the solubility and chemical stability of the valuable material, as well as the convenience of the reaction planned after volume reduction.

[0029] (Coexistence of second solvent and secondary components) The raw material liquid in the present disclosure may contain a valuable substance, a first solvent, a second solvent, and a subcomponent. In this case, the method for reducing the volume of a raw material liquid of the present invention can provide a reduced volume liquid in which the concentrations of the second solvent and the subcomponent are adjusted to desired values. Among raw material liquids containing valuable materials, a first solvent, a second solvent, and a subcomponent, examples that are preferably applied to the raw material liquid volume reduction method of the present invention include: the first solvent is water; The second solvent is at least one selected from acetonitrile, methanol, ethanol, and isopropanol; The auxiliary component may be at least one selected from acetic acid and trifluoroacetic acid. In particular, the first solvent is water, the second solvent is acetonitrile, and the secondary component is acetic acid, and these are typically contained in a weight ratio of 50 parts water:49 parts acetonitrile:1 part acetic acid.

[0030] <Transparency> In the present disclosure, permeability refers to the degree of ease with which a second solvent or a secondary component can permeate a membrane. In the present disclosure, permeability can be measured as follows. A test solution is prepared by dissolving a second solvent or a subcomponent in a first solvent at a predetermined concentration. Meanwhile, a reference solution made of the first solvent is prepared. When these test solutions and the reference solution are contacted via a membrane for a predetermined time, the amount of the second solvent or subcomponent that permeates the membrane and moves from the test solution to the reference solution is quantified. Then, the amount of the permeated component is assigned to the concentration of the test solution, the membrane area, and the contact time, and the value is evaluated as permeability. The predetermined concentration of the second solvent or subcomponent in the test solution and the contact time are typically 1 mol / L and 20 minutes. However, in the case of a component that destroys membranes at a concentration of 1 mol / L (e.g., trifluoroacetic acid, etc.), the predetermined concentration of the second solvent or subcomponent in the test solution and the contact time may be 0.01 mol / L and 180 minutes. Specifically, the measurement can be performed, for example, by the method described in the Examples below.

[0031] <Yield of valuable materials> In this disclosure, the yield of valuable materials refers to the value obtained by dividing the total amount of valuable materials obtained by the feedstock liquid volume reduction method by the total amount of valuable materials input into the feedstock liquid volume reduction process, expressed as a percentage. However, if the valuables precipitate or aggregate during the implementation of the method for reducing the volume of the raw liquid, they will not be considered to be the same valuables even if their chemical structure remains unchanged. Also, of course, if the chemical structure of the valuables changes during the implementation of the method for reducing the volume of the raw liquid, they will not be considered to be the same valuables. According to the method for reducing the volume of raw material liquid disclosed herein, the yield of valuable materials can be 70% or more, 80% or more, 90% or more, 95% or more, and even 99% or more.

[0032] <Volume reduction ratio> In the present disclosure, the volume reduction ratio refers to the value obtained by dividing the mass of the raw material liquid before volume reduction by the mass of the raw material liquid after volume reduction. According to the raw material liquid volume reduction method of the present invention, the raw material liquid can be reduced in volume at a high volume reduction ratio without impairing the stability of valuable materials. According to the method for reducing the volume of a raw material liquid of the present invention, the volume of the raw material liquid can be reduced by a volume reduction factor of 3 or more, 4 or more, or 5 or more without impairing the stability of the valuables. The upper limit of the volume reduction factor is approximately 50 times, although it depends on the concentration and solubility of the valuables contained in the raw material liquid.

[0033] <Molecular sieve membrane> In the present disclosure, the molecular sieve membrane refers to a membrane having a molecular weight cutoff smaller than the pore size of the ultrafiltration membrane. The molecular sieve membrane in the present disclosure is defined as having a molecular weight cutoff of 5,000 or less, 4,000 or less, or 3,000 or less. The molecular weight cutoff of the molecular sieve membrane in the present invention may be, for example, 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 about 100. Therefore, in the first treatment in the method for reducing the volume of a raw material liquid according to the present disclosure, a molecular sieve membrane may be used as the forward osmosis membrane, nanofiltration membrane, or the like.

[0034] As described above, the method for reducing the volume of a raw material liquid of the present invention is a method for reducing the volume of a raw material liquid containing at least a valuable material and a first solvent, The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or The solvent includes a mixed solvent including a first solvent and a second solvent, The method for reducing the volume of the raw material liquid comprises: a first process for removing the first solvent from the raw material liquid; a second process of adjusting a concentration of the second solvent or the subcomponent in the raw material solution by dialysis using a dialysis membrane; This is a method that combines the above. Preferred embodiments of the present invention will now be described in detail by way of specific, non-limiting examples.

[0035] <First Processing> The first treatment in the method for reducing the volume of a raw material liquid of the present invention is a treatment for mainly removing the first solvent from the raw material liquid. 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, forward osmosis membrane method, etc. The evaporation method is a method in which a gas is passed through a container containing the raw material liquid to vaporize the first solvent in the raw material liquid and remove it from the container. Among these treatments, the evaporation method, the reverse osmosis membrane method, the nanofiltration membrane method, and the forward osmosis membrane method are effective because they can remove the first solvent from the raw material liquid without heating, and therefore cause less denaturation of valuable materials due to heat. From the viewpoint of volume reduction efficiency, the first treatment is preferably a volume reduction treatment using a membrane, such as reverse osmosis, nanofiltration, or forward osmosis.

[0036] (Forward osmosis method) Of these processes, forward osmosis is particularly effective because it uses an appropriate draw solution to move the first solvent with a high driving force without the need for a mechanical driving force. Hereinafter, a forward osmosis method will be described as an example of the first treatment in the method for reducing the volume of a raw material liquid of the present invention. FIG. 1 is a schematic diagram showing the mechanism of solvent transport using a forward osmosis membrane. 1, the feed liquid (a) flows on one side of the forward osmosis membrane (520), and the draw solution (d) having a higher osmotic pressure than the feed liquid (a) flows on the other side, and the two liquids are in contact with each other via the forward osmosis membrane (520). Then, driven by the osmotic pressure difference between the feed liquid (a) and the draw solution (d), mainly the first solvent (b) in the feed liquid (a) passes through the forward osmosis membrane (520) and moves into the draw solution (d).

[0037] The forward osmosis membrane (520) in Fig. 1 has a base layer (521) and an active layer (522) formed on one side of the base layer (521). The active layer (522) has a very dense structure that allows small molecules to pass through but does not allow valuable substances to pass through, and is formed on the surface of the base layer (521) that comes into contact with the raw material liquid (a).

[0038] A porous membrane is generally used as the material for the base layer (521). The draw solution (d) permeates the portion of the forward osmosis membrane (520) that is the base layer (521) made of a porous membrane, and the raw liquid (a) and the draw solution (d) are in contact with each other via the active layer (522). In this case, the first solvent in the raw liquid (a) moves to the draw solution (d) side, which has a higher osmotic pressure, and the volume is reduced. The forward osmosis membrane may have any structure, such as a hollow fiber membrane, a tubular membrane, or a flat membrane. A hollow fiber membrane is preferable because it can form a flow path through which the raw material solution and the draw solution pass without using a spacer or the like, and can perform uniform volume reduction.

[0039] The material of the porous membrane constituting the substrate layer can be selected from widely used materials. However, materials that dissolve or swell in the organic solvent contained in the raw material liquid and cannot maintain the pore shape of the membrane cannot be used. Specific examples of the material of the porous membrane constituting the base layer include polysulfone, polyethersulfone, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polypropylene, cellulose polymer, polyketone, polyamide, polyimide, polyetheretherketone, polybenzimidazole, etc., and crosslinked bodies thereof, and it is preferable to use at least one selected from these as the main component. As the material of the porous membrane constituting the hollow fiber forward osmosis membrane, it is preferable to use at least one selected from polysulfone, polyethersulfone, polyketone, polyamide, polyimide, and crosslinked bodies thereof as the main component from the viewpoint of solvent resistance.

