JPH0365224A - Manufacturing of ultrafilter membrane - Google Patents

Abstract

PURPOSE:To obtain an ultrafilter membrane having heat resistance and a high water permeability by bringing the ultrafilter membrane composed of regenerated cellulose into contact with a multifunctional reacting agent to improve the solute stopping rate of the membrane. CONSTITUTION:The ultrafilter membrane composed of the regenerated cellulose having a larger division molecular weight than the intended division molecular weight is brought into contact with a multifunctional reacting agent such as epichlorohydrine and formaldehyde reactive with the hydroxyl group of this regenerated cellulose so as to be cross-linked, thereby improving the solute stopping rate of the membrane. This method gives a greatly improved water permeability than the lower conventional one and the ability to withstand the steam sterilization at a temp. of about 120-130 deg.C, leading to the manufacturing of the ultrafilter membrane of the regenerated cellulose having a great water permeability.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing an ultrafiltration membrane having heat resistance and high water permeability.

The ultrafiltration membrane obtained by the method of the present invention is particularly useful for concentrating and purifying biochemical substances such as proteins, enzymes, or nucleic acids in the field of biochemistry.

[Conventional technology] Conventionally, polysulfone has been used as a material for ultrafiltration membranes.

Polyacrylonitrile, polyvinylidene fluoride.

Polyether sulfone, acetyl cellulose, regenerated cellulose, etc. are known (``Latest Membrane Treatment Technology and Its Applications'', edited by Shimizu and Nishimura, Fuji Techno System). Does not withstand steam sterilization at °C.

Furthermore, in the field of biochemistry, proteins that are present in a very dilute state or in trace amounts are often concentrated and purified, and regenerated cellulose membranes with high hydrophilicity are suitable for this purpose. This is because hydrophobic membranes cause non-specific adsorption of proteins due to hydrophobic bonds, which may significantly impair the recovery rate.

However, in the case of hydrophilic membranes, membranes with fractionation performance in the low molecular weight region (about 1,000 to tens of thousands) tend to have a significantly lower permeation rate (flux) per unit membrane area, which poses a problem in actual use. becomes.

On the other hand, several attempts have been made so far to impart desirable properties to membranes by utilizing cross-linking reactions for membrane modification.

For example, JP-A-60-129105 discloses crosslinking a regenerated cellulose membrane with a bifunctional reactant. The purpose of this invention is to improve the selectivity of nonaqueous liquids by crosslinking the regenerated cellulose membrane, and does not mention the control of the membrane's molecular weight cutoff and water permeability, or the improvement of the membrane's heat resistance. Not yet.

Also, U.S. Patent Nos. 3,232.916 and 3,2
No. 65,536 describes the crosslinking of polyvinyl alcohol membranes by heat treatment and the action of formaldehyde, respectively. In addition to these, crosslinking of aromatic polyamide membranes by chemical reactions and light irradiation has been proposed in U.S. Patent Nos. 3 and 9.
No. 04.519, cross-linking of nylon-polyvinyl alcohol membranes is described in U.S. Pat. No. 3,951.621, and cross-linking of polybenzimidazole membranes is described in U.S. Pat. No. 4,020,142.

Furthermore, crosslinking of membranes using plasma has been proposed in U.S. Pat.
It is stated in No. 5. The above-mentioned known documents describe that a crosslinking reaction can be used to impart oil resistance, salt blocking performance, flux stability, etc. to a membrane.

On the other hand, crosslinking reactions of polysaccharide polymers using epichlorohydrin and 1,4-butanediol diglylyle ether are also known (for example, Organic Synthetic Chemistry Vol. 38, No. 2, 128
~138 pages, 1980). However, it has not been known so far to adjust the molecular weight cut-off of an ultrafiltration membrane made of regenerated cellulose by crosslinking to obtain a membrane with a large flux and excellent heat resistance.

