WO2015108148A1

WO2015108148A1 - Method for removing low molecular weight components

Info

Publication number: WO2015108148A1
Application number: PCT/JP2015/051086
Authority: WO
Inventors: 満哉下田
Original assignee: 国立大学法人九州大学
Priority date: 2014-01-16
Filing date: 2015-01-16
Publication date: 2015-07-23
Also published as: JPWO2015108148A1; JP6146831B2

Abstract

A method for removal of low molecular weight components contained in a sample solution by dialysis, the method being characterized in that the direction of movement of the dialysate inside the dialysis membrane is in the direction opposite to the direction of movement of the solutes in the sample solution inside the dialysis membrane and the rate of movement of the dialysate is smaller than the rate of movement of the low molecular weight components.

Description

Method for removing low molecular weight components

The present invention relates to a method for dialysis removal of low molecular weight components contained in a sample solution.

Examples of methods for desalting soy sauce using an electrodialyzer include “a method for producing unsalted soy sauce” (Patent Document 1) and “a method for producing reduced salt soy sauce” (Patent Document 2). In these methods, a cation exchange membrane and an anion exchange membrane are disposed between a cation electrode and an anion electrode, and soy sauce is supplied to the space between the both ion exchange membranes, An appropriate concentration of saline solution is supplied to the space between the electrodes, and the sodium ions in the soy sauce are diffused to the cathode side through the cation exchange membrane by the action of a direct current between the electrodes, and the chloride ions are anionized. The soy sauce is desalted by diffusing to the anode side through an ion exchange membrane.

In the electrodialysis method using an ion exchange membrane of this type, when a predetermined energization voltage is reached due to the performance of the exchange membrane, electrolysis of water in the ion exchange membrane, so-called neutral disturbance, occurs and current efficiency decreases. It is known to do. This neutral disturbance has a problem in that it causes an increase in the pH of soy sauce and a loss of amino acids as important unexposed components. Since neutral disturbance affects the quality of low-salt soy sauce, it is necessary to perform a desalting treatment within a predetermined energizing voltage range. Therefore, the desalting of soy sauce by this method is also an industrial problem that it takes a relatively long time.

Recognizing the problems associated with desalting soy sauce with such an electrodialysis machine using an ion exchange membrane, a new technology was developed ("Method for producing reduced soy sauce and manufacturing apparatus" (patent Reference 3)). That is, this technique relates to a method for producing low-salt soy sauce that can be desalted while minimizing changes in the pH of soy sauce and minimizing changes in the amino acid composition in the soy sauce, and an apparatus for producing the same.

Specifically, one or more sets of repeating units arranged in the order of a cation exchange membrane, a bipolar membrane, and an anion exchange membrane from the anode side between the anion and cation electrodes, and a cation exchange membrane and an anion exchange membrane arranged in this order 1 A low-salt soy sauce production apparatus characterized by having an electrodialysis apparatus composed of at least a pair of repeating units, and using this, the soy sauce is fed to the desalting chamber, and the salt content in the soy sauce is A method for producing reduced-salt soy sauce, characterized in that it is reduced. Such a method using a three-chamber electrodialysis tank is thought to reduce the pH increase of soy sauce and the loss of amino acids, but there is a concern that the configuration and operation of the apparatus become complicated. Furthermore, since the time required for desalting depends on the total ion amount (salt concentration) to be desalted in the electrodialysis method, the time required for desalting is unavoidable in soy sauce with a high salt concentration.

As a technique that replaces the electrodialysis desalting method, a method using a nanofiltration membrane has been studied (Non-patent Documents 1 and 2). That is, soy sauce was desalted by using a diafiltration module equipped with a membrane that allowed sodium ions and chloride ions to permeate freely while having a 59.47% blocking rate for amino nitrogen compounds. Continuously supply soy sauce diluted twice, with transmembrane pressure (treatment pressure) constant at 24 bar, and cross-flow filtration until the volume of soy sauce supplied is ½, that is, the original concentration Went. The salt removal rate of this method was 51%, and the amino nitrogen compound removal rate (loss rate) was 25.27%. Desalting using nanofiltration membranes is used in many fields, such as desalting from dyes. That is, since the dye molecule and the molecule to be removed (ion) size are significantly different, the salt content can be selectively diafiltered, but in soy sauce desalting, the molecular size of sodium ion and amino acid is not so different. It is considered that a loss of 25% of amino acids occurred for a desalting rate of 51%. Furthermore, membrane fouling becomes a problem when a concentrated solution having a complicated composition such as soy sauce is filtered by a nanofiltration method.

Japanese Patent Publication No. 47-46360 Japanese Examined Patent Publication No. 61-20263 Japanese Patent Publication No. 7-313098

Dialysis methods have been used exclusively to eliminate low molecular components in dilute aqueous solutions. However, when the osmotic pressure of the sample solution is considerably higher than that of the dialysate, any solute molecules (ions) in the sample solution can be osmotically flowed because the rate of the dialysate flowing into the sample solution (osmotic flow) is large. It is impossible to diffuse and move to the dialysis side against this. An object of the present invention is to provide a method for selectively dialysis-removing a low molecular weight component in a sample solution by controlling the movement flow rate or movement speed of a solvent in the pores of a dialysis membrane.

As a result of intensive studies to solve the above problems, the present inventor found that the movement direction of the dialysate in the dialysis membrane was opposite to the movement direction of the solute in the sample solution in the dialysis membrane, and It has been found that the above problem can be solved by making the advection speed of the dialysate smaller than the movement speed of the low molecular weight component, and the present invention has been completed.
That is, the present invention is as follows.
(1) A method for removing low molecular weight components contained in a sample solution by dialysis, wherein the moving direction of the dialysate in the dialysis membrane is opposite to the moving direction of the solute in the sample solution in the dialysis membrane. And the said dialysate moving speed is made smaller than the moving speed of the said low molecular weight component, The method characterized by the above-mentioned.
(2) The method according to (1), comprising at least one step selected from the group consisting of the following (a) to (c):
(A) The step of independently controlling the supply flow rate and the discharge flow rate of the sample solution (b) The step of independently controlling the supply flow rate and the discharge flow rate of the dialysate (c) The pressure that applies the pressure applied to the sample solution to the dialysate (3) The ratio (A / B) of the supply flow rate (A) and the discharge flow rate (B) of the sample solution is in the range of 0.7 or more and less than 1.0, (1) or ( The method according to 2).
(4) The method according to any one of (1) to (3), wherein the sample solution is a seasoning or an alcoholic beverage.
(5) The method according to any one of (1) to (4), wherein the dialysate is water.
(6) Performed in a dialysis apparatus having a sample solution flow path 1, a dialysate flow path 2 and a dialysis membrane separating the flow path 1 and the flow path 2 (1) to (5) The method of any one of these.
(7) Sample solution flow path 1, dialysate flow path 2, dialysis membrane separating the flow path 1 and flow path 2, and a sample flow rate control mechanism for independently controlling the supply flow rate and discharge flow rate of the sample solution; A dialysis apparatus provided with at least one flow rate control mechanism selected from a dialysate flow rate control mechanism that independently controls a supply flow rate and a discharge flow rate of a dialysate.
(8) Sample solution channel 1, dialysate channel 2, dialysis membrane separating channel 1 and channel 2, and pressure control for controlling pressure applied to sample solution and pressure applied to dialysate Dialysis machine with mechanism.
(9) The flow rate control mechanism independently controls the supply flow rate and the discharge flow rate of the sample solution so that the ratio of the supply flow rate and the discharge flow rate of the sample solution is in the range of 0.7 to less than 1.0. Or the apparatus according to (7), wherein the supply flow rate and the discharge flow rate of the dialysate are controlled independently.
(10) The pressure control mechanism controls the pressure so that the ratio (A / B) of the supply flow rate (A) to the discharge flow rate (B) of the sample solution is in a range of 0.7 or more and less than 1.0. The apparatus according to (8).
(11) In the sample solution using the method described in any one of (1) to (6) or using the apparatus described in any one of (7) to (10) The method for producing a low molecular weight component removing solution is characterized in that the low molecular weight component contained in is dialyzed and the sample solution after dialysis treatment is collected.
(12) The method according to (11), wherein the sample solution is a seasoning or an alcoholic beverage.
(13) The method according to (12), wherein the seasoning is soy sauce.

According to the present invention, it is possible to selectively dialyze only low molecular weight components contained in a sample solution.

It is a schematic diagram explaining the concept of this invention. It is a figure which shows the dialysis module in the dialysis apparatus of this invention. It is a figure which shows the aspect which connected the dialysis module. It is a figure which shows the dialysis apparatus by the flow control of this invention based on the supply flow rate and discharge flow rate control of a sample solution. It is a figure which shows the dialysis apparatus by the flow control of this invention based on the supply flow rate and discharge flow rate control of a dialysate. It is a figure which shows the dialysis apparatus by the pressure control of this invention. 3 is a graph summarizing the influence of membrane permeation rate on the reduction rate of Na ⁺ ions and amino nitrogen compounds (Examples 1-1 to 1-3, Comparative Example 1). However, membrane permeation rate = (solvent movement rate in dialysis membrane pores) × (dialysis membrane porosity). FIG. 3 is a diagram showing the results of desalting treatment of soy sauce (Examples 2-1 to 2-3, Comparative Example 2). FIG. 3 is a diagram showing the results of desalting treatment of soy sauce (Examples 3-1 to 3-3, Comparative Example 3). It is a figure which shows the influence of the membrane permeation | transmission speed | rate which has on the selectivity of dialysis. It is a figure which shows the influence of the dialysate supply flow rate on the removal rate of Na ⁺ ion and amino nitrogen.

