JPS61209007A - Selective separation of coenzyme - Google Patents

Abstract

PURPOSE:To selectively separate and recover only coenzyme from a solution containing coenzyme, by treating said solution with a semipermeable membrane having a sulfonic acid group. CONSTITUTION:Sulfonated polyaryl ether obtained by treating polyaryl ether with conc. sulfuric acid is dissolved in polyethylene glycol monomethyl ether and an additive such as lactic acid is added to the resulting solution to prepare a film forming solution which is, in turn, applied to an ultrafiltration membrane as a support and the solvent is subsequently evaporated to obtain a composite semipermeable membrane having a sulfonic acid group. For example, a liquid reaction mixture after enzymatic reaction is treated by using this membrane to selectively separate and recover coenzyme from the reaction mixture.

Description

[Detailed description of the invention] (Industrial application field)゛ The present invention relates to a method for selectively separating coenzymes.

(Prior art) Enzyme reactions are partially carried out industrially in the manufacturing process of pharmaceuticals, foods, etc. Conventionally, enzymes are dissolved in an aqueous solution of a substrate and the reaction is carried out in this aqueous solution. . but,
Some enzymes require coenzymes to exhibit their catalytic activity. That is, as is well known, such an apoenzyme combines with a coenzyme to become a holoenzyme and performs an enzymatic reaction, but in many cases, the binding between a coenzyme and an enzyme is reversible; In addition, coenzymes are relatively weak, so they can be said to be common substrates for many similar reactions.

Therefore, when carrying out industrial enzymatic reactions, it is important to separate and recover these enzymes and coenzymes from the product without deactivating their activity after the reaction, and reuse them to increase productivity and improve economic efficiency. It is essential to increase.

For this purpose, many methods have already been proposed in which enzymes and coenzymes are immobilized on water-insoluble carriers and separated from the reaction system using ultrafiltration membranes after the required enzymatic reaction. Immobilization of enzymes generally requires complex chemical operations, and their activity often decreases during the course of these chemical treatments, which in turn reduces the productivity and economic efficiency of enzyme reactions.

It has also been proposed to directly separate the coenzyme from the reaction system using a semipermeable membrane after the enzymatic reaction; Since both the coenzyme and the reaction product are organic compounds with relatively low molecular weight, both are often removed to approximately the same extent, and it is possible to selectively separate and recover essentially only the coenzyme from the reaction system. It is difficult.

Furthermore, in the case of semipermeable membranes made of cellulose acetate, pH resistance
When the solution containing the coenzyme is acidic or alkaline, it is difficult to separate the coenzyme from such a solution. However, the method of membrane cleaning after coenzyme separation treatment is limited. Furthermore, semipermeable membranes cannot be sterilized by heat.

On the other hand, ultrafiltration membranes made of polysulfone are known as semipermeable membranes with excellent pH resistance, chlorine resistance, heat resistance, etc. However, all conventional polysulfone ultrafiltration membranes have a molecular weight cutoff. Because of their large size, it is difficult to separate the reaction products and coenzymes as described above.

(Objective of the Invention) As a result of intensive research to solve the above-mentioned problems, the present inventors have discovered that a semipermeable membrane having a sulfonic acid group, particularly a skin layer having solute separation activity, has a sulfonic acid group and , a composite semipermeable membrane formed into an extremely thin film,
Due to its strong anionic properties based on sulfonic acid groups, it blocks the passage of negatively charged coenzymes due to mutual charge repulsion, but it is effective against neutral solutes and lightly charged solutes over a wide concentration range. In addition, due to the hydrophilicity based on the sulfonic acid group, the water permeation rate during membrane treatment is extremely high. They also discovered that by adjusting the pH of a solution containing coenzymes, it is possible to efficiently separate coenzymes from each other by taking advantage of the difference in the number of charges of coenzymes. ,
This led to the present invention.

Accordingly, an object of the present invention is to provide a method for selectively separating coenzymes, which can selectively separate and recover substantially only coenzymes from a solution containing coenzymes.

(Structure of the Invention) The method for selectively separating coenzymes according to the present invention is characterized by treating a solution containing coenzymes with a semipermeable membrane having sulfonic acid groups.

The semipermeable membrane having sulfonic acid groups used in the method of the present invention is a semipermeable membrane made of a polymer in which sulfonic acid groups account for most of the total ion exchange groups, preferably 70% or more, particularly preferably 90% or more. be.

