Method and system for reducing the volume of raw material liquid

Abstract

A method for reducing the volume of a raw material liquid, the raw material liquid containing at least a valuable and a first solvent, wherein the raw material liquid further contains an accessory component other than the valuable and the first solvent, or contains a mixed solvent including the first solvent and a second solvent as a 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 the concentration of the second solvent or the accessory component is adjusted from the raw material liquid using a dialysis method with a dialysis membrane.

Description

Technical Field

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

Background Art

[0002] The volume reduction of a raw material liquid containing valuable substances is industrially carried out in many cases. For example, in the purification process of peptides, DNA, RNA, enzymes, and their derivative compounds, and these raw materials (hereinafter referred to as "peptides, etc."), the raw material liquid may contain various organic solvents, organic acids, salts, etc. in addition to peptides, etc. and water. Such a raw material liquid can stably contain valuable substances in the raw material liquid by adjusting the composition of the solvent and the concentrations of organic acids, salts, etc. to predetermined ranges, respectively. Therefore, in the process of reducing the volume of the raw material liquid, if the solvent composition changes or the concentrations of organic acids, salts, etc. fluctuate, peptides, etc. may precipitate, aggregate, denature, etc., resulting in a poor yield of volume reduction. In this regard, since peptides, etc. are very expensive, a high yield is required for the volume reduction process of the raw material liquid containing them.

[0003] Also, for example, in the case of a raw material liquid that is expected to be subjected to a reaction that dislikes the presence of water 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, 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 is required. As a method for reducing the volume of a raw material liquid while maintaining the organic solvent concentration, a method of membrane concentration while adding a solvent to the raw material liquid is known (Patent Document 1). Also, as a method for moving a specific component in a raw material liquid through a membrane, a dialysis method is known. (Non-Patent Document 1)

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Japanese Patent Publication No. 2020-196009 [Non-patent literature]

[0006] [Non-Patent Document 1] Biotechnol. Prog., 2019, Vol. 35, No. 2, e2763 [Overview of the project] [Problems that the invention aims to solve]

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

[0008] This invention was made to achieve the above objective. In other words, an example of an embodiment of the present invention is as follows. <Aspect 1> A method for reducing the volume of a raw material liquid, which contains at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The above method for reducing the volume of the raw material liquid is: A first treatment to remove the first solvent from the raw material liquid, A second process in which the concentration of the second solvent or the auxiliary component in the raw material solution is adjusted by a dialysis method using a dialysis membrane, This method involves combining different approaches. Method for reducing raw material liquid volume. [Aspect 2] The method for reducing the volume of a raw material solution according to aspect 1, wherein the dialysis membrane used in the second process is a molecular sieve membrane. <Aspect 3> The 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, which is one of the reverse osmosis method, nanofiltration method, or forward osmosis method. [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 film used in the first treatment to the second solvent or the minor component is greater than the permeability of the film used in the first treatment. The molecular sieve membrane used in the second process has greater permeability to the second solvent or the minor component. A method for reducing the volume of a raw material liquid according to embodiment 3 or 4. [Aspect 6] A method for reducing the volume of a raw material liquid according to any one of aspects 1 to 5, comprising performing the second process after performing the first process. [Aspect 7] A method for reducing the volume of a raw material liquid according to any one of aspects 1 to 5, comprising performing the first treatment after performing 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 performing the first treatment and the second treatment in parallel and mixing the raw material liquids after each treatment. <Aspect 9> A 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 performed cyclically on the raw material liquid. Aspect 10: A method for reducing the volume of a raw material liquid according to aspect 9, comprising measuring the concentration of at least one component in the cyclically reduced volume of the raw material liquid, and determining whether to carry out or stop at least one of the first and second processes, or to change the operating conditions, according to the obtained measurement values. <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, conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy, and gravimetric measurement of the raw material liquid that is being cyclically 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 substance is a pharmaceutical raw material. [Aspect 13] A method for reducing the volume of a raw material liquid according to any one of aspects 1 to 12, wherein the number average molecular weight of the valuable substance is 100 to 50,000. "Aspect 14": The method for reducing the volume of the 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 one or more selected from the group consisting of water, acetonitrile, methanol, ethanol, and isopropanol, and the sub-component is one or more selected from the group consisting of organic acids, polymers (excluding the valuable substance), and buffer salts. The method for reducing the volume of the raw material liquid according to any one of Aspects 1 to 14. "Aspect 16": The method for reducing the volume of the raw material liquid according to any one of Aspects 1 to 15, wherein the temperature of the raw material liquid is adjusted within the range of 1°C or higher and 50°C or lower. "Aspect 17": The method for reducing the volume of the raw material liquid according to any one of Aspects 3 to 5, wherein at least one selected from the group consisting of methanol, ethanol, isopropanol, and t-butanol is used as the solute of the induction solution used in the forward osmosis method. "Aspect 18": A raw material liquid volume reduction system for reducing the volume of a raw material liquid containing at least a valuable substance and a first solvent, wherein the raw material liquid further contains sub-components other than the valuable substance and the first solvent, or contains a mixed solvent containing the first solvent and a second solvent as the solvent, and the raw material liquid volume reduction system comprises a first unit for removing the first solvent from the raw material liquid, and a second unit for adjusting the concentration of the second solvent or the sub-component in the raw material liquid by a dialysis method using a dialysis membrane, and is a system combining the above. Raw material liquid volume reduction system. "Aspect 19": The raw material liquid volume reduction system according to Aspect 18, wherein the dialysis membrane used in the second unit is a molecular sieve membrane. "Aspect 20": The raw material liquid volume reduction system according to Aspect 19, wherein the first unit is a unit for performing a volume reduction treatment using a membrane in any one of reverse osmosis, nanofiltration, and forward osmosis methods. The raw material liquid volume reduction system according to Aspect 20, wherein the first unit is a unit that performs forward osmosis. Aspect 22: The permeability of the second solvent or the sub-component of the membrane included in the first unit is lower than the permeability of the second solvent or the sub-component of the molecular sieve membrane included in the second unit. The raw material liquid volume reduction system according to Aspect 20 or 21. Aspect 23: The raw material liquid volume reduction system according to 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: The raw material liquid volume reduction system according to 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: The raw material liquid volume reduction system according to 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: The raw material liquid volume reduction system according to any one of Aspects 23 to 25, including a mechanism for cyclically processing the raw material liquid by the first unit and the second unit. Aspect 27: A concentration measurement mechanism for measuring the concentration of at least one of the components in the raw material liquid that is cyclically volume-reduced, and a mechanism for determining the operation or stop, or the change of the operation conditions, of at least one of the first unit and the second unit according to the measurement value obtained from the concentration measurement mechanism. The raw material liquid volume reduction system according to Aspect 26. Aspect 2 : The raw material liquid volume reduction system according to Aspect 27, wherein the concentration measurement mechanism is a mechanism for determining 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 spectroscopic analysis, and weight measurement of the raw material liquid that is cyclically volume-reduced. [Aspect 29] A raw material liquid volume reduction system according to 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 number average molecular weight of the valuable substance is 100 to 50,000. [Aspect 31] A raw material liquid volume reduction system according to any one of aspects 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. <Aspect 32> The second solvent is one or more selected from water, acetonitrile, methanol, ethanol, and isopropanol. The raw material liquid volume reduction system according to any one of embodiments 18 to 31, wherein the aforementioned auxiliary component is one or more selected from the group consisting of organic acids, polymers (excluding the aforementioned valuable substances), and buffer salts. [Aspect 33] A raw material liquid volume reduction system according to any one of aspects 18 to 32, comprising a mechanism for adjusting the temperature of the raw material liquid to a range of 1°C to 50°C. [Aspect 34] A raw material liquid volume reduction system according to any one of aspects 20 to 22, wherein an alcohol selected from methanol, ethanol, isopropanol, and t-butanol is used as the solute of the induction solution used in the forward osmosis method. [Effects of the Invention]

[0009] According to the raw material liquid volume reduction method 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 by the method of the present invention has the precipitation, aggregation, and modification of valuable substances suppressed to the greatest extent possible, has excellent yield of valuable substances, and has a composition that is suitable for the requirements of the next process. The volume reduction system of the present invention allows for the efficient implementation of a raw material liquid volume reduction method having the advantages described above. [Brief explanation of the drawing]

[0010] [Figure 1]This is a conceptual diagram illustrating the mechanism of action of the forward osmosis method, which is an example of the first treatment in the raw material solution volume reduction method of the present invention. [Figure 2] This 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. [Figure 3] This is a conceptual diagram illustrating the mechanism of action of a dialysis method, which is an example of a second treatment in the raw material solution volume reduction method of the present invention. [Figure 4] This 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. [Figure 5] This is a conceptual diagram illustrating an example of the raw material liquid volume reduction system of the present invention. [Figure 6] This is a conceptual diagram illustrating another example of the raw material solution volume reduction system of the present invention. [Figure 7] This is a conceptual diagram illustrating yet another example of the raw material solution volume reduction system of the present invention. [Figure 8] This is a conceptual diagram illustrating yet another example of the raw material solution volume reduction system of the present invention. [Figure 9] This is a conceptual diagram illustrating yet another example of the raw material solution volume reduction system of the present invention. [Modes for carrying out the invention]

[0011] Raw material liquid volume reduction system The present invention relates to a method for reducing the volume of a raw material liquid, which reduces the volume of a raw material liquid containing at least a valuable substance and one solvent. The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The above method for reducing the volume of the raw material liquid is: A first treatment to remove the first solvent from the raw material liquid, A second process in which the concentration of the second solvent or the auxiliary component in the raw material solution is adjusted by a dialysis method using a dialysis membrane, This method involves combining several approaches.