C Problems to be Solved by the Invention The purpose of the present invention is to improve the low heat resistance of conventional polymer ultrafiltration membranes and the low water permeability of hydrophilic regenerated cellulose ultrafiltration membranes. Withstands steam sterilization at -20 to 130℃,
An object of the present invention is to provide a method for manufacturing an ultrafiltration membrane with high water permeability.

[Means for Solving the Problems] As a result of intensive research in view of the above-mentioned current situation, the present inventors have found that a regenerated cellulose ultrafiltration membrane (starting membrane) having a molecular weight cut-off larger than the target molecular weight cut-off is a regenerated cellulose ultrafiltration membrane (starting membrane). By bringing the membrane into contact with a polyfunctional reactant that reacts with the hydroxyl groups of
The present inventors have discovered that an ultrafiltration membrane (target membrane) that can withstand steam sterilization and has high water permeability can be obtained, and has arrived at the present invention.

That is, the present invention improves the solute rejection rate of the membrane by bringing an ultrafiltration membrane made of regenerated cellulose into contact with a polyfunctional reactant that reacts with the hydroxyl groups of regenerated cellulose. The present invention provides a method for producing an ultrafiltration membrane having properties.

[Action Co. The present invention will be explained in detail below.

Regenerated cellulose as used herein refers to a group of well-known polymers obtained by precipitating cellulose from its solution, and to polymers obtained by saponifying cellulose acetate. This ultrafiltration membrane made of regenerated cellulose is produced by a precipitation method (cuprammonium method or viscose method) from a cellulose solution, or by saponifying a membrane obtained by a precipitation method from a cellulose acetate solution with an aqueous sodium hydroxide solution. It is made by This regenerated cellulose membrane may have any shape, such as a sheet, a tube, or a hollow fiber.

In addition, regenerated cellulose membrane is a membrane consisting of a thin dense layer on one or both surfaces of an asymmetric MC membrane made of regenerated cellulose alone, or polyethylene, polypropylene,
Either a regenerated cellulose asymmetric membrane laminated with a porous support membrane (nonwoven fabric, etc.) such as polyester may be used. The thickness of these regenerated cellulose membranes is usually in the range of 5 to 1000 microns.

The molecular weight cutoff of an ultrafiltration membrane is determined by measuring the exclusion rate R of a plurality of solutes having different molecular weights. Here, the exclusion rate R is defined by the following equation.

R (%) - (1-C2/CI)xlOO (1) where,
C1 and 02 are the solute concentrations in the feed and membrane permeate, respectively. Here, the molecular weight cutoff is defined as the molecular weight at which the exclusion rate is 90% when the solute is a protein.

The starting membrane in the present invention has a higher molecular weight cutoff than the target membrane. That is, in order to obtain a target membrane that excludes 90% or more of the protein molecule ff1M, the starting membrane must have an exclusion rate of 20 to 85% for the protein molecule ff1M.

In general, in membrane formation by the precipitation method, if the membrane formation conditions are changed to increase the rejection rate of the resulting membrane, the water permeability will deteriorate. The purpose of the present invention is to increase the rejection rate without significantly impairing the water permeability (flux) by crosslinking a starting membrane with a low rejection rate and high water permeability. However, if the rejection rate of the starting membrane is lower than 20%, it is difficult to obtain the target membrane by the reaction used in the present invention.

The molecular weight cutoff of the starting membrane in the present invention ranges from 10,000 to 10
Ten thousand. If the molecular weight fraction is not within this range, the effects of the present invention will be impaired. Furthermore, the molecular weight cutoff of the membrane obtained by reacting this with a polyfunctional reactant is in the range of 1,000 to 50,000.

The regenerated cellulose starting membrane is chemically modified by contacting the hydroxyl groups present in the regenerated cellulose with a polyfunctional reagent that reacts with the hydroxyl groups. This reaction reduces the molecular weight cutoff of the membrane and improves its heat resistance. on the other hand,
Although the water permeability is somewhat lower than that of the starting membrane, the degree of this decrease can be suppressed by appropriately setting the reaction conditions.