As long as the sulfonic acid group is within the above range among all ion exchange groups, the remaining ion exchange group may be an ion exchange group other than the sulfonic acid group, for example, a carboxylic acid group.

In the present invention, as a semipermeable membrane having a sulfonic acid group that can be particularly suitably used, a sulfonated polyaryl ether obtained by sulfonating a polyaryl ether consisting of repeating units, or the above repeating unit A and repeating unit B (provided that , R represents -C〇- or -5O1-, R゛ represents a carbon-carbon bond or a divalent group). Examples include a composite semipermeable membrane in which a skin layer is integrally laminated on an ultrafiltration membrane as a support membrane.

Such a composite semipermeable membrane is preferably produced by sulfonating the polyaryl ether consisting of the above-mentioned repeating unit A or the linear polyarylether copolymer consisting of the above-mentioned repeating unit A and repeating unit B, respectively. The aryl ether is prepared and mixed with an alkylene glycol alkyl ether such as ethylene glycol monomethyl ether, which may contain a small amount of an aprotic polar organic solvent, and a water-soluble and low-volatility organic compound as an additive or It can be obtained by applying a film-forming solution containing an inorganic salt as an additive onto a dried support film, and then evaporating the organic solvent from this film-forming solution.

The above-mentioned sulfonated polyaryl ether can be obtained by treating the corresponding polyaryl ether with concentrated sulfuric acid, but in the present invention, the sulfonated polyaryl ether obtained in this way is
The logarithmic viscosity measured at a temperature of 30 ° C. of a solution prepared by dissolving g in 100 ml of N-methyl-2-pyrrolidone is 0.2 or more, and the ion exchange capacity is 2.3 milliequivalents/g or less. is desirable, but when the ion exchange capacity exceeds 2.3 milliequivalents/g, the sulfonated polyaryl ether becomes water-soluble and is unsuitable as a material for semipermeable membranes for treating aqueous solutions. ,
This is because when the logarithmic viscosity is smaller than 0.2, it is difficult to form a uniform skin layer without defects such as pinholes.

In addition, when forming a skin layer using a sulfonated polyaryl ether obtained by sulfonating the linear polyaryl ether copolymer, the linear polyaryl ether copolymer has a repeating content of 10 mol% or more. Unit A and 9
It is preferable that the repeating unit B is composed of 0 mol% or less of the repeating unit B'.

The sulfonic acid group possessed by the sulfonated polyaryl ether used in the method of the present invention is represented by the formula -SO,M, where M represents hydrogen, an alkali metal or a tetraalkylammonium.

For example, by sulfonating a polyaryl ether, washing the sulfonated polyaryl ether with water, and drying it, a sulfonated polyaryl ether having a free sulfonic acid group can be obtained. Furthermore, by suspending and treating this sulfonated polyaryl ether in an aqueous solution, methanol, ethanol solution, etc. of an alkali metal hydroxide or alkali metal alcoholade, the sulfonic acid group can be converted into an alkali metal salt. As the alkali metal hydroxide, for example, sodium hydroxide, potassium hydroxide, lithium hydroxide, etc. are used, and as the alkali metal alcoholade, for example, sodium methylate, potassium methylate, potassium ethylate, etc. are used. Furthermore, if a sulfonated polyaryl ether is similarly treated with a solution of a tetraalkylammonium, such as tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrapropylammonium hydroxide, or tetrabutylammonium hydroxide, the sulfonated polyaryl ether can be The acid group can be the corresponding tetraalkylammonium salt.

The composite semipermeable membrane according to the present invention has the above-mentioned sulfonated point.
' Realyl ether and a water-soluble and low-volatility compound as an additive are dissolved and contained in an alkylene glycol alkyl ether which may contain a small amount of an aprotic polar organic solvent to prepare a film-forming solution. It can be obtained by coating a dried support film on a dried support film and then evaporating the organic solvent from this film forming solution.

As the organic solvent for preparing the film forming solution, in the present invention, alkylene glycol alkyl ethers in which the alkylene group has 2 to 4 carbon atoms and the alkyl group has 1 to 4 carbon atoms are particularly preferably used. . This solvent has excellent solubility in the sulfonated polyaryl ether used in the present invention and is highly volatile. This is because it does not dissolve. Specific examples of such alkylene glycol alkyl ethers include alkylene glycol monoalkyl ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol monomethyl ether, and propylene glycol monoethyl ether, ethylene glycol dimethyl ether, and ethylene glycol monoethyl ether. Examples include alkylene glycol dialkyl ethers such as glycol methyl ethyl ether and ethylene glycol diethyl ether. In particular, ethylene glycol monomethyl ether is preferably used because it has excellent solubility in sulfonated polyaryl ether and is highly volatile.