[0012] Raw material liquids containing valuable substances often use a mixture of multiple solvents as a solvent, or contain auxiliary components such as salts or buffer salts, in order to ensure the solubility and chemical stability of the valuable substances. Conventionally, distillation, vacuum distillation, membrane distillation, permeation membrane method, vapor permeation membrane method, reverse osmosis membrane method, nanofiltration membrane method, and forward osmosis membrane method have been used as means to concentrate raw material liquids containing such valuable substances. However, regardless of the method used, differences in the chemical and physical properties of multiple components contained in the raw material liquid may cause certain components to be preferentially removed from the raw material liquid, resulting in changes to the solvent composition or the concentration of minor components. When this happens, there is a concern that valuable substances may precipitate, aggregate, or denature during the volume reduction of the raw material liquid. One way to address this is to sequentially add the solvent and minor components to the raw material liquid during volume reduction while maintaining the solvent composition and the concentration of the minor components. However, with this method, the concentration of the solvent or minor components changes rapidly near where they are added, so the risk of precipitation, aggregation, and degradation of valuable substances is not eliminated.

[0013] Therefore, the inventors focused on dialysis as a means of maintaining or gradually adjusting the solvent composition and the concentration of auxiliary components. In dialysis, the solvent composition or the concentration of auxiliary components in the raw material solution gradually approaches the solvent composition or the concentration of auxiliary components in the dialysate over time. By combining this dialysis method with the volume reduction method described above, it became possible to reduce the volume of the raw material liquid while maintaining the solubility and chemical stability of the valuable substances. The present invention, through the mechanism of action described above, can reduce the volume of the raw material liquid while minimizing the risk of valuable substances precipitation, aggregation, and modification.

[0014] Explanation of Terms <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 substance and a first solvent. This raw material liquid is It further contains auxiliary components other than valuable substances and the first solvent, or The solvent includes a mixed solvent comprising a first solvent and a second solvent. Examples of raw material liquids to which the volume reduction method of the present invention can be applied include food products, pharmaceuticals, seawater, and associated water discharged from gas and oil fields. However, considering the advantage of the present invention that volume reduction is possible without heating, the volume reduction method of the present invention is particularly effective when applied to raw material liquids containing substances that are prone to decomposition by heating, especially pharmaceutical raw materials, functional chemical species, etc., as valuable materials.

[0015] It is preferable that the temperature of the raw material liquid used in the raw material liquid volume reduction method of the present invention is adjusted to a range of 1°C to 50°C.

[0016] <Valuable Goods> In this disclosure, "valuable materials" refers 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, and vitamins.

[0017] An amino acid is a compound having one amino acid skeleton, which consists of a carboxyl group, an amino group, and a molar linking them. In this specification, the term "amino acid" encompasses essential amino acids, non-essential amino acids, and unnatural amino acids. Essential amino acids include, for example, tryptophan, lysine, methionine, phenylalanine, threonine, valine, leucine, and isoleucine. Non-essential amino acids include, for example, arginine, glycine, alanine, serine, tyrosine, cysteine, asparagine, glutamine, proline, aspartic acid, and glutamic acid. Non-natural amino acids refer to artificial compounds that do not exist in nature and have one amino acid skeleton within their molecule. Examples of non-natural amino acids used as pharmaceutical raw materials in this disclosure include labeled amino acids and functionalized amino acids. Labeled amino acids are compounds in which a desired labeling compound is bound to the amino acid skeleton. Examples of labeling compounds include dyes, fluorescent substances, luminescent substances, enzyme substrates, coenzymes, antigenic substances, and protein-binding substances. Examples of functionalized amino acids include photoresponsive amino acids, photoswitchable amino acids, fluorescent probe amino acids, and fluorescently labeled amino acids.

[0018] A peptide refers to a compound consisting of 2 to less than 70 amino acid residues, and may be linear or cyclic. Examples of peptides in this disclosure include L-alanyl-L-glutamine, β-alanyl-L-histidine cyclosporine, and glutathione. Generally, proteins refer to compounds formed by the linkage of amino acid residues that are longer chains than peptides. Examples of proteins used herein include interferon α, interferon β, interleukin 1-12, growth hormone, erythropoietin, insulin, granular colony-stimulating factor (G-CSF), tissue plasminogen activator (TPA), natriuretic peptide, blood coagulation factor VIII, somatomedin, glucagon, growth hormone-releasing factor, serum albumin, calcitonin, and lipase G amano 50.

[0019] Examples of sugars include monosaccharides, disaccharides, sugar chains (excluding disaccharides), and sugar chain derivatives. Examples of monosaccharides include glucose, fructose, galactose, mannose, ribose, and deoxyribose. Examples of disaccharides include maltose, sucrose, and lactose. In this disclosure, the term "glycan" refers to a concept excluding disaccharides, and examples include cellulose, glycosaminoglycans, starch, sacran, dextran, dextrin, inulin, curdlan, fucoidan, fructan, pullulan, pectin, polydextrose, maltodextrin, lignin, xylan, mannan, glucomannan, glucuronoxylan, and xylose. Examples of glycan derivatives include sugar derivatives such as N-acetylglucosamine, N-acetylgalactosamine, and N-acetylneuraminic acid.

[0020] Examples of vaccines include the hepatitis A vaccine, hepatitis B vaccine, and hepatitis C vaccine; Nucleic acids include, for example, oligonucleotides, RNA, aptamers, and decoys; Examples of antibiotics include streptomycin and vancomycin; Examples of antibody-drug conjugates (ADCs) include brentuximab vedotin (Adcetris), trastuzumab emtansine (Kadcyla), and gemtuzumab ozogamicin (Mylotarg); Each of these can be listed. Examples of yeast species include Saccharomyces cerevisiae, Pichia stipitis, Candida shehatae, and Pachysolen tannophilus, as well as their mutant strains. Examples of vitamins include vitamin A, vitamin B, and vitamin C, as well as their derivatives and salts. Vitamin B includes, for example, vitamin B6 and vitamin B12.

[0021] Functional chemical species refer to various chemical species used as functional chemicals, as well as their modified forms, 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 modifiers, precursors, and raw materials.

[0022] The molecular weight of the valuable substance contained in the raw material liquid used in the raw material liquid volume reduction method 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 measured by gel permeation chromatography in terms of the number average molecular weight of polyethylene oxide.

[0023] <solvent> In this disclosure, "solvent" refers to a compound capable of dissolving or dispersing a valuable substance and, if present, a minor component. The solvent is typically one or more selected from water and organic solvents. An organic solvent is an organic compound having one or more carbon atoms, and in one embodiment, it is a compound that exists as a liquid at atmospheric pressure at temperatures between 0°C and 50°C. However, carboxylic acids are excluded from the solvents in this invention. Examples of organic solvents include alcohols, esters, ethers, aprotic polar compounds, aromatic compounds, aliphatic compounds, chlorinated hydrocarbons, and ketones.

[0024] Examples of organic solvents include: Examples of alcohols include methanol, ethanol, 1-propyl alcohol, isopropanol, n-butanol, sec-butanol, t-butanol, and hexafluoroisopropyl alcohol; Examples of esters include methyl formate, ethyl formate, methyl acetate, ethyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, etc. Examples of ethers include tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, cyclopentyl methyl ether, t-butyl methyl ether, anisole, and 1,2-dimethoxyethane; Examples of aprotic polar compounds include acetonitrile, dimethylacetamide, N-methylpyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, and sulfolane; Examples of aromatic compounds include benzene, toluene, xylene, cumene, and pyridine; Examples of aliphatic compounds include heptane, hexane, cyclohexane, methylcyclohexane, and tetraline; Examples of chlorinated hydrocarbons include dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2-dichloroethene, 1,1,1-trichloroethane, 1,1,2-trichloroethene, and chlorobenzene; Examples of ketones include acetone, methyl butyl ketone, methyl ethyl ketone, and methyl isobutyl ketone; Examples of aldehydes include formaldehyde, acetaldehyde, propionaldehyde, butanal, acrolein, benzaldehyde, furfural, and vanillin; Each of these can be listed.

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

[0026] The amount of the first solvent in the raw material solution may be arbitrarily set, both before and after volume reduction, depending on the solubility and chemical stability of the valuable substances, as well as the requirements of the reaction planned after volume reduction. When the solvent of the raw material solution contains a first solvent and a second solvent, the mixing ratio of the first solvent and the second solvent may be arbitrarily set, both before and after volume reduction, in accordance with the solubility and chemical stability of the valuable substance, as well as the requirements of the reaction planned after volume reduction.

[0027] <Minor components> In this disclosure, "auxiliary components" refer to components optionally included in the raw material liquid, excluding valuable substances and solvents among the components included in the raw material liquid. When the solvent of the raw material liquid includes a first solvent and a second solvent, the auxiliary components refer to components included in the raw material liquid excluding valuable substances, the first solvent, and the second solvent. The minor components include, for example, organic acids, polymers (excluding valuable substances), and buffer salts. Examples of organic acids used as auxiliary components 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] Polymers that are considered valuable are excluded from the polymers used as auxiliary components. Examples of polymers used as auxiliary components in this invention include polyethylene oxide, polypropylene oxide, and copolymers of ethylene oxide and propylene oxide. Examples of salts or buffer salts include sodium chloride, magnesium chloride, calcium chloride, sodium bicarbonate, potassium bicarbonate, sodium sulfate, sodium bisulfate, potassium bisulfate, magnesium sulfate, potassium sulfate, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium acetate, magnesium acetate, sodium citrate, magnesium citrate, and other organic acid salts, as well as ammonium chloride, ammonium sulfate, ammonium carbonate, ammonia, and the like. The raw material liquid often contains multiple by-components. When the raw material liquid contains auxiliary components, the amount of auxiliary components in the raw material liquid may be arbitrarily set according to the solubility and chemical stability of the valuable substances, as well as the requirements for the reaction planned after volume reduction.

[0029] (Coexistence of the second solvent and minor components) The raw material liquid in this disclosure may contain a valuable substance, a first solvent, a second solvent, and a minor component. In this case, the raw material liquid volume reduction method of the present invention can be used to obtain a volume-reduced liquid in which the concentrations of the second solvent and the minor component are adjusted to desired values. Among the raw material liquids containing valuable substances, a first solvent, a second solvent, and auxiliary components, the following are examples of those preferably applied to the raw material liquid volume reduction method of the present invention: The first solvent is water. The second solvent is one or more selected from acetonitrile, methanol, ethanol, and isopropanol. This includes cases where the minor component is one or more selected from acetic acid and trifluoroacetic acid. In particular, a case where the first solvent is water, the second solvent is acetonitrile, and the minor component is acetic acid is typical, with these being present in a weight ratio of 50 parts water, 49 parts acetonitrile, and 1 part acetic acid.

[0030] <Transparency> In this disclosure, permeability refers to the degree of ease with which a second solvent or minor component permeates through the film. The transparency in this disclosure can be measured as follows: A test solution is prepared by dissolving a second solvent or a minor component at a predetermined concentration in a first solvent. Meanwhile, a reference solution consisting of the first solvent is prepared. When these test solutions and the reference solution are brought into contact with each other via a membrane for a predetermined time, the amount of the second solvent or minor component that permeates through the membrane and moves from the test solution to the reference solution is quantified. The amount of this permeated component is then allocated to the concentration of the test solution, the membrane area, and the contact time, and the resulting value is evaluated as permeability. The predetermined concentration of the second solvent or minor component in the test solution, and the contact time, are typically 1 mol / L and 20 minutes. However, in the case of components that would destroy the film at a concentration of 1 mol / L (e.g., trifluoroacetic acid), the predetermined concentration of the second solvent or minor component in the test solution and the contact time may be set to 0.01 mol / L and 180 minutes. Specifically, it can be measured, 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 raw material liquid volume reduction method by the total amount of valuable materials introduced into the raw material liquid volume reduction process, expressed as a percentage. However, if valuable substances precipitate or aggregate during the raw material liquid volume reduction process, they will not be considered the same valuable substances, even if their chemical structure remains unchanged. Furthermore, naturally, if the chemical structure of a valuable substance changes during the raw material liquid volume reduction process, it will not be considered the same valuable substance. According to the raw material liquid volume reduction method of this disclosure, the yield of valuable materials can be increased to 70% or more, 80% or more, 90% or more, 95% or more, and even 99% or more.

[0032] <Volume reduction ratio> In this 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 volume of the raw material liquid can be reduced at a high volume reduction ratio without impairing the stability of the valuable material. According to the raw material liquid volume reduction method of the present invention, the volume of the raw material liquid can be reduced by a volume reduction ratio of 3 times or more, 4 times or more, or 5 times or more without impairing the stability of the valuable substances. The upper limit of the volume reduction ratio depends on the concentration and solubility of the valuable substances contained in the raw material liquid, but is generally around 50 times.

[0033] <Molecular sieve membrane> In this disclosure, a molecular sieve membrane refers to a membrane with a molecular weight cutoff smaller than the pore size of an ultrafiltration membrane. In this disclosure, a molecular sieve membrane is defined as having a molecular weight cutoff of 5,000 or less, 4,000 or less, or 3,000 or less. In the present invention, the molecular weight cutoff of the molecular sieve membrane 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 of the raw material liquid volume reduction method of this disclosure, a molecular sieve membrane may be used as a forward osmosis membrane, nanofiltration membrane, etc.

[0034] As described above, the present invention is a method for reducing the volume of a raw material liquid, which reduces the volume of a raw material liquid containing at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising a first solvent and a second solvent. The above method for reducing the volume of the raw material liquid is: A first treatment to remove the first solvent from the raw material liquid, A second process in which the concentration of the second solvent or the auxiliary component in the raw material solution is adjusted by a dialysis method using a dialysis membrane, This method involves combining several approaches. Hereinafter, preferred embodiments of the present invention will be described in detail as non-limiting examples.

[0035] <First process> The first treatment in the method for reducing the volume of a raw material liquid according to the present invention is a treatment that mainly removes a first solvent from the raw material liquid. Examples of such first processing methods include evaporation, thin-film distillation, evaporation method, membrane distillation method, permeation vaporization membrane method, vapor permeation membrane method, reverse osmosis membrane method, nanofiltration membrane method, and forward osmosis membrane method. The evaporation method described above is a method in which 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. Of these processes, the evaporation method, reverse osmosis method, nanofiltration method, and forward osmosis method are effective because they can remove the first solvent from the raw material liquid without heating, resulting in less thermal degradation of valuable substances. Furthermore, 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, the forward osmosis membrane method is particularly effective because, by using an appropriate induction solution, it can move the first solvent with a high degree of driving force without requiring mechanical driving force. Below, the forward osmosis method will be described as an example of the first treatment in the raw material liquid volume reduction method of the present invention. Figure 1 is a schematic diagram illustrating the mechanism of solvent transfer using a forward osmosis membrane. In Figure 1, the raw material solution (a) flows on one side of the forward osmosis membrane (520), while the induction solution (d), which has a higher osmotic pressure than the raw material solution (a), flows on the opposite side, and the two solutions are in contact through the forward osmosis membrane (520). Then, driven by the osmotic pressure difference between the raw material solution (a) and the induction solution (d), the primary solvent (b) in the raw material solution (a) moves through the forward osmosis membrane (520) into the induction solution (d).

[0037] The forward osmosis membrane (520) in Figure 1 has a substrate layer (521) and an active layer (522) formed on one side of the substrate layer (521). The active layer (522) has a very dense structure that allows small molecules to permeate but prevents valuable substances from permeating, and is formed on the side of the substrate layer (521) that is in contact with the raw material liquid (a).

[0038] A porous membrane is generally used as the material for the base layer (521). The induction solution (d) permeates the portion of the base layer (521) that is made of a porous membrane within the forward osmosis membrane (520), and the raw material liquid (a) and the induction solution (d) are in contact via the active layer (522). In this case, the first solvent in the raw material liquid (a) moves to the side of the induction solution (d), which has a higher osmotic pressure, and volume reduction occurs. The forward osmosis membrane can take any of the following forms: hollow fiber membrane, tubular, or flat membrane. A hollow fiber membrane is preferred because it can form a channel through which the raw material liquid and the induction solution pass without the use of spacers, and can perform uniform volume reduction.

[0039] The material of the porous membrane constituting the base layer can be selected from materials that are widely available on the market. However, materials that dissolve or swell in the organic solvent contained in the raw material liquid, preventing the membrane from maintaining its pore shape, cannot be used. Specifically, examples of materials for the porous membrane constituting the base layer include polysulfone, polyethersulfone, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polypropylene, cellulose polymers, polyketone, polyamide, polyimide, polyetheretherketone, polybenzimidazole, etc., and crosslinked versions thereof. It is preferable that at least one selected from these be used as the main component. From the viewpoint of solvent resistance, it is preferable that the porous membrane constituting the hollow fiber-like forward osmosis membrane be mainly composed of polysulfone, polyethersulfone, polyketone, polyamide, and polyimide, and at least one selected from crosslinked versions thereof.

[0040] Polyamide is primarily used as the material for the active layer. The active layer, which is made of polyamide, can be formed on a substrate layer by interfacial polymerization of polyfunctional acid halides and / or polyfunctional amines. A polyfunctional acid halide is an acid halide compound that has two or more acid halide groups in a single molecule. Specifically, for example, Fatty acid halide compounds 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 can be used. These acid halide compounds can be used individually or in combination of two or more. In the present invention, from the viewpoint of economy, availability, ease of handling, and ease of reaction, trimesic acid chloride alone, a mixture of trimesic acid chloride and isophthalic acid chloride, or a mixture of trimesic acid chloride and terephthalic acid chloride are particularly preferred.

[0041] A polyfunctional amine is an amino compound having two or more amino groups in a single molecule, and examples include aromatic amino compounds and aliphatic amino compounds. Examples of aromatic amino compounds include, specifically, m-phenylenediamine, p-phenylenediamine, 3,3'-diaminodiphenylmethane, 4,4'-diaminodiphenylamine, 4,4'-diaminodiphenyl ether, 3,4'-diaminodiphenyl ether, 3,3'-diaminodiphenylamine, 3,5-diaminobenzoic acid, 4,4'-diaminodiphenyl sulfone, 3,3'-diaminodiphenyl sulfone, 3,4'-diaminodiphenyl sulfone, 1,3,5-triaminobenzene, and 1,5-diaminonaphthalene. These can be used individually or in mixtures thereof. In the present invention, one or more aromatic amino compounds selected from m-phenylenediamine and p-phenylenediamine are particularly preferred, considering factors such as cost-effectiveness, availability, ease of handling, and ease of reaction.

[0042] Examples of aliphatic amino compounds 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, and the like. These can be used individually or in mixtures thereof. Interfacial polymerization of polyfunctional acid halides and polyfunctional amines can be carried out according to standard methods.

[0043] The resulting active layer may be obtained through a heat treatment as appropriate. This heat treatment may be carried out with hot water or with high-temperature, high-pressure steam in a pressure vessel such as an autoclave. By applying heat treatment to the active layer, although the reason is not clear, it is expected that the back diffusion of the induction solution will be reduced.

[0044] When using hollow fiber-shaped forward osmosis membranes, the outer diameter of the hollow fiber membrane is, for example, 300 μm to 5,000 μm, preferably 350 μm to 4,000 μm, and the inner diameter of the hollow fiber membrane is, for example, 200 μm to 4,000 μm, preferably 250 μm to 1,500 μm. If the inner diameter of the hollow fiber is less than 200 μm, high back pressure may be generated when liquid flows through the space inside the hollow fiber. If the inner diameter of the hollow fiber exceeds 4,000 μm, when multiple forward osmosis membranes are used in a modularized manner, the membrane area per module may become excessively small, and effective volume reduction may not be achieved.

[0045] For use in forward osmosis, the induction solution can include a solute containing an organic solvent, an organic acid, a buffer salt, or the like. As the organic solvent, any of the organic solvents listed above may be used as the solvent contained in the raw material solution. Specifically, at least one selected from methanol, ethanol, isopropanol, and t-butanol is preferred. Examples of organic acids include formic acid, acetic acid, propionic acid, citric acid, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, oxalic acid, gluconic acid, lactic acid, glycolic acid, and glyceric acid. Examples of buffer salts include, in addition to the metal salts of the aforementioned organic acids, inorganic salts such as sodium chloride, magnesium chloride, calcium chloride, sodium sulfate, sodium bicarbonate, potassium bicarbonate, sodium bisulfate, potassium bisulfate, magnesium sulfate, potassium sulfate, sodium phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, dipotassium hydrogen phosphate, dipotassium dihydrogen phosphate, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide; organic acid salts such as sodium acetate, magnesium acetate, sodium citrate, and magnesium citrate; and the like.

[0046] The concentration of the solute in the induction solution may be appropriately set according to the composition of the raw material solution, the type of solute in the induction solution, etc., so as to ensure the movement of the first solvent from the raw material solution to the induction solution and to generate an osmotic pressure difference that can produce a driving force within a range where the composition of the raw material solution near the forward osmosis membrane does not change rapidly.

[0047] In the forward osmosis method, the driving force for the movement of the first solvent (b) from the raw material solution (a) to the induction solution (d) is the osmotic pressure difference between the raw material solution (a) and the induction solution (b). Therefore, liquid renewal is necessary between the active layer (522) of the forward osmosis membrane (520) and the interface between the raw material solution (a) or the induction solution. Consequently, it is necessary to flow the raw material solution (a) and the induction solution (d) at an appropriate flow rate on both sides of the forward osmosis membrane (520). In Figure 1, the raw material liquid (a) and the derived solution (d) are flowing in parallel, but the flow of the two liquids may also be in opposite directions.

[0048] Figure 2 is a schematic diagram showing the configuration of an example of a forward osmosis membrane module, which is preferably applied as a first unit for carrying out the first treatment in the raw material liquid volume reduction method of the present invention. In the forward osmosis membrane module (500) shown in Figure 2, multiple hollow fiber-like forward osmosis membranes (520) are housed within a housing (510). Both ends of the forward osmosis membranes (520) are bonded and fixed to the housing (510) by adhesive resin (530). There are two housing side tubes on the side of the housing (510). One of these housing side tubes is the induction solution inlet (511), and the other is the induction 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 induction solution (d) flows. The two spaces are fluidly separated, except that the first solvent can move back and forth through the inner wall of the forward osmosis membrane (520).

[0049] When the raw material liquid (a) is introduced from one end of the forward osmosis membrane module (500), the raw material liquid (a) flows through the inside of the hollow fiber-like forward osmosis membrane (520) and flows out from the other end face as a reduced-volume raw material liquid (c). Similarly, when the induction solution (d) is introduced from the induction solution inlet (511) of the side tube of the housing (510), the induction solution (d) flows through the outer space of the hollow fiber-like forward osmosis membrane (520) and flows out from the induction solution outlet (512). These mechanisms allow the raw material liquid (a) and the derived solution (d) to come into contact via the forward osmosis membrane (520). At this time, non-valuable substances move from the raw material liquid (a) to the derived solution (d) due to the difference in osmotic pressure between the two liquids. In the forward osmosis membrane method, volume reduction is achieved through this mechanism.

[0050] When the forward osmosis membrane (520) has a base layer and an active layer formed on one side of the base layer, as described above, the active layer is formed on the side of the base layer that is in contact with the raw material liquid. Therefore, in the forward osmosis membrane module (500) of Figure 1, in which the raw material liquid (a) flows inside the hollow fiber-like forward osmosis membrane, it is preferable that the active layer is on the inner surface of the hollow fiber-like base layer. When the flow rate of the raw material solution (a) and / or the flow rate of the derived solution (d) is large, the effect of the osmotic pressure difference on both sides of the forward osmosis membrane (520), especially the active layer, becomes greater, and the amount of first solvent permeating per unit area of ​​the forward osmosis membrane increases. In the forward osmosis membrane module (500) shown in Figure 2, the raw material liquid (a) and the induction solution (d) are flowed in parallel, but the flow of the two liquids may also be in opposite directions.

[0051] The material of the housing (510) in the forward osmosis membrane module (500) shown in Figure 2 is selected from the viewpoint of chemical resistance, pressure resistance, heat resistance, impact resistance, weather resistance, etc., so that various properties do not deteriorate due to the components contained in the raw material liquid (a) and the induction solution (d). As the material of the housing (510), for example, resins, metals, etc. can be used. From the above viewpoint, it is preferable to select from resins such as polypropylene, polysulfone, polyethersulfone, polyvinylidene fluoride, polytetrafluoroethylene, perfluoroalkoxyalkane, ABS resin, fiber-reinforced plastic, and polyvinyl chloride resin; and metals such as stainless steel, brass, and titanium. The adhesive resin (530) in the forward osmosis membrane module (500) shown in Figure 2 is preferably 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. Epoxy resins are preferred from the viewpoint of heat resistance, and urethane resins are preferred from the viewpoint of handling ease. The method for bonding and fixing the forward osmosis membrane (520) to the housing (510) can be the same as known bonding methods for the fabrication of hollow fiber membrane modules.

[0052] (Nanofiltration method) As another example of the first treatment method, we will describe the nanofiltration method. In nanofiltration, the raw material liquid is supplied to one side of the nanofiltration membrane, and the raw material liquid supply side is pressurized. As a result, the primary solvent of the raw material liquid is mainly removed by passing through the nanofiltration membrane, reducing the volume of the raw material liquid. The secondary solvent or by-components remain in the raw material liquid. As the nanofiltration membrane, known nanofiltration membranes can be used. The nanofiltration membrane can take any of the following forms: hollow fiber membrane, tubular, or flat membrane. A hollow fiber membrane nanofiltration membrane is preferred because it can form channels through which the raw material liquid and permeate (first solvent) pass without the use of spacers, and can achieve uniform volume reduction.

[0053] The nanofiltration method is preferably performed using a nanofiltration membrane module, which comprises multiple hollow fiber-like nanofiltration membranes housed in a suitable housing. Examples of materials for the nanofiltration membrane include polysulfone, polyethersulfone, polyvinylidene fluoride, polyacrylonitrile, polyethylene, polypropylene, cellulose polymers, polyketone, polyamide, polyimide, polyetheretherketone, polybenzimidazole, and crosslinked versions thereof. It is preferable that at least one selected from these be used as the main component.

[0054] The housing of the nanofiltration membrane module and the remaining module configurations can be described using the above explanation for the forward osmosis membrane module, provided that "forward osmosis membrane" is replaced with "nanofiltration membrane."

[0055] (Evaporation method) As yet another example of the first process, we will describe the evaporation method. In the evaporation method, gas is circulated through a container holding the raw material liquid, preferentially vaporizing the component with the highest vapor pressure (first solvent) and removing it from the container, thereby reducing the volume of the raw material liquid. Components with the lowest vapor pressure (second solvent or minor components) remain in the raw material liquid. Examples of gases that can be circulated through the container holding the raw material liquid include air, nitrogen, and argon.

[0056] <Second process> The second treatment in the raw material solution concentration method of the present invention is a treatment to adjust the concentration of the second solvent or auxiliary component in the raw material solution by a dialysis method using a dialysis membrane, and to maintain the component composition of the raw material solution after volume reduction within a range in which valuable substances do not denature, aggregate, or precipitate. In the second treatment, dialysis is used. In particular, using a molecular sieve membrane as the dialysis membrane is effective because it can effectively prevent valuable substances from permeating and dissipating through the dialysis membrane. Below, as an example of a second treatment in the raw material volume reduction system of the present invention, a dialysis method using a molecular sieve membrane as the dialysis membrane will be described.

[0057] Figure 3 is a schematic diagram illustrating the mechanism of action of dialysis using a dialysis membrane. In Figure 3, the raw material (a) flows on one side of the dialysis membrane (120), and the dialysate (e) flows on the opposite side, with both fluids in contact through the dialysis membrane (120). At this time, if there is a difference in the concentration of the second solvent or by-component (g) in the raw material solution (a) and the second solvent or by-component (g) in the dialysate (e), the second solvent or by-component (g) will move from the concentrated solution to the dilute solution. Since this movement is driven by the concentration difference of the second solvent or by-component (g) in both solutions, it can move in either direction. In the second process of the raw material liquid volume reduction system of the present invention, such movement causes the concentration of the second solvent or by-component (g) in the raw material liquid (a) to asymptotically approach the concentration of the dialysate (d), and the component composition of the raw material liquid (a) is maintained within a desired range.

[0058] Furthermore, when the forward osmosis method is adopted as the first treatment, the induced solute in the induced solution may be mixed into the raw material solution. The second treatment in the raw material solution volume reduction method of the present invention also has the effect of removing the induced solute mixed into the raw material solution from the raw material solution. In this case, since the dialysate (e) does not contain the induced solute, the induced solute preferentially moves from the raw material solution (a) to the dialysate (e), and the induced solute is effectively removed from the raw material solution.

[0059] The dialysis membrane (120) in Figure 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 permeate but prevents valuable substances from permeating, and is formed on the side of the base layer (121) that is in 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) permeates the portion of the dialysis membrane (120) that is made up of a porous membrane (base layer (121)), and the raw material solution (a) and the dialysis fluid (d) are in contact via the active layer (122).

[0061] The material of the porous membrane constituting the base layer can be selected from materials that are widely available on the market. However, materials that dissolve or swell in the organic solvent contained in the raw material liquid, preventing the membrane from maintaining its pore shape, cannot be used. If the first process is a volume reduction process using a membrane, The permeability of the membrane used in the first treatment to the second solvent or by-component is greater than the permeability of the membrane used in the first treatment. The permeability of the second solvent or by-component of the dialysis membrane used in the second process is, The larger the better. The greater the permeability of the dialysis membrane to the second solvent or by-component, the faster the movement of the second solvent or by-component through the dialysis membrane occurs, making it easier to obtain the effect of asymptotically approaching the concentration of the second solvent or by-component to the concentration of the dialysate. This is preferable because it allows for effective correction of the concentration of the second solvent or by-component in the raw material solution. In this regard, polyamide is preferable as the material for the active layer because the permeability of the second solvent or minor components can be arbitrarily controlled by selecting the monomer when forming the active layer on the substrate layer.

[0062] The material of the porous membrane constituting the base layer and the method for forming the polyamide constituting the active layer can be described by referring to the above-described explanations for the base layer and active layer of the forward osmosis membrane, respectively. Furthermore, polyfunctional acid halide compounds converted to acid anhydrides may be used as part or all of the polyfunctional acid halides used to form the active layer of the dialysis membrane. Specifically, examples include trimellitic anhydride chloride, 3,3',4,4'-biphenyltetracarboxylic dianhydride, pyromellitic dianhydride, benzophenonetetracarboxylic dianhydride, and diphenyl ethertetracarboxylic dianhydride. Furthermore, using piperazines as some or all of the polyfunctional amines used to form the active layer of the dialysis membrane is desirable because it increases the permeability of the second solvent or minor components.

[0063] When the first treatment is performed by forward osmosis, as described above, the forward osmosis membrane used for forward osmosis and the dialysis membrane used for the second treatment (dialysis) both have a common structure in that they consist of a substrate layer made of a porous membrane and an active layer made of polyamide. On the other hand, as also mentioned above, regarding the permeability of the second solvent or by-components contained in the raw material solution, it is preferable that the permeability of the dialysis membrane is greater than that of the forward osmosis membrane. In forward osmosis and dialysis membranes made of the same material, differences in the permeability of the second solvent or minor components can be created, for example, by selecting monomers, adjusting interfacial polymerization conditions, or performing post-treatment after interfacial polymerization when forming the active layer on the substrate layer. For example, by using an aliphatic amine compound as the polyfunctional amine used in interfacial polymerization, the permeability of the second solvent or minor components can be increased.

[0064] The dialysis membrane can take any of the following forms: hollow fiber membrane, tubular, or flat membrane. A hollow fiber membrane is suitable because it can form a channel through which the raw material and dialysate pass without the use of spacers, and can maintain a uniform flow.

[0065] When using hollow fiber dialysis membranes, the outer diameter of the hollow fiber membrane is, for example, 300 μm to 5,000 μm, preferably 350 μm to 4,000 μm, and the inner diameter of the hollow fiber membrane is, for example, 200 μm to 4,000 μm, preferably 250 μm to 1,500 μm. For reasons that are not entirely clear, if the inner diameter of the hollow fiber is less than 200 μm, precipitation, aggregation, or modification 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 modularized manner, the membrane area per module may become excessively small, and the transfer of the second solvent or minor component concentration may not occur sufficiently.

[0066] The composition of the dialysate used in dialysis should ideally allow for the stable presence of valuable substances. The appropriate composition of the dialysate should be determined appropriately based on the chemical and physical properties of the valuable substances contained in the raw fluid. As an example, one option is to use a dialysate with the same composition as the raw fluid from which the valuable substances have been removed. From the viewpoint of avoiding adverse effects on piping, analytical equipment, etc., the pH of the dialysate is preferably between pH 1 and 14, and more preferably between pH 2 and 13.

[0067] In dialysis, the driving force for the movement of the second solvent or by-components between the raw material solution and the dialysate is the concentration difference between the two. Therefore, for effective component transfer, fluid renewal is necessary at the interface between the active layer of the dialysis membrane and the raw material solution or dialysate. Therefore, it is necessary to flow the raw material solution and the dialysate at an appropriate flow rate on both sides of the dialysis membrane (120). In Figure 3, the raw material liquid (a) and the derived solution (d) are flowing in parallel, but the liquids may also flow in opposite directions. Depending on the composition of the raw material solution, the osmotic pressure difference between the raw material solution and the dialysate may cause the first solvent in the dialysate to permeate the dialysate and move into the raw material solution, potentially increasing the volume of the raw material solution. In this case, the volume increase of the raw material solution can be suppressed by pressurizing the raw material solution in contact with the dialysate. The pressurized pressure of the raw material solution is preferably 0.05 MPaG or higher, more preferably 0.1 MPaG or higher, and even more preferably 0.2 MPaG or higher.

[0068] Figure 4 is a schematic diagram showing the configuration of an example of a dialysis membrane module that is preferably applied as a second unit for carrying out the second treatment in the raw material liquid volume reduction method of the present invention. In the dialysis membrane module (100) shown in Figure 4, multiple hollow fiber-like dialysis membranes (120) are housed within a housing (110). Both ends of the dialysis membranes (120) are bonded and fixed to the housing (110) by adhesive resin (130). There are two housing side tubes on the side of the housing (110). One of these housing side tubes is the dialysate inlet (111), and the other is the 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 material liquid (a) flows and a space through which the dialysate (d) flows. The two spaces are fluidly separated except for the fact that the second solvent or by-components can move back and forth through the inner wall of the dialysis membrane (120).

[0069] When raw material solution (a) is introduced from one end of the dialysis membrane module (100), the raw material solution (a) flows inside the membrane of the hollow fiber dialysis membrane (120) and flows out from the other end face as raw material solution (f) with adjusted component concentration. Similarly, when dialysate (d) is introduced from the dialysate inlet (111) of the side tube of the housing (110), the dialysate (e) flows through the space outside the hollow fiber-like dialysate membrane (120) and flows out from the dialysate outlet (112). As a result, the raw material solution (a) and the dialysate (e) can come into contact with each other via the dialysate membrane (120). At this time, depending on the relative concentrations of the components contained in the raw material solution (a) and the dialysate (d), the second solvent or by-component (g) moves from the raw material solution (a) to the dialysate (e), or from the dialysate (d) to the raw material solution (a). In the dialysis method, the concentration of the second solvent or by-component is adjusted by this mechanism. When the flow rate of the raw material solution (a) and / or the flow rate of the dialysate (e) is large, the effect of the concentration difference on both sides of the dialysis membrane (120), especially the active layer, becomes greater, and the amount of the second solvent or by-component transferred per unit area of ​​the dialysis membrane increases. In the dialysis membrane module (100) shown in Figure 4, the raw material (a) and the dialysate (e) are flowed in parallel, but the flow of the two fluids may also be in opposite directions.

[0070] The materials of the housing (110) and adhesive resin (130) in the dialysis membrane module (100) in Figure 4, as well as the method for bonding and fixing the dialysis membrane (120) to the housing (110), can be directly applied to the explanation given above for the forward osmosis membrane module (500) in Figure 2.

[0071] <Embodiments of the first and second processes> The order in which the first and second processes are performed is arbitrary. For example, You may perform the second process after performing the first process; You may perform the first process after performing the second process; The first and second processes may be performed simultaneously. Performing the first and second processes simultaneously means, for example, carrying out the first and second processes in parallel and mixing the raw material liquids after each process. When the first and second processes are performed in any order, the piping for supplying the raw material liquid to one of the processes and the piping for supplying the processed raw material liquid to the other process may be connected in series. When the first and second processes are carried out in parallel, for example, the piping for supplying the raw material liquid to the first process and the piping for supplying the raw material liquid to the second process may be connected in parallel.

[0072] The first and second processes are preferably carried out cyclically. For example, The process involves storing the raw material liquid in a raw material liquid tank, taking a portion of the raw material liquid from the tank and using it in the order of the first and second processes, and then returning the raw material liquid after the first and second processes to the raw material liquid tank, and repeating this operation; The process involves storing the raw material liquid in a raw material liquid tank, taking a portion of the raw material liquid from the tank and using it in the second and first processes in that order, and then returning the raw material liquid after the second and first processes to the raw material liquid tank, and repeating this operation; The raw material liquid is stored in the raw material liquid tank. The process involves repeatedly taking out a portion of the raw material liquid from the raw material liquid tank, subjecting it to the first treatment, and returning the raw material liquid after the first treatment to the raw material liquid tank, and The process involves repeatedly taking a portion of the raw material liquid from the raw material liquid tank, subjecting it to a second treatment, and returning the raw material liquid after the second treatment to the raw material liquid tank. The act of repeatedly performing an operation in parallel (simultaneously); Such methods are preferred.

[0073] When the first and second processes are carried out cyclically, it is preferable to measure the concentration of at least one component in the cyclically volume-reduced raw material liquid and, based on the obtained measurement values, decide whether to carry out or stop at least one of the first and second processes, or to change the operating conditions. 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 may be considered to temporarily suspend the first process or to moderate the processing conditions of the first process. On the other hand, if the concentration of the first solvent in the raw material liquid is about to exceed the upper limit of the appropriate range, it may be considered to tighten the processing conditions of the first treatment. Furthermore, if the concentration of the second solvent or auxiliary component in the raw material solution is about to fall outside the appropriate range, it is possible to change the concentration of the second solvent or auxiliary component in the dialysate used for the second treatment. Specifically, the rate of volume reduction tends to be faster in the latter half of the volume reduction process than in the initial stage. Therefore, in the latter half of the volume reduction process, the concentration of the second solvent or auxiliary component in the dialysate being circulated may increase, and the efficiency of adjusting the concentration of the second solvent or auxiliary component in the raw material solution may decrease. In such cases, for example, it is possible to discard the dialysate being circulated during the volume reduction process and replace it with dialysate of the initial composition to improve the efficiency of adjusting the concentration of the second solvent or auxiliary component in the raw material solution.

[0074] The concentration of at least one component in the raw material liquid can be determined, for example, by using measurement results of the raw material liquid, such as specific gravity measurement, pH measurement, conductivity measurement, liquid level measurement, optical rotation measurement, refractive index measurement, near-infrared spectroscopy, and gravimetric analysis. Then, once the raw material liquid has been reduced to the desired volume reduction rate, both the first and second processes are stopped, and the volume reduction of the raw material liquid is completed. The volume reduction rate can be determined by appropriate methods 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 such as ICP-MS (inductively coupled radio frequency plasma mass spectrometry), nuclear magnetic resonance spectroscopy (NMR), gas chromatography-mass spectrometry (GC / MS), colorimetric methods, fluorescence methods, and high-performance liquid chromatography (HPLC) can be used. In order to achieve a high volume reduction rate while suppressing the precipitation and modification of valuable substances contained in the raw material liquid, it is preferable to perform the first and second treatments in parallel. Performing the first and second treatments 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 raw material 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 that reduces the volume of a raw material liquid containing at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The aforementioned raw material liquid volume reduction system is A first unit for removing the first solvent from the raw material liquid, A second unit that adjusts the concentration of the second solvent or the auxiliary component in the raw material solution by a dialysis method using a dialysis membrane, It is a system that combines these elements.

[0077] Details of the raw material liquid volume reduction system of the present invention can be derived from the above-mentioned description of the raw material liquid volume reduction method of the present invention, either as is or modified according to the understanding of those skilled in the art to be compatible with the invention of the "system". The configuration of the raw material liquid volume reduction system of the present invention will be described in more detail below with reference to the drawings. Figures 5 to 8 show examples of the configuration of the raw material liquid volume reduction system of the present invention.

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

[0079] In the raw material liquid volume reduction system (1) shown in Figure 5, a blower (BL) provided in the evaporation unit (900) sends gas (e.g., air) into the raw material liquid tank (200). The volume of the raw material liquid is then reduced by discharging the introduced gas and the first solvent (b) evaporated by this gas outside the raw material liquid tank (200). The vapor of the first solvent (b) discharged from the raw material liquid tank (200) can be liquefied again and recovered by the trap (400). In the method of using an evaporation unit (900) as the first unit to supply gas into the raw material liquid tank (200), volume reduction occurs at and near the liquid surface of the raw material liquid (a), raising concerns that the composition of the raw material liquid (a) may differ depending on its location within the raw material liquid tank (200). In this regard, by providing a stirring device (not shown) in the raw material liquid tank (200), the composition of the raw material liquid (a) in the raw material liquid tank (200) can be kept uniform, and volume reduction can be performed while suppressing the precipitation, aggregation, and modification of valuable substances. In the raw material liquid volume reduction system (1) shown in Figure 5, the evaporation unit (900) preferentially removes components with high vapor pressure (first solvent). Therefore, in the raw material liquid (a) after volume reduction by the evaporation unit (900), the concentration of components with low vapor pressure (e.g., valuable substances and the second solvent or by-components) is generally higher.

[0080] In the raw material volume reduction system (1) shown in Figure 5, along with the evaporation unit (900), a dialysis membrane module (100) for performing dialysis is provided as a second unit. In the raw material volume reduction system (1) shown in Figure 5, a pump (P) sends raw material (a) at an appropriate flow rate from the bottom of a raw material tank (200) filled with raw material (a) 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 raw material (a) is adjusted manually or automatically by a flow meter or the like (not shown). Meanwhile, dialysate (d) is supplied from a dialysate tank (300) filled with dialysate (d) to the other space of the dialysis membrane module (100) (for example, the space outside the hollow fiber membrane) by a pump (P). Then, due to the concentration difference between raw material (a) and dialysate (d), the concentration of the second solvent or by-component in raw material (a) is corrected to approach the concentration of the second solvent or by-component in dialysate (d). After the concentration has been corrected, the raw material solution (a) exits the dialysis membrane module (100) and returns to the raw material solution tank (200) for circulation.

[0081] As the dialysis membrane module (100) corrects the concentration of the second solvent or minor components in the raw material solution (a), the concentration of the second solvent or minor components in the dialysate (d) will change. Therefore, in order to correct the concentration of the second solvent or minor components to a suitable level for continuous operation, it is necessary to either continuously refresh the dialysate (d) or regenerate the dialysate using a device that has a function to restore the concentration of the second solvent or minor components in the dialysate (d) to a predetermined value. Such a regeneration device is not shown in Figure 5.

[0082] The raw material volume reduction system shown in Figure 6 is an example in which a forward osmosis membrane module for performing forward osmosis is used as the first unit. The raw material volume reduction system (2) in Figure 6 comprises a forward osmosis membrane module (500), a raw material tank (200), an induction solution tank (600), a dialysis membrane module (100), and a dialysate tank (300). In the raw material volume reduction system (2) shown in Figure 6, a forward osmosis membrane module (500) and a dialysis membrane module (100) are connected in parallel to the raw material tank (200). The concentration of the second solvent or by-component is adjusted by the dialysis membrane module (100) in the same manner as in the raw material volume reduction system (1) shown in Figure 5. In volume reduction using a forward osmosis membrane module (500), the raw material liquid (a) is supplied at an appropriate flow rate from the bottom of the raw material 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 hollow fiber membrane, the raw material liquid (a) is returned to the raw material liquid tank (200) and circulated. It is preferable that this return position is far from the sampling position for supplying to the forward osmosis membrane module (500) and is at the bottom of the raw material liquid tank (200). Returning to a position far from the sampling position can suppress the excessive increase in the concentration of the second solvent or by-components in the raw material liquid (a) due to short-passing. In addition, returning to the bottom of the raw material liquid tank can prevent valuable substances in the raw material liquid (a) from precipitating and being lost on the walls of the raw material liquid tank (200). Meanwhile, in the other space of the forward osmosis membrane module (500) (for example, the space outside the membrane for hollow fiber membrane distillation), an induction solution (d) with a higher osmotic pressure than the raw material liquid (a) is introduced using a pump (P).

[0083] As a result, due to the difference in osmotic pressure between the raw material solution (a) and the induction solution (d), the first solvent moves from the raw material solution (a) to the induction solution (d), reducing the volume of the raw material solution (a). The reduced volume of the raw material solution (a) exits the forward osmosis membrane module (500) and returns to the raw material solution tank (200). The volume of the induction solution (d) increases due to the mixing of the first solvent from the raw material solution (a). Therefore, the induction solution tank (600) needs to be sufficiently large in capacity, or measures such as discharging a portion of the solution outside the induction solution tank (600) by overflow are necessary. Figure 6 does not show any equipment for discharging the induction solution (d) outside the induction solution tank (600).

[0084] The raw material volume reduction system shown in Figure 7 is an example in which a nanofiltration module for performing nanofiltration membrane processing is used as the first unit. The raw material volume reduction system (3) in Figure 7 comprises a nanofiltration membrane module (700), a raw material tank (200), a permeate tank (800), a dialysis membrane module (100), and a dialysate tank (300). In the raw material volume reduction system (3) shown in Figure 7, a nanofiltration membrane module (700) and a dialysis membrane module (100) are connected in parallel to the raw material tank (200). The concentration of the second solvent or by-component is adjusted by the dialysis membrane module (100) in the same manner as the raw material volume reduction system (1) in Figure 5. In volume reduction using the nanofiltration membrane module (700), the raw material liquid (a) is supplied at an appropriate flow rate from the bottom of the raw material 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 the raw material liquid (a) passes through the hollow fiber membrane, the flow rate is restricted by a valve (V), thereby applying pressure to the nanofiltration membrane module (700). This pressure causes the permeate (first solvent) that has permeated through the nanofiltration membrane to be collected in the permeate tank (800). The raw material liquid (a) that has passed through the valve (V) is returned to the raw material liquid tank (200) and circulated. Preferably, this return position is far from the sampling position for supplying to the nanofiltration membrane module (700) and is at the bottom of the raw material liquid tank (200). Returning the sample to a location far from the sampling point can prevent the concentration of the second solution or by-components in the raw material liquid (a) from being excessively increased by the short pass. Furthermore, returning the sample to the bottom of the raw material liquid tank can prevent valuable substances in the raw material liquid (a) from precipitating and being lost on the walls of the raw material liquid tank (200).

[0085] The raw material liquid (a) is reduced in volume by the permeation of the first solvent through the nanofiltration membrane under pressure. The reduced volume of raw material liquid (a) exits the nanofiltration membrane module (700) and returns to the raw material liquid tank (200) via the valve (V).

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

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

[0088] In all of the raw material liquid volume reduction systems shown in Figures 5 to 9, removing the raw material liquid (a) from the bottom of the raw material liquid tank (200) and returning it to the bottom of the raw material liquid tank (200) is effective in preventing the loss of valuable substances in the raw material liquid (a) by adhesion to the tank walls. Furthermore, installing a stirring device inside the raw material liquid tank (200) is also effective in ensuring stable volume reduction. In the raw material liquid volume reduction system shown in Figures 5 to 9, the specific gravity of the raw material liquid (a) can be tracked using a hydrometer (HM). This allows monitoring of the concentration of the second component or minor components in the raw material liquid (a). Then, as needed, the first or second unit can be started or stopped, or the operating conditions can be changed to adjust the composition of the raw material liquid (a) while reducing its volume, within a range where valuable substances do not precipitate, aggregate, or denature.

[0089] The degree of volume reduction of the raw material liquid (a) can be determined by measuring its volume using a liquid level gauge (LG). Finally, when the target volume reduction ratio is reached, the volume reduction can be completed. In addition to the specific gravity measurement exemplified above, other parameters that can be used to monitor the properties of the raw material liquid (a) (for example, the concentration of at least one component in the raw material liquid) include pH measurement, conductivity measurement, optical rotation measurement, refractive index measurement, ultraviolet light analysis, visible light analysis, infrared light analysis, and near-infrared light analysis. Using one or more measurement results selected from these analyses, the concentration of at least one component in the raw material liquid can be determined, for example. By simultaneously monitoring this result, the reading from 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 of the raw material liquid (a) can be reduced while maintaining the concentration of the second solvent or minor component. Furthermore, it is preferable to use an estimation model obtained by known AI technologies such as regression analysis, classification, clustering, or deep learning using neural networks, or a combination thereof, to estimate the concentration of the second solvent or minor component in the raw material liquid (a), as this allows for more accurate concentration estimation. This method allows for high-precision monitoring of the concentration of the second solvent or auxiliary component in the raw material liquid (a), and by appropriately manipulating the operating conditions, the volume can be reduced while maintaining the concentration of the second solvent or auxiliary component within a suitable range with greater precision. Therefore, the risk of valuable substances precipitation, aggregation, or degradation can be further reduced, which is preferable. [Examples]

[0090] The following describes specific examples illustrating the structure and effects of the present invention, but the present invention is not limited in any way by the following examples.

[0091] <Dialysis Membrane Module 1> As the base layer, a hollow fiber ultrafiltration membrane made of polyethersulfone with an inner diameter of 0.7 mm and an outer diameter of 1.0 mm was used. 130 of these hollow fiber ultrafiltration membranes were packed into a cylindrical plastic housing with a diameter of 2 cm and a length of 10 cm, and both ends were fixed with adhesive, resulting in an effective membrane inner surface area of ​​approximately 0.02 m². 2 A substrate layer module was fabricated. 2.5 g of piperazine and 0.8 g of sodium lauryl sulfate were placed in a 0.5 L container, and then 489.2% pure water was added to dissolve them, preparing 0.5 kg of the first solution to be used for interfacial polymerization. In a separate 0.5 L container, 0.8 g of trimesinate chloride was added and dissolved with 399.2 g of n-hexane to prepare 0.4 kg of the second solution to be used for interfacial polymerization. These solutions were passed through the support layer module described above, 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. Interfacial polymerization occurred on the inner surface of the hollow fiber ultrafiltration membrane, forming an active layer on the support layer and creating a hollow fiber dialysis membrane. Subsequently, by washing the inside of the obtained hollow fiber dialysis membranes with pure water, a dialysis membrane module 1 was fabricated 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 Module 1> In the preparation of the first solution, 10 g of m-phenylenediamine was used instead of 2.5 g of piperazine, except that the procedure was the same as for the dialysis membrane module. A module was prepared 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. Next, hot water at 85°C was flowed through the inner space of the hollow fibers for 30 minutes, followed by water at 20°C for 30 minutes. Subsequently, the module was placed in an autoclave (Tommy Seikou Co., Ltd., ES-315) and subjected to high-temperature steam at 125°C for 4 hours for heat treatment. After that, the module was washed by flowing water at 20°C through the inner space of the hollow fibers for more than 30 minutes, thereby producing a forward osmosis membrane module 1 containing 130 hollow fiber-like forward osmosis membranes.

[0093] <Dialysis Membrane Module 2> A module fabricated in the same manner as the "Forward Osmosis Membrane Module 1" described above was used as "Dialysis Membrane Module 2".

[0094] <Nanofiltration Membrane Module 1> A module fabricated in the same manner as the "Forward Osmosis Membrane Module 1" described above was used as the "Nanofiltration Membrane Module 1".

[0095] <Evaporation Unit> An evaporation unit 1 with the same configuration as the evaporation unit (900) shown in Figure 5 was fabricated using a blower (BL) that supplies air into a raw material liquid tank (200), piping for discharging the introduced gas and the first solvent (b) evaporated by this gas to the outside of the raw material liquid tank (200), and a trap (400) for storing the first solvent (b) sent through the piping.

[0096] <Membrane distillation membrane module 1> A porous hollow fiber membrane made of PVDF with an inner diameter of 0.7 mm, an outer diameter of 1.3 mm, an average pore size of 0.21 μm, a maximum pore size of 0.29 μm, and a porosity of 72% (as determined according to ASTM-F316-86) was cut to a length of 15 cm. Using multiple hollow fiber membranes obtained, a membrane module 1 for membrane distillation was fabricated. The membrane module was fabricated by using a thermosetting epoxy resin as the adhesive and bonding the hollow fiber membrane to the housing by centrifugal adhesion. At this time, the length of the portion of the hollow fiber membrane not embedded in the adhesive resin was approximately 10 cm, and the total membrane surface area of ​​the inner surface of the hollow fiber membrane was approximately 0.02 m². 2 I adjusted it so that it would be as follows. Two membrane modules with the same specifications were fabricated. Among these membrane modules, FS-392B manufactured by Fluorotechnology, Inc. was passed through the outer space of the hollow fiber membrane in a 3:1 concentration, coated onto 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 and the porous hollow fiber membrane was analyzed, and its contact angle was measured. The water contact angle of the porous hollow fiber membrane was determined by dropping 2 μL of pure water onto it under conditions of 23°C and 50% relative humidity, 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 resulting contact angle of the outer surface of the hollow fiber membrane was 132°, confirming that it possesses extremely strong hydrophobicity. The remaining membrane module 1 for membrane distillation was used in Comparative Example 3.

[0097] <Measurement of molecular weight cutoff> A 0.002 wt% aqueous solution of rhodamine B (molecular weight 479) was used as the test feed solution, and the fractional molecular weights of the obtained dialysis membrane module 1 and forward osmosis membrane module 1 were measured. Filtration was initiated by flowing the above-mentioned test supply solution through the inner space of the hollow fibers in 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 to stabilize the conditions, after which the filtrate was collected. The absorbance of the collected filtrate at a wavelength of 552 nm was measured to determine the concentration of rhodamine B in the filtrate. In both dialysis membrane module 1 and forward osmosis membrane module 1, the concentration of rhodamine B was found to be less than 1 / 10 of the concentration of rhodamine B in the test supply solution. This result means that the molecular weight cutoffs of both dialysis membrane module 1 and forward osmosis membrane module 1 are 479 or less. These results confirmed that both dialysis membrane module 1 and forward osmosis membrane module 1 are molecular sieve membrane modules.

[0098] <Measurement of permeability> The permeability of the obtained dialysis membrane module 1 and forward osmosis membrane module 1 was measured with water as the first solvent, acetonitrile as the second solvent, and acetic acid as a by-component. The permeability of acetonitrile was evaluated using water as the reference solution and a 1M aqueous solution of acetonitrile with a concentration of 1 mol / L as the test solution. The test solution 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 solution 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 solutions were parallel. Twenty minutes after the start of circulation, the acetonitrile concentration in the reference solution was measured, and the amount of acetonitrile that moved from the test solution through the hollow fiber membrane to the reference solution was quantified. The obtained value (g) was expressed as the initial concentration of the test solution (M=mol / L) and the membrane area (m²) of each module. 2 ) and the product of the cycle time (h) (m 2 The value assigned by (h·M) was defined as transparency. The permeability of acetic acid was also evaluated in the same manner as described above, except that a 1 mol / L aqueous solution of acetic acid was used as the test solution. The results described above are shown in Table 1.

[0099] [Table 1]

[0100] [Example 1] In Example 1, the first treatment was performed by forward osmosis using the raw material liquid volume reduction system (2) shown in Figure 6, and the forward osmosis membrane module (500) was the forward osmosis membrane module (500) prepared above. 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 the first solvent, 298.2 g of acetonitrile as the second solvent, and 3.6 g of acetic acid as a minor component. The initial concentration of acetonitrile in the solvent of this raw material solution (a) was 50 wt%. 600g of this raw material solution (a) was filled into a raw material solution tank (200) with a capacity of 1,000mL. Meanwhile, 1,200g of a 50wt% aqueous solution of isopropanol was filled into a induction solution tank (600) as the induction solution (d). Furthermore, 1,200g of water, to be used as dialysate (e), was filled into the dialysate tank (300).

[0101] To perform the first treatment, forward osmosis, the above-mentioned raw material liquid (a) and induction solution (d) were flowed through a forward osmosis membrane module (500) as the first unit. The flow rate of raw material liquid (a) was set to 120 mL / min, and the flow rate of induction solution (d) was set to 240 mL / min, and the two liquids were flowed in parallel. To perform dialysis as the second treatment, the raw material solution (a) and dialysate (e) were flowed through a dialysis membrane module (100) as a second unit. The flow rate of raw material solution (a) was set to 120 mL / min, and the flow rate of dialysate (e) was set to 240 mL / min, with both solutions flowing in parallel.

[0102] 4.7 hours after the start of operation, the dialysate was replaced. Specifically, the entire amount of dialysate in the dialysate tank (300) was discarded, and 1,200g of water was added. After changing the dialysate, operation was continued for a total of 8 hours. As a result, the mass of the raw material (a) became 46.2 g, and the volume reduction ratio reached 13 times. At this point, operation was stopped. The glutathione disulfide concentration in the raw material solution (a) was analyzed by ICP-MS, and the yield was calculated. The yield of glutathione disulfide was over 99%. Furthermore, a small amount of the raw material solution (a) was withdrawn every hour from the start of operation, and the concentration of acetonitrile was tracked by gas chromatography analysis. The results showed that the concentration of acetonitrile in the solvent of the raw material solution (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 its solvent composition within a desired range, and that it reduced the volume of the raw material liquid without damaging any valuable components.

[0103] [Examples 2-6] The operation was carried out in the same manner as in Example 1, except that the composition of the raw material solution and the dialysate (e) circulated through the second unit, the dialysis membrane module (100), 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 second unit, the dialysis membrane module (100).

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

[0106] [Example 9] In Example 9, the raw material liquid volume reduction system (1) shown in Figure 5 was used, in which the first treatment was performed by evaporation. The evaporation unit 1 prepared above was used as the evaporation unit (900), and the operation was carried out in the same manner as in Example 1, except that the composition of the raw material liquid and the dialysate (e) circulated to the second unit, the dialysis membrane module (100), were changed as shown in Table 2.

[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 starting operation, when the volume reduction ratio reached 2.6 times, cloudiness was observed in the raw material liquid, so operation was stopped. The turbid raw material solution was filtered to remove precipitated solids, and the yield of valuable substances was calculated by analyzing the glutathione disulfide concentration in the filtrate. The yield of valuable substances in Comparative Example 1 was 59.9%. Furthermore, by taking small amounts of the raw material liquid every hour from the start of operation and tracking the acetonitrile concentration using gas chromatography analysis, it was confirmed that the acetonitrile concentration increased over time, rising from an initial concentration of 50 wt% to 61 wt% at the time of shutdown.

[0108] [Comparative Example 2] The operation was carried out in the same manner as in Example 1, except that the forward osmosis membrane module (500) was not used. While monitoring the weight of the raw material liquid in the raw material liquid tank (200), no decrease in the mass of the raw material liquid was observed even after 1 hour from the start of operation. Therefore, in this comparative example, it was determined that volume reduction was not progressing, and the operation was stopped.

[0109] [Comparative Example 3] As a second unit, membrane distillation membrane module 1 was used instead of dialysis membrane module (100), and membrane distillation was performed while circulating 10°C cooling water instead of dialysis. Otherwise, the operation was carried out in the same manner as in Example 1. Four hours after the start of operation, a change in appearance suggesting membrane wetting of the membrane distillation membrane module was observed, and the operation was stopped. The glutathione disulfide concentration in the raw material solution (a) was analyzed by ICP-MS analysis, and the yield at the time of operation stoppage 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 for Examples 1-9 and Comparative Examples 1-4 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 above, when only the first treatment was performed, although the volume of the raw material liquid decreased, precipitates formed in the raw material liquid as the volume decreased, and the yield of valuable substances was low. The formation of precipitates in the raw material liquid is thought to be due to the fact that while the concentration of valuable substances increased as the volume decreased, the solvent composition or the concentration of minor components was not adjusted to a range in which valuable substances could exist stably, resulting in the precipitation of valuable substances. Furthermore, the results from Comparative Example 2 showed that when only the second treatment was performed, the volume of the raw material liquid was not reduced. Furthermore, the results from Comparative Example 3 showed that when the second treatment was performed by membrane distillation, although the volume of the raw material liquid was reduced, the yield of valuable substances contained in the raw material liquid remained low. In contrast to these, it has been verified that the method of the present invention, which combines volume reduction by the first treatment with the second treatment, dialysis, can achieve a high degree of volume reduction without the generation of precipitates in the raw material solution. This is thought to be because, according to the method of the present invention, the volume of the raw material solution is reduced while the solvent composition and the concentration of minor components in the raw material solution are maintained within the desired range. From the above, it has been verified that the method of the present invention can achieve a high volume reduction ratio with a high yield of valuable materials. [Explanation of Symbols]

[0115] 1, 2, 3, 4 Raw material liquid volume reduction system 100 dialysis membrane modules 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 liquid tanks 300 dialysis fluid tanks 400 traps 500 Forward Osmosis Membrane Modules 510 Housing 511 Induction solution inlet 512 Induction solution outlet 520 Forward Osmosis Membrane 521 Base material layer 522 Active layer 600 Induction Solution Tanks 700 nanometer filtration membrane module 800 Permeate Tank 900 Evaporation Unit a Raw material liquid b. First solvent c. Reduced volume raw material liquid d inducing solution e Dialysis fluid f. Raw material liquid with adjusted component concentration. g Second solvent or minor component 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, which contains at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The above method for reducing the volume of the raw material liquid is: A first treatment to remove the first solvent from the raw material liquid, A second process in which the concentration of the second solvent or the auxiliary component in the raw material solution is adjusted by a dialysis method using a dialysis membrane, This method involves performing the following steps in parallel and mixing the raw material liquids after each process. Method for reducing raw material liquid volume.

2. The method for reducing the volume of a raw material liquid according to Claim 1, wherein the first treatment and the second treatment are performed cyclically on the raw material liquid.

3. A method for reducing the volume of a raw material liquid, comprising at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The above method for reducing the volume of the raw material liquid is: A first treatment to remove the first solvent from the raw material liquid, A second process in which the concentration of the second solvent or the auxiliary component in the raw material solution is adjusted by a dialysis method using a dialysis membrane, This method involves combining various techniques. This includes performing the second process after performing the first process, and The first treatment and the second treatment are performed cyclically on the raw material liquid. Method for reducing raw material liquid volume.

4. A method for reducing the volume of a raw material liquid, comprising at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The above method for reducing the volume of the raw material liquid is: A first treatment to remove the first solvent from the raw material liquid, A second process in which the concentration of the second solvent or the auxiliary component in the raw material solution is adjusted by a dialysis method using a dialysis membrane, This method involves combining various techniques. This includes performing the first process after performing the second process, and The first treatment and the second treatment are performed cyclically on the raw material liquid. Method for reducing raw material liquid volume.

5. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 4, wherein the dialysis membrane used in the second process is a molecular sieve membrane.

6. The method for reducing the volume of a raw material liquid according to claim 5, wherein the first treatment is a volume reduction treatment using a membrane, which is one of the following: reverse osmosis, nanofiltration, or forward osmosis.

7. The method for reducing the volume of a raw material liquid according to claim 5, wherein the first treatment is a forward osmosis method.

8. The permeability of the film used in the first treatment to the second solvent or the minor component is greater than the permeability of the film used in the first treatment. The molecular sieve membrane used in the second process has greater permeability to the second solvent or the minor component. The method for reducing the volume of a raw material liquid according to claim 6 or 7.

9. A method for reducing the volume of a raw material liquid according to any one of claims 2 to 4, comprising measuring the concentration of at least one component in the cyclically volume-reduced raw material liquid, and determining whether to carry out or stop at least one of the first and second processes, or to change the operating conditions, according to the obtained measurement values.

10. The method for reducing the volume of a raw material liquid according to claim 9, wherein the concentration measurement is performed 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, and gravimetric measurement of the raw material liquid that is being cyclically reduced in volume.

11. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 10, wherein the valuable substance is a pharmaceutical raw material.

12. A method for reducing the volume of a raw material liquid according to any one of claims 1 to 11, wherein the number average molecular weight of the valuable substance is 100 to 50,000.

13. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 12, 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.

14. The second solvent is one or more selected from water, acetonitrile, methanol, ethanol, and isopropanol. The aforementioned auxiliary component is one or more selected from the group consisting of organic acids, polymers (excluding the aforementioned valuable substances), and buffer salts. A method for reducing the volume of a raw material liquid according to any one of claims 1 to 13.

15. The method for reducing the volume of a raw material liquid according to any one of claims 1 to 14, wherein the temperature of the raw material liquid is adjusted to a range of 1°C to 50°C.

16. The method for reducing the volume of a raw material liquid according to any one of claims 6 to 8, wherein at least one selected from methanol, ethanol, isopropanol, and t-butanol is used as the solute of the induction solution used in the forward osmosis method.

17. A raw material liquid volume reduction system that reduces the volume of a raw material liquid containing at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The aforementioned raw material liquid volume reduction system is A first unit for removing the first solvent from the raw material liquid, A second unit that adjusts the concentration of the second solvent or the auxiliary component in the raw material solution by a dialysis method using a dialysis membrane, However, the system is connected in parallel and includes a mechanism for mixing the raw material liquids discharged from each unit. Raw material liquid volume reduction system.

18. The raw material liquid volume reduction system according to claim 17, further comprising a mechanism for cyclically processing the raw material liquid by the first unit and the second unit.

19. A raw material liquid volume reduction system for reducing the volume of a raw material liquid containing at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The aforementioned raw material liquid volume reduction system is A first unit for removing the first solvent from the raw material liquid, A second unit that adjusts the concentration of the second solvent or the auxiliary component in the raw material solution by a dialysis method using a dialysis membrane, It is a system that combines these elements, In the flow direction of the raw material liquid, the first unit and the second unit are connected in series in this order, and The system includes a mechanism for cyclically processing the raw material liquid using the first unit and the second unit. Raw material liquid volume reduction system.

20. A raw material liquid volume reduction system for reducing the volume of a raw material liquid containing at least a valuable substance and a first solvent, The aforementioned raw material liquid is It further contains auxiliary components other than the aforementioned valuable substance and the first solvent, or The solvent includes a mixed solvent comprising the first solvent and the second solvent, The aforementioned raw material liquid volume reduction system is A first unit for removing the first solvent from the raw material liquid, A second unit that adjusts the concentration of the second solvent or the auxiliary component in the raw material solution by a dialysis method using a dialysis membrane, It is a system that combines these elements, In the flow direction of the raw material liquid, the second unit and the first unit are connected in series in this order, and The system includes a mechanism for cyclically processing the raw material liquid using the first unit and the second unit. Raw material liquid volume reduction system.

21. The raw material liquid volume reduction system according to any one of claims 17 to 20, wherein the dialysis membrane used in the second unit is a molecular sieve membrane.

22. The raw material liquid volume reduction system according to claim 21, wherein the first unit is a unit that performs a volume reduction treatment using a membrane, which is one of the reverse osmosis method, nanofiltration method, and forward osmosis method.

23. The raw material liquid volume reduction system according to claim 22, wherein the first unit is a unit that performs forward osmosis.

24. The permeability of the film included in the first unit to the second solvent or the minor component is greater than the permeability of the second solvent or the minor component. The permeability of the molecular sieve membrane contained in the second unit to the second solvent or the minor component is greater. A raw material liquid volume reduction system according to claim 22 or 23.

25. A concentration measuring mechanism for measuring the concentration of at least one component in a raw material liquid that is being cyclically reduced in volume, and A mechanism that determines whether to operate or stop, or change the operating conditions of at least one of the first and second units, according to the measurement values ​​obtained from the concentration measuring mechanism. A raw material liquid volume reduction system according to any one of claims 18 to 20, including the above.

26. The raw material liquid volume reduction system according to claim 25, wherein the concentration measurement mechanism is a mechanism that determines the concentration of the cyclically volume-reduced raw material liquid 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, and gravimetric measurement.

27. The raw material liquid volume reduction system according to any one of claims 17 to 26, wherein the valuable substance is a pharmaceutical raw material.

28. A raw material liquid volume reduction system according to any one of claims 17 to 27, wherein the number average molecular weight of the valuable substance is 100 to 50,000.

29. The raw material liquid volume reduction system according to any one of claims 17 to 28, 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.

30. The second solvent is one or more selected from water, acetonitrile, methanol, ethanol, and isopropanol. The raw material liquid volume reduction system according to any one of claims 17 to 29, wherein the aforementioned auxiliary component is one or more selected from the group consisting of organic acids, polymers (excluding the aforementioned valuable substances), and buffer salts.

31. A raw material liquid volume reduction system according to any one of claims 17 to 30, comprising a mechanism for adjusting the temperature of the raw material liquid to a range of 1°C to 50°C.

32. The raw material liquid volume reduction system according to any one of claims 22 to 24, wherein an alcohol selected from methanol, ethanol, isopropanol, and t-butanol is used as the solute of the induction solution used in the forward osmosis method.

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