[0040] Polyamide is mainly used as the material for the active layer. The active layer made of polyamide can be formed by carrying out interfacial polymerization of a polyfunctional acid halide or the like and / or a polyfunctional amine on a base layer. A polyfunctional acid halide is an acid halide compound having two or more acid halide groups in one molecule. Halide compounds 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; Acid 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; These acid halide compounds may be used alone or in combination of two or more. In the present invention, in terms of economy, availability, ease of handling, ease of reaction, and the like, it is particularly preferable to use trimesoyl chloride alone, a mixture of trimesoyl chloride and isophthaloyl chloride, or a mixture of trimesoyl chloride and terephthaloyl chloride.

[0041] The polyfunctional amine is an amino compound having two or more amino groups in one molecule, and examples of the polyfunctional amine include aromatic amino compounds and aliphatic amino compounds. Specific examples of aromatic amino compounds include m-phenylenediamine, p-phenylenediamine, 3,3'-diaminodiphenylmethane, 4,4'-diaminodiphenylamine, 4,4'-diaminodiphenylether, 3,4'-diaminodiphenylether, 3,3'-diaminodiphenylamine, 3,5-diaminobenzoic acid, 4,4'-diaminodiphenylsulfone, 3,3'-diaminodiphenylsulfone, 3,4'-diaminodiphenylsulfone, 1,3,5-triaminobenzene, 1,5-diaminonaphthalene, etc. These can be used alone or in mixtures. As the aromatic amino compound in the present invention, from the viewpoints of economy, availability, ease of handling, ease of reaction, etc., it is particularly preferable to use at least one selected from m-phenylenediamine and p-phenylenediamine.

[0042] Specific examples of the aliphatic amino compound include 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, bispiperidylpropane, etc. These can be used alone or in mixtures. The interfacial polymerization of the polyfunctional acid halide and the polyfunctional amine can be carried out according to a conventional method.

[0043] The active layer obtained may be optionally subjected to a heat treatment, which may be carried out with hot water or with steam at high temperature and pressure in a pressure cooker such as an autoclave. By subjecting the active layer to a heat treatment, it is expected that back diffusion of the draw solution is reduced, although the reason for this is unclear.

[0044] When a hollow fiber-shaped forward osmosis membrane is used, 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 be generated when liquid flows through the space inside the hollow fiber. If the inner diameter of the hollow fiber is more than 4,000 μm, when multiple forward osmosis membranes are used in a modularized form, the membrane area per module may be excessively small, and effective volume reduction may not be achieved.

[0045] The draw solution used in the forward osmosis method may be a solution containing an organic solvent, an organic acid, a buffer salt, or the like as a solute. The organic solvent may be any of the organic solvents listed above as the solvent contained in the raw material liquid, and more specifically, at least one selected from the group consisting of methanol, ethanol, isopropanol, and t-butanol is preferred. Examples of the organic acid 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. Examples of the buffer salt include, in addition to the metal salts of the organic acids, inorganic salts such as sodium chloride, magnesium chloride, calcium chloride, sodium sulfate, sodium bicarbonate, potassium bicarbonate, sodium hydrogen sulfate, potassium hydrogen sulfate, 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.

[0046] The concentration of the solute in the draw solution may be appropriately set depending on the composition of the raw material liquid, the type of solute in the draw solution, etc., so as to ensure the transfer of the first solvent from the raw material liquid to the draw solution and generate an osmotic pressure difference capable of generating a driving force within a range in which the composition of the raw material liquid near the forward osmosis membrane does not change suddenly.

[0047] In the forward osmosis method, the driving force for the first solvent (b) to move from the feed liquid (a) to the draw solution (d) is the osmotic pressure difference between the feed liquid (a) and the draw solution (b). Therefore, it is necessary to refresh the liquid between the active layer (522) of the forward osmosis membrane (520) and the interface between the feed liquid (a) or the draw solution. Therefore, it is necessary to pass the feed liquid (a) and the draw solution (d) on both sides of the forward osmosis membrane (520) at an appropriate flow rate. In FIG. 1, the raw material liquid (a) and the draw solution (d) are flowed in parallel, but the flows of the two liquids may be countercurrent.

[0048] FIG. 2 is a schematic diagram showing the configuration of an example of a forward osmosis membrane module that is preferably used as the first unit for carrying out the first treatment in the method for reducing the volume of a feed liquid of the present invention. In the forward osmosis membrane module (500) of Fig. 2, a plurality of hollow fiber forward osmosis membranes (520) are housed in a housing (510). Both ends of the forward osmosis membrane (520) are bonded and fixed to the housing (510) with an adhesive resin (530). Two housing side tubes are provided on the side of the housing (510). One of these housing side tubes is a draw solution inlet (511), and the other is a draw solution outlet (512). The inside of the housing (510) is divided into two spaces by the outer wall of the forward osmosis membrane (520) and the adhesive resin (530): a space through which the raw material liquid (a) flows and a space through which the draw solution (d) flows. The two spaces are fluidically isolated from each other except that the first solvent can pass between them via the inner wall of the forward osmosis membrane (520).

[0049] When the raw liquid (a) is introduced into one end of the forward osmosis membrane module (500), the raw liquid (a) flows inside the hollow fiber forward osmosis membrane (520) and flows out from the other end as reduced-volume raw liquid (c). Similarly, when the draw solution (d) is introduced through the draw solution inlet (511) in the side tube of the housing (510), the draw solution (d) flows through the outer space of the hollow fiber forward osmosis membrane (520) and flows out from the draw solution outlet (512). As a result, the feed liquid (a) and the draw solution (d) can come into contact with each other through the forward osmosis membrane (520). At this time, substances other than valuable materials move from the feed liquid (a) to the draw solution (d) due to the difference in osmotic pressure between the two liquids. In the forward osmosis membrane method, volume reduction is performed by such a mechanism.

[0050] When the forward osmosis membrane (520) has a base layer and an active layer formed on one side of the base layer, the active layer is formed on the surface of the base layer that contacts the feed liquid, as described above. Therefore, in the forward osmosis membrane module (500) of Fig. 1 in which the feed liquid (a) flows inside the hollow fiber-shaped forward osmosis membrane, it is preferable that the active layer is formed on the inner surface of the hollow fiber-shaped base layer. When the flow rate of the feed solution (a) and / or the flow rate of the draw solution (d) is high, the effect of the osmotic pressure difference on both sides of the forward osmosis membrane (520), particularly the active layer, becomes greater, and the amount of the first solvent permeating the forward osmosis membrane per membrane area becomes greater. In the forward osmosis membrane module (500) of FIG. 2, the feed solution (a) and the draw solution (d) are passed in parallel flow, but the flows of the two solutions may be countercurrent.

[0051] The material of the housing (510) in the forward osmosis membrane module (500) in Fig. 2 is selected from the viewpoints of chemical resistance, pressure resistance, heat resistance, impact resistance, weather resistance, etc., so that the various performances are not deteriorated by the components contained in the feed solution (a) and the draw solution (d). For example, resin, metal, etc. can be used as the material of the housing (510). From the above viewpoints, it is preferable to select the material from among resins such as polypropylene, polysulfone, polyethersulfone, polyvinylidene fluoride, polytetrafluoroethylene, perfluoroalkoxyalkane, ABS resin, fiber reinforced plastic, polyvinyl chloride resin, etc.; and metals such as stainless steel, brass, titanium, etc. The adhesive resin (530) in the forward osmosis membrane module (500) in Fig. 2 is desirably one that has good mechanical strength and heat resistance at 100°C. Examples of resins that can be used as the adhesive resin (530) include thermosetting epoxy resins, thermosetting urethane resins, ceramic-type adhesives, and sealing materials obtained by melting polyethylene or low-melting-point metals. From the viewpoint of heat resistance, epoxy resins are preferred, and from the viewpoint of handling, urethane resins are preferred. The forward osmosis membrane (520) may be fixed to the housing (510) by adhesive bonding according to known adhesive methods for producing hollow fiber membrane modules.

[0052] (Nanofiltration method) As another example of the first treatment, a nanofiltration method will be described. In the nanofiltration method, the raw liquid is fed to one side of the nanofiltration membrane, and the feed side is pressurized. Then, mainly the first solvent in the raw liquid passes through the nanofiltration membrane and is removed, reducing the volume of the raw liquid. The second solvent or subcomponents remain in the raw liquid. As the nanofiltration membrane, a known nanofiltration membrane can be used. The nanofiltration membrane may have any of the following structures: a hollow fiber membrane, a tubular membrane, and a flat membrane. A hollow fiber nanofiltration membrane is preferable because it can form a flow path through which the raw material liquid and the permeate (first solvent) pass without using a spacer or the like, and can perform uniform volume reduction.