Hereinafter, the present invention will be described in detail. It should be noted that documents cited in the present specification, as well as published gazettes, patent gazettes, and other patent documents are incorporated herein by reference. This specification also includes the content of the specification of Japanese Patent Application No. 2014-6023 (filed on Jan. 16, 2014), which is the basis for claiming priority of the present application.
1. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for selectively dialysis removing low molecular weight components in a sample solution using a dialysis membrane in order to dialyze off low molecular weight components contained in the sample solution.
Specifically, the present invention relates to a method for dialysis removal of low molecular weight components contained in a sample solution, the dialysis fluid moving speed and direction in the pores of the dialysis membrane, and the low molecular weight components in the sample. A method characterized by adjusting the moving speed and the direction thereof (hereinafter referred to as “dialysis method of the present invention”) is provided.
In one aspect of the present invention, in the dialysis method of the present invention, the direction of movement of the dialysate in the dialysis membrane is opposite to the direction of movement of the solute in the sample solution in the dialysis membrane, and The moving speed is made smaller than the moving speed of the low molecular weight component. In one embodiment of the present invention, the dialysis method of the present invention includes (1) independently controlling the supply flow rate and the discharge flow rate of the sample solution, and (2) independently controlling the supply flow rate and the discharge flow rate of the dialysate. Or (3) The pressure applied to the sample solution is higher than the pressure applied to the dialysate.

The dialysis method includes a diffusion dialysis method using a nonionic semipermeable membrane, and an electrodialysis method or an electrodialysis method using an ion exchange membrane or a charged membrane. In general, “dialysis” means a method using a non-ionic membrane.
Dialysis is classified into the following modes according to the flow state of the solution in the pores of the nonionic dialysis membrane.
(a) The solvent does not substantially move (convect) in the pores of the dialysis membrane. In this case, the solute molecules move from the high concentration side to the low concentration side only by diffusion.
(b) While filtering a part of the sample solution to the dialysate side, low molecular weight components are discharged to the dialysate side by molecular diffusion. This is called filtration dialysis. The filtration dialysis method is characterized in that not only diffusion but also relatively large molecules (ions) having a low diffusion rate can be discharged to the dialysis side by solution movement accompanying filtration.

The dialysis methods (a) and (b) are known. In these dialysis methods, the size of the molecule to be dialyzed depends on the molecular weight cut off of the dialysis membrane.
In contrast, the method of the present invention dialyzes only the low molecular weight component while allowing the dialysate to permeate through the dialysis membrane to the sample solution side at a controlled flow rate. In the method of the present invention, the excluded molecule size does not depend on the molecular weight cut off of the dialysis membrane, but the ratio between the rate of movement of the dialysate toward the sample solution (permeation rate) and the rate of movement of the solute component (diffusion rate). Control by (Peclet number).
That is, the method of the present invention performs dialysis while independently controlling the supply flow rate and the discharge flow rate of the sample solution. Here, in this specification, the movement of the dialysate toward the sample solution is referred to as “permeation” or “advection”, and the movement speed is also referred to as “permeation speed” or “advection speed”. The movement of the solute component in the sample solution is called “diffusion”, and the moving speed is also called “diffusion speed”. In this specification, the movement of a substance or solution is expressed by the term “movement”. However, according to the above definition, “movement” of dialysate means “permeation” or “advection”, and a solute in a sample solution. Those skilled in the art can easily understand that the movement of components means “diffusion”.

The method of the present invention will be described with reference to FIG.
FIG. 1 is a schematic diagram showing movement of a solvent and a solute (advection and diffusion, respectively) in the dialysis membrane pores. A dialysis membrane exists between the sample and the dialysate, and has A component (●) and B component (▲) in the sample, and pores through which the dialysate moves. The components and dialysate in the sample move through the pores. FIG. 1 shows an embodiment in which the A component, the B component, and the dialysate are present in the pores of the dialysis membrane. The direction and length of the arrow indicate the moving direction and moving speed of the A component and the B component, and the moving direction and moving speed of the dialysate (solvent). In FIG. 1, the moving direction is considered as a vector in the left-right direction (x-axis direction in the three-dimensional right-handed system coordinate), and the vertical direction (y-axis direction in the three-dimensional right-handed system coordinate) and the front-back direction (three-dimensional right-handed system). The presence of a vector in the z-axis direction in the coordinates can be ignored.

As shown in FIG. 1a, when the ratio between the supply flow rate and the discharge flow rate of the sample solution (supply flow rate / discharge flow rate) is small (for example, less than 0.7), the dialysate (water) moves (transfers). The speed (left arrow in FIG. 1a) is larger than the movement (diffusion) speed of both components A and B (right arrow in FIG. 1a). For this reason, dialysate advances toward the sample, and components in the sample do not advance toward the dialysate.
FIG. 1b shows a state in which the ratio between the supply flow rate and the discharge flow rate of the sample solution (supply flow rate / discharge flow rate) is within a predetermined value range. The “predetermined value” is a value in which the moving speed of the dialysate (membrane permeation speed) is smaller than the moving speed (diffusion speed) of the A component and is larger than the moving speed (diffusion speed) of the B component Value. In this aspect, the membrane permeation direction of the dialysate is opposite to the A component and the B component, but the membrane permeation rate of the dialysate (the length of the arrow) is smaller than the A component and larger than the B component. . In this case, since the diffusion rate of the A component is higher than the advection rate of the dialysate, the A component moves to the dialysate side. On the other hand, since the diffusion rate of the B component is smaller than the advection rate of the dialysate, the B component does not move to the dialysate side.
FIG. 1c shows a state in which the ratio of the supply flow rate and the discharge flow rate of the sample solution (supply flow rate / discharge flow rate) is larger than 1. In this embodiment, since the direction of advection of the dialysate (solvent) in the pores is the same as the diffusion direction of both components A and B, both components A and B are discharged to the dialysate side (filtering). Dialysis).

In the present invention, the embodiment shown in FIG. 1b is used. If the A component is sodium ions or ethanol molecules, and the B component is an amino acid or aroma component, the ratio of the sample solution supply flow rate to the discharge flow rate in FIG. 1b is set to a predetermined value, or a predetermined pressure is applied. Thus, the A component (Na ions, ethanol molecules, etc.) can be removed from the sample, while the B component (amino acid, aroma component, etc.) can remain in the sample.

According to the method of the present invention, only low molecular weight components that can diffuse against the flow of the dialysate in the pores of the dialysis membrane are discharged to the dialysate side. For example, Na ions, K ions, Cl ions, and even ethanol molecules can be discharged to the dialysate side while holding a compound having a molecular weight of about 100 such as amino acids and aromatic components in the sample.
Therefore, the method of the present invention is a method that utilizes the fact that the flow direction of the liquid that permeates through the dialysis membrane is the opposite of conventional filtration dialysis.

In addition, the present invention makes it possible to selectively dialyze low molecular weight components by controlling the flow rate (osmosis) of the dialysate generated by osmotic pressure into the sample solution. Thereby, only low molecular weight substances can be removed by dialysis from high osmotic pressure samples such as soy sauce and wine.

The present invention adjusts the ratio of the supply flow rate and the discharge flow rate of the sample solution (supply flow rate / discharge flow rate) within a range of 0.7 or more and less than 1.0 (that is, not including 1.0). While holding, desalting or ethanol removal is performed. In this method, since a nonionic semipermeable membrane is used, not only an ionic substance but also a nonionic substance can be removed.

In the present invention, the moving speed of the solution in the pores of the dialysis membrane is controlled by (1) controlling the supply flow rate and discharge flow rate of the sample solution, and (2) controlling the supply flow rate and discharge flow rate of the dialysate. (3) The desired value can be set by the difference in pressure applied to the sample solution and the dialysate, or by appropriately combining the above (1) to (3). At this time, the present inventors have been able to permeate the membrane against the movement of the solvent while the component having a high diffusion rate (low molecular weight component), but to prevent the component having a low diffusion rate from permeating the membrane. By controlling the speed of movement of the solvent in the pores of the membrane, it was found that only low molecular weight components can be selectively dialyzed, and the present invention has been completed.

In the dialysis method of the present invention, the low molecular weight component has a molecular weight of 20 to 150, preferably 20 to 100, more preferably 20 to 80, still more preferably 20 to 70, and still more preferably 20 to 60. .
In the dialysis method of the present invention, the low molecular weight solute is at least one molecule or ion selected from the group consisting of alkali metals, alkaline earth metals, alcohols, carboxylic acids, and inorganic acids / bases.