However, depending on the sulfonated polyaryl ether used, it may be difficult to dissolve it in the alkylene glycol alkyl ether, or it may simply swell. It was found that it dissolves well in a mixed solvent made by adding a small amount of aprotic polar organic solvent to ether. Examples of such aprotic polar organic solvents include dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide,
N,N-dimethylacetamide and the like are preferably used. In such a mixed solvent, the proportion of the aprotic polar organic solvent is preferably 5 parts by weight or less, particularly 3 parts by weight or less, based on 100 parts by weight of the alkylene glycol alkyl ether.

In the mixed solvent, when the aprotic polar organic solvent is more than 5 parts by weight with respect to 100 parts by weight of the alkylene glycol alkyl ether, when the membrane forming solution is applied on a dry polysulfone ultrafiltration membrane as a support membrane,
This is because the ultrafiltration membrane dissolves or swells, making it impossible to obtain a composite semipermeable membrane with good performance.

As described above, using alkylene glycol alkyl ether or a mixed solvent of alkylene glycol alkyl ether and a small amount of the above-mentioned aprotic polar organic solvent as a solvent for the membrane-forming solution is effective in applying the membrane-forming solution to the support membrane, as described below. After that, in the step of evaporating and removing the solvent from this film forming solution, it is advantageous because substantially all the solvent can be removed by heating at room temperature or a small amount, and a uniform thin film without defects can be obtained. be.

The concentration of the sulfonated polyaryl ether in the membrane-forming solution is related to the thickness of the semipermeable membrane formed by these polymers in the resulting composite semipermeable membrane, but is preferably in the range of 0.05 to 10% by weight. Particularly preferred is a range of 0.1 to 5% by weight.

The film forming solution contains certain additives. Among such additives, at least one selected from the group consisting of polyhydric alcohols, polyalkylene glycols, carboxylic acids, salts thereof, hydroxycarboxylic acids and salts thereof is used as the organic compound.

These organic compounds as additives are water-soluble, and
In addition, it is required to have low volatility and be dissolved in the film forming solution, and therefore polyhydric alcohols having 2 to 5 carbon atoms, low molecular weight polyalkylene glycols, carboxylic acids, salts thereof, hydroxycarboxylic acids or their Salt is preferably used. Specific examples include ethylene glycol, propylene glycol, glycerin, and 1.4 polyhydric alcohols.
-butanediol, etc., polyalkylene glycols such as diethylene glycol, triethylene glycol, dipropylene glycol, etc., carboxylic acids such as citric acid, oxalic acid, hydroxycarboxylic acids such as lactic acid,
Examples of salts of carboxylic acids and hydroxycarboxylic acids include sodium salts and potassium salts.

Furthermore, inorganic salts that are water-soluble and dissolve in the membrane forming solution can also be used as additives. Examples of such inorganic salts include lithium chloride, lithium nitrate, and magnesium perchlorate.

The concentration of these additives in the film forming solution is usually 0.1
~80% by weight. The effects of these additives on the formation of composite semipermeable membranes are not always clear;
This is related to the micropore diameter of the semipermeable membrane formed from sulfonated polyarylether, and when coating the membrane forming solution on the ultrafiltration membrane that is the supporting membrane, the solvent and additives of the membrane forming solution are It is believed that the additives modify the surface of the ultrafiltration membrane, and thus, by selecting the type and amount of additives used, the performance of the composite semipermeable membrane, in particular the removal rate for solutes and the membrane The amount of permeated water can be controlled over a wide range.

In the method of the present invention, the membrane forming solution prepared as described above is then applied onto a dry ultrafiltration membrane as a support membrane. As is well known, a dry ultrafiltration membrane is produced by heating a wet ultrafiltration membrane prepared by a wet method to an appropriate temperature to evaporate and dry the water contained in the membrane's micropores. You can get it by doing this.

In the above method, the ultrafiltration membrane used as the support membrane for applying the membrane forming solution is not particularly limited, but is preferably an ultrafiltration membrane made of polysulfone, for example, made of a repeating unit of the following formula C, and , the molecular weight cut-off is 100 in a wet state.
0 to 200,000, especially 5oooo to 150,000
Ultrafiltration membranes are preferably used.

In the present invention, as described above, since alkylene glycol alkyl ether or a mixed solvent containing a small amount of the aprotic polar organic solvent is used as the solvent for the membrane forming solution, heating is usually not required. Although virtually all the solvent can be evaporated at room temperature,
After applying the film-forming solution onto the support film, heating may be performed as necessary to evaporate the solvent. The heating temperature may be appropriately selected depending on the solvent used, but a temperature of 150° C. or lower is usually sufficient. Incidentally, in order to promote evaporation of the solvent after the film-forming solution is applied onto the support film, the film-forming solution may be heated in advance and then applied onto the support film.

The thickness of the thin semipermeable membrane based on sulfonated polyarylether in the composite semipermeable membrane thus obtained depends on the concentration of these polymers in the membrane forming solution and the coating thickness of the membrane forming solution on the support membrane. Depending on the composite semipermeable membrane, it is better to be thinner to increase the water permeation rate, and thicker to increase its strength; therefore, in particular, but not limited to, membranes based on sulfonated polyarylethers The semipermeable membrane having solute separation activity usually preferably has a thickness in the range of 0.01 to 5 μm.

Depending on the type of additive used, additives may remain in the composite semipermeable membrane obtained in this way. water,
Alternatively, these additives can be removed from the membrane by immediate treatment of the aqueous liquid.

In this way, the thickness is usually 10 μm or less,
A sulfonated polyaryl ether composite semipermeable membrane can be obtained in which a skin layer containing sulfonic acid groups and having separation performance is made of sulfonated polyaryl ether, and this skin layer is integrally laminated on a support membrane.

As described above, the composite semipermeable membrane having a skin layer made of the above-mentioned sulfonated polyarylether and preferably having a thickness of 10 II m or less has a high removal rate for coenzymes, and also removes uncharged neutral solutes and It has a low removal rate for solutes with low chargeability, and furthermore, since the skin layer having separation activity is extremely thin, the water permeation rate for an aqueous solution containing a coenzyme is high. Furthermore, since it can be used over a wide pH range, coenzymes can also be separated from each other by adjusting the pi of the aqueous solution and utilizing the difference in the number of charges.

The method of the present invention can be applied to any negatively charged coenzyme, but as a preferred specific example,
For example, ATPSADP, AMP.

Examples include NADP and NAD.

In the method of the present invention, the conditions for treating the aqueous solution are appropriately selected taking into account the nature of the semipermeable membrane used as well as the type and concentration of the solute. It can be easily selected. However, the membrane processing temperature is usually in the range of 0 to 95°C.

The higher the temperature, the higher the water permeation rate, but since there is a risk of a decrease in coenzyme activity, the temperature is preferably between 5 and 7.
It is 0°C. Furthermore, the higher the treatment pressure, the higher the water permeation rate, which is usually in the range of 0.1 to 100 kg/ad.

The above-described composite semipermeable membrane used in the method of the present invention has excellent chlorine resistance and heat resistance, so when cleaning the composite semipermeable membrane, an aqueous sodium hypochlorite solution can be used. In particular, sodium hypochlorite concentration 11000p
An aqueous solution having p or less can be suitably used. Further, the composite semipermeable membrane described above can be heat sterilized at temperatures up to 95° C., if necessary.

(Effects of the Invention) As described above, according to the method of the present invention, a semipermeable membrane having a sulfonic acid group, particularly a semipermeable membrane having a sulfonic acid group having a solute separation activity in the form of an ultra-thin film made of sulfonated polyarylether Semipermeable membranes repel negatively charged coenzymes due to their strong anionic properties based on sulfonic acid groups, blocking their permeation. It has an almost constant low removal rate over a certain range, and also has hydrophilicity based on sulfonic acid groups, so it is possible to substantially selectively separate coenzymes from solutions containing coenzymes, and at the same time, it has low water permeability. The speed is also significantly higher.

Therefore, the method of the present invention is not particularly limited in its application mode, but can be applied, for example, to selectively separate and recover coenzymes from a reaction mixture after an enzyme reaction.

(Examples) The present invention will be described below with reference to Examples, but the present invention is not limited to these Examples in any way. In the examples, the solute removal rate and water permeation rate were determined by the following formulas.

Example 1 (1) Repeating unit A for producing sulfonated polysulfone
.

10 g of polysulfone was added to 80 ml of 97% concentrated sulfuric acid, and the mixture was stirred gently at room temperature for 4 hours to obtain a dark brown viscous reaction liquid. This was placed in a water bath to solidify the sulfonated polysulfone. After washing with water, 0.
The mixture was left overnight in 800 ml of 5N aqueous sodium hydroxide solution. Next, the polymer was washed until the washing solution became neutral, and then vacuum-dried at 30° C. for 7 hours. The pale yellow granular sulfonated polysulfone thus obtained has a logarithmic viscosity of 3.00 and a sulfonic acid group of 10% of all ion exchange groups.
0%, and the ion exchange capacity was 1.92 meq/g.

(2) Preparation of composite semipermeable membrane Consisting of repeating units of formula C, average molecular weight 20,000
An anisotropic ultrafiltration membrane having a removal rate of 10% for polyethylene glycol and a molecular weight cut-off of 100,000 was dried at a temperature of 60°C to obtain a dry ultrafiltration membrane for a support membrane. .

After dissolving 0.8 g of the sulfonated polysulfone obtained above in 79.2 g of ethylene glycol monomethyl ether, 20 g of lactic acid was added, and the resulting polymer solution was filtered through a 10 μm filter paper and used as a membrane forming solution.

This membrane-forming solution was applied onto the dry ultrafiltration membrane, and after volatilizing most of the solvent at room temperature, it was heat-treated at 60°C for 5 minutes to form a composite film with a skin layer of 0.5 μm in thickness. A semipermeable membrane was obtained.

The performance of this composite semipermeable membrane has a molecular weight cut-off of 10,000.0.
When a 5% aqueous sodium chloride solution was treated at 25°C and 50 kg/-, the removal rate was 10.1% and the water permeation rate was 6.
2m3/m”.

In addition, the molecular weight cut-off here refers to 0.05% aqueous solutions of polyethylene glycols with different molecular weights at 25°C, 20 kg/
It refers to the dextran-equivalent molecular weight of the polyethylene glycol measured by GPC when the removal rate is about 90% when treated under ad conditions.

(3) Coenzyme separation test Add potassium hydroxide aqueous solution little by little to 100ml of a mixed solution containing ATP, ADP, AMP and adenosine (manufactured by Oriental Yeast ■) at a concentration of 2.5mM.
After adjusting H to 7, use a flat membrane tester (effective membrane area 11.3
cd), and a permeation test was carried out at a pressure of 5 and a +r/-1 temperature of 15°C.

As a result of analyzing the permeate by liquid chromatography, the removal rates were 98.0%, 85.2%, 73°2%, and 0% for ATPSADP, AMP, and adenosine, respectively.
Met. Moreover, the water permeation rate was 1.2×1 (I'cm/sec).

Example 2 (1) Production of sulfonated polysulfone copolymer 10 g of a linear polysulfone copolymer consisting of 57 mol% of repeating units of the above formula A and 43 mol% of repeating units of NiB1.
was added to 80ml of 97% concentrated sulfuric acid, dissolved, and dissolved at room temperature for 4 hours.
The reaction was stirred for a period of time to obtain a blackish brown viscous reaction liquid. This was placed in a water bath to solidify the sulfonated polysulfone copolymer. After washing with water, it was left in 800 ml of 0.5 N aqueous sodium hydroxide solution overnight. The polymer was then washed until the washing solution became neutral, and then heated at 60°C.
It was vacuum dried for 5 hours.

The sulfonated polysulfone copolymer thus obtained had a logarithmic viscosity of 0.84, sulfonic acid groups accounted for 100% of the total ion exchange groups, and an ion exchange capacity of 1.2 meq/g. .

(2) 0.8 g of linear sulfonated polysulfone copolymer obtained in the preparation of composite semipermeable membrane
79.2 g of ethylene glycol monomethyl ether
After dissolving in the solution, 20 g of glycerin was added, and the resulting polymer solution was filtered through a 10 μm filter paper, and the resulting polymer solution was used as a membrane forming solution.

This membrane forming solution was applied onto the same polysulfone dry ultrafiltration membrane as in Example 1, and after volatilizing most of the solvent at room temperature,
A heat treatment was performed at a temperature of 60° C. for 5 minutes to obtain a composite semipermeable membrane having a skin layer with a thickness of 0.5 μm.

The performance of this composite semipermeable membrane has a molecular weight cut-off of 10,000.0.
When a 5% sodium chloride aqueous solution was treated at 25°C and 50ksr/-, the removal rate was 6.3% and the water permeation rate was 6.
5m'/m''.

(3) Coenzyme separation test The same coenzyme mixed aqueous solution used in Example 1 was used in Example 1.
The membrane was treated in the same manner as above.

As a result of analyzing the permeate by liquid chromatography, the removal rates were 97.0%, 84°8%, 72°4%, and 0% for ATPSADP, AMP, and adenosine, respectively.
Met. Further, the water permeation rate was 1.2 x 10-3 cm/sec.

Further, the relationship between the pH of the aqueous solution containing the above coenzyme mixture and the removal rate of each coenzyme is shown in the drawing. It is understood that by setting the pH to about 7 or higher, ATP and AMP can be effectively separated from adenosine.

In addition, by setting the pH to about 4 to 6, ATP and A
It is also understood that MPs can be separated from each other.

Example 3 (1) Production of sulfonated polyaryletherketone) Polyaryletherketone consisting of repeating unit At (PE manufactured by IC1)
EK 45G) 10g - 80ml of 97% concentrated sulfuric acid
1 and reacted at room temperature for 8 hours, and then left at room temperature for an additional 17 hours to obtain a concentrated sulfuric acid solution of the above polymer.

The above solution was poured into a thin thread onto pure water cooled in a water bath to solidify the polymer, collected by filtration, and poured with pure water for 50 minutes.
Washed twice. 600 ml of IN sodium hydroxide aqueous solution was added to this polymer, and after being allowed to stand for 3 hours, the polymer was washed until the pH of the washing solution became 7.

Thereafter, the polymer was dried at 60° C. for 16 hours to obtain 11.6 g of sulfonated polyaryletherketone. This polymer is sulfonated.

This was confirmed by its infrared absorption spectrum and nuclear magnetic resonance spectrum.

The ion exchange capacity of this polymer is 1.5 meq/g, and the logarithmic viscosity measured at 30°C of a solution of 065 g of the polymer dissolved in 100 ml of N-methylpyrrolidone is 1.
．． It was 30.

(2) 9 g of the sulfonated polyaryl ether ketone obtained in the preparation of the composite semipermeable membrane was mixed with 89.1 g of ethylene glycol methyl ether.
After dissolving in the solution, 10 g of glycerin was added, and the resulting solution was filtered through a 10 μm filter paper, and the resulting solution was used as a membrane forming solution.

The above membrane forming solution was applied onto the same dry polysulfone ultrafiltration membrane as used in Example 1, and after volatilizing most of the solvent at room temperature, it was heat treated at a temperature of 60 ° C. for 5 minutes. A composite semipermeable membrane was obtained.

The performance of this composite semipermeable membrane is that it has a molecular fraction of 10,000.
0.5% sodium chloride aqueous solution at 25℃, 50kg/d
When treated under these conditions, the removal rate was 13.8% and the water permeation rate was 12.1 m3/m''.

(3) Coenzyme separation test The same coenzyme mixed aqueous solution used in Example 1 was used in Example 1.
The membrane was treated in the same manner as above.

As a result of analyzing the permeate by liquid chromatography, the removal rates were 97.5%, 85.2%, 74°0% and 0% for ATP, ADP, AMP and adenosine, respectively.
Met. Further, the water permeation rate was 1.0 x IO arc 1 second.

[Brief explanation of drawings]

The drawing is a graph showing the relationship between the pH of an aqueous solution and the removal rate of each coenzyme when an aqueous solution containing a coenzyme mixture is treated with a composite semipermeable membrane having a skin layer made of sulfonated polysulfone.

Claims (3)

[Claims] (1) A method for selectively separating coenzymes, which comprises treating a solution containing coenzymes with a semipermeable membrane having sulfonic acid groups. (2) a thin film-like skin layer in which the semipermeable membrane has a sulfonic acid group and has a solute separation activity;
2. The method for selectively separating coenzymes according to claim 1, which is a composite semipermeable membrane comprising a support membrane that integrally supports the membrane. (3) A composite semipermeable membrane having a sulfonic acid group is a sulfonated polyaryl ether made by sulfonating a polyaryl ether consisting of the repeating unit A ▲There are mathematical formulas, chemical formulas, tables, etc.▼A, or the above repeating unit A
and repeating unit B ▲There are mathematical formulas, chemical formulas, tables, etc.▼B (However, R represents -CO- or -SO_2-, and R' represents a carbon-carbon bond or a divalent group.) A linear polyaryl consisting of Claim No. 1, characterized in that a skin layer having a solute separation activity and made of a sulfonated polyarylether obtained by sulfonating an ether copolymer is integrally laminated on an ultrafiltration membrane as a support membrane. 2. The method for selectively separating coenzymes according to item 2.