[0053] The nanofiltration method is preferably carried out using a nanofiltration membrane module, which comprises a plurality of hollow fiber nanofiltration membranes housed in a suitable housing. Examples of materials for the nanofiltration membrane include polysulfone, polyethersulfone, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polypropylene, cellulose-based polymers, polyketone, polyamide, polyimide, polyether ether ketone, polybenzimidazole, and crosslinked products thereof. It is preferable that the nanofiltration membrane contains at least one selected from these as the main component.

[0054] For the housing of the nanofiltration membrane module and the other module configurations, the above description of the forward osmosis membrane module can be applied with the substitution of "nanofiltration membrane" for "forward osmosis membrane."

[0055] (Evaporation method) As yet another example of the first treatment, an evaporation method will be described. In the evaporation method, a gas is passed through a container containing the raw material liquid, and the component with a high vapor pressure (first solvent) in the raw material liquid is preferentially vaporized and removed from the container, thereby reducing the volume of the raw material liquid. The component with a low vapor pressure (second solvent or subcomponent) remains in the raw material liquid. Examples of the gas that can be circulated through the container containing the raw material liquid include air, nitrogen, and argon.

[0056] <Second Processing> The second treatment in the raw material liquid concentrating method of the present invention is a treatment for adjusting the concentration of the second solvent or auxiliary component in the raw material liquid by dialysis using a dialysis membrane, and maintaining the component composition of the raw material liquid after volume reduction within a range in which valuable substances are not denatured, aggregated, or precipitated. In the second treatment, a dialysis method is used. In particular, it is effective to use a molecular sieve membrane as the dialysis membrane, since it can effectively prevent valuable substances from permeating through the dialysis membrane and being lost. Hereinafter, as an example of the second treatment in the raw material liquid volume reduction system of the present invention, a dialysis method using a molecular sieve membrane as the dialysis membrane will be described.

[0057] FIG. 3 is a schematic diagram showing the mechanism of action of dialysis using a dialysis membrane. In FIG. 3, a raw liquid (a) flows on one side of a dialysis membrane (120), and a dialysate (e) flows on the other side, the two liquids being in contact with each other via the dialysis membrane (120). In this case, if there is a difference between the concentration of the second solvent or subcomponent (g) in the feed solution (a) and the concentration of the second solvent or subcomponent (g) in the dialysis solution (e), the second solvent or subcomponent (g) will move from the concentrated solution to the diluted solution. This movement is driven by the concentration difference of the second solvent or subcomponent (g) between the two solutions, so movement in either direction is possible. In the second process in the raw liquid volume reduction system of the present invention, such movement causes the concentration of the second solvent or subcomponent (g) in the raw liquid (a) to asymptotically approach the concentration of the dialysis liquid (d), and the component composition of the raw liquid (a) is maintained within the desired range.

[0058] In addition, when forward osmosis is used as the first treatment, the draw solute in the draw solution may be mixed into the raw solution. The second treatment in the method for reducing the volume of a raw solution of the present invention also has the effect of removing the draw solute mixed into the raw solution from the raw solution. In this case, since the draw solute is not contained in the dialysis solution (e), the draw solute preferentially moves from the raw solution (a) to the dialysis solution (e), and the draw solute is effectively removed from the raw solution.

[0059] The dialysis membrane (120) in Fig. 3 has a base layer (121) and an active layer (122) formed on one side of the base layer (121). The active layer (122) has a very dense structure that allows small molecules to pass through but not valuable substances to pass through, and is formed on the surface of the base layer (121) that comes into contact with the raw material liquid (a).

[0060] A porous membrane is generally used as the material for the base layer (121). The dialysis fluid (d) is permeated into the portion of the dialysis membrane (120) that is the base layer (121) made of a porous membrane, and the raw liquid (a) and the dialysis fluid (d) are in contact with each other via the active layer (122).

[0061] The material of the porous membrane constituting the substrate layer can be selected from widely used materials. However, materials that dissolve or swell in the organic solvent contained in the raw material liquid and cannot maintain the pore shape of the membrane cannot be used. When the first treatment is a volume reduction treatment using a membrane, than the permeability of the membrane used in the first treatment to the second solvent or subcomponent, The permeability of the dialysis membrane used in the second treatment to the second solvent or auxiliary component is The larger the better. The greater the permeability of the dialysis membrane to the second solvent or subcomponent, the more rapidly the second solvent or subcomponent will move through the dialysis membrane, making it easier to achieve the effect of the second solvent or subcomponent concentration approaching that of the dialysis fluid, and thus making it possible to effectively correct the concentration of the second solvent or subcomponent in the raw material solution, which is preferable. In this regard, polyamide is desirable as the material for the active layer, since the permeability of the second solvent or the subcomponent can be freely controlled by selecting the monomer when forming the active layer on the base layer.

[0062] The material of the porous membrane constituting the substrate layer and the method of forming the polyamide constituting the active layer can be the same as those described above for the substrate layer and the active layer of the forward osmosis membrane, respectively. In addition, a polyfunctional acid halide compound converted into an acid anhydride may be used as a part or the whole of the polyfunctional acid halide used to form the active layer of the dialysis membrane, specifically, for example, trimellitic acid chloride anhydride, 3,3',4,4'-biphenyltetracarboxylic dianhydride, pyromellitic dianhydride, benzophenonetetracarboxylic dianhydride, diphenylethertetracarboxylic dianhydride, etc. In addition, it is desirable to use piperazines as part or all of the polyfunctional amines used to form the active layer of the dialysis membrane, since this increases the permeability of the second solvent or the auxiliary component.

[0063] When the first treatment is carried out by forward osmosis, as described above, the forward osmosis membrane used in forward osmosis and the dialysis membrane used in the dialysis method of the second treatment have a common configuration in that they both have a base layer made of a porous membrane and an active layer made of polyamide. On the other hand, as described above, it is preferable that the permeability of the second solvent or the subcomponent contained in the raw material liquid is greater through the dialysis membrane than through the forward osmosis membrane. In forward osmosis and dialysis membranes, both of which are made of the same material, differences in permeability to the second solvent or minor component can be achieved, for example, by selecting a monomer when forming an active layer on a base layer, adjusting the interfacial polymerization conditions, or by post-treatment after interfacial polymerization. For example, by using an aliphatic amine compound as the polyfunctional amine used in the interfacial polymerization, the permeability of the second solvent or the subcomponent can be increased.

[0064] The dialysis membrane may be in any of the following forms: hollow fiber membrane, tubular membrane, and flat membrane. Hollow fiber membrane dialysis membranes are suitable because they can form flow paths for the raw material solution and the dialysis solution without using spacers or the like and can maintain uniform flow.

[0065] When a hollow fiber dialysis membrane is used, 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. Although the reason is unclear, if the inner diameter of the hollow fiber is less than 200 μm, precipitation, aggregation, or denaturation of valuable substances may occur. If the inner diameter of the hollow fiber exceeds 4,000 μm, when multiple dialysis membranes are used in a module, the membrane area per module may become excessively small, and the second solvent or subcomponent concentration may not move sufficiently.

[0066] The composition of the dialysis fluid used in dialysis is preferably one in which valuable substances can be present stably. The appropriate composition of the dialysis fluid should be set appropriately depending on the chemical and physical properties of the valuable substances contained in the raw solution, but one possible example is to use a dialysis fluid with the same composition as the raw solution after removing the valuable substances. The pH of the dialysis fluid is preferably from 1 to 14, more preferably from 2 to 13, from the viewpoint of avoiding adverse effects on piping, analytical instruments, and the like.

[0067] In dialysis, the driving force for the movement of the second solvent or subcomponent between the raw liquid and the dialysis solution is the concentration difference between the raw liquid and the dialysis solution. Therefore, for effective component movement, it is necessary to renew the liquid between the active layer of the dialysis membrane and the interface between the raw liquid or the dialysis solution. Therefore, it is necessary to allow the raw material solution and the dialysate to flow on both sides of the dialysis membrane (120) at appropriate flow rates. In FIG. 3, the raw material liquid (a) and the draw solution (d) are flowed in parallel, but the two liquids may be flowed in countercurrent. Depending on the composition of the raw liquid, the first solvent in the dialysis solution may permeate the dialysis membrane and move into the raw liquid due to the osmotic pressure difference between the raw liquid and the dialysis solution, causing the volume of the raw liquid to increase. In this case, the increase in volume of the raw liquid can be suppressed by pressurizing the raw liquid in contact with the dialysis membrane. The pressurization pressure of the raw liquid is preferably 0.05 MPaG or more, more preferably 0.1 MPaG or more, and even more preferably 0.2 MPaG or more.

