JPS61283304A - Semipermeable membrane and its manufacture - Google Patents

Abstract

PURPOSE:To produce a medical semipermeable membrane which does not create thrombus during membrane contact with blood by adding acid other than telephthalic acid and polyethylene glycol to a copolymer of telephthalic acid and low molecular weight glycol. CONSTITUTION:A fixed quantity of decarboxylic acid demethyl ester and low molecular weight glycol like 1,4-butanediol are exchange-reacted in the presence of catalyst so that the polymer contains telephthalic acid as essential ingredient, isophthalic acid, adipic acid and other acids totally by 20-60mol%. Then polymeric catalyst and polyethylene glycol of average molecular weight 1,000-60,000 are so added that their sub-total is 5-30wt% of total weight of polymer and a polyester copolymer is provided after polycondensing under high temperature vacuum. It is solved in a solution such as 1,3-dioxolan solvent to produce membrane liquid to be formed up into membrane by a well-known process to be spun into hollow yarn to produce membrane.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a novel semipermeable membrane.

More specifically, the present invention relates to a novel semipermeable membrane suitable for ultrafiltration, dialysis, etc. that is used in direct contact with blood components, and in particular to a medical semipermeable membrane suitable for artificial kidneys.

[Conventional technology]

In recent years, as the use of polymeric materials in the medical industry has progressed, various types of polymers in addition to the conventional "cuprophane" are being used as semipermeable membrane materials for artificial kidneys. Each membrane material has recently come to be required to have permeability and strength depending on the purpose of use, as well as biocompatibility such as antithrombotic properties.

Commercially available polymethyl methacrylate, SE/L10
- Semipermeable membranes made of materials such as suacetate, ethylene vinyl alcohol, and polyacrylonitrile are generally satisfactory in mechanical properties such as permeability and strength, but have biocompatibility problems such as thrombus formation when they come into contact with blood. There are still major unresolved issues regarding this.

Regarding semipermeable membranes produced by wet or wet-dry membrane formation using polyester polymer as a material, the main component is polyethylene terephthalate by D. The only known membrane is a membrane made from a copolymer made of
o, 7. 985 (1964)).

The membrane of Lyman et al. required copolymerization of a large amount of polyethylene glycol to increase solubility in organic solvents, and as a result, the strength of the membrane became extremely low, making it impossible to put it to practical use. Furthermore, because billions of polyethylene glycol and ethylene glycol are used as the equinox predistortion glycol, there is a large amount of elution from the membrane material, making it impractical for medical use.

[Problem that the invention seeks to solve]

An object of the present invention is to provide an excellent medical semipermeable membrane that maintains or improves the permeability and mechanical properties of conventional polymeric materials, and which does not form thrombus when it comes into contact with blood.

[Means for solving problems]

The present invention uses glycol components other than polynystere whose main components are terephthalic acid and pre-strained glycol with a molecular weight of 250 or less, and which have a number average molecular weight of about 1000 to 5000.
oo of polyethylene glycol to the total amount of polymer
The present invention provides a semipermeable membrane made of a polyester copolymer containing up to 30% by weight, and a method for producing the same. A more preferable composition of this polyester copolymer is when the prestrained glycol is 1,4-butanediol.

In the present invention, when forming a semipermeable membrane, the solubility in a Ti-containing solvent is adjusted by copolymerizing acids other than terephthalic acid (e.g., isophthalic acid, adipic acid), and the water permeability and solute permeability are compared. By adjusting the amount of polyethylene glycol in a suitable amount, a semipermeable membrane can be obtained which has high strength not only in a dry state but also in a hydrated state. Further, the molecular weight of this polyethylene glycol is about 1000 or more, preferably 2000 or more.
If the polymer is long and has high flexibility and hydrophilicity, it should be 5% by weight or more, preferably 10% by weight based on the total amount of the polymer.
The present inventors have discovered that when the above-mentioned components are contained, the adhesion of platelets and the like to the semipermeable membrane obtained therefrom is suppressed, resulting in good biocompatibility such as antithrombotic properties, and the present invention has been achieved.

In this way, there has never been a semipermeable membrane that itself has biocompatibility such as antithrombotic properties, and this is a major advance. This reduces the use of anticoagulants such as Hepa-4J used during treatment, and reduces the amount of plasma protein adhesion.
Deterioration over time during use is small, and reuse is also easy.

In the case of medical semipermeable membranes, especially semipermeable membranes for artificial kidneys, the performance required of the membrane is not only biocompatibility but also water permeability (UFR).
and solute permeability as well as its mechanical strength. That is, one of the objects of the present invention is to provide a membrane whose permeability characteristics can be varied over a wide range depending on the purpose of use, and a method for producing the membrane. According to the method of the present invention, membranes with various permeability performances can be obtained from stock solutions with similar polymer concentrations in a fixed membrane forming process.

It is desirable for solute permeability to be high enough to prevent plasma proteins (especially albumin) from permeating, but ultrafiltration capacity is determined by ultrafiltration rate (UFR), as the amount of water removal required varies greatly depending on the patient. Preferably, it can be adjusted over a wide range.

In addition to regular dialysis therapy, hemofiltration therapy (H
Developments have been seen in portable artificial kidneys and wearable artificial kidneys based on emofiltratton, and semipermeable membranes with extremely high UFR are also desired.

That is, as a semipermeable membrane for medical use, albumin does not substantially permeate and the water permeation rate (UF'R) is 0.
1-1.000nl/hr, m, mmHg,
Preferably 0.5-200m1/hr, rd, m
mHg is desired.

For typical dialysis therapy applications, it is substantially impermeable to albumin and has a water permeation rate (ultrafiltration rate, UFR).
is 0.1-10 m1/hr, rd, mmHg.

Preferably 0.5-3ml/hr, rd, mm
Near Hg is required, and UFR is 20rnl/hr for hemofiltration therapy, etc.
There is a demand for a membrane that exhibits as high a UFR as possible at rrr, mmHg or higