JPS5898105A - Fluoride type wet separation membrane and preparation thereof - Google Patents

Abstract

PURPOSE:To prepare a fluoride type humidity separation membrane having a network structure formed by uniform porosity and suitable for precise filtration, by a method wherein a resin based on a vinylidene fluoride polymer is dissolved in a solvent and the obtained solution is formed into a membrane in a wet state. CONSTITUTION:A resin based on a vinylidene fluoride polymer, a vinylidene fluoride/tetrafluoroethylene copolymer or one prepared by mixing both polymer and copolymer in a range of 5/95-20/80 on the wt. basis is dissolved in dimethylsulfoxide or a solvent prepared by adding 5-15wt% glycerine to dimethylsulfoxide to obtain a stock liquid and this stock liquid is formed into a film in a coagulating bath such as a water bath under a wet condition to obtain a fluoride type wet separation membrane having a network structure of which the surface and the interior are formed from uniform multiple pores with pore sizes of 0.01-1mu and water content of 30% or more when water is contained. In addition, the above stated stock liquid can be formed into a hollow yarn separation membrane by dry and wet spinnings.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel separation membrane suitable for precision r-filtration, ultra-rip-filtration, concentration of aqueous solutions, and substance separation.

In recent years, separation technology using membranes has attracted attention in application fields such as wastewater treatment, the food industry, and the medical field, and further development is expected.

As this membrane separation technology, methods such as precision filtration, ultrafiltration, or dialysis are used depending on the size of the substances suspended, dispersed, or dissolved in the aqueous medium. In particular, in the pharmaceutical, biological drug industry, or medical field, blood,
Efforts are being made to develop precision filtration or ultrafiltration membranes for biological components such as plasma, serum, and bacterial cells.

Some specific examples related to blood purification, which are preferred applications of the membrane of the present invention, include plasma separation (separation of formed components in blood and plasma), high molecular weight proteins such as immune complexes and low molecular weight proteins such as albumin. (removal of cell proliferation signal components, etc.).

In the case of plasma separation, it is desirable that plasma proteins such as albumin and globulin pass through at a high permeability, but that red blood cells, white blood cells, and platelets do not pass through at all, and that the plasma separation rate is high without causing hemolysis or coagulation. .

Plasma separation rate is determined by blood hematocrit value, protein concentration,
It is affected by blood flow velocity, f overpressure, etc., but considering clinical use, when blood flow is 100 me/min, 3
A level of 0 to 60 ml/min is desired. A container for this purpose has an albumin permeability of 90 or more, preferably substantially complete permeation, and a water permeation rate (water UF 几, UPBS) of 2 to 60 t/I]r.
−~2・mm I−I g, preferably 4 to 30
Performance in the vicinity of L/hr - 2-1 ηm Hg is required. In other words, the membrane has uniform pore diameters of around 0.1 to 0.8 microns on the membrane surface and inside, and the requirements are different for a membrane with high porosity, but generally the albumin permeability is 30.
-100%, preferably 70-100%, and the water permeability (water UFFL) measured in water is 01-20t/1]r-
~2・mmHg trench or 1~101/hr -m2m
Performance around mHg is required.

In other words, a membrane with a uniform pore diameter of around 0.01 to 0.02 microns on the membrane surface and inside, and a high porosity is desired.

Although there are many currently known separation membranes, there are few that satisfy the above-mentioned performances, and furthermore, it is difficult to obtain membranes that can be applied to various technical methods using the same material and the same manufacturing process.

The present inventors used a vinylidene fluoride polymer and a vinylidene fluoride-tetrafluoroethylene copolymer to produce a separation membrane (precision f-filtration membrane) with wide permeability in accordance with the above purpose in the same manufacturing process. , it was discovered that an ultra-transparent film can be obtained, and the present invention was achieved.

That is, the present invention provides a fluorine-based wet separation membrane whose surface and interior have a network structure formed by a large number of uniform pores of 0.01 to 1μ, and whose water content when hydrated is 60 coefficients or more; It concerns its manufacturing method.

