JP2501891B2 - Hydrophilic polypropylene porous membrane and plasma separation device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a hydrophilic polypropylene porous membrane and a plasma separation device. More specifically, the present invention relates to a flat membrane polypropylene porous membrane used for plasma separation for separating blood into blood cell components and plasma components, removal of bacteria in blood, etc., a method for producing the same, and a plasma separator. It is about. More specifically, the present invention has a high plasma separation rate when used for plasma separation, and has a flat membrane type blood compatibility and excellent hydrophilicity with dimensional stability with less risk of blood cell entrapment and hemolysis. The present invention relates to a polypropylene porous membrane and a plasma separation device.

BACKGROUND ART Conventionally, various permeable membranes have been used to separate blood into blood cell components and plasma components. These permeable membranes, systemic lupus erythematosus, rheumatoid arthritis, glomerulonephritis, abnormal proteins in diseases due to immune disorders such as myasthenia gravis, immune complex, antigen, plasma purification for the purpose of removal of antibodies, Furthermore, it is used for preparation of plasma preparations for transfusion of components, pretreatment of artificial kidneys, and the like. As the permeable membrane used for such plasma separation,
Cellulose acetate film (JP-A-54-15476), polyvinyl alcohol film, polyester film, polycarbonate film, polymethylmethacrylate film, polyethylene film (JP-A-57-84,702), polypropylene film and the like have been used. However, these permeable membranes are not only insufficient in mechanical strength, porosity and plasma separation ability of the membrane, but when used for plasma separation, erythrocyte damage due to clogging occurs, and in plasma. The complement component of erythrocyte was activated and the separated plasma was greatly damaged (Artificial Organs Vol. 16 No. 2 1045-1050) (198
7).

Further, a crystalline polyolefin, a polymer having poor stretchability and solubility in a solvent such as polyamide, and a compound partially compatible with the polymer and easily soluble in a solvent A permeable membrane has been proposed in which the mixture is formed into a film, a sheet or a hollow body, the formed body is treated with a solvent, dried and then stretched uniaxially or biaxially by 50 to 15,000%. 57-20, 970). However,
Since such a membrane is stretched to increase the pore size, it has a large heat shrinkage and cannot be sterilized by autoclave when used in medical applications. Furthermore, since the pore structure that is formed is formed by stretching, it is a straight line that is substantially parallel to the film thickness direction, and because the pore structure on both surfaces and inside is almost uniform, plasma separation is performed. When used in the above, clogging of proteins and blood cells was likely to occur.

Furthermore, regarding the permeable membrane for plasma separation, attention has been paid to polyolefin-based polymers as a material with less complement activity,
Studies on a permeable membrane using a polyolefin-based polymer are underway. For example, a molten mixture of 10 to 80% by weight of paraffin and 90 to 20% by weight of polypropylene resin is extruded through a die into a film, a sheet or a hollow fiber shape, and is rapidly cooled and solidified by being introduced into water maintained at 50 ° C or lower in a molten state Then, a method for producing a porous membrane in which paraffin is extracted and separated from the obtained molded product is disclosed. (Japanese Patent Laid-Open No. 55-
No. 60,537). However, since the porous membrane obtained by this method is rapidly cooled by water having a large specific heat, both the surface pore size and the internal pore size are small and the porosity is also low, so that the filtration rate is low and rapid plasma separation is possible. Was not suitable.

Further, as a means for cooling and solidifying the molten mixture, a cooling and solidifying liquid having good compatibility with the organic filler such as a metal roller or paraffin is used (Japanese Patent Application No. 60-237,069).
No.) Method has been proposed. However, in the former method, the surface pore diameter of the obtained porous membrane becomes extremely small and the plasma permeation rate becomes slow. Further, in the latter method, since the cooled solidified liquid has a smaller specific heat than water, it promotes the crystallization of polypropylene at an appropriate cooling rate, and has a small pore size inside so that it can be used for plasma separation. Although pores are formed, a very large network structure is considered to be formed on the surface portion of the pores, which is considered to be generated by the dissolution of the polypropylene on the surface into the cooling solidification liquid before solidification. In the porous membrane having such a surface layer, the surface layer acts as a prefilter, so that the clogging of the protein is small,
Further, although it was possible to perform plasma separation with a good plasma separation rate, it was likely that blood cells would engulf when contacting blood, and that hemolysis may occur when pressure is applied.