Examples of the alkali metal molecule include lithium, sodium, potassium, rubidium, cesium, and francium, preferably lithium, sodium, and potassium.
Examples of alkaline earth metal molecules include beryllium, magnesium, calcium, strontium and barium, preferably beryllium, magnesium and calcium.

Examples of alcohol molecules include lower alcohols, and more specifically, methanol, ethanol, propyl alcohol, butyl alcohol, ethylene glycol, glycerin, and the like, preferably methanol, ethanol, and propyl alcohol.
Examples of carboxylic acids include formic acid, acetic acid, propionic acid, butyric acid, lactic acid, and the like, preferably acetic acid and lactic acid.
Examples of the inorganic acid include hydrochloric acid, nitric acid, phosphoric acid, and sulfuric acid, and examples of the inorganic base include sodium hydroxide and ammonia.

The dialysis method of the present invention can be performed using the dialysis membrane module shown in FIGS. According to this dialysis membrane module, advection diffusion dialysis can be performed. Examples of such devices include a sample solution flow path (referred to as flow path 1), a dialysate flow path (referred to as flow path 2), and Examples thereof include a dialysis apparatus having a dialysis membrane that separates the sample solution flow path (flow path 1) and the dialysate flow path (flow path 2).
When the dialysis method of the present invention is performed using such an apparatus, (1) the supply flow rate and the discharge flow rate of the sample solution are controlled independently, and (2) the supply flow rate and the discharge flow rate of the dialysate are made independent. (3) by supplying the sample solution to the flow path 1 at a supply pressure higher than the supply pressure of the dialysate, or by appropriately combining the above (1) to (3) Low molecular weight components contained in the sample solution can be selectively removed by dialysis. Details of the flow rate control will be described later.

In the dialysis method of the present invention, the sample solution and the dialysate may be supplied to the respective flow paths 1 and 2 at the same flow rate, or may be supplied at different flow rates.
The flow rates of the sample solution and the dialysate are set in consideration of the removal rate of components to be removed and the residual rate of components that should not be removed. Furthermore, although pressure loss occurs due to the flow of the sample solution and dialysate in the membrane module, it is preferable to reduce these pressure losses in the dialysis method of the present invention. That is, it is necessary to control the flow rates of the sample solution and the dialysate so that the pressure loss is 1.0 times or less, preferably 0.5 times or less, more preferably 0.1 times or less of the transmembrane pressure difference. Furthermore, since the generated pressure loss also depends on the inner diameter of the hollow fiber membrane, a hollow fiber membrane having a large inner diameter is preferable in order to reduce the pressure loss. However, the mass transfer in the direction perpendicular to the flow of the sample solution in the hollow fiber membrane should not have an excessively large inner diameter so as not to be rate limiting in the dialysis of the present invention. In the dialysis method of the present invention, the hollow fiber membrane has an inner diameter of 0.1 mm or more and 2.0 mm or less, preferably 0.2 mm or more and 1.0 mm or less, more preferably 0.3 mm or more and 0.6 mm or less.

The sample solution is not particularly limited as long as it contains a low molecular weight component, but is preferably a seasoning or an alcoholic beverage. Examples of seasonings include soup stock, soy sauce, fish sauce, amino acid mixture, mirin, bouillon, fruit vinegar, and brewed vinegar. Examples of alcoholic beverages include distilled liquors such as whiskey, brandy, liqueur, tequila, vodka, and rum in addition to brewed liquors such as beer, wine, and sake.
Furthermore, sodium ions and potassium ions in the whey can be selectively reduced. It is also effective for dialysis of hydrogen ions and chloride ions from hydrochloric acid hydrolyzate of protein or dialysis of sodium ions and chloride ions after neutralization. Furthermore, although chloropropanols produced during the decomposition of hydrochloric acid are substances that are carcinogenic, they can be reduced by the dialysis method of the present invention.
The present invention is also applicable to ethanol fermentation liquid, ethanol from acetone-butanol fermentation liquid, and recovery of acetone and butanol.

The dialysate used in the present invention is not particularly limited, and water can be preferably used. For example, water that does not contain the low-molecular-weight component to be removed, or the concentration of the component in the sample solution is less than 10%, preferably less than 5%, more preferably less than 2% of the concentration in the sample. Aqueous solution (water substantially free of the components in question) can be used as the dialysate. Examples of such water include water commercially available as drinking water, tap water, deionized water, precision filtered water, and distilled water. When advection diffusion dialysis is performed in multiple stages, it is possible to reuse the dialysate flown in the second stage in the first stage.
In order to remove dissolved oxygen from the sample solution or avoid an increase in the dissolved oxygen concentration, degassed water can be used as the dialysate.

By carrying out the dialysis method of the present invention or using the dialysis apparatus of the present invention, the low molecular weight component contained in the sample solution is removed by dialysis, and the resulting sample solution after dialysis treatment is recovered. A solution with a reduced concentration of molecular weight components can be produced. Therefore, the present invention provides, as another aspect, a method for producing a solution in which the concentration of the low molecular weight component is reduced by carrying out the dialysis method of the present invention, and the concentration of the low molecular weight component produced by the production method is reduced. Provide the prepared solution. A low molecular weight component taken into the dialysate can be newly used effectively. For example, a dialysate containing ethanol can be used as a material for a new low alcohol beverage. It can also be used for the purpose of recovering the target substance from the fermentation broth.
Examples of the sample solution after the dialysis treatment include desalted seasonings and low-concentration alcoholic beverages. When soy sauce or alcoholic beverage is used as the sample solution, desalted soy sauce and low-concentration alcoholic beverage are produced by the method of the present invention.

Although the application of the present invention is not limited to the desalination of soy sauce and the preparation of a low alcohol beverage, the present invention will be described with respect to the desalting of soy sauce as one of application examples.
When a high-concentration sample solution and dialysate (water) are present across the dialysis membrane, water molecules flow from the dialysis side to the sample side through the membrane pores. This is called osmotic flow. On the other hand, low molecular weight solute molecules (ions) in the sample diffuse and move from the sample solution side to the dialysate side. The flow rate of the dialysate into the sample, that is, the flow rate of the osmotic flow depends on the pressure difference (osmotic pressure) between the sample solution and the dialysate unless the characteristics of the dialysis membrane (for example, pore diameter and film thickness) are considered. To do. The osmotic pressure in the present invention is not a little different from that generally known, and will be described below. That is, the osmotic pressure is considered to be a transmembrane pressure difference generated depending on the concentration difference of all solutes when two solutions contact each other through a semipermeable membrane. It is known that the osmotic pressure of soy sauce exceeds 10 MPa. On the other hand, the transmembrane pressure difference generated in a dialysis membrane having a molecular weight cut-off of 10 kD is approximately 18.5 kPa (Example 1, subtracting 1.5 kPa of pressure loss from the additional pressure of 20 kPa at which the solvent moving speed is zero) in the method of the present invention. ) Was found to be extremely low. This osmotic pressure is considered to decrease as the pore size (fractional molecular weight) of the membrane increases.

It is clear that the fractional molecular weight of the dialysis membrane used in the dialysis of the present invention does not mean a molecular weight that can be dialyzed. It is sufficient if the osmotic pressure generated by this membrane can be easily controlled by the pressure applied from the outside. Or what is necessary is just to be able to control the supply amount and discharge | emission amount of a sample solution easily. However, since it is important that the moving speed of the solvent flowing in each pore of the dialysis membrane is uniform, the pore size distribution should be as small as possible.
As a further aspect, in order to control the movement of the solvent in the pores of the dialysis membrane, the following method is possible.

1. Flow rate control-The movement speed of the solvent in the pores of the dialysis membrane can be controlled by individually controlling the flow rate of the sample solution flowing into the membrane module and the flow rate of discharge from the membrane module.
-The moving speed of the solvent in the pores of the dialysis membrane can be controlled by individually controlling the flow rate of the dialysate into the membrane module and the discharge flow rate from the membrane module.
The above controls can be used alone or in combination as appropriate.

2. Pressure control ・ By generating a differential pressure between the sample solution and the dialysate separated by the dialysis membrane, the moving speed of the solvent in the membrane pores can be controlled.
In the method of supplying the sample solution to the membrane module by a pump, a differential pressure valve is installed at the membrane module outlet of the sample solution.
-A differential pressure valve is installed at the inlet where the dialysate flows into the membrane module, a pump is installed at the outlet of the membrane module, and the dialysate is sucked and discharged by the pump.
A differential pressure can be applied between the sample solution and the dialysate by the head pressure difference between the position where the sample solution discharge port communicates with the atmosphere and the position where the dialysate outlet communicates with the atmosphere.
The above controls can be used alone or in combination as appropriate.

The pressure loss generated when the sample solution or dialysate flows through the membrane module is 1.0 times or less of the osmotic pressure generated in the system, preferably 0.5 times or less of the osmotic pressure, and more preferably The osmotic pressure is 0.1 times or less.

透析 The dialysis membrane used in the present invention may be either a homogeneous membrane or a heterogeneous membrane, and is preferably a heterogeneous membrane having a dense thin layer on the inner surface of the hollow fiber. The polysulfone membrane (Spectrum Laboratories) used in the examples is a heterogeneous membrane having a dense layer on the inner surface.