In the present invention, a membrane having a uniform pore size means a membrane having a substantially uniform pore structure in which the surface layer and the inner layer are easily distinguishable. 5 or less and has a structure in which pores with the smallest pore diameter that governs membrane permeability are uniformly distributed within the membrane.

Specifically, such a fluorine-based wet separation membrane of the present invention is produced by using a vinylidene fluoride polymer, a fluorinated hynyritene-tetrafluoroethylene copolymer, or a mixture thereof, with dimethyl sulfoxide as the main component. It can be obtained by forming a film in a wet state from a stock solution dissolved in a solvent.

The weight average molecular weight of the raw material fluororesin used in the present invention, that is, vinylidene fluoride polymer and vinylidene fluoride-tetrafluoroethylene copolymer, is
Although it can be changed in consideration of the mechanical properties required depending on the method and purpose of use of the membrane, it is generally desirable that it is 10,000 or more, preferably 50,000 to 500,000.

Here, the weight average molecular weight is - ゛ for a dimethylformamide solution of the resin.

- Calculated by measuring with high performance Kelpalmeation chromatography (OPC) and calibrating with standard monodisperse polystyrene. Further, in the case of a copolymer, one having a vinylidene fluoride content of 50 mol or more is preferable from the viewpoint of solubility and the like.

Furthermore, vinylidene fluoride polymer and vinylidene fluoride
A mixture of tetrafluoroethylene copolymers is a particularly suitable raw material resin for obtaining a separation membrane with uniform pore size, wide permeation performance, and excellent mechanical properties.
Its composition is vinylidene fluoride polymer/vinylidene fluoride-tetrafluoroethylene copolymer in a weight ratio of 5 to 95.
~20/80 is preferred.

When the solvent system described below is used, the solution viscosity of the raw resin in this mixing range becomes specifically high as shown in FIG. 1, which is advantageous for film formation, especially hollow fiber spinning.

Among these fluororesins, other multi-component copolymers containing one or more monomers in a small amount can also be used as the membrane material of the present invention as long as they do not lose solubility in the membrane forming solvent. can.

Next, dimethylformhokind (DMSO), which is the main component of the solvent preferably used in the present invention, has a moderate affinity with the resin, so it has good film forming and thread forming properties, and can be used in the same process under the film forming conditions. Precise f
Separation membranes ranging from permeation membranes to dialysis membranes with uniform and wide pore diameters can be easily obtained.

When a solvent that exhibits greater affinity for the resin than DMSO, such as dimethylacetamide, N-methylpyrrolidone, dimethylformamide, or trimethylphosphate, is used as the main solvent component, such a wide range of separation performance can be obtained. It is difficult to easily obtain membranes, especially ultrafiltration membranes and plasma separation membranes with large pore sizes. In addition, when such a solvent is used, there is a 0.0
A skin layer with a pore size of less than 1 μm is often formed, making it difficult to obtain wide permeability.

Additionally, solvents that have a lower solubility for the resin than DMSO, such as dioxane, tetrahydrofuran,
When methyl ethyl ketone or the like is used as the main solvent component, film forming and thread forming properties are particularly poor, and it is difficult to obtain the desired film performance.

Furthermore, DMSO is infinitely soluble in water, and can be easily removed by washing with water after membrane formation and yarn spinning.It is also extremely low in toxicity compared to other solvents, making it suitable for use in working environments or for medical purposes. It has extremely excellent properties from the standpoint of product safety.

Furthermore, when preparing the membrane forming stock solution, water, formamide, alcohols (butanol, pronominol, ethylene glycol, chrycerin, etc.), urea, calcium chloride, etc. are used to control the pore size according to the purpose of the separation membrane. It is also a preferable method to add a non-solvent, or to add a surfactant such as polyoxyethylene ether lauryl alcohol or inoctylphenoxypolyethoxyethanol. Among these, glycerin has a large addition effect and is used to form ultrafiltration membranes and plasma separation membranes with uniform pore sizes (
It is a particularly preferable additive when manufacturing (including yarn spinning).

The fraction of additives in this solvent system is between 5 and 15, DM
This is preferable in order to obtain a membrane having a wide range of separation characteristics without losing the good membrane forming properties of SO.

The concentration of the resin in the membrane forming or yarn forming stock solution varies depending on the type of solvent used, the membrane forming method, the pore diameter of the intended separation membrane, etc., but is usually 5 to 35% by weight, preferably 10 to 60% by weight. % range.

The film-forming stock solution obtained in this way can be used to form a film by various known methods.

The membrane production of the present invention includes not only the production of flat membranes but also spinning into hollow fibers, etc. For example, after casting a stock solution onto a flat plate such as a glass plate or metal plate, it is immersed in a coagulation bath. It can be solidified or extruded into a coagulation bath through a die with elongated holes to form a film. In this case, it is also possible to apply it to a support fabric such as polyester taffeta. In addition to flat membranes, fibers can be spun from spindles with concentric circular holes to form cylindrical or hollow fibers, or they can be spread on convex, concave, or other irregularly shaped surfaces and solidified to form various shapes. membrane can be obtained.

The coagulation bath is generally water, aliphatic lower alcohol, a mixture thereof, or a mixture thereof.
Ya, add 0. did. . 8 good.

commonly used. The temperature of the coagulation bath at that time has a great influence on the permeability of the membrane, and generally a membrane having high water permeability can be obtained at a high temperature.

The normal coagulation bath temperature is around 0°C to 98°C,
In order to obtain a membrane with uniform and large pore diameters, the temperature is preferably 50°C or higher.

When the membrane of the present invention is formed and stored in a water-containing or wet state immediately after drying from the coagulation bath, large changes in permeation performance and mechanical properties do not occur over a long period of time. It is sufficient to keep it moist by applying a suitable wetting agent such as hydrated glycerin.

In addition to the above, examples of wetting agents include ethylene glycol, polyethylene glycol, and various surfactants. Furthermore, it is also possible to change the permeation performance and mechanical properties (dimensional stability, etc.) of the membrane by heat treatment after membrane formation. The heat treatment is carried out under tension or without tension, and the temperature is usually in the range of 50 to 110°C, preferably 70 to 90°C.

Fluorine-based separation membranes obtained by such external methods usually have a network structure formed by many fine and uniform pores on the surface and inside, but especially ultrapolar membranes and plasma separation membranes. As such, it is necessary that its moisture content be 0% or more. A particularly preferable water content is 60% or more. The water content can be easily changed by film forming conditions during film forming.

Here, the water content (W) is defined by the following formula.

G1: Water-containing membrane weight, G2: Dry membrane weight, moisture content is 30%
In the following cases, the separation rate is too low for one pass or is not suitable for practical use such as blood purification.

The average pore diameter of the separation membrane of the present invention is 0.001 to 1 μm. If the pore size is less than 0.01 μ, the pore size may be slow and the target protein component may not be passed through. If the pore size exceeds 1 μ, organic components in the blood, such as blood cells, lymphocytes, etc., may enter the f fluid. This is not preferable because it may cause mixing.

Next, the most preferable hollow fiber separation membrane among the separation membrane shapes of the present invention will be explained in more detail.

The above-mentioned membrane-forming stock solution is made into a hollow fiber separation membrane by dry-wet spinning. The spinneret used in the present invention can be any spinneret used for spinning ordinary hollow fibers, but for the purposes of the present invention, a spinneret consisting of an annular orifice with a hollow capillary in the spinneret hole is suitable. is preferably used.

Various methods have been proposed for spinning hollow fibers using such spinnerets, but the hollow fiber separation membrane used in the separation device for mixed substances, which is the object of the present invention, has a uniform cross-sectional shape and a perfect circle. Closeness is required.

In the present invention, the solvent used for the spinning stock solution, the mixture of the solvent and water, or the mixture of the solvent and polyhydric alcohol is quantitatively injected into the hollow fiber from the hollow tube located in the center of the spinneret. Spinning. The injection liquid is important because it participates in the formation of the inner wall structure of the hollow fiber when it comes into contact with the spinning dope. The properties of the spinning dope must be carefully investigated and the spinning dope must be selected appropriately depending on the purpose.

Commonly used polyhydric alcohols include glycerin,
Ethylene glycol, diethylene glycol, propanediol, etc. can be used, but they are not limited to these. The composition of these injection solutions can also be used as a means of controlling the separation performance of hollow fiber membranes.

In the present invention, depending on the conditions, it is also possible to introduce gas into the hollow part of the hollow fiber for spinning.

The injection gas is not particularly limited, but air or an inert gas such as nitrogen is usually used.

Compared to the case of flat membranes, the spinnability of hollow fibers is greatly influenced by the concentration of the stock solution, especially the viscosity. Usually, the viscosity of the spinnable stock solution is preferably 10 to 5,000 voids, preferably 100 to 3,000 voids at the spindle temperature.

The viscosity of the spinning dope is measured by falling ball viscosity or rotational viscosity (d).

The hollow fiber sol spun from the spinneret is led to a coagulation bath while passing through air or an inert gas. The atmospheric conditions during air travel vary depending on the thickness of the spun yarn, the spinning speed, the spinning temperature, etc., and cannot be generally specified. However, as a condition that is usually preferably adopted, the distance from the mouth surface to the introduction into the coagulation bath is 0.1 cm or more - more preferably 0.2 cm.
It is in the range of m or more and 200L:rn or less. Outside this range, stable spinning becomes difficult. Furthermore, as for the temperature of the atmosphere, the atmospheric temperature or indoor hot water temperature may be used as is, but depending on the case, it may be used after being cooled. It is also possible to finely control membrane performance by adjusting the humidity appropriately.

The coagulation bath employed in the present invention may be a non-solvent for the polymer of the present invention and is compatible with the solvent of the spinning dope, either alone or as a mixture with the solvent of the spinning dope. Can be used.

In order to finally obtain a hollow fiber in a water-containing state, a solvent for the spinning dope must be selected that is compatible with water, and the coagulation bath should be water or a mixture of water and the solvent used for the spinning dope. is practical.

The temperature of the coagulation bath affects the water permeability of the membrane, and in general, higher temperatures tend to increase water permeability, so it must be selected appropriately depending on the purpose. It is usually set in the range of 0 to 98°C.

After thoroughly washing the hollow fiber membrane obtained by the present invention with water,
It is stored in a water-containing state or in a state in which water is replaced with glycerin or ethylene glycol, but in some cases heat treatment may affect the membrane's permeability, mechanical properties, etc.
It is also possible to change the dimensional stability etc. The heat treatment is carried out under tension or without tension, usually at a temperature in the range of 50 to 110°C.

The hollow fiber membrane obtained in the present invention has a substantially circular hollow section, and a constant membrane thickness within a range of about 5 to 500μ,
The inner diameter varies depending on the purpose of use, but is preferably in the range of 70 to 1000 microns.

As mentioned above, the separation membrane of the present invention is most suitable for medical applications related to blood purification, but it is also suitable for separating fine particles in a solution in which the fine particles to be separated are deformable and form a suspension as a whole. It is also suitable for emulsion oils, oil/water separation, concentration of milk particles, concentration of latex liquid, clarification of beer, grape oil, sake, juice, etc. It can also be used for clarifying suspensions of ground inorganic particles, sterile filtration, and producing ultrapure water.

Next, the present invention will be specifically explained using examples.

Example 1 Vinylidene fluoride polymer (manufactured by Pennwalt, USA, Ic
ynar 460) and vinylidene fluoride-tetrafluoroethylene copolymer (Daikin Industries, Ltd., VTO60)
08) and dissolved in 440 parts of dimethyl sulfoxide solvent containing 10 parts of glycerin at 120°C. (Polymer concentration: 12% by weight) This solution was cooled to room temperature (27°C), cast using a doctor caster onto a glass plate with a 250μ thick polyester film spacer, and immediately poured at 90°C.
The membrane was immersed in hot water for 5 minutes, and then transferred to water at 25°C to form a flat membrane. The moisture content of all membranes was 73%.

Scanning electron micrographs of this flat film are shown in FIGS. 2 and 6. As seen in the photograph, uniform pore diameters of 0.2 to 0.5 microns were observed on the membrane surface and inside, and no skin layer formation accompanied by a decrease in permeability was observed on the membrane surface.

The water permeation rate UFR8 of this membrane is 15°8t/l+
r, y++2. mm1-1 g, 0.2
% membrane 1 overrate (MF'Ij) of albumin aqueous solution is 9.
6 L/hr, m2·mm I-1g, and albumin transmittance was 98% or higher.

Furthermore, this membrane was processed using Amicon's thin-layer vortex flow device (TOF).
'type 2) and fresh rabbit blood (heparin 7 U/m
l) under a pressure of 50 gmHg, 1 me/m
The plasma f overrate when flowing at i n was 601 nl/
hr, ~2. mmHg, and the total protein transmittance was 95 coefficients or higher. Note that no leakage of platelets or red blood cells into this Δ day-old plasma was observed.

Comparative Example 1 440 parts of 60 parts of a fluororesin mixture having the same composition as Example 1
Example 1
A flat membrane was prepared in exactly the same manner. The moisture content of this membrane was 25%.

Furthermore, the pure water permeation rate of this membrane measured by the same method as in Example 1 was 0.031/hr, ~2. mm1
-1 g, and the albumin transmittance was 1% or less. When this film was observed under a scanning electron microscope (3000x magnification), a skin layer with a thickness of about 0.2 μm was formed on the surface and no pores were observed, and pores of 0.05 to 1 μm were found inside. The membrane was found to be asymmetric.

Example 2 A mixture of 9 parts of the vinylidene fluoride polymer used in Example 1 and 51 parts of vinylidene fluoride-tetrafluoroethylene was dissolved at 120° C. in a dimethyl sulfoxide solution containing 12% glycerin at a polymer concentration of 15%. Using this solution as a spinning stock solution, spinning was carried out while injecting a solution consisting of 40% dimethyl sulfoxide containing 60% water as a core solution into the hollow fiber through the annular spinning hole at a spinneret temperature of 60°C.
After running on the side, the hollow fiber was coagulated through a coagulation bath at about 90° C. consisting of an aqueous solution containing about 10% dimethyl sulfoxide, and then wound up at 20 m/min through a water washing bath and a glycerin bath.

Met.

Furthermore, uniform pore diameters of 0.2 to 0.5μ, which are almost the same as those of the flat membrane of Example 1, were observed on the surface and inside of this hollow fiber, and no skin layer was observed on the surface of the hollow fiber. .

Ten of these hollow fibers were housed in a small case with an effective diameter of 12 Crn, a test module with an effective area of 13 ctA was prepared, and the permeation characteristics were tested.

The water permeability measured by applying a pressure of 50 mmHg to this test module (4.5 t/hr・~2・m for water UFIJ)
m I-1g, membrane f of 02% albumin aqueous solution
Overspeed (MFl[j) is 1.5t/I]r・~2・mm
Hg and albumin permeability was approximately 100%.

Further, 2,500 of these hollow fibers were housed in a case with an effective length of 17.5 mm to create a module with an effective area of 0.5 m2, and all in vitro 'trm flow experiments were conducted using a 12 kg dog.

Blood flow rate 100 me/min 20-3
Plasma collection rate was 1.8 L under pressure of 0 mm) I g.
/ hr to 1.67/hr (after 3 hours), and there were many problems such as hemolysis and coagulation, and the total amount of protein in the excess plasma during that period was obtained by centrifugation from the corresponding blood. , and more than 95% of albumin, globulin, and riboprotein were transmitted. Furthermore, no leakage of platelets or red blood cells into the extracorporeal plasma was observed, and no decrease in platelets or white blood cells was observed in the dogs before and after extracorporeal perfusion.

That is, the separation membranes of Examples 1 and 2 are suitable for use as precision filtration membranes for plasma separation and the like.

Example 6 7 parts of vinylidene fluoride polymer used in Example 1 and 96 parts of vinylidene fluoride-tetrafluoroethylene copolymer were mixed, and this was dissolved in 700 parts of dimethyl sulfoxide solvent containing 10% glycerin at 120°C. did.

This solution was cooled to room temperature, cast using a doctor playdough onto a glass plate having a 250 μm thick polyester film spacer, and immediately immersed in cold water at 4° C. to form a flat film.

The water content of this flat membrane was 65q6.

It was found by scanning electron microscopy that pores of 0.02 to 0.03 μm were uniformly distributed on the surface and inside of this flat membrane.

The water permeability ('UFR8) of this membrane measured with the il+M filtration device used in Example 1 was 1.2 t/m211r.
m m Hg, 0.2% albumin aqueous solution membrane 1
Overspeed (MF'lj) is 0.8 t/m2・hr
・Albumin permeability is 94% at mmHg, and membrane 1 overrate (MF'R) measurement of 02-group γ-globulin (cattle, Seikagaku Corporation ■) saline solution, IA/hr-m2・
mmHg and transmittance was 53.5%.

Furthermore, the amount of filtration when adult cow plasma was Δj-filtered under the same conditions was 75
me/hr 11rn2emml (g,
The albumin to globulin ratio (A/G ratio) varies from 07 for plasma to 1.8 for the filtrate, and a considerable separation of albumin and globulin can be achieved.

Example 4 12 parts of the vinylidene fluoride-tetrafluoroethylene copolymer used in Example 1 was dissolved in 88 parts of dimethyl sulfoxide solvent containing 5% glycerin Z at 110°C, and cast in the same manner as in Example 1. After forming a film in a 75° C. coagulation bath containing about 10% dimethyl sulfoxide and washing with water, a flat film was prepared with glycerin attached. The water content of this flat membrane was 62%. 0.01 on the surface and inside of this film
Pores of ~0.03μ were uniformly distributed, and the water permeation rate was 1 t/hr-m2·mm Hg. Still, 2% albumin aqueous solution was added at 25°C, 50 mmH, g.
When flowing at a linear velocity of 5 cm/sec at the inlet under pressure of
h r -m2·mmHg, albumin transmittance was 99%.

Furthermore, the membrane overrate of the 0.2 coefficient γ-globulin saline solution (
MFR) is 0.05t/hr-m2·mmHg.

The transmittance was 214%.

Furthermore, the filtration amount when adult cow plasma was filtered under the same conditions was 21
ml/hr-m2·mmHg, and the albumin-to-globulin ratio (A,/G ratio) changed from 0.7 for plasma to 2.5 for r-permeate.

Examples 3 and 4 are suitable for use as a protein separation membrane for separating albumin and globulin from plasma.

[Brief explanation of drawings]

FIG. 1 shows the relationship between the mixing ratio and viscosity of vinylidene fluoride IJ polymer and vinylidene fluoride-tetrafluoroethylene copolymer. (Polymer concentration 10 parts, glycerin/DMSO
= 10/90.30°C (measured with a B-type rotational viscometer) Figure 2 is a scanning electron micrograph of the surface of the flat membrane prepared in Example 1, and Figure 6 is a scanning electron micrograph of a cross section of the same membrane (magnification +3000x). ) is shown. Patent applicant Toshi Co., Ltd. Vinyritine fluoride weight fraction (%) Figure 1

Claims (1)

[Scope of Claims] (1) The surface and inside thereof have a network structure formed by uniform pores of [1,01 to III], and the water content when hydrated is 60% or more. Fluorine-based wet separation membrane. (3) Forming a film in a wet state using a stock solution in which a resin containing vinylidene fluoride polymer, vinylidene fluoride-tetrafluoroethylene copolymer, or a mixture thereof as a main component is dissolved in a solvent containing dimethyl sulfoxide as a main component. A method for producing a fluorine-based wet separation membrane, characterized by: (4) The method for producing a fluorine-based wet separation membrane according to claim (3), using dimethyl sulfoxide with 5 to 15 weight percentages of glycerin added as a solvent. (5) Claim (3) in which the resin is a mixture of vinylidene fluoride polymer and vinylidene fluoride-tetrafluoroethylene copolymer in a weight ratio of 5/95 to 20/80. A method for producing a fluorine-based wet separation membrane as described in .