Examples of polyfunctional reagents used in the present invention that react with the hydroxyl groups of regenerated cellulose include epichlorohydrin, formaldehyde, and divinyl sulfone.

Examples include dimethylchlorosilane, diisocyanate, and compounds having two or more epoxy groups in one molecule. Examples of the compounds having two or more epoxy groups in one molecule include sorbitol polyglycidyl ether, polyglycerol polyglycidyl ether, pentaerythritol polyglycidyl ether, diglycerol polyglycidyl ether, glycerol polyglycidyl ether, and ethylene glycidyl ether. Examples include glycidyl ether, polyethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, and polypropylene glycol diglycidyl ether.

The polyfunctional reactant is contacted in the form of a homogeneous solution or suspension with an ultrafiltration membrane made of regenerated cellulose. The concentration of this polyfunctional reactant is preferably 3 to 30% by weight of the total solution or suspension.

As the solvent, water, an organic solvent that is non-reactive with the polyfunctional reactant, or a mixed system of water and an organic solvent that is non-reactive with the polyfunctional reactant and compatible with water is used. The reaction is carried out at a temperature of 10 to 100°C for 0.1 to 24 hours,
It is more desirable to conduct the treatment at a temperature of 20 to 60°C for 0.5 to 10 hours. As the concentration of the polyfunctional reactant increases, the reaction temperature increases, and the reaction time increases, the molecular weight cutoff of the membrane decreases, but the water permeability of the membrane also decreases. Therefore, it is important to set optimal reaction conditions according to the molecular weight cutoff of the starting membrane.

Examples of organic solvents used include aliphatic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons, ketones, ethers such as dioxane, dimethyl sulfoxide, N, N--
Other polar aprotic solvents include dimethylformamide, dimethylacetamide, and N-methylpyrrolidone.

This reaction generally progresses more easily at higher temperatures, but
If the reaction temperature is too high, the raw material film will deteriorate, which is undesirable, so it is preferable to proceed in the above temperature range under a basic catalyst. At this time, the amount of catalyst is desirably 1/10 to 2 times the equivalent of the polyfunctional reactant used. Triethylamine, sodium hydroxide, etc. may be used as a catalyst.

If the reaction solvent contains water, there is a risk that the polyfunctional reactant will react with the water and be rapidly lost, so the polyfunctional reactant should be added after the starting membrane is immersed in the solvent, or
It is necessary to immerse the starting membrane immediately after adding the polyfunctional reactant to the solvent. If a catalyst is used, it is desirable to add the catalyst at about the same time or after contacting the starting membrane with the polyfunctional reactant. Further, a catalyst may be added during the reaction if necessary.

[Examples] The present invention will be described in more detail below with reference to Examples, but the present invention is not limited thereto. In the following examples, the permeation rate of pure water was determined by applying a pressure of 1 atm, and the rejection rate of protein was determined by pressurization of 1 atm using a 0.9% saline solution containing 1 g/fl of protein. Do (
1) Calculated according to formula.

I performed purification.

The membrane thus obtained has a pure water permeation rate of 45f!
/rrrhr, and the inhibition rate for bovine serum albumin was approximately 100%, and the inhibition rate for cytochrome C was 95%.

Additionally, this membrane can be steam sterilized at 121℃ for 30 minutes for 10 minutes.
There was no change in performance even with ethanol, acetone, and acetonitrile.

No change in performance was observed even after immersion in organic solvents such as benzene and dioxane for 300 hours.

Example: The permeation rate of pure water is 652/rrfhr, the inhibition rate of bovine serum albumin is 94%, and the inhibition rate of cytochrome C is 40%.
% regenerated cellulose membrane was immersed in 500 g of 0.5N aqueous sodium hydroxide solution at 40°C, 0.5 mol of epichlorohydrin was immediately added, and reaction was carried out while stirring the liquid vigorously. 0.18 mol of sodium hydroxide was added 2 and 4 hours after starting the reaction, respectively.