Furthermore, hydrophobic membranes such as polyolefins have the drawback that although the ability to activate the complement system is not high, the recovery rate of useful molecules such as fibrinogen and blood coagulation factors decreases.

Furthermore, the hydrophobic membrane has a drawback that it must be subjected to a hydrophilic treatment at the time of use.

Further, a porous membrane in which the membrane surface and the pore surface are hydrophilized by a graft chain of a hydrophilic monomer is also disclosed in Japanese Patent Application No. 61-10
Although described in 3,011, the production method as described in (Examples and photographs) specification results in a membrane in which hemolysis easily occurs, in which blood cells having a large surface pore diameter on the surface of the membrane are entangled. Furthermore, in order to express high blood compatibility, it is not enough to simply bond a graft chain of a hydrophilic monomer, and it is necessary to chemically bond a water-soluble polymer by itself. .

Therefore, an object of the present invention is to provide a novel hydrophilic polypropylene porous membrane and a method for producing the same.

The present invention also provides a flat membrane type hydrophilic polypropylene porous membrane used for plasma separation for separating blood into blood cell components and plasma components, removal of bacteria in blood, etc., and a method for producing the same. With the goal.

Furthermore, the present invention has a flat plasma-type blood compatibility and dimensional stability with high plasma separation rate when used for plasma separation, less damage to the separated plasma, and less risk of blood cell entrapment and hemolysis. An object of the present invention is to provide a hydrophilic polypropylene porous material having excellent properties and a method for producing the same.

DISCLOSURE OF THE INVENTION These various objects are hydrophilic porous membranes having a fine network structure, and a surface layer having the same network structure as the inside is formed on at least one membrane surface of the porous membrane, Moreover, the hydrophilic polymer is chemically bonded to the membrane surface and the pore surface, and the average pore diameter is 0.1 to 2.0 μm and the bubble point is
2.0 kg / cm ² or less, porosity 60 to 85%, water permeability 2 ml / min ・
It is achieved by a hydrophilic polypropylene porous membrane characterized in that it is substantially composed of polypropylene having a mmHg · m ² or more.

Further, the present invention is a hydrophilic polypropylene porous membrane having a shrinkage ratio of 5.0% or less after heat treatment at 120 ° C. for 20 minutes. Furthermore, the present invention is the hydrophilic polypropylene porous membrane according to claim 1, wherein the swelling ratio when wet is within 1.0%. The present invention provides a hydrophilic polymer having the formula I (However, R ¹ is H or CH ₃ , and R ² is CONHR ³ , (However, R ³ and R ⁴ are alkyl having 1 to ⁴ carbons), COOM (where M is a metal), COOR ⁵ NHR ⁶ (where R ⁵ is alkylene having 1 to 4 carbon atoms, and R ⁶ is 1 to 1 carbon atoms)
4 alkyl), (Wherein R ⁵ and R ⁶ are as described above, and R ⁷ is alkyl having 1 to 4 carbons) or And R ² is In which R ¹ is H, and n is 10 to 10 ⁴ ), which is at least one kind of hydrophilic polypropylene porous. Further, the present invention is a hydrophilic polymer having the following formula II (However, n is as described above and R ⁸ is H or CH ₃ , R
⁹ and R ¹⁰ are alkyl groups, and the total carbon number of R ⁸ , R ⁹ and R ¹⁰ is 8 or less), which is a hydrophilic polypropylene porous membrane.

These various purposes are also a hydrophilic porous membrane having a fine network structure, the surface layer of the same degree of network structure as the inside is formed on at least one membrane surface of the porous membrane,
In addition, a hydrophilic polymer is chemically bonded to the membrane surface and pore surface, the average pore diameter is 0.1 to 2.0 μm, the bubble point is 2.0 kg / cm ² or less, the porosity is 60 to 85%, and the water permeability is Is 2 ml / m
^Two or more hydrophilic polypropylene porous membranes consisting essentially of polypropylene of in · mmHg · m ² or more are combined to form a plasma channel inside to seal the peripheral portion and at least one location of the separation membrane. A plurality of separation membrane units each having a plasma outlet are stacked on top of each other and housed in a case having a blood inlet, a blood cell outlet, and a plasma outlet, and the plasma outlet of each separation membrane unit is It is also achieved by a plasma separation device in communication with the plasma outlet.