[0068] FIG. 4 is a schematic diagram showing the configuration of an example of a dialysis membrane module that is preferably used as the second unit for carrying out the second treatment in the method for reducing the volume of a raw material liquid of the present invention. In the dialysis membrane module (100) of Fig. 4, a plurality of hollow fiber dialysis membranes (120) are housed in a housing (110). Both ends of the dialysis membrane (120) are adhesively fixed to the housing (110) with an adhesive resin (130). Two housing side tubes are provided on the side of the housing (110). One of these housing side tubes is a dialysate inlet (111), and the other is a dialysate outlet (112). The inside of the housing (110) is divided into two spaces by the outer wall of the dialysis membrane (120) and the adhesive resin (130): a space through which the raw liquid (a) flows and a space through which the dialysis fluid (d) flows. The two spaces are fluidically isolated from each other except that the second solvent or the minor component can pass between them via the inner wall of the dialysis membrane (120).

[0069] When raw liquid (a) is introduced into one end of the dialysis membrane module (100), the raw liquid (a) flows inside the hollow fiber dialysis membrane (120) and flows out from the other end as raw liquid (f) with an adjusted component concentration. Similarly, when dialysate (d) is introduced through the dialysate inlet (111) of the side tube of the housing (110), the dialysate (e) flows through the outer space of the hollow fiber dialysis membrane (120) and flows out from the dialysate outlet (112). As a result, the raw liquid (a) and the dialysis liquid (e) can come into contact with each other via the dialysis membrane (120). At this time, the second solvent or the subcomponent (g) moves from the raw liquid (a) to the dialysis liquid (e) or from the dialysis liquid (d) to the raw liquid (a) depending on the concentration of the components contained in the raw liquid (a) and the dialysis liquid (d). In the dialysis method, the concentration of the second solvent or the subcomponent is adjusted by such a mechanism. When the flow rate of the raw material liquid (a) and / or the flow rate of the dialysis solution (e) is high, the effect of the concentration difference on both sides of the dialysis membrane (120), particularly the active layer, becomes greater, and the amount of the second solvent or subcomponent transferred per membrane area of ​​the dialysis membrane becomes greater. In the dialysis membrane module (100) of FIG. 4, the raw material liquid (a) and the dialysis liquid (e) are caused to flow in parallel, but the flows of the two liquids may be countercurrent.

[0070] The above description of the forward osmosis membrane module (500) in FIG. 2 can be directly applied to the materials of the housing (110) and adhesive resin (130) in the dialysis membrane module (100) in FIG. 4, and the method of adhesively fixing the dialysis membrane (120) to the housing (110).

[0071] <Embodiments of the first and second processes> The order in which the first process and the second process are performed is arbitrary. For example, After the first treatment, a second treatment may be performed; The second treatment may be performed before the first treatment; The first and second treatments may be carried out simultaneously. The term "concurrently carrying out the first and second treatments" refers to, for example, the case where the first and second treatments are carried out in parallel and the raw material liquids after each treatment are mixed. When the first treatment and the second treatment are performed in any order, a pipe for supplying the raw material liquid to one of the treatments and a pipe for supplying the raw material liquid after the treatment to the other treatment may be connected in series. When the first treatment and the second treatment are performed in parallel, for example, a pipe for supplying the raw material liquid to the first treatment and a pipe for supplying the raw material liquid to the second treatment may be connected in parallel.

[0072] It is preferable that the first process and the second process are performed cyclically. For example, a process of storing the raw material liquid in a raw material liquid tank, taking out a part of the raw material liquid in the raw material liquid tank, subjecting the part to a first treatment and a second treatment in this order, and returning the raw material liquid after the first treatment and the second treatment to the raw material liquid tank; a process of storing the raw material liquid in a raw material liquid tank, taking out a part of the raw material liquid in the raw material liquid tank, subjecting the part to the second treatment and the first treatment in this order, and returning the raw material liquid after the second treatment and the first treatment to the raw material liquid tank; The raw material liquid is stored in a raw material liquid tank, Repeating the operation of taking out a part of the raw material liquid in the raw material liquid tank, subjecting it to a first treatment, and returning the raw material liquid after the first treatment to the raw material liquid tank; and A part of the raw material liquid in the raw material liquid tank is taken out, subjected to a second treatment, and the raw material liquid after the second treatment is returned to the raw material liquid tank. This operation is repeated. Repeating operations in parallel (simultaneously); etc. are preferred.

[0073] When the first process and the second process are performed in a cyclical manner, it is preferable to measure the concentration of at least one of the components in the raw material liquid that is being cyclically reduced in volume, and to decide whether to carry out or stop at least one of the first process and the second process, or to change the operating conditions, depending on the obtained measurement value. For example, if this component analysis indicates that the concentration of the first solvent in the raw material liquid is about to fall below the lower limit of the appropriate range, it is possible to temporarily suspend the first process or to make the process conditions for the first process milder. On the other hand, when the concentration of the first solvent in the raw material liquid is about to exceed the upper limit of the appropriate range, it is possible to make the treatment conditions of the first step stricter. In addition, when the concentration of the second solvent or the subcomponent in the raw liquid is about to deviate from the appropriate range, it is possible to change the concentration of the second solvent or the subcomponent in the dialysis solution used in the second treatment. Specifically, the rate of volume reduction tends to be faster in the latter half of the volume reduction than in the early stage. Therefore, in the latter half of the volume reduction, the concentration of the second solvent or the subcomponent in the dialysis solution being circulated increases, and the efficiency of adjusting the concentration of the second solvent or the subcomponent in the raw liquid is considered to be low. In such a case, for example, during the volume reduction, the dialysis solution being circulated is discarded and replaced with a dialysis solution of the initial composition, thereby improving the efficiency of adjusting the concentration of the second solvent or the subcomponent in the raw liquid.

[0074] The concentration of at least one of the components in the raw material liquid can be determined using the results of measurements such as specific gravity measurement, pH measurement, electrical conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy analysis, and weight measurement of the raw material liquid. Then, when the volume of the raw material liquid is reduced to a desired volume reduction rate, both the first process and the second process are stopped to terminate the volume reduction of the raw material liquid. The volume reduction rate can be known by an appropriate method such as measuring the weight of the raw material liquid or measuring the liquid level.

[0075] The component analysis of the final volume-reduced raw material liquid (e) may be appropriately selected depending on the types of components contained in the volume-reduced raw material liquid. For example, various 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, and high performance liquid chromatography (HPLC). In order to achieve a high volume reduction rate while suppressing precipitation, denaturation, etc. of valuable materials contained in the raw material liquid, it is preferable to perform the first treatment and the second treatment in parallel. Performing the first treatment and the second treatment in parallel tends to make it easier to maintain the composition of the raw material liquid within a predetermined range during volume reduction.

[0076] <Raw material liquid volume reduction system> According to another aspect of the present invention, a feedstock liquid volume reduction system is provided. The raw material liquid volume reduction system of the present invention is a system for carrying out the raw material liquid volume reduction method of the present invention. Therefore, the raw material liquid volume reduction system of the present invention is A raw material liquid volume reduction system for reducing the volume of a raw material liquid containing at least a valuable material and a first solvent, The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or As a solvent, a mixed solvent containing the first solvent and the second solvent is included, The raw material liquid volume reduction system includes: a first unit for removing the first solvent from the raw material liquid; a second unit for adjusting a concentration of the second solvent or the subcomponent in the raw material solution by dialysis using a dialysis membrane; It is a system that combines the above.

[0077] For details of the raw material liquid volume reduction system of the present invention, the above-mentioned description of the raw material liquid volume reduction method of the present invention can be used as is, or after being modified by a person skilled in the art so as to conform to the invention of the "system." Hereinafter, the configuration of the raw material liquid volume reduction system of the present invention will be described in more detail with reference to the drawings. 5 to 8 show configuration examples of the raw material liquid volume reduction system of the present invention.

[0078] The raw liquid volume reduction system in Figure 5 is an example in which an evaporation unit is applied as a first unit, in which gas is passed through a container storing the raw liquid to evaporate the first solvent in the raw liquid and move it outside the container. The raw liquid volume reduction system (1) of FIG. 5 includes an evaporation unit (900), a dialysis membrane module (100), a raw liquid tank (200), a dialysis fluid tank (300), and a trap (400). The evaporation unit (900) has a blower (BL) for blowing gas into the raw material liquid tank (200) and a pipe for sending the evaporated first solvent (b) to the trap (400).

[0079] In the raw liquid volume reduction system (1) of Fig. 5, a gas (e.g., air) is sent into the raw liquid tank (200) by a blower (BL) provided in the evaporation unit (900). The introduced gas and the first solvent (b) evaporated by the gas are then discharged outside the raw liquid tank (200), thereby reducing the volume of the raw liquid. The vapor of the first solvent (b) discharged from the raw material liquid tank (200) can be re-liquefied and collected by the trap (400). In the method of using an evaporation unit (900) as the first unit and sending gas into the raw liquid tank (200), volume reduction occurs at the liquid surface of the raw liquid (a) and its vicinity, which may result in the composition of the raw liquid (a) varying depending on the location in the raw liquid tank (200). In this regard, by providing a stirring device (not shown) in the raw liquid tank (200), the composition of the raw liquid (a) in the raw liquid tank (200) can be kept uniform, and volume reduction can be performed while suppressing precipitation, aggregation, and denaturation of valuable materials. In the raw liquid volume reduction system (1) of Fig. 5, the component with a high vapor pressure (first solvent) is preferentially removed by the evaporation unit (900). Therefore, in the raw liquid (a) after the volume reduction by the evaporation unit (900), the concentration of the components with a low vapor pressure (e.g., valuable materials, and the second solvent or subcomponent) is generally high.

[0080] The raw material liquid volume reduction system (1) of FIG. 5 includes an evaporation unit (900) and a dialysis membrane module (100) for performing dialysis as a second unit. In the raw liquid volume reduction system (1) of FIG. 5, the raw liquid (a) is sent from the lower part of the raw liquid tank (200) filled with the raw liquid (a) by the pump (P) to one space of the dialysis membrane module (100) (for example, the space inside the hollow fiber membrane). At this time, the flow rate of the raw liquid (a) is adjusted manually or automatically by a flow meter or the like (not shown). Meanwhile, the dialysis liquid (d) is supplied from the dialysis liquid tank (300) filled with the dialysis liquid (d) to the other space of the dialysis membrane module (100) (for example, the space outside the hollow fiber membrane) by the pump (P). Then, due to the concentration difference between the raw liquid (a) and the dialysis liquid (d), the concentration of the second solvent or minor component in the raw liquid (a) is corrected so as to approach the concentration of the second solvent or minor component in the dialysis liquid (d). The raw material liquid (a) whose concentration has been corrected leaves the dialysis membrane module (100) and returns to the raw material liquid tank (200) for circulation.

[0081] As the concentration of the second solvent or subcomponent in the raw liquid (a) is corrected by the function of the dialysis membrane module (100), the concentration of the second solvent or subcomponent in the dialysis fluid (d) changes. Therefore, in order to perform a suitable correction of the concentration of the second solvent or subcomponent in continuous operation, it is necessary to either successively renew the dialysis fluid (d) or regenerate the dialysis fluid using a device that has a function of returning the concentration of the second solvent or subcomponent in the dialysis fluid (d) to a predetermined value. Such a regeneration device is not shown in FIG. 5.

[0082] The feedstock liquid volume reduction system in FIG. 6 is an example in which a forward osmosis membrane module for performing forward osmosis is used as the first unit. The feed solution volume reduction system (2) of FIG. 6 includes a forward osmosis membrane module (500), a feed solution tank (200), a draw solution tank (600), a dialysis membrane module (100), and a dialysis solution tank (300). In the raw liquid volume reduction system (2) of FIG. 6, a forward osmosis membrane module (500) and a dialysis membrane module (100) are connected in parallel to a raw liquid tank (200). The adjustment of the concentration of the second solvent or the subcomponent by the dialysis membrane module (100) is performed in the same manner as in the raw liquid volume reduction system (1) of FIG. In the volume reduction by the forward osmosis membrane module (500), the feed liquid (a) is supplied at an appropriate flow rate from the bottom of the feed liquid tank (200) to one space of the forward osmosis membrane module (500) (for example, the space inside the hollow fiber membrane) using a pump (P). After passing through the inside of the hollow fiber membrane, the feed liquid (a) is returned to the feed liquid tank (200) and circulated. This return position is preferably a position far from the collection position for supplying the feed liquid to the forward osmosis membrane module (500) and at the bottom of the feed liquid tank (200). Returning the feed liquid to a position far from the collection position can prevent the concentration of the second solvent or the subcomponent in the feed liquid (a) from being excessively increased due to a short path. In addition, returning the feed liquid to the bottom of the feed liquid tank can prevent valuable materials in the feed liquid (a) from being precipitated on the wall surface of the feed liquid tank (200) and being lost. On the other hand, a draw solution (d) having an osmotic pressure higher than that of the raw liquid (a) is introduced into the other space of the forward osmosis membrane module (500) (for example, the outer space of the hollow fiber membrane distillation membrane) using a pump (P).

[0083] As a result, due to the difference in osmotic pressure between the feed solution (a) and the draw solution (d), the first solvent moves from the feed solution (a) to the draw solution (d), and the volume of the feed solution (a) is reduced. The reduced volume of the feed solution (a) leaves the forward osmosis membrane module (500) and returns to the feed solution tank (200). The volume of the draw solution (d) increases due to the mixing of the first solvent from the feed solution (a). For this reason, it is necessary to take measures such as making the draw solution tank (600) sufficiently large in capacity or discharging a part of the draw solution out of the draw solution tank (600) by overflow or the like. In FIG. 6, a device for discharging the draw solution (d) out of the draw solution tank (600) is not shown.

[0084] The feedstock liquid volume reduction system in FIG. 7 is an example in which a nanofiltration module for carrying out a nanofiltration membrane method is used as the first unit. The feed liquid volume reduction system (3) of FIG. 7 includes a nanofiltration membrane module (700), a feed liquid tank (200), a permeate liquid tank (800), a dialysis membrane module (100), and a dialysate tank (300). In the raw liquid volume reduction system (3) of FIG. 7, a nanofiltration membrane module (700) and a dialysis membrane module (100) are connected in parallel to a raw liquid tank (200). The concentration of the second solvent or the subcomponent is adjusted by the dialysis membrane module (100) in the same manner as in the raw liquid volume reduction system (1) of FIG. In the volume reduction using the nanofiltration membrane module (700), the raw liquid (a) is supplied at an appropriate flow rate from the bottom of the raw liquid tank (200) to one space of the nanofiltration membrane module (700) (for example, the space inside the hollow fiber membrane) using a pump (P). After passing through the inside of the hollow fiber membrane, the flow rate of the raw liquid (a) is throttled by a valve (V), so that pressure is applied to the nanofiltration membrane module (700). The permeated liquid (first solvent) that permeates the nanofiltration membrane due to this pressure is collected in the permeated liquid tank (800). The raw liquid (a) that has passed through the valve (V) is returned to the raw liquid tank (200) and circulated. This return position is preferably a position far from the collection position for supplying to the nanofiltration membrane module (700) and is the bottom of the raw liquid tank (200). Returning the raw liquid (a) to a position far from the collection position can prevent the concentration of the second solution or the subcomponent in the raw liquid (a) from being excessively increased due to a short path, and returning the raw liquid (a) to the bottom of the raw liquid tank can prevent valuable materials in the raw liquid (a) from being lost due to precipitation on the wall surface of the raw liquid tank (200) or the like.

[0085] The first solvent permeates through the nanofiltration membrane under pressure, thereby reducing the volume of the raw material liquid (a). The reduced volume of the raw material liquid (a) leaves the nanofiltration membrane module (700) and returns to the raw material liquid tank (200) via the valve (V).

[0086] The raw liquid volume reduction system (4) in Fig. 8 is another embodiment in which a forward osmosis membrane module (500) is used as the first volume reduction unit, and 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 arranged in series in this order in the flow direction of the raw liquid (a). In the raw liquid volume reduction system (4) in Fig. 8, the raw liquid (a) taken out from the bottom of the raw liquid tank (200) first passes through the dialysis membrane module (100) and then passes through the forward osmosis membrane module (500). However, it may be configured so that the raw liquid (a) first passes through the forward osmosis membrane module (500) and then passes through the dialysis membrane module (100).

[0087] The feed liquid volume reduction system (5) in Fig. 9 is another embodiment in which a nanofiltration membrane module (700) is used as the first volume reduction unit, and 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 this order in the flow direction of the feed liquid (a). In the feed liquid volume reduction system (5) in Fig. 9, the feed liquid (a) taken out from the bottom of the feed liquid tank (200) first passes through the dialysis membrane module (100) and then passes through the nanofiltration membrane module (700). However, it may be configured so that the feed liquid (a) first passes through the nanofiltration membrane module (700) and then passes through the dialysis membrane module (100).

[0088] 5 to 9, it is effective to take out the raw liquid (a) from the bottom of the raw liquid tank (200) and return it to the bottom of the raw liquid tank (200) in order to prevent valuable materials in the raw liquid (a) from adhering to the tank wall and being lost. It is also effective to provide a stirring device inside the raw liquid tank (200) in order to perform stable volume reduction. In the raw material liquid volume reduction system of Figures 5 to 9, the specific gravity of the raw material liquid (a) can be tracked by the specific gravity meter (HM). This makes it possible to monitor the concentration of the second component or subcomponent in the raw material liquid (a). Then, as necessary, the first or second unit can be operated or stopped, or the operating conditions can be changed, so that the volume can be reduced while adjusting the composition of the raw material liquid (a) within a range in which valuable materials do not precipitate, coagulate, or denature.

[0089] The degree of volume reduction of the raw material liquid (a) can be known by measuring the volume of the raw material liquid (a) using a liquid level gauge (LG). Finally, the volume reduction can be completed when the target volume reduction rate is reached. In addition to the specific gravity measurement given above, the properties of the raw liquid (a) (e.g., the concentration of at least one of the components in the raw liquid) can be monitored by pH measurement, electrical conductivity measurement, optical rotation measurement, refractive index measurement, ultraviolet light analysis, visible light analysis, infrared light analysis, near-infrared light analysis, etc. Using one or more measurement results selected from these analyses, for example, the concentration of at least one of the components in the raw liquid can be determined. By simultaneously monitoring these results, the measured value of the liquid level gauge, the weight of the liquid, etc., and operating or stopping the first or second unit, or changing the operating conditions as necessary, the volume can be reduced while maintaining the concentration of the second solvent or subcomponent in the raw liquid (a). Furthermore, it is more preferable to use known AI techniques such as regression analysis, classification, clustering, and deep learning using neural networks, or estimation models obtained by a combination of these techniques, to estimate the concentration of the second solvent or subcomponent in the raw material liquid (a), since this allows for more accurate concentration estimation. By using this method, the concentration of the second solvent or the subcomponent in the raw material liquid (a) can be monitored with high accuracy, and the operating conditions can be appropriately controlled to reduce the volume while maintaining the concentration of the second solvent or the subcomponent in a suitable range with higher accuracy. Therefore, the risk of precipitation, aggregation, or denaturation of valuable materials can be further reduced, which is preferable. EXAMPLES

[0090] The configuration and effects of the present invention will be further described below with reference to examples, but the present invention is not limited to the following examples in any way.

[0091] <Dialysis membrane module 1> 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 as the substrate layer. 130 pieces of this hollow fiber ultrafiltration membrane were packed into a cylindrical plastic housing with a diameter of 2 cm and a length of 10 cm, and both ends were fixed with an adhesive, resulting in an effective inner membrane surface area of ​​about 0.02 m. 2 A substrate layer module having the above structure was fabricated. In a 0.5 L container, 2.5 g of piperazine and 0.8 g of sodium lauryl sulfate were placed, and 489.2 g of pure water was further added to dissolve them, to prepare 0.5 kg of a first solution to be used in the interfacial polymerization. In another 0.5 L container, 0.8 g of trimesoyl chloride was placed, and 399.2 g of n-hexane was added thereto to dissolve the same, thereby preparing 0.4 kg of a second solution to be used in the interfacial polymerization. These solutions were passed through the support layer module in the order of the first solution and then the second solution, so as to pass through the inside of the hollow fiber ultrafiltration membrane, and interfacial polymerization was carried out on the inner surface of the hollow fiber ultrafiltration membrane, forming an active layer on the support layer, thereby forming a hollow fiber dialysis membrane. Thereafter, the inside of the obtained hollow fiber dialysis membrane was washed with pure water to produce a dialysis membrane module 1 containing 130 hollow fiber dialysis membranes, each having an active layer made of polyamide on the inner surface of a support layer made of a hollow fiber ultrafiltration membrane made of polyethersulfone.

[0092] <Forward osmosis membrane module 1> In the preparation of the first solution, except that 10 g of m-phenylenediamine was used instead of 2.5 g of piperazine, a module having an active layer made of polyamide on the inner surface of a support layer made of a hollow fiber ultrafiltration membrane made of polyethersulfone was prepared in the same manner as the dialysis membrane module. Next, hot water at 85°C was passed through the inner space of the hollow fiber for 30 minutes, and then water at 20°C was passed through for 30 minutes. Next, the module was placed in an autoclave (manufactured by Tomy Seiko Co., Ltd., ES-315) and subjected to heat treatment by supplying high-temperature steam at 125°C for 4 hours, and then water at 20°C was passed through the inner space of the hollow fiber for 30 minutes or more to wash it, thereby preparing a forward osmosis membrane module 1 containing 130 hollow fiber forward osmosis membranes.

[0093] <Dialysis membrane module 2> A module prepared in the same manner as the above-mentioned "forward osmosis membrane module 1" was used as "dialysis membrane module 2".

[0094] <Nanofiltration membrane module 1> A module prepared in the same manner as the above-mentioned "forward osmosis membrane module 1" was used as "nanofiltration membrane module 1".

[0095] <Evaporation unit> An evaporation unit 1 having the same configuration as the evaporation unit (900) shown in Figure 5 was produced using a blower (BL) for blowing air into the raw liquid tank (200), piping for discharging the introduced gas and the first solvent (b) evaporated by the gas to the outside of the raw liquid tank (200), and a trap (400) for storing the first solvent (b) delivered by the piping.

[0096] <Membrane distillation membrane module 1> A porous hollow fiber membrane made of PVDF having an inner diameter of 0.7 mm, an outer diameter of 1.3 mm, an average pore size of 0.21 μm determined in accordance with ASTM-F316-86, a maximum pore size of 0.29 μm, and a porosity of 72% was cut into a length of 15 cm. A membrane module 1 for membrane distillation was produced using a plurality of the obtained hollow fiber membranes. The membrane module was fabricated by using a thermosetting epoxy resin as an adhesive resin and fixing the hollow fiber membrane to the housing by centrifugal adhesion. At this time, the length of the hollow fiber membrane that was not buried in the adhesive resin was about 10 cm, and the total membrane area of ​​the inner surface of the hollow fiber membrane was about 0.02 m. 2 It was adjusted so that Two membrane modules with the same specifications were fabricated. Among these membrane modules, FluoroTechnologies' FS-392B was passed through the outer space of the hollow fiber membrane in a state of being concentrated three times, and the liquid was applied to the outside of the hollow fiber membrane and then dried to obtain membrane module 1 for membrane distillation. Of the membrane distillation membrane modules 1 obtained by the above method, one module was disassembled to measure the contact angle without analyzing the porous hollow fiber membrane. The water contact angle of the porous hollow fiber membrane was determined by dropping 2 μL of pure water under conditions of a temperature of 23° C. and a relative humidity of 50%, and calculating the angle formed between the droplet and the outer surface of the hollow fiber membrane by image analysis. The measurement was performed five times, and the number average value was calculated. The contact angle of the obtained outer surface of the hollow fiber membrane was 132°, and it was confirmed that the membrane had extremely strong hydrophobicity. The remaining one of the membrane distillation membrane modules 1 was used in Comparative Example 3.

[0097] <Measurement of molecular weight cutoff> The molecular weight cutoffs of the obtained dialysis membrane module 1 and forward osmosis membrane module 1 were measured using a 0.002 wt % aqueous solution of Rhodamine B (molecular weight 479) as a test feed liquid. Filtration was started under the conditions that the above test feed liquid was circulated in the inner space of the hollow fibers of each module at an average linear velocity of 4 cm / sec and a pressure of 0.2 MPaG. This filtration was continued for 20 minutes, and after the condition was stabilized, the filtrate was collected. The absorbance of the collected filtrate was measured at a wavelength of 552 nm to examine the concentration of Rhodamine B in the filtrate. For both dialysis membrane module 1 and forward osmosis membrane module 1, the Rhodamine B concentration was less than 1 / 10 of the Rhodamine B concentration in the test supply solution. This result means that the molecular weight cutoff of both the dialysis membrane module 1 and the forward osmosis membrane module 1 was 479 or less. From these results, it was confirmed that the dialysis membrane module 1 and the forward osmosis membrane module 1 were both molecular sieve membrane modules.

[0098] <Permeability measurement> The permeability of the obtained dialysis membrane module 1 and forward osmosis membrane module 1 was measured for water as the first solvent, acetonitrile as the second solvent, and acetic acid as the minor component. Acetonitrile permeability was evaluated using water as the reference liquid and a 1M aqueous solution of acetonitrile with a concentration of 1 mol / L as the test liquid. The test liquid was circulated in the inner space of the hollow fibers of each module at an average linear velocity of 0.04 m / sec, and the reference liquid was circulated in the outer space of the hollow fibers at an average linear velocity of 0.025 m / sec, so that the flows of both liquids were parallel. 20 minutes after the start of circulation, the concentration of acetonitrile in the reference liquid was measured, and the amount of acetonitrile that had passed from the test liquid through the hollow fiber membrane to the reference liquid was quantified. The obtained value (g) was then used as a function of the initial concentration of the test liquid (M = mol / L) and the membrane area of ​​each module (m 2 ) and the circulation time (h) (m 2 The value assigned by (h·M) was taken as the permeability. The permeability of acetic acid was also evaluated in the same manner as above, except that an aqueous solution of acetic acid with a concentration of 1 mol / L was used as the test liquid. The above results are shown in Table 1.

[0099] [Table 1]

[0100] [Example 1] In Example 1, the feed liquid volume reduction system (2) shown in FIG. 6 was used, in which the first treatment was performed by forward osmosis, and the forward osmosis membrane module 1 prepared above was used as the forward osmosis membrane module (500). The raw material solution (a) used was a solution containing 0.2 wt% glutathione disulfide as a valuable substance, 298.2 g of water as a first solvent, 298.2 g of acetonitrile as a second solvent, and 3.6 g of acetic acid as a subcomponent. The initial concentration of acetonitrile in the solvent of the raw material solution (a) was 50 wt%. 600 g of this raw liquid (a) was filled into a raw liquid tank (200) having a capacity of 1,000 mL. On the other hand, 1,200 g of an aqueous isopropanol solution having a concentration of 50 wt % was filled into a draw solution tank (600) as a draw solution (d). Furthermore, 1,200 g of water as the dialysis fluid (e) was filled into the dialysis fluid tank (300).

[0101] To carry out the first treatment, the forward osmosis method, the above-mentioned feed solution (a) and draw solution (d) were passed through the forward osmosis membrane module (500) as the first unit. The flow rates of the feed solution (a) and the draw solution (d) were set to 120 mL / min and 240 mL / min, respectively, and the two liquids were passed through in parallel flow. To perform dialysis as the second treatment, the above-mentioned raw liquid (a) and dialysis liquid (e) were passed through the dialysis membrane module (100) as the second unit. The flow rate of the raw liquid (a) was 120 mL / min, and the flow rate of the dialysis liquid (e) was 240 mL / min, and the two liquids were passed in parallel flow.

[0102] 4.7 hours after the start of operation, the dialysis fluid was renewed by discarding the entire amount of dialysis fluid in the dialysis fluid tank (300) and refilling it with 1,200 g of water. After the dialysis fluid was renewed, the operation was continued. After a total of 8 hours of operation, the mass of the raw liquid (a) became 46.2 g, and the volume reduction ratio reached 13 times. At this point, the operation was stopped. The glutathione disulfide concentration in the raw material solution (a) was analyzed by ICP-MS analysis, and the yield was calculated. The yield of glutathione disulfide was 99% or more. In addition, a small amount of raw liquid (a) was withdrawn every hour from the start of operation, and the acetonitrile concentration was tracked by gas chromatography analysis. As a result, the acetonitrile concentration in the solvent of raw liquid (a) decreased from the initial concentration of 50 wt% to 31 wt% 120 minutes after the start of operation, and a water-rich composition was maintained thereafter. This verified that the method of the present invention reduced the volume of the raw material liquid while maintaining the solvent composition of the raw material liquid within the desired range, and that the volume of the raw material liquid was reduced without damaging valuable materials.

[0103] [Examples 2 to 6] The operation was carried out in the same manner as in Example 1, except that the composition of the raw material liquid and the dialysis liquid (e) circulated through the dialysis membrane module (100), which is the second unit, were changed as shown in Table 2.

[0104] [Example 7] The operation was carried out in the same manner as in Example 1, except that the dialysis membrane module 2 was used as the dialysis membrane module (100) which is the second unit.

[0105] [Example 8] In Example 8, the first treatment was performed by a nanofiltration method using the raw material liquid volume reduction system (3) shown in FIG. 7, and the nanofiltration membrane module 1 prepared above was used as the nanofiltration membrane module (700). Except for this, the operation was carried out in the same manner as in Example 1.

[0106] [Example 9] In Example 9, the raw liquid volume reduction system (1) shown in FIG. 5 was used, in which the first treatment was performed by an evaporation method. The evaporation unit (900) was the evaporation unit 1 prepared above. The composition of the raw liquid and the dialysis fluid (e) circulated through the dialysis membrane module (100), which is the second unit, were changed as shown in Table 2. Except for this, the operation was performed in the same manner as in Example 1.

[0107] [Comparative Example 1] The operation was carried out in the same manner as in Example 1, except that the dialysis membrane module (100) was not used. Four hours after the start of operation, when the volume reduction rate reached 2.6 times, the raw material liquid became cloudy, so the operation was stopped. The cloudy raw material liquid was filtered to remove the precipitated solid, and the glutathione disulfide concentration in the filtrate was analyzed to calculate the yield of valuable products. The yield of valuable products in Comparative Example 1 was 59.9%. In addition, a small amount of the raw liquid was withdrawn every hour after the start of operation, and the acetonitrile concentration was tracked by gas chromatography analysis. It was confirmed that the acetonitrile concentration increased over time, from an initial concentration of 50 wt% to 61 wt% at the time operation was stopped.

[0108] [Comparative Example 2] Except for not using the forward osmosis membrane module (500), the operation was performed in the same manner as in Example 1. When the operation was performed while tracking the weight of the raw liquid in the raw liquid tank (200), no reduction in the mass of the raw liquid was confirmed even one hour after the start of the operation. Therefore, in this comparative example, it was determined that the volume reduction was not progressing, and the operation was stopped.

[0109] [Comparative Example 3] The operation was carried out in the same manner as in Example 1, except that a membrane distillation membrane module 1 was used as the second unit instead of the dialysis membrane module (100), and a membrane distillation process was carried out while circulating cooling water at 10°C instead of the dialysis process. Four hours after the start of operation, an external change was observed suggesting membrane wetting of the membrane distillation membrane module, and the operation was stopped. The glutathione disulfide concentration in the raw material liquid (a) was analyzed by ICP-MS analysis, and the yield at the time of stopping the operation was calculated. The yield of glutathione disulfide was 45%.

[0110] [Comparative Example 4] The operation was carried out in the same manner as in Example 9, except that the dialysis membrane module (100) was not used.

[0111] The results of Examples 1 to 9 and Comparative Examples 1 to 4 are shown in Table 2.

[0112] [Table 2]

[0113] [Table 3]

[0114] As can be seen from the results of Comparative Examples 1 and 4, when only the first treatment was performed, the volume of the raw material liquid was reduced, but as the volume reduction progressed, precipitates were generated in the raw material liquid, and the yield of valuable materials was low. The occurrence of precipitates in the raw material liquid is considered to be due to the fact that, while the concentration of valuable materials increases as the volume reduction progresses, the solvent composition or the concentration of subcomponents was not adjusted to a range in which the valuable materials can stably exist, causing the valuable materials to precipitate. Moreover, the results of Comparative Example 2 revealed that when only the second treatment was carried out, the volume of the raw material liquid was not reduced. Furthermore, from the results of Comparative Example 3, when the second treatment was carried out by membrane distillation, although the volume of the raw material liquid was reduced, the yield of valuable materials contained in the raw material liquid remained low. In contrast, it has been verified that the method of the present invention, which combines the volume reduction by the first treatment with the dialysis method as the second treatment, can achieve a high degree of volume reduction without the formation of precipitates in the raw material liquid. This is believed to be because the method of the present invention reduces the volume of the raw material liquid while maintaining the solvent composition and the concentrations of the subcomponents in the raw material liquid within the desired range. From the above, it has been verified that the method of the present invention can achieve a high volume reduction rate with a high yield of valuable materials. [Explanation of symbols]

[0115] 1, 2, 3, 4 Raw material volume reduction system 100 Dialysis Membrane Module 110 Housing 111 Dialysis fluid inlet 112 Dialysate outlet 120 Dialysis Membrane 121 Base material layer 122 Active layer 130, 530 Adhesive resin 200 Raw material tank 300 Dialysis fluid tank 400 Trap 500 Forward Osmosis Membrane Module 510 Housing 511 Induction solution inlet 512 Induction solution outlet 520 Forward Osmosis Membrane 521 Base material layer 522 Active layer 600 Induction Solution Tank 700 Nanofiltration Membrane Module 800 Permeate Tank 900 Evaporation Unit a Raw material liquid b First solvent c Reduced volume of raw material liquid d inducing solution e. Dialysis fluid f. Raw material liquid with adjusted component concentration g. Second solvent or subcomponent BL blower HM hydrometer LG liquid level gauge P-Pump V-Valve

Claims

1. A method for reducing the volume of a raw material liquid comprising: The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or As a solvent, a mixed solvent containing the first solvent and the second solvent is included, The method for reducing the volume of the raw material liquid comprises: a first process for removing the first solvent from the raw material liquid; a second process of adjusting a concentration of the second solvent or the subcomponent in the raw material solution by a dialysis method using a dialysis membrane; This is a method that combines Method for reducing raw material liquid volume.

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

3. 3. The method for reducing the volume of a raw material liquid according to claim 2, wherein the first treatment is a volume reduction treatment using a membrane, such as a reverse osmosis method, a nanofiltration method, or a forward osmosis method.

4. The method for reducing the volume of a raw material liquid according to claim 2 , wherein the first treatment is a forward osmosis method.

5. than the permeability of the membrane used in the first treatment to the second solvent or the subcomponent, The molecular sieve membrane used in the second treatment has a higher permeability to the second solvent or the subcomponent; The method for reducing the volume of a raw material liquid according to claim 3 or 4.

6. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 5, comprising carrying out the second treatment after carrying out the first treatment.

7. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 5, comprising carrying out the first treatment after carrying out the second treatment.

8. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 5, comprising carrying out the first treatment and the second treatment in parallel and mixing the raw material liquid after each treatment.

9. The method for reducing a volume of a raw material liquid according to any one of claims 6 to 8, wherein the first treatment and the second treatment are cyclically performed on the raw material liquid.

10. The method for reducing the volume of a raw material liquid according to claim 9, further comprising the steps of: measuring the concentration of at least one of the components in the raw material liquid being circulatedly reduced in volume; and determining whether to carry out or stop at least one of the first process and the second process, or to change the operating conditions, based on the obtained measurement value.

11. The method for reducing the volume of a raw material liquid according to claim 10, wherein the concentration measurement is performed using one or more measurement results selected from the group consisting of specific gravity measurement, pH measurement, electrical conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy, and weight measurement of the raw material liquid being circulatedly reduced in volume.

12. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 11, wherein the valuable material is a pharmaceutical raw material.

13. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 12, wherein the valuable material has a number average molecular weight of 100 to 50,000.

14. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 13, wherein the valuable substance is one or more selected from the group consisting of amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), and vitamins.

15. The second solvent is at least one selected from water, acetonitrile, methanol, ethanol, and isopropanol; The auxiliary component is at least one selected from the group consisting of an organic acid, a polymer (excluding the valuable substance), and a buffer salt; The method for reducing the volume of a raw material liquid according to any one of claims 1 to 14.

16. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 15, wherein the temperature of the raw material liquid is adjusted to a range of 1°C or more and 50°C or less.

17. The method for reducing the volume of a raw material liquid according to any one of claims 3 to 5, wherein at least one selected from methanol, ethanol, isopropanol, and t-butanol is used as a solute of the draw solution used in the forward osmosis method.

18. A raw material liquid volume reduction system for reducing the volume of a raw material liquid containing at least a valuable material and a first solvent, The raw material liquid is Further comprising a subcomponent other than the valuable substance and the first solvent; or As a solvent, a mixed solvent containing the first solvent and the second solvent is included, The raw material liquid volume reduction system includes: a first unit for removing the first solvent from the raw material liquid; a second unit for adjusting a concentration of the second solvent or the subcomponent in the raw material solution by dialysis using a dialysis membrane; It is a system that combines Raw material liquid volume reduction system.

19. The system for reducing the volume of a raw material liquid according to claim 18, wherein the dialysis membrane used in the second unit is a molecular sieve membrane.

20. 20. The raw material liquid volume reduction system according to claim 19, wherein the first unit is a unit that performs a volume reduction treatment using a membrane, any one of reverse osmosis, nanofiltration, and forward osmosis.

21. The raw material liquid volume reduction system according to claim 20, wherein the first unit is a unit that performs forward osmosis.

22. than the permeability of the membrane contained in the first unit to the second solvent or the subcomponent, The molecular sieve membrane contained in the second unit has a higher permeability to the second solvent or the auxiliary component. The raw material liquid volume reduction system according to claim 20 or 21.

23. A raw material liquid volume reduction system according to any one of claims 18 to 22, wherein the first unit and the second unit are connected in series in this order in the flow direction of the raw material liquid.

24. A raw material liquid volume reduction system according to any one of claims 18 to 22, wherein the second unit and the first unit are connected in series in this order in the flow direction of the raw material liquid.

25. The raw material liquid volume reduction system according to any one of claims 18 to 22, wherein the first unit and the second unit are connected in parallel and include a mechanism for mixing the raw material liquid discharged from each unit.

26. The raw material liquid volume reduction system according to any one of claims 23 to 25, comprising a mechanism for cyclically treating the raw material liquid by the first unit and the second unit.

27. A concentration measuring mechanism for measuring the concentration of at least one of the components in the raw material liquid being circulated and reduced in volume; a mechanism for determining whether to operate or stop, or to change an operating condition of, at least one of the first unit and the second unit, depending on a measurement value obtained from the concentration measuring mechanism; The feedstock liquid volume reduction system according to claim 26, comprising:

28. The raw liquid volume reduction system of claim 27, wherein the concentration measurement mechanism is a mechanism that determines the concentration using one or more measurement results selected 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 of the raw liquid being circulatedly reduced in volume.

29. The raw material liquid volume reduction system according to any one of claims 18 to 28, wherein the valuable material is a pharmaceutical raw material.

30. The raw material liquid volume reduction system according to any one of claims 18 to 29, wherein the number average molecular weight of the valuable material is 100 to 50,000.

31. The system for reducing the volume of a raw material liquid according to any one of claims 18 to 30, wherein the valuable substance is one or more selected from the group consisting of amino acids, peptides, proteins, sugars, vaccines, nucleic acids, antibiotics, antibody-drug conjugates (ADCs), and vitamins.

32. The second solvent is at least one selected from water, acetonitrile, methanol, ethanol, and isopropanol; The raw material liquid volume reduction system according to any one of claims 18 to 31, wherein the auxiliary component is one or more selected from the group consisting of organic acids, polymers (excluding the valuable substances), and buffer salts.

33. The raw material liquid volume reduction system according to any one of claims 18 to 32, comprising a mechanism for adjusting the temperature of the raw material liquid to a range of 1 ° C. or more and 50 ° C. or less.

34. The raw material liquid volume reduction system according to any one of claims 20 to 22, wherein an alcohol selected from methanol, ethanol, isopropanol, and t-butanol is used as a solute of the draw solution used in the forward osmosis method.

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