After 6 hours, the membrane was taken out of the reaction tank and washed with pure water. In Example 2, Example 1, the membrane was taken out from the reaction tank 2 hours after the reaction was started, and the membrane was washed with pure water. The membrane thus obtained has a pure water permeation rate of 6 (N!/rr
rhr, and the inhibition rate for bovine serum albumin was 98% and the inhibition rate for cytochrome C was 80%.

Example 3 The same regenerated cellulose membrane used in Example 1 was heated to 0.5N at 40°C containing 40% by volume of dimethyl sulfoxide.
Immediately immerse in 500% sodium hydroxide aqueous solution,
5 mol of epichlorohydrin was added, and the reaction was carried out while stirring the solution vigorously.

0 after 2 hours and 4 hours after starting the reaction.
．． 18 moles of sodium hydroxide were added.

After 6 hours, the membrane was taken out from the reaction tank and washed with pure water.

The membrane thus obtained has a pure water permeation rate of 401/
rrrhr, and the inhibition rate of cytochrome C was 97%. In addition, this membrane showed no change in performance even after being steam sterilized at -221℃ for 30 minutes 10 times, and even after being immersed in organic solvents such as ethanol, acetone, acetonitrile, benzene, and dioxane for 300 hours. No change was observed at all.

Example 4 A regenerated cellulose membrane was chemically treated in the same manner as in Example 1, except that epichlorohydrin was replaced with glycerol polyglycidyl ether, and the pure water permeation rate was 50%.
/ rrrhr, and the inhibition rate of bovine serum albumin is 9
At 8%, a membrane with a cytochrome C rejection of 85% was obtained. In addition, this membrane showed no change in performance even after being steam sterilized for 30 minutes at 121°C 10 times, and even after being immersed in organic solvents such as ethanol, acetone, acetonitrile, benzene, and dioxane for 300 hours. No changes were observed.

Example 5 The permeability rate of pure water is 45 J2/dhr, the inhibition rate of bovine serum albumin is 98%, and the inhibition rate of cytochrome C is 80%.
A regenerated cellulose membrane with 20% dimethyl sulfoxide
It was immersed in 500 mN of a 0.25N aqueous sodium hydroxide solution at 60°C containing % by volume, and immediately 0.25 mol of shrimp chlorohydrin was added, and the reaction was carried out while stirring the liquid vigorously. 0.09 mol of sodium hydroxide was added 2 and 4 hours after starting the reaction, respectively.

After 6 hours, the membrane was taken out from the reaction tank and washed with pure water.

The flow rate of pure water in the membrane thus obtained is 351)
/rrfhr, and the inhibition rate of cytochrome C is 98
%Met. In addition, this membrane showed no change in performance even after being steam sterilized for 30 minutes at 121°C 10 times, and even after being immersed in organic solvents such as ethanol, acetone, acetonitrile, benzene, and dioxane for 300 hours. No changes were observed.

[Effects of the present invention] According to the present invention, it is possible to obtain an ultrafiltration membrane that has high water permeability and can withstand steam sterilization at 120 to 140°C.

Furthermore, since the obtained membrane has a crosslinked structure, it has excellent solvent resistance, and is resistant to most organic solvents, alkalis, and acids. Furthermore, since this membrane is hydrophilic, it adsorbs few proteins and lipids, and is particularly useful in the field of biochemistry for concentrating and purifying biochemical substances such as proteins, enzymes, and nucleic acids.

Claims (1)

[Claims] (1) The ultrafiltration membrane made of regenerated cellulose is brought into contact with a polyfunctional reactant that reacts with the hydroxyl groups of regenerated cellulose, thereby improving the membrane's solute rejection rate.It has high water permeability and heat resistance. A method for producing an ultrafiltration membrane.