The movement of the low molecular weight component dissolved in the sample in the pores of the dialysis membrane is caused not only by the diffusion of the target molecules and ions but also by the movement of the solution. That is, the movement of the low molecular weight component must be considered as the sum of movement due to diffusion and movement due to the advection of the solution. This phenomenon is called advection diffusion. In order to apply this advection diffusion phenomenon to the dialysis removal process of low molecular weight components such as salt and alcohol, the movement speed of the solvent in the pores of the dialysis membrane is precisely related to the movement speed of the low molecular weight components. It is important to control.

Consider again the case where a high-concentration sample solution and dialysate (for example, water) are present with the dialysis membrane sandwiched. As described above, water molecules flow to the sample side through the pores of the dialysis membrane. At the same time, the low molecular weight component diffuses and moves from the sample side to the dialysis side according to the inherent diffusion rate. When the osmotic pressure difference between the sample solution and dialysate is large, the movement speed of the water in the pores is also large, so that low molecular weight components in the sample diffuse and move to the dialysis side against the momentum of dialysate inflow. I can't. Therefore, the Peclet number (Pe = uL / d) is considered as a dimensionless number representing the ratio of solute movement due to solvent flow and solute movement due to diffusion. u is the flow rate of water, L is the pore length (film thickness), and d is the diffusion coefficient of the solute.

When the Peclet number is greater than 1, the movement of the solute indicates that the solvent flow contributes more than the diffusion, and conversely when the Peclet number is less than 1, the diffusion contributes more than the solution flow. Film thickness is an important parameter directly related to the Peclet number. In order to reduce the distribution of the Peclet number determined for each pore of the membrane, the pore diameter variation and the thickness variation due to the site of the hollow fiber membrane should be minimized. When the film thickness is thin, it is necessary to increase the moving speed of the solvent. This increases the dilution of the sample solution with dialysate, so an excessively thin membrane is not suitable for use. However, when the film thickness is large, the mass transfer speed through the film is greatly reduced, which is also not preferable. From the above, in the dialysis method of the present invention, the preferred film thickness is 20 μm or more and 80 μm or less, more preferably 30 μm or more and 60 μm or less.
In the present invention, with respect to the low molecular weight component to be discharged, the Peclet number is preferably 0 or more and 1.0 or less, more preferably 0.1 or more and 0.6 or less. Regarding the component to be left in the sample, the Peclet number is preferably 0.6 or more and 2.0 or less, more preferably 0.8 or more and 1.5 or less.

The present invention is characterized in that a dialysis membrane is used to move a solution through a very short flow path by a plug flow method. Solvent movement and solute molecule movement (diffusion) are performed when the solvent movement direction in the pores and the solute molecule (ion) diffusion direction are opposite (that is, when dialysate flows in), and the solvent movement. In some cases, the direction of the solute and the direction of movement of the solute are the same (that is, a portion of the soy sauce is extruded through the pores). When the solvent moving direction and the solute moving direction are opposite and the solvent moving speed is larger than the diffusion speed of the component, the component is not discharged to the dialysate side. If the solvent movement direction and the diffusion direction are opposite and the solvent movement rate is greater than the diffusion rate of components other than the low molecular weight component and smaller than the diffusion rate of the low molecular weight component to be dialyzed, the low molecular weight component is selectively selected. Dialysis can be performed.

When the solvent movement rate is near zero, the movement of solute molecules is governed only by diffusion. When the solvent movement direction and the solute diffusion direction are the same, that is, when a part of the sample solution is discharged to the dialysis side, the solute movement is the sum of the solvent movement and the solute diffusion contribution. Since the molecular weight of the dialysis membrane is from several kD to several tens of kD, when the solvent movement direction and the solute diffusion direction are the same, not only low molecular weight components but also relatively large molecules (ions) below the molecular weight cut-off As a result, the selectivity of dialysis of low molecular weight components decreases.
In the present invention, the selectivity (selectivity coefficient) for allowing the target molecule to remain in the sample while dialyzing the low molecule is represented by, for example, the Na ⁺ ion removal rate / amino nitrogen reduction rate. If this value is 10 or more, it is judged that selectivity is good and low molecules can be efficiently removed. The removal efficiency of the low molecular weight component when the selection coefficient is 4 to 20 is 90% to 30%. That is, 90% to 30% of the entire low molecular weight substance contained before dialysis is removed.

In short, in order to efficiently perform dialysis of low molecular weight components to be eliminated while controlling the loss of the solute to be retained in the sample by controlling the moving speed of the solvent in the pores of the dialysis membrane, The dialysis of the present invention, that is, the advection diffusion dialysis method has been devised.
In the present invention, the loss of the solute (amino nitrogen such as amino acid) to be retained in the sample can be suppressed to 25% or less, preferably 15% or less, more preferably 10% or less.

As one application example of the present invention, soy sauce was desalted. That is, the movement of sodium ions, potassium ions and chloride ions toward the dialysate side is governed by diffusion, while the movement of amino nitrogen compounds (amino acids) and aroma components is governed by the movement of the solvent. By controlling the moving speed of the solvent in the pores, low-salt soy sauce was produced without any deterioration in flavor.
Furthermore, according to this method, since the soy sauce does not permeate the membrane and only the dialysate (water) permeates the membrane, it is also a feature of this method that the membrane is hardly soiled.

3. The apparatus of the present invention independently controls the sample solution flow path 1, the dialysate flow path 2, the dialysis membrane separating the flow path 1 and the flow path 2, and the supply flow rate and the discharge flow rate of the dialysate. It is a dialysis apparatus provided with a flow rate control mechanism that permeates through a dialysis membrane.
FIG. 4 is an example of the advection diffusion dialysis apparatus 40 including the flow path 1, the flow path 2, the dialysis membrane, and a flow rate control mechanism for the solution that permeates the dialysis membrane. The sample solution storage tank 401, the treatment solution storage tank 402, A dialysate storage tank 403, a discharge dialysate storage tank 404, a sample supply pump 405, a sample treatment liquid discharge pump 406, a dialysate supply pump 407, a pressure gauge 408, a dialysis module 409, and the like are provided. The dialysis module 409 includes a sample solution channel, a dialysate channel, and a dialysis membrane that separates the sample solution channel and the dialysate channel. The flow rate control mechanism includes a sample supply pump 405 and a sample processing liquid discharge pump 406. In the present specification, the same reference numerals indicate the same elements in the apparatus of the present invention.

In the advection diffusion dialysis apparatus 40 shown in FIG. 4, the dialysis module 409 can be configured as shown in FIG. 2. Approximately 5,000 membranes can be stored in a polypropyne cylindrical container (diameter 33 mm, length 250 mm). In this case, the surface area of the dialysis membrane accommodated in the dialysis module 409 is about 6500 cm ² .
An upper surface and a lower surface of the dialysis module 409 have an inlet 201 and an outlet 202 for sample solution such as soy sauce, respectively, and are provided with a sample solution flow path 1 and a dialysate flow path 2 (not shown).
A cylindrical side surface (for example, made of polypropylene) of the dialysis module 409 is provided with an introduction port 203 for supplying dialysate (for example, water) and a discharge port 204 for discharging.
The sample solution in the sample solution storage tank 401 is sucked by the sample supply pump 405 having a variable flow rate and supplied to the dialysis module 409. The sample supply pressure at this time is measured by a pressure gauge 408. The tube 210 (FIG. 2) of the dialysis module 409 is connected to the top of the dialysis module 409, and the sample solution is supplied from the sample supply port 201 to the top of the dialysis module 409 through the tube 210. The sample solution supplied to the top of the dialysis module 409 descends in the sample solution flow path in the dialysis module 409, that is, in the hollow fiber membrane, and passes through the sample discharge port 202 at the bottom through the sample discharge pump 406 whose flow rate is variable, and the treatment solution It reaches the storage tank 402.

On the other hand, the dialysate (for example, water) in the dialysate storage tank 403 is introduced from the introduction port 203 on the cylindrical side near the bottom of the dialysis module 409 by a dialysate feed pump 407 having a variable flow rate. It rises through the gap, is discharged from the discharge port 204 on the cylindrical side near the top of the dialysis module 409, and reaches the discharged dialysate storage tank 404.
Since the sample solution flow path 1 and the dialysate flow path 2 communicate with each other through the pores of the dialysis membrane, the sample solution supply amount and discharge amount are set, and the dialysate supply amount is set. The amount of dialysate discharged is automatically determined.

FIG. 5 is an example of the advection diffusion dialysis apparatus 50 including the flow path 1, the flow path 2, the dialysis membrane and the flow rate control mechanism that permeates the dialysis membrane, and includes a sample solution storage tank 401, a treatment solution storage tank 402, and a dialysate A storage tank 403, a discharged dialysate storage tank 404, a sample supply pump 405, a dialysate supply pump 407, a dialysate discharge pump 507, a pressure gauge 408, a dialysis module 409, and the like are provided. The dialysis module 409 includes a sample solution channel 1, a dialysate channel 2, and a dialysis membrane that separates the channel 1 and the channel 2. The flow control mechanism of the dialysate that permeates through the dialysis membrane includes a dialysate supply pump 407 and a dialysate discharge pump 507.
The configuration example of the dialysis module 409, the flow of the sample solution and the dialysate, and the like can be based on the description of the advection diffusion dialysis apparatus 40 shown in FIG.

Furthermore, the dialysis apparatus of the present invention is applied to the sample solution flow path 1, the dialysate flow path 2, the dialysis membrane separating the flow path 1 and the flow path 2, and the pressure applied to the sample solution and the dialysate. A dialysis apparatus including a pressure control mechanism for controlling pressure, and includes a differential pressure control mechanism between a sample solution and a dialysis solution.
FIG. 6 is an example of a dialysis apparatus 60 provided with a sample solution flow path 1, a dialysate flow path 2, a dialysis membrane separating the flow path 1 and the flow path 2, and a transmembrane differential pressure control mechanism. , Sample solution reservoir 401, treatment solution reservoir 402, dialysate reservoir 403, discharge dialysate reservoir 404, sample supply pump 405, back pressure adjustment valve 606, dialysate feed pump 407, pressure gauge 408, and dialysis A module 409 and the like are provided.

In the advection diffusion dialysis apparatus 60 shown in FIG. 6, the dialysis module 409 can be configured as shown in FIG. 2, for example, a polysulfone hollow fiber having an outer diameter of 280 μm, an inner diameter of 200 μm, a length of 208 mm, and a molecular weight cut off of 10,000 Da. Approximately 5,000 membranes can be stored in a polypropyne cylindrical container (diameter 33 mm, length 250 mm). The surface area of the dialysis membrane accommodated in the dialysis module 409 at this time is about 6500 cm ² . On the upper and lower surfaces of the dialysis module 409 are a sample solution inlet 201 and an outlet 202, respectively. A cylindrical side surface made of polypropylene is provided with an inlet 203 for supplying dialysate and an outlet 204 for discharging. The sample solution in the sample solution storage tank 401 is sucked by the sample supply pump 405 having a variable flow rate and supplied to the dialysis module 409. The sample supply pressure at this time is measured by a pressure gauge 408. The sample solution supplied to the top of the dialysis module 409 descends through the hollow fiber membrane in the dialysis module 409, is discharged from the sample outlet at the bottom, and reaches the treatment solution storage tank 402. The back pressure regulating valve 606 is provided on the sample solution outlet side of the dialysis module 409, and suppresses the inflow of the dialysate into the sample solution by applying a predetermined pressure to the sample solution.

The dialysate (for example, water) in the dialysate storage tank 403 is introduced from the introduction port 203 on the cylindrical side near the bottom of the dialysis module 409 by a dialysate supply pump 407 having a variable flow rate, and passes through the gaps of a number of hollow fiber membranes. Ascended and discharged from the outlet 204 on the side of the cylinder near the top of the dialysis module 409. In this system, the membrane permeation rate of the dialysate is determined by individually setting the flow rates of the sample supply pump 405 and the treatment liquid discharge pump 406. That is, if the flow rate of the sample supply pump 405 is V5 [ml / min], the flow rate of the sample treatment liquid discharge pump 406 is V6 [ml / min], and the total surface area of the dialysis membrane is S [cm ² ],
Membrane permeation rate = (V6−V5) / S [cm / min].
As the sample supply pump 405, the sample processing liquid discharge pump 406, and the dialysate liquid feed pump 407, a gear pump, a mono pump, or the like is preferably used, but a cheving pump can also be used.

On the other hand, the sample solution supplied from the sample solution storage tank 401 to the top of the dialysis module 409 descends through the hollow fiber membrane in the dialysis module 409 by the sample supply pump 405 having a variable flow rate, and the sample outlet at the bottom. It is discharged from 202 and reaches the processing solution storage tank 402. In this system, the membrane permeation rate of the dialysate can be controlled by independently controlling the flow rates of the dialysate supply pump 407 and the dialysate discharge pump 507. That is, when the flow rate of the dialysate supply pump 407 is V6 [ml / min], the flow rate of the dialysate discharge pump 507 is V7 [ml / min], and the total surface area of the dialysis membrane is S [cm ² ], the membrane permeation rate is It can be obtained by the following equation.
Membrane permeation rate = (V6−V7) / S [cm / min].

Here, in order to increase the processing speed of the sample solution, the apparatus of the present invention includes a plurality of dialysis modules as shown in FIG. 2 in parallel with respect to the flow of the sample solution and the dialysate (2 to several hundreds). Can be arranged. FIG. 3 is an example of an embodiment of a multiple dialysis module system 30 in which ten dialysis modules 409 are arranged.
The multiple dialysis module system 30 includes a dialysis module 409, a sample solution supply pipe 301, a sample processing liquid discharge pipe 302, a dialysate supply pipe 303, a dialysate discharge pipe 304, a first flow variable pump 305, and a second flow variable pump. 306, a third variable flow rate pump 307 is provided. The first flow rate variable pump 305, the second flow rate variable pump 306, and the third flow rate variable pump 307 are respectively a sample supply pump 405, a sample processing liquid discharge pump 406, and a dialysate supply pump 407 (FIGS. 4 to 6). Corresponding to
In FIG. 3, the top of the dialysis module 409 is connected to the sample solution supply pipe 301 via the tube 311 and connected to the dialysate discharge pipe 304 via the tube 312. The bottom of the dialysis module 409 is connected to the dialysate supply pipe 303 via the tube 313 and is connected to the sample processing liquid discharger 302 via the tube 314.

The membrane of the dialysis module 409 for carrying out the present invention can be any of a hollow fiber membrane, a spiral membrane, or a flat membrane, but in order to increase the membrane area per volume of the dialysis module 409, the hollow fiber membrane is used. preferable. In the dialysis method of the present invention, the osmotic pressure is at most about 20 kPa. Therefore, in order to reduce the fluctuation due to the site of the solvent moving speed within the pore diameter in the entire area of the hollow fiber membrane, the sample solution and the dialysis solution are used for the membrane module. The smaller the pressure loss when circulating, the better. That is, it is necessary to control the flow rates of the sample solution and the dialysate so that the pressure loss is 1.0 times or less, preferably 0.5 times or less, more preferably 0.1 times or less of the osmotic pressure. When the sample solution flows through the hollow fiber membrane, the generated pressure loss depends not only on the flow rate of the sample solution but also on the inner diameter of the hollow fiber membrane. Therefore, in order to maintain a high processing speed and reduce the pressure loss, A large hollow fiber membrane is preferred. On the other hand, the inner diameter should not be excessively large so that mass transfer in the direction perpendicular to the flow of the sample solution in the hollow fiber membrane is not rate-limiting in the dialysis of the present invention. The inner diameter of the hollow fiber membrane in the dialysis method of the present invention is 0.1 mm or more and 2.0 mm or less, preferably 0.2 mm or more and 1.0 mm or less, more preferably 0.3 mm or more and 0.6 mm or less.

It was revealed that the transmembrane pressure difference (osmotic pressure of the present invention) generated in this Example using a dialysis membrane having a molecular weight cut off of 10 kD was as low as about 18 kPa. This osmotic pressure is considered to decrease as the membrane pore diameter increases. The molecular weight cutoff of the osmotic membrane used in the dialysis of the present invention does not mean a molecular weight that can be dialyzed. It is sufficient that the generated osmotic pressure is easily controlled by operating parameters (pressure and flow rate) applied from the outside. However, since it is important that there is no fluctuation in the moving speed of the solvent flowing in each pore of the dialysis membrane, the pore size distribution should be as small as possible.
As is apparent from the definition equation for the Peclet number, the film thickness is an important parameter related to the moving speed of the solvent in the dialysis of the present invention. From the results of the examples, the preferred film thickness is 20 μm or more and 80 μm or less, more preferably 30 μm or more and 60 μm or less.

When soy sauce was dialyzed using a polysulfone hollow fiber membrane having an inner diameter of 0.2 mm, a length of 208 mm, a film thickness of 40 μm, and a molecular weight cut off of 10000 Da, the osmotic pressure was 18 kPa. On the other hand, when the average linear velocity of the soy sauce flowing through the hollow fiber membrane was 6.3 mm / s, the pressure loss was 1.5 kg, 2.5 kPa at 10 mm / s, and 7.7 kPa at 17 mm / s. When no pressure is applied to the soy sauce in the hollow fiber membrane, the dialysate flows into the soy sauce side, whereas the pressure control valve provided at the dialysis module outlet applies a pressure of 20 to 42 kPa to the soy sauce. Apparently, the inflow of dialysate could be suppressed. When the soy sauce inlet flow rate was large and the pressure loss was as large as 7.7 kPa, the soy sauce inlet flow rate and outlet flow rate were equal when the soy sauce supply pressure was 41.8 kPa. Apparently, the moving speed of the solvent in the membrane pores is zero, but actually the transmembrane pressure difference in the upstream part of the hollow fiber membrane is large, and a part of the soy sauce is discharged to the dialysis side. On the other hand, the transmembrane pressure difference is small in the downstream portion of the hollow fiber membrane, and the dialysate flows into the soy sauce side. Since such a phenomenon occurs, selective dialysis removal of low molecular weight components becomes difficult when the pressure loss of the sample solution is large.

As a method for controlling the moving speed of the solvent in the pores, the following method can be considered.
The transmembrane pressure can be controlled by installing a differential pressure valve at the sample solution outlet.
Alternatively, the differential pressure can be generated by controlling the head pressure difference between the storage tank that temporarily stores the processing liquid discharged from the sample solution discharge port and the opening of the dialysate to be discharged. That is, the transmembrane pressure can be adjusted by the difference between the installation position of the treated sample storage tank and the opening position of the dialysate discharge port. The movement speed of the solvent in the pores can also be adjusted by controlling the inlet flow rate and outlet flow rate of the sample solution, or controlling the inlet flow rate and outlet flow rate of the dialysate. For example, it is possible to install a pump that can control the flow rate highly and does not generate a pulsating flow, such as a mono pump, in the sample solution supply part and the sample solution discharge part, respectively, and operate the pumps with slightly different flow rates. Can be achieved. Alternatively, the object can be achieved by applying the same control to the dialysate.

In designing the dialysis machine, the polymer material of the dialysis membrane, the molecular weight cut off, the film thickness, the aperture ratio (void ratio) of the dialysis membrane, the inner diameter and length of the hollow fiber membrane, the method of controlling the membrane permeation rate (convection rate), It is necessary to fully consider the flow rate and flow direction of the sample solution and the flow rate and flow direction of the dialysate.

Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

Example 1
Using a dialysis module equipped with SP polysulfone hollow fiber membrane manufactured by Spectrum Laboratories (fractionated molecular weight 10kD, inner diameter 200μm × outer diameter 280μm, number of hollow fiber membranes 5750, membrane surface area 6500cm2 (inner surface), 9100cm2 (outer surface)) Then, desalting of commercially available concentrated soy sauce was performed. That is, dialysis was performed by flowing soy sauce inside the hollow fiber membrane and flowing the dialysate outside in a countercurrent manner. A roller pump RP-2100 manufactured by Tokyo Rika Kikai Co., Ltd. was used for feeding soy sauce and dialysate. As shown in FIG. 6, a differential pressure was generated between the soy sauce and the dialysate by attaching a pressure adjusting valve to the soy sauce outlet. A pressure sensor was attached to the soy sauce inlet side to monitor the soy sauce supply pressure.
The following experiment was conducted at a soy sauce flow rate of 60 ml / min and a dialysate flow rate of 60 ml / min.

Comparative Example 1
Example 1-1) Dialysis was performed by adjusting the supply pressure of soy sauce to 9.0 kPa with a pressure adjusting valve.
Example 1-2) Dialysis was performed by adjusting the supply pressure of soy sauce to 20 kPa using a pressure adjusting valve.
Example 1-3) Dialysis was performed by adjusting the supply pressure of soy sauce to 32 kPa using a pressure control valve.
Comparative Example 1) Since normal dialysis does not assume transmembrane pressure and solvent permeation, dialysis was performed with the pressure adjustment valve at the soy sauce outlet fully opened, and a comparative experiment was conducted. At this time, the soy sauce supply pressure was 1.5 kPa.

Table 1 shows the inlet flow rate and outlet flow rate of soy sauce and the inlet flow rate and outlet flow rate of dialysate in Examples 1-1 to 1-3 and Comparative Example 1. The membrane permeation rate was calculated by dividing the difference between the soy sauce inlet flow rate and the outlet flow rate by the dialysis membrane area. Further, Table 1 shows the reduction rate of Na + ions and K + ions and the reduction rate of amino nitrogen in Examples 1-1 to 1-3 and Comparative Example 1.

Comparative Example 1 The soy sauce inlet pressure was 1.5 kPa when the pressure regulating valve attached to the soy sauce outlet was fully opened. At this time, the outlet flow rate was 102 ml / min with respect to the soy sauce inlet flow rate of 60 ml / min, the dialysate permeated 42 ml per minute into the soy sauce side, and the membrane permeation rate was 0.0065 cm / min. At this time, the decrease rate of Na + ion was only 1.4%, and almost no decrease of amino nitrogen was observed. As a result, in Comparative Example 1, even when trying to dialy remove low molecular weight components (ions) from a sample with high osmotic pressure such as soy sauce, the permeation rate of the dialysate in the dialysis membrane is high, which is against this. Diffusing movement was difficult. That is, dialysis could not be performed.
Therefore, dialysis was performed while controlling the permeation rate of the dialysate in the dialysis membrane.

Example 1-1: Dialysis was performed by setting the pressure of a soy sauce inlet to 9.0 kPa using a pressure adjusting valve attached to the soy sauce outlet, and the soy sauce outlet flow rate was 72 ml / min with respect to the soy sauce inlet flow rate of 60 ml / min. It was min. As a result, while the soy sauce passed through the hollow fiber membrane, the dialysate permeated 12 ml per minute into the soy sauce. The membrane permeation rate at this time was 0.0018 cm / min.
Example 1-2: At the soy sauce inlet pressure of 20 kPa, the soy sauce inlet flow rate and outlet flow rate were equal, and the dialysate flow stopped (the membrane permeation rate was zero). Therefore, the osmotic pressure under this condition is 20 kPa.
Example 1-3; At a soy sauce inlet pressure of 32 kPa, the outlet flow rate was 43 ml / min with respect to the soy sauce inlet flow rate of 60 ml / min, and a portion of soy sauce was discharged to the 17 ml dialysate side per minute. The membrane permeation rate at this time was -0.0026 cm / min.
The decrease rate of Na + ions increased to 1.4, 20.9, 39.3, and 54.7% as the membrane permeation rate of the dialysate flowing into the soy sauce side decreased to 0.0065, 0.0018, 0.000, and -0.0026 cm / min. The reduction rate of amino nitrogen under the same conditions was <0.1, 0.8, 7.3, 23.2%.

FIG. 7 shows the results of Table 1 (Comparative Example 1, Examples 1-1 to 1-3). In the figure, there are four plots of the reduction rate of sodium ion and amino nitrogen, respectively, which show the results of Comparative Example 1, Examples 1-1, 1-2, and 1-3 in order from the right.

FIG. 7 shows the influence of the dialysate permeation flow rate (membrane permeation rate) on the decrease rate of Na + ions and the decrease rate of amino nitrogen. A positive value is a direction in which the dialysate permeates and flows into the soy sauce side, and a negative value indicates a membrane permeation rate when a part of the soy sauce flows out to the dialysate side.
Comparative Example 1: The membrane permeation rate of the dialysate when no pressure was applied to the soy sauce was 0.0065 cm / min, and both Na + ions and amino nitrogen components (amino acids) were substantially diffusely transferred to the dialysate side according to the concentration gradient. Can not do it. That is, dialysis is impossible.
Example 1-1: Dialysis was performed at a membrane permeation rate of 0.0018 cm / min by applying a pressure of 9.0 kPa to soy sauce. At this time, the decrease rate of Na + ions was 20.9%, but almost no decrease in amino nitrogen component was observed.
Example 1-2: Dialysis was performed in a state where the pressure of 20 kPa was applied to soy sauce and the dialysate was stationary in the membrane. At this time, the decrease rate of Na + ions was 39.3%, and the decrease rate of amino nitrogen component was 7.3%.
Example 1-3: Under a situation where the pressure applied to soy sauce is increased to 32 kPa to reverse the direction of the membrane permeate flow (-0.0026 cm / min), and a portion of the soy sauce is discharged (filtered) to the dialysate side Dialysis was performed. At this time, the decrease rate of Na + ions was 54.7%, and the decrease rate of amino nitrogen component was 23.2%.

As described above, the influence of diffusion and solvent advection on the movement of Na + ions and amino nitrogen components could be clarified. That is, in a region where the diffusion rate is larger than the advection rate (Peclet number> 1), a linear relationship was observed between the solute reduction rate and the advection rate. The membrane permeation rate at which the Peclet number = 1 for Na + ions was about 0.0045 cm / min, and the amino nitrogen component was found to have a Peclet number = 1 near the membrane permeation rate of 0.001 cm / min.

In this experiment, Na + in concentration was measured with Na + ion selective electrode (HORIBA B-722), and K + ion concentration was measured with K + ion selective electrode (HORIBA B-731). The amino nitrogen was measured from the absorbance of the ninhydrin reaction product at 570 nm.

Dialysis similar to Example 1 and Comparative Example 1 was performed with the soy sauce inlet flow rate of 120 ml / min and the dialysate inlet flow rate of 120 ml / min.
Example 2-1) Dialysis was performed by adjusting the supply pressure of soy sauce to 15 kPa using a pressure adjusting valve.
Example 2-2) Dialysis was performed by adjusting the supply pressure of soy sauce to 25 kPa using a pressure adjusting valve.
Example 2-3) Dialysis was performed by adjusting the supply pressure of soy sauce to 35 kPa using a pressure adjusting valve.
Comparative Example 2) Since normal dialysis does not assume transmembrane pressure and solvent permeation, dialysis was performed with the pressure adjustment valve at the soy sauce outlet fully opened, and a comparative experiment was conducted. At this time, the supply pressure of soy sauce was 2.5 kPa.
The results of Examples 2-1 to 2-3 and Comparative Example 2 are shown in Table 2.

Comparative Example 2: The pressure at the soy sauce inlet when the pressure control valve attached to the soy sauce outlet was fully opened was 2.5 kPa. At this time, the outlet flow rate was 150 ml / min with respect to the soy sauce inlet flow rate of 120 ml / min, the dialysate permeated 30 ml per minute into the soy sauce side, and the membrane permeation rate was 0.0046 cm / min. At this time, the decrease rate of Na + ion was only 6.6% and almost no decrease of amino nitrogen was observed. As a result, when dialyzing without applying pressure to the soy sauce, Na + ions could be excluded selectively, but the removal rate was as low as 6.6%, and the sample solution was diluted with dialysate by about 25%. It became clear.

Therefore, dialysis was performed while controlling the permeation rate of the dialysate in the dialysis membrane.
Example 2-1: Dialysis was performed at a membrane permeation rate of 0.0009 cm / min by applying a pressure of 15 kPa to soy sauce. At this time, the decrease rate of Na + ions was 39.5%, but the decrease rate of the amino nitrogen component was 4.2%.
Example 2-2: Dialysis was performed at a membrane permeation rate of -0.0009 cm / min by applying a pressure of 25 kPa to soy sauce. At this time, the decrease rate of Na + ions was 47.5%, and the decrease rate of amino nitrogen component was 13.1%.
Example 2-3: Dialysis was performed at a membrane permeation rate of -0.0018 cm / min by applying a pressure of 35 kPa to soy sauce. At this time, the decrease rate of Na + ion was 52.1%, but the decrease rate of amino nitrogen component was 21.2%.
As the dialysate membrane permeation rate decreased to 0.0046, 0.0009, -0.0009, -0.0018 cm / min, the decrease rate of Na + ions increased to 6.6, 39.5, 47.3, 52.1%. Under the same conditions, the decrease rate of amino nitrogen was 0.16, 4.2, 13.1, 21.2%. The selectivity was 41, 9.4, 3.6, and 2.4 under the same conditions. The above results show that the removal rate and selectivity of sodium ions are inversely proportional. A negative membrane permeation rate (Examples 2-2, 2-3) indicates that filtration dialysis is occurring. Advection diffusion dialysis is performed in Example 2-1, which shows that both the removal rate and selectivity of sodium ions are satisfied.

The results of Table 2 (Comparative Example 2, Examples 2-1 to 2-3) are shown in FIG. In the figure, there are four plots of the reduction rate of sodium ion and amino nitrogen, respectively, which show the results of Comparative Example 2, Examples 2-1, 2-2 and 2-3 in order from the right.
When no pressure was applied to soy sauce, the decrease rate of Na + ions was 6.6%, which was able to diffuse and move slightly against the osmotic flow of the dialysate, but the diffusion rate of amino nitrogen component was as large as Na + ions As a result, it was hardly discharged to the dialysate side.
At the membrane permeation rate of 0.0009 cm / min, the decrease rate of Na + ions was 39.5%, and the decrease of amino nitrogen component was 4.2%. At the membrane permeation rate of -0.0009 cm / min, the decrease rate of Na + ions was 47.3%, and the decrease rate of amino nitrogen components was 13.1%. Furthermore, when the pressure applied to soy sauce was increased and dialysis was performed at a membrane permeation rate of -0.0018 cm / min, the decrease rate of Na + ions was 52.1%, and the decrease rate of amino nitrogen components was 21.2%.
As described above, in the region where the solute diffusion rate is larger than the advection rate (Peclet number <1), a linear relationship was observed between the solute reduction rate and the advection rate.

Dialysis was performed in the same manner as in Example 1 and Comparative Example 1 with a soy sauce inlet flow rate of 180 ml / min and a dialysate inlet flow rate of 180 ml / min.
Example 3-1: Dialysis was performed by adjusting the supply pressure of soy sauce to 17.2 kPa with a pressure control valve.
Example 3-2: Dialysis was performed by adjusting the supply pressure of soy sauce to 28.1 kPa with a pressure control valve.
Example 3-3: Dialysis was performed by adjusting the supply pressure of soy sauce to 41.8 kPa with a pressure control valve.
Comparative Example 3: Since normal dialysis does not assume the transmembrane pressure difference and the permeation of the solvent, dialysis was performed with the pressure adjustment valve at the soy sauce outlet fully opened, and a comparative experiment was conducted.
Table 3 shows the results of Examples 3-1 to 3-3 and Comparative Example 3.

Comparative Example 3: The pressure at the soy sauce inlet when the pressure control valve attached to the soy sauce outlet was fully opened was 7.7 kPa. At this time, the outlet flow rate was 250 ml / min with respect to the soy sauce inlet flow rate of 180 ml / min, the dialysate permeated 70 ml per minute into the soy sauce side, and the membrane permeation rate was 0.011 cm / min. At this time, the decrease rate of Na + ion was only 25.4% and almost no decrease of amino nitrogen was observed. As a result, when dialyzing without applying pressure to the soy sauce, Na + ions could be selectively removed, but it was revealed that the sample solution was diluted by about 39% with the dialysate.

Therefore, dialysis was performed while controlling the permeation rate of the dialysate in the dialysis membrane.
Example 3-1: Dialysis was performed at a membrane permeation rate of 0.0065 cm / min by applying a pressure of 17.2 kPa to soy sauce. At this time, the decrease rate of Na + ions was 32.5%, but the decrease rate of amino nitrogen component was 2.9%.
Example 3-2: Dialysis was performed at a membrane permeation rate of 0.0046 cm / min by applying a pressure of 28.1 kPa to soy sauce. At this time, the decrease rate of Na + ions was 40.9%, but the decrease rate of amino nitrogen component was 6.5%.
Example 3-3: Dialysis was performed at a membrane permeation rate of 0.0000 cm / min by applying a pressure of 41.8 kPa to soy sauce. At this time, the decrease rate of Na + ions was 52.5%, but the decrease rate of amino nitrogen component was 13.0%.
The decrease rate of Na + ions increased to 25.4, 32.5, 40.9, and 52.5% as the membrane permeation rate of the dialysate decreased to 0.011, 0.0065, 0.0046, and 0.000 cm / min. Under the same conditions, the decrease rate of amino nitrogen was 0.9, 2.9, 6.5, 13.0%. In addition, the selectivity decreased to 28.8, 10.8, 6.4, and 4.0 under the same conditions. The above results show that the removal rate and selectivity of sodium ions are inversely proportional.

The results of Table 3 (Comparative Example 3, Examples 3-1 to 3-3) are shown in FIG. In the figure, there are four plots of the reduction rate of sodium ion and amino nitrogen, respectively, which show the results of Comparative Example 2, Examples 2-1, 2-2 and 2-3 in order from the right.
The results of FIG. 9 differed from the results of FIGS. That is, no pressure was applied to the soy sauce, and 25.4% of Na + ions were discharged to the dialysate side despite the high permeation inflow rate of the dialysate as 0.011 cm / min. At this time, almost no amino nitrogen component was discharged to the dialysate side. This is thought to be because the flow rate of soy sauce in the dialysis membrane increased and the properties of the boundary layer formed on the dialysis membrane surface changed.

In the desalting of soy sauce, the value obtained by dividing the rate of Na + ion reduction by the rate of reduction of amino nitrogen components (amino acids) (hereinafter referred to as the selectivity factor) has a significant effect on the quality of the reduced salt soy sauce. Therefore, it is necessary to clarify the influence of the membrane permeation rate of dialysate and the soy sauce supply flow rate (dialysis rate) to the dialysis module on the selection factor in dialysis of soy sauce. FIG. 10 plots the selectivity coefficient against the membrane permeation rate of the dialysate using the dialysis rate as a parameter.
Selection factor = Na + ion removal rate / amino nitrogen reduction rate Soy sauce supply flow rate: △ 60 ml / min; ▲ 120 ml / min; ○ 180 ml / min

FIG. 10 revealed that a linear relationship was established between dialysis selectivity and dialysate membrane permeation rate under constant dialysis rate conditions. The larger the dialysate membrane permeation rate, the higher the selection factor, but the lower molecular weight solute discharge rate becomes smaller. Therefore, in order to perform efficient dialysis, consider the balance between the selection factor and the dialysis rate. It is necessary to set conditions. At any dialysis rate, it was found that the permeation rate of dialysate was around -0.002 and the selectivity coefficient was about 0.35. In the situation where there is no solvent movement in the dialysis membrane, the movement of each component depends on the diffusion rate of each component, so it is ideal that the selectivity coefficient converges to a constant value at a membrane permeation rate of zero. A difference of about 0.002 cm / min occurred between the theoretical value and the theoretical value. In addition, the slope of the straight line of each dialysis treatment is predicted to be theoretically the same, but in practice, it was significantly affected by the dialysis rate. That is, it has been found that the greater the dialysis rate, the smaller the influence of the membrane permeation rate of the dialysate on the selection coefficient (the smaller the slope of the straight line).