The present invention also provides a hydrophilic polypropylene porous membrane 12
This is a plasma separation apparatus having a shrinkage rate of 5.0% or less after heat treatment at 0 ° C for 20 minutes. Furthermore, the present invention is the plasma separation apparatus, wherein the swelling rate of the hydrophilic polypropylene porous membrane when wet is within 1.0%.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an electron micrograph showing a surface structure of a hydrophilic polypropylene porous membrane according to the present invention obtained in Example 1, and FIG. 2 is an electron micrograph showing a cross section of the porous membrane. FIG. 3 is a manufacturing apparatus showing a manufacturing method of the present invention, FIG. 4 is a cross-sectional view of a plasma separation apparatus according to the present invention, FIG. 5 is a schematic diagram of a plasma separation experiment circuit, and FIG. FIG. 7 is an electron micrograph of the surface of the membrane after plasma separation of bovine blood using the hydrophilic porous membrane of Example 1, and FIG. 7 shows that the hydrophilic porous membrane of Comparative Example 1 was used. 3 is an electron micrograph of the surface of the membrane after plasma separation of bovine blood.

BEST MODE FOR CARRYING OUT THE INVENTION The hydrophilic polypropylene porous membrane of the present invention has a thickness of 30 to
300 μm, preferably a membrane having a hydrophilic polymer chemically bonded to the membrane surface and the pore surface of 60 to 200 μm. The film structure of this hydrophilic polypropylene porous film changes depending on the film forming conditions, but as described below, when polyethylene glycol (molecular weight: 200) or the like is used as a cooling and solidifying liquid,
It has a structure as seen in the scanning electron micrographs shown in FIGS. That is, a fine net-like structure in which filaments made of a string of polypropylene particles are entangled with each other is three-dimensionally isotropically developed, and a surface layer having a net-like structure similar to the inside is formed on the film surface. Because
When it is used as a plasma separation membrane, there is very little risk of blood cell entrapment or hemolysis. Further, unlike the porous membrane formed by the stretching method, since the network structure of the membrane is isotropically developed, it becomes a membrane having extremely small heat shrinkage due to an autoclave or the like, and various sterilization methods can be applied.

In order for the hydrophilic polypropylene porous membrane of the present invention to exhibit a sufficient plasma separation ability, the average pore diameter is 0.1 to 2.0 μm, preferably 0.2 to 1.0 μm, and the bubble point is 2.0 kg / cm ² or less,
Preferably 0.2 to 1.6 kg / cm ² , porosity 60 to 85%, preferably 65 to 80%, water permeability 2 ml / min · mmHg · m ² or more, preferably 4 to 400 ml / min · mmHg · m ² . Is desirable. That is, if the average pore size is less than 0.1 μm, the permeability of proteins with large molecular weight in plasma (eg, blood coagulation factor VIII and various immune complexes) decreases,
This is because separation / fractionation becomes difficult. On the other hand, when the thickness exceeds 2.0 μm, blood cells are liable to engulf in the membrane during plasma separation to cause hemolysis, the physical properties of the polypropylene membrane are changed, and the membrane becomes brittle, which causes problems in use. When the bubble point exceeds 2.0 kg / cm ² , the plasma separation ability of the membrane decreases. When the porosity is less than 60%, the plasma separation ability of the membrane decreases, while when it exceeds 85%, the physical properties of the polypropylene membrane change and the membrane becomes brittle, which tends to cause problems in use. If the water permeation rate is less than 2 ml / min · mmHg · m ² , the plasma separation ability of the membrane will decrease.

The terms and measuring methods used in the present invention are as follows.

First, the average pore diameter is a value measured by a mercury porosimeter [maximum value of dV / d log r (where V is the volume of the hole and r is the radius of the hole)], and the bubbling point is ASTM F.
According to the 316 revision method, using a stainless steel holder with a diameter of 47 mm,
It was measured using isopropyl alcohol as the liquid phase. Then, the pressure was raised and the pressure at which a series of air bubbles of nitrogen in isopropyl alcohol began to rise evenly and unequally from the center of the filter was taken as the bubble point.

The film thickness is a value measured using a micrometer.

The water permeability is a value measured by using distilled water at 25 ° C under a pressure of 0.7 kg / cm ² .

The porosity (P) was measured by immersing the porous membrane in ethanol, substituting it with water, and allowing it to hydrate to measure the weight (W _w ) after hydration.
When the dry weight is W _d and the polymer density is a [g / cm ³ ], the porosity is calculated by the following formula.

The swelling ratio is a value obtained by actually measuring the dimensional change of the film after being immersed in distilled water at 25 ° C. for 5 minutes.

The hydrophilic polymer graft-polymerized to the hydrophobic polypropylene membrane and chemically bonded is not particularly limited as long as it is hydrophilic, but the one containing no -OH group can suppress the activation of the complement system to a low level. preferable. As the at least one monomer unit obtained by forming such a hydrophilic polymer, the following formula I ′ can be used. (However, R ¹ is H or CH ₃ , and R ² is CONH ₂ , CONHR ³ , (However, R ³ and R ⁴ are alkyl having 1 to ⁴ carbons), COOM (where M is a metal, for example, an alkali metal such as sodium, potassium or lithium), COOR ⁵ NHR
⁶ (provided that R ⁵ is alkylene having 1 to 4 carbon atoms and R ⁶ is alkyl having 1 to 4 carbon atoms), (Wherein R ⁵ and R ⁶ are as described above, and R ⁷ is alkyl having 1 to 4 carbons) or And R ² is In which R ¹ is H). Specific examples of the hydrophilic polymer include, for example, poly N-vinylpyrrolidone, poly (meth) acrylamide, poly N-lower alkyl (meth) acrylamide, poly N, N-dilower alkyl (meth) acrylamide, poly (meth). There are acryloylmorpholine, diacetone (meth) acrylamide and the like, and a copolymer of these monomer units may be used. The degree of polymerization n of these hydrophilic polymers is 10 to 10 ⁴ , preferably 10 ² to 10 ³ .

The hydrophilic polymer has the following formula II (However, n is as described above and R ⁸ is H or CH ₃ , R
⁹ and R ¹⁰ are alkyl groups, and the total carbon number of R ⁸ , R ⁹ and R ¹⁰ is preferably 8 or less) and is preferably alkyl (meth) acrylamide.

The hydrophilic polymer composed of alkyl acrylamide in formula II has a strong hydrophobicity in the molecule even though it has a very high affinity with water, and therefore has a good affinity with polypropylene. The binding reaction inside the pores proceeds smoothly, and the membrane surface can exist in a stable state. Furthermore, since it does not have a structure (for example, a hydroxy group) that activates the complement system in the molecule, the membrane has high blood compatibility.

Further, as the hydrophilic monomer reacted with the hydrophobic polypropylene porous membrane, for example, the following formula III (Wherein R ¹ and R ² are as described above) are preferred, and especially the following formula IV (However, R ⁸ , R ⁹ and R ¹⁰ are as described above), and an alkyl (meth) acrylamide is preferable.

The water-soluble polymer bound to the membrane surface and the pore surface is
It suppresses the adsorption of plasma proteins such as fibrinogen and blood coagulation factors to the membrane, functions to reduce clogging of the membrane and improve blood compatibility.

The hydrophilic polypropylene porous membrane of the present invention having such characteristics is manufactured as follows. That is,
First, the hydrophobic polypropylene porous membrane can be uniformly dispersed in polypropylene under melting conditions and is easily soluble in the extract used, as described in, for example, US Pat. No. 4,743,375. A compound 11 comprising an organic filler and optionally a crystal nucleating agent is fed from a hopper 12 to a kneader, for example a twin-screw extruder 13 as shown in FIG. The kneaded material is discharged in the molten state from the die 14 and cooled and solidified.
A guide roller 16 provided in a cooling tank 15 accommodating 17 is contacted above the liquid surface of the cooling and solidifying liquid 17, and is guided into the cooling and solidifying liquid 17 by rotation of the guide roller 16 to be cooled and solidified, and then by cooling and solidifying. It is obtained by bringing the obtained membrane into contact with an extract which does not dissolve the hydrophobic polymer to extract and remove the organic filler. Further, the melted kneaded product may be formed into a film by a casting method using a suitable coagulating solvent.

In the embodiment, the guide roller is used to bring the molten film into contact with the cooling and solidifying liquid, but it is also possible to directly discharge the molten film into the cooling and solidifying liquid. The molten film is completely cooled and solidified while passing through the cooling tank 15, and then wound around the winding roller 18. Further, during this time, the cooling solidified liquid 17 supplied from the line 19 is discharged from the line 20 and then cooled to a predetermined temperature by a cooling device (for example, a heat exchanger) 20a and recirculated. Then, the wound film material is further introduced into an extraction tank (not shown) containing an extraction liquid to extract the organic filler. If necessary, it may be re-extracted, dried, and heat-treated before being wound up. From the standpoint of stabilizing the structure and permeation performance of the obtained porous membrane, it is preferable to fix the membrane-like material to a certain length and heat-treat it. Further, the extraction of the organic filler may be performed by providing an extraction tank before winding.

The hydrophobic polypropylene porous membrane thus obtained was placed in a reactor, irradiated with low temperature plasma to form a polymerization initiation point on the polypropylene molecule, and then depressurized to 0.01 torr or less, and then a hydrophilic monomer was added. The body is supplied to grow water-soluble polymer chains bound to the membrane surface and the pore surface. By irradiating the plasma with low temperature and then sufficiently removing decomposition products, gas, and the like by the plasma, linear water-soluble polymer chains are synthesized in a short time up to the pore surface inside the membrane.

The polypropylene used as a raw material in the production method of the present invention is not limited to propylene homopolymer, but includes a block polymer with another monomer containing propylene as a main component (for example, polyethylene), but the melt index ( MI) of 5 to 70 is preferable, and MI of 5 to 40 is particularly preferable. In order to further increase the strength of the membrane, the molecular weight is high, that is, MI
It is preferable to mix low polypropylene, for example MI0.100 against 100 parts by weight of polypropylene of MI5-40.
05 to 5 polypropylene, 0 to 150 parts by weight, especially 20 to 100
A kneaded part by weight is preferably used. Further, among the polypropylenes, propylene homopolymer is particularly preferable, and among them, those having high crystallinity are most preferable.

As the organic filler, it is necessary that it can be uniformly dispersed in the polypropylene while being melted and that it is easily soluble in the extract as described later.
Examples of such fillers include liquid paraffin (number average molecular weight 100 to 2000), α-olefin oligomer [eg ethylene oligomer (number average molecular weight 100 to 2,000), propylene oligomer (number average molecular weight 100 to 2,000), ethylene-propylene]. Oligomer (number average molecular weight 100-2,000)
Etc.], paraffin wax (number average molecular weight 100 to 2,500,
There are various hydrocarbons and the like, and liquid paraffin is preferable.

The mixing ratio of the polypropylene and the organic filler is 100 to 100 parts by weight of the polypropylene, the organic filler is 200 to 60.
It is 0 part by weight, preferably 300 to 500 parts by weight. That is, if the organic filler is less than 200 parts by weight, the porosity of the obtained polypropylene porous membrane, the water permeability is too low to obtain sufficient permeation performance, and if it exceeds 600 parts by weight, the viscosity is too low. This is because the moldability of the film-like material is reduced. Such a raw material mixture is prepared by a pre-kneading method in which a mixture having a predetermined composition is melt-kneaded using an extruder such as a twin-screw extruder, extruded and then pelletized.

The crystal nucleating agent to be blended in the raw material in the present invention is an organic heat-resistant substance having a melting point of 150 ° C. or higher, preferably 200 to 250 ° C., and a gelation point of the crystallization start temperature of the polypropylene used or higher. is there.

The reason for incorporating such a crystal nucleating agent is to reduce the size of polypropylene particles and thereby control the gap between solid phases, that is, the pore size of the pores formed. As an example, for example, 1.3,2.4-di-benzylidene sorbitol, 1.3,2.4-di- (methylbenzylidene) sorbitol, 1.3,2.4-di (ethylbenzylidene) sorbitol and 1.3,2.4-di- (propylbenzylidene) 1.3,2.4-di- (alkylbenzylidene) sorbitol, bis (4-t-butylphenyl)
Examples of crystal nucleating agents include sodium phosphate and sodium benzoate. Of these, 1.3,2.4-dibenzylidene sorbitol, 1.3,2.4-di- (p-ethylbenzylidene) sorbitol and 1.3,2.4-di- (p-methylbenzylidene) sorbitol are preferable because they are less likely to be eluted into blood.

The mixing ratio of polypropylene and the crystal nucleating agent,
Crystal nucleating agent is 0.1 with respect to 100 parts by weight of polypropylene.
-5 parts by weight, preferably 0.2-1.0 parts by weight.

The hydrophilic polypropylene porous membrane thus obtained has a shrinkage ratio of 5.0% or less, preferably 2% or less, when heat-treated at 120 ° C. for 20 minutes. The expansion coefficient when wet is 1.0% or less, preferably 0.5% or less. In addition, the film thickness of the hydrophilic polymer is required to be such that pores are not blocked, from the viewpoint of plasma separability, and is, for example, 200 nm or less, preferably 100 nm or less.

The hydrophilic polypropylene porous membrane of the present invention can be obtained as described above, and its applications include a plasma separation membrane for separating blood into blood cell components and plasma components, for removing bacteria in blood. And the like, and is particularly preferably used as a plasma separation membrane when using separated plasma such as in donor pheresis or for treating immune diseases.

The membrane thus obtained is used for various applications depending on the membrane properties of the permeable membrane main body 1 as described above.
In particular, it exhibits excellent performance when incorporated in a module as a plasma separation membrane as shown below.

FIG. 4 shows an embodiment of the plasma separation device of the present invention. In this embodiment, a cylindrical case body 24 having a blood inlet 21 at the center of the upper plate, a plasma outlet 22 at the outer peripheral portion of the upper plate, and a blood outlet 23 at the side wall, and an O-ring 25 at the circular edge are attached. In the case consisting of the bottom lid 26, a circular plasma flow path forming body 27 made of a screen mesh or a non-woven fabric having an opening 28 in the center and a plasma passage hole 29 in the vicinity of the plasma separation membrane 10a on the outside, A membrane unit 31 narrowed by 10b and sealing the outer peripheral edge and the peripheral edge of the central opening is provided with a central opening 28 and a plasma passage hole 29 corresponding to the unit 31, and is provided on the outer periphery of the plasma passage hole 29. A plurality of sheets are laminated with a flow path restricting body 32 having a plurality of minute projections 34 to which a sealing material 30 is attached sandwiched. In addition, the membrane unit 31 and the flow path restricting body 32 are integrally joined by the sealing material 30.

In the flow path restrictor 32, the fine protrusions 34 have a height
It is preferable that the diameter is 20 to 200 μm, the base diameter is 100 to 1,000 μm, the gap between the apexes is 300 to 2,000 μm, and the area occupied by the microprojections with respect to the entire film surface is 3 to 20%.
More preferably, the height is 50-100 microns and the base diameter is 2
00-500 microns, gap between vertices is 500-1,000 microns, occupying 5-15% of the surface area of microprotrusions
It is desirable that

That is, the height of each microprojection on the permeable membrane surface is an important factor that determines the thickness of the body fluid channel. From the viewpoint of the filtration industry, if the height of the microprotrusions is less than 20 microns, the body fluid flow path thickness becomes too thin, resulting in high pressure loss, and if it exceeds 200 microns, the shear rate can be increased. It is not possible to obtain sufficient bodily fluid filtration.

From the above, it is preferable that the height of the minute projection is 20 to 200 microns. The height is preferably constant, but is not necessarily limited, and the height may change stepwise along the flow direction of the body fluid.

Hereinafter, the present invention will be described in more detail based on examples.

Example 1 and Comparative Example 1 400 parts by weight of liquid paraffin (number average molecular weight 324) and 0.3 parts by weight of crystal nucleating agent per 100 parts by weight of polypropylene mixture having a melt index of 30 and 0.3 (mixing polymerization ratio 100: 40). , 1.3-2.4-bis (p-ethylbenzylidene) sorbitol was melt-kneaded and pelletized by a twin-screw extruder (PCM-30-25, manufactured by Ikegai Tekko KK). The pellets are melted at 150 to 200 ° C. using the above extruder and extruded into the air through a T die having a slit of 0.6 mm,
After dropping onto a guide roller of a cooling liquid tank placed just below the T-die, the roller was rotated to guide it into the cooling and solidifying liquid for cooling and solidifying and then winding. The cooling solidification liquid and the temperature are as shown in Table 1. Cut the wound film into a fixed length (about 200 x 200 mm), fix it in both length and width directions, and put it in 1,1,2-trichloro-1,2,2-trifluoroethane (liquid temperature 25 ℃). Liquid paraffin was extracted by immersing it 4 times in total for 10 minutes, and then heat-treated in air at 135 ° C. for 2 minutes.

The hydrophobic polypropylene porous film thus obtained was irradiated with low-temperature plasma (Ar.0.1 torr) for 10 seconds, the pressure was reduced to 0.001 torr, and then N, N-dimethylacrylamide was supplied at 25 ° C. The reaction was carried out for 5 minutes. The membrane was washed with methanol for 2 days and then dried to obtain a hydrophilic polypropylene porous membrane in which the hydrophilic polymer poly (N, N-dimethylacrylamide) was bonded to the membrane surface and the pore surface.

1 and 2 show electron micrographs of the hydrophilic polypropylene porous membrane obtained in Example 1, where FIG. 1 shows the membrane surface and FIG. 2 shows the membrane cross section.

As shown in FIG. 5, the hydrophilic porous materials of Example 1 and Comparative Example 1 were incorporated into a plasma separation module 40, housed in a flask 41 equipped with a stirrer 42 and kept at 37 ° C. for blood plasma separation. Electron micrographs of the surface of the film after the above are shown in FIGS. 6 and 7. In the figure, P is a pump,
G _{1 to} G ₃ are pressure gauges. In comparison with Comparative Example 1, in Example 1, almost no blood cell entrapment on the membrane surface was observed. The results are shown in Table 1.

Example 2 and Comparative Examples 2-3 In the same manner as in Example 1, bubble point 1.2 kg / c
A hydrophilic polypropylene porous membrane with m ² and a film thickness of 140 μm was obtained.

A hydrophobic polypropylene membrane having the same membrane structure as in Example 1 but having no water-soluble polymer bonded to the membrane surface and the pore surface was used in Comparative Example 2 and a hydrophilic porous membrane was used in the same manner as in Example. Comparative Example 3 was a cellulose acetate membrane (manufactured by Toyo Roshi Kaisha, Ltd.) having a pore size of about 3 mm.

With respect to these porous membranes for plasma separation, an in vitro plasma separation experiment was performed using human blood, and the recovery rates of fibrinogen and F.VIII: C were measured as an index of the recovery rate of coagulation factors in filtered plasma. In addition, the concentration of C _3a in the filtered plasma was measured as an index of activation of the complement system.

The experiment was carried out using a disk-shaped module having a membrane area of 130 cm ² and a filtration pressure of 25 mmHg and 37 ° C., using the circuit shown in FIG. Table 2 shows the values at the initial stage of filtration (10 minutes after the start of separation) in which the structures of the membrane surface and the pore surface strongly influence the adsorption and activation of plasma proteins and the like. The hydrophilic polypropylene porous membrane of the present invention comprises fibrinogen,
The membrane had a high recovery rate of F.VIII: C and excellent blood binding with less activation of the complement system.

 Table 2 shows the results.

Industrial Possibility As described above, the hydrophilic polypropyne porous membrane of the present invention is a hydrophilic porous membrane having a fine network structure, and at least one of the porous membranes has the same surface as the inside. Since a surface layer with a mesh structure of a certain degree is formed and a water-soluble polymer is chemically bonded to the membrane surface and the pore surface, when used as a plasma separation membrane, the blood cells go around inside the membrane. There is little risk of congestion or hemolysis. In addition, since the water-soluble polymer bound to the surface of the pores exists in a state of high molecular mobility such that it is partially dissolved in plasma, adsorption denaturation of plasma proteins is suppressed, and separated plasma is separated. Less damage. As a result, the recovery rate of coagulation factors in plasma is high, the activation of the complement system is small, and it becomes an excellent blood-compatible membrane. It has a great effect. Further, the hydrophilic polypropylene porous membrane of the present invention, due to its excellent blood compatibility, is not only useful as a membrane for blood treatment, a porous carrier, but also as an ultrafiltration and sterilization filter as a medical product industry, food. As a separation membrane in the industrial field, it is very effective as a membrane that is less likely to be clogged.