As described above, the theoretical consideration and the measured value do not agree with each other in that the thickness of the boundary layer formed on the inner surface of the hollow fiber membrane and the electric strength of the electric double layer are different depending on the flow of soy sauce in the hollow fiber. It is thought to be caused.
When considering desalination of soy sauce by this method, it is considered appropriate to set the selection coefficient to about 10. Therefore, when the selection coefficient is 10 and a broken line is given, it can be seen that the greater the dialysis rate, the greater the membrane permeation rate of the dialysate.

In each of Examples 1 to 3 and Comparative Examples 1 to 3, the experiment was performed with the sample solution supply flow rate and the dialysate supply flow rate equal. In dialysis treatment, the rate of decrease in the components to be dialyzed can be increased as the flow rate of the dialysate is increased.
Then, the influence of the dialysate flow rate on the desalination of soy sauce was examined using the advection diffusion dialysis apparatus schematically shown in FIG. In the system of FIG. 6, the membrane permeation rate of the solvent in the dialysis membrane was controlled by controlling the pressure of the soy sauce flowing through the hollow fiber membrane by the pressure adjustment valve installed at the treated soy sauce outlet, In the system of FIG. 4, the membrane permeation rate of the solvent in the dialysis membrane is controlled by independently controlling the soy sauce supply flow rate and the soy sauce discharge flow rate. Dialysis was performed with the soy sauce inlet flow rate of 180 ml / min, the outlet flow rate of 220 ml / min and the dialysate flow rates of 180, 270, 360, and 450 ml / min. FIG. 11 is a plot of Na + ion reduction rate and amino nitrogen component reduction rate against dialysate flow rate at a soy sauce supply flow rate of 180 ml / min and a soy sauce discharge flow rate of 220 ml / min.

As is clear from FIG. 11, the decrease rate of Na + ions increased with the flow rate of the dialysate, and 50% or more of desalting could be performed by flowing a dialysate more than twice the soy sauce.
On the other hand, the decrease rate of the amino nitrogen component was hardly affected by the flow rate of the dialysate, and did not exceed 2% at any dialysate flow rate. As a result, it was found that a high desalting efficiency (50%) and a large selection factor (30) were obtained at a dialysate flow rate twice that of the soy sauce supply. In actual adaptation, a selection factor of about 10 is used as a guideline, so the membrane permeation rate of the dialysate is set to a smaller value (by reducing the difference between the soy sauce supply flow rate and the discharge flow rate), and desalting of 50% or more is possible. It becomes.

Example 4
Using the same dialysis machine used in Example 1, an attempt was made to reduce alcohol in white wine. The alcohol in wine was dialyzed with a wine flow rate of 50 ml / min and a dialysate flow rate of 100 ml / min.
Example 4-1) Dialysis was performed with the wine outlet pressure regulating valve fully opened (wine supply pressure 1.4 kPa).
Example 4-2) Dialysis was performed using a pressure regulating valve at a wine supply pressure of 8.4 kPa.
Example 4-3) Wine supply pressure was 18.4 kPa.
The results of this example are shown in Table 4.

It can be seen that the supply pressure of wine when the pressure regulating valve is fully opened is 1.4 kPa, and the pressure loss when flowing through the membrane module is 1.4 kPa. Then the wine inlet pressure is 8.4 k
As Pa increased to 18.4 kPa, the outlet flow rate of wine decreased. That is, when the supply pressure is low, the dialysate flows into the wine side. However, when the supply pressure increases, a portion of the wine is discharged to the dialysate side. It is judged that there is no change in wine volume due to dialysis when the wine inlet pressure is around 8 kPa. That is, the osmotic pressure of wine is about 8 kPa in dialysis according to the present invention. The decrease rate of ethanol increased as the wine supply pressure increased, but the amount of wine discharged into the dialysate increased. This is due to the fact that filtration dialysis occurs under these conditions. The ethanol removal rate of wine treated at a wine supply pressure of 8.4 kPa was 79.8%, and its flavor was kept good. As mentioned above, it turned out that this method is also important as a technique for reducing ethanol from alcoholic beverages.
The ethanol was quantified by adsorbing and collecting ethanol in the headspace by the micro solid phase extraction (SPME) method (supplied by SUPELCO) and analyzing this by GC (Shimadzu GC-14A).

Analysis of aroma components in white wine was carried out by solid phase microextraction using Polyacrylate®coating®SPME®Fiber manufactured by Spellco. That is, 20 liters of wine was collected in a 50 liter ml headspace gas sampling glass container and incubated in a thermostatic bath at 30 ° C. for 20 minutes to achieve vapor-liquid equilibrium of fragrance components. Next, the fragrance components were collected by exposing SPME Fiber in the head space for 20 minutes. Analysis of the aroma component was performed using GC-MS (Shimadzu GC-MS QP2010 plus) equipped with a capillary column (DB-WAX).

Table 8 shows the concentration in the raw material and the concentration in the dialysis wine as the peak area of the gas chromatogram for the eight components considered to be important for the wine aroma. Furthermore, the residual ratio of each component in the dialysis wine relative to the raw wine is shown in parentheses. As a result, it was found that more than 83% remained except for Ethyl octanoate. The decrease in Ethyl octanoate was thought to be due to sorption on the dialysis membrane. Therefore, after the sorption equilibrium to the membrane is achieved, the decrease due to this treatment is not considered to be a problem.
As described above, according to the dialysis method of the present invention, it is possible to produce a dealcoholized wine in which 55% or more (mostly 80% or more) of aroma components remain and about 80% of ethanol is removed with little reduction in aroma. I was able to.

According to the present invention, a method for selectively dialysis removing low molecular weight components contained in a sample solution is provided.

30: Multiple dialysis module system, 40: Advection diffusion dialysis machine,
50: advection diffusion dialysis device, 60: dialyzer 401: sample solution reservoir, 402: treatment solution reservoir, 403: dialysate reservoir,
404: discharge dialysate storage tank, 405: sample supply pump, 406: sample processing solution discharge pump,
407: Dialysate supply pump, 408: Pressure gauge, 409: Dialysis module 507: Dialysate discharge pump, 606: Back pressure adjustment valve

Claims

A method for dialysis removal of low molecular weight components contained in a sample solution, wherein the direction of movement of the dialysate in the dialysis membrane is opposite to the direction of movement of the solute in the sample solution in the dialysis membrane, and The method according to claim 1, wherein the moving speed of the dialysate is made smaller than the moving speed of the low molecular weight component.
The method according to claim 1, comprising at least one step selected from the group consisting of the following (a) to (c):
(A) Step of independently controlling the supply flow rate and the discharge flow rate of the sample solution (b) Step of independently controlling the supply flow rate and the discharge flow rate of the dialysate (c) Pressure for applying the pressure applied to the sample solution to the dialysate Higher than the process
The method according to claim 1 or 2, wherein the ratio (A / B) of the supply flow rate (A) and the discharge flow rate (B) of the sample solution is in the range of 0.7 or more and less than 1.0.
方法 The method according to any one of claims 1 to 3, wherein the sample solution is a seasoning or an alcoholic beverage.
The method according to any one of claims 1 to 4, wherein the dialysate is water.
6. The dialysis apparatus having a sample solution flow path 1, a dialysate flow path 2 and a dialysis membrane separating the flow path 1 and the flow path 2 from each other. The method described in 1.
Sample solution flow path 1, dialysate flow path 2, dialysis membrane separating the flow path 1 and flow path 2, sample flow rate control mechanism for independently controlling the supply flow rate and discharge flow rate of the sample solution, and the dialysate flow rate A dialysis apparatus comprising at least one flow rate control mechanism selected from a dialysate flow rate control mechanism that independently controls a supply flow rate and a discharge flow rate.
A sample solution flow path 1, a dialysate flow path 2, a dialysis membrane separating the flow path 1 and the flow path 2, and a pressure control mechanism for controlling the pressure applied to the sample solution and the pressure applied to the dialysate are provided. Dialyzer.
The flow rate control mechanism is configured to supply a flow rate of the sample solution so that a ratio (A / B) of the supply flow rate (A) to the discharge flow rate (B) of the sample solution is in a range of 0.7 or more and less than 1.0. And the discharge flow rate is controlled independently, or the supply flow rate and the discharge flow rate of the dialysate are controlled independently.
The pressure control mechanism controls the pressure so that the ratio (A / B) between the supply flow rate (A) and the discharge flow rate (B) of the sample solution is in the range of 0.7 or more and less than 1.0. The apparatus of claim 8.
The low molecular weight component contained in the sample solution is removed by dialysis using the method according to any one of claims 1 to 6 or the apparatus according to any one of claims 7 to 10. And collecting the obtained sample solution after the dialysis treatment, a method for producing a sample solution from which low molecular weight components have been removed.
The method according to claim 11, wherein the sputum sample solution is a seasoning or an alcoholic beverage.
The method according to claim 12, wherein the koji seasoning is soy sauce.