Since the hydrophilic polypropylene porous membrane of the present invention has excellent dimensional stability during heat treatment and wetness, it can be used in the fields of medical products industry and food industry that require sterilization. Further, it becomes possible to prevent the channeling phenomenon due to the swelling deformation of the film, which is often a problem when the module is used.

The production method of the present invention can easily produce the porous membrane having the above-mentioned excellent performance.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yukio Kiyota 2656, Ohuchi, Fuji City, Shizuoka Prefecture-1 Terumo Co., Ltd. Examiner Koichi Nakano (56) References JP 62-97603 (JP, A) JP A 62-179540 (JP, A) JP-A-62-201604 (JP, A)

Claims (8)

(57) [Claims] 1. A hydrophilic porous membrane having a fine network structure, wherein at least one membrane surface of the porous membrane is formed with a surface layer having a network structure of the same degree as the inside, and A hydrophilic polymer is chemically bonded to the surface of the pores, the average pore diameter is 0.1-2.0 μm, and the bubble point is 2.0 kg / cm.
² or less, porosity 60 to 85%, water permeability 2 ml / min ・ mmHg ・ m ²
A hydrophilic polypropylene porous membrane comprising the above polypropylene. 2. The shrinkage ratio by heat treatment at 120 ° C. for 20 minutes is 5.0.
The hydrophilic polypropylene porous membrane according to claim 1, wherein the hydrophilic polypropylene porous membrane is less than or equal to%. 3. The hydrophilic polypropylene porous membrane according to claim 1, wherein the swelling ratio when wet is within 1.0%. 4. A hydrophilic polymer has the formula I (However, R ¹ is H or CH ₃ , and R ² is CONH ₂ , CONHR ³ , (However, R ³ and R ⁴ are alkyl having 1 to ⁴ carbons), COOM (where M is a metal), COOR ⁵ NHR ⁶ (where R ⁵ is alkylene having 1 to 4 carbon atoms, and R ⁶ is 1 to 1 carbon atoms)
4 alkyl), (However, R ⁵ and R ⁶ are as described above, and R ⁷ is alkyl having 1 to 4 carbon atoms), or And R ² is Wherein R ¹ is H and n is 10 to 10 ⁴ ), and the hydrophilic polypropylene porous membrane according to claim 1. 5. A hydrophilic polymer has the following formula II: (However, n is as described above and R ⁸ is H or CH ₃ , R
^9. The hydrophilic polypropylene porous membrane according to claim 4, wherein ⁹ and R ¹⁰ are alkyl groups, and the total carbon number of R ⁸ , R ⁹ and R ¹⁰ is 8 or less. 6. A hydrophilic porous membrane having a fine network structure, wherein a surface layer having the same network structure as the inside is formed on at least one membrane surface of the porous membrane, and A hydrophilic polymer is chemically bonded to the surface of the pores, the average pore diameter is 0.1-2.0 μm, and the bubble point is 2.0 kg / cm.
² or less, porosity 60 to 85%, water permeability 2 ml / min ・ mmHg ・ m ²
Separation by combining two hydrophilic polypropylene porous membranes made of polypropylene above and below, forming a plasma channel inside to seal the peripheral portion and providing a plasma outlet at at least one location of the separation membrane. A plasma separation apparatus in which a plurality of membrane units are superposed, housed in a case having a blood inlet, a blood cell outlet, and a plasma outlet, and the plasma outlet of each separation membrane unit communicates with the plasma outlet of the case. . 7. A hydrophilic polypropylene porous membrane at 2 ° C. at 2 ° C.
The plasma separation apparatus according to claim 6, which has a contraction rate of 5.0% or less due to heat treatment for 0 minutes. 8. The plasma separation apparatus according to claim 6, wherein the swelling ratio of the hydrophilic polypropylene porous membrane when wet is within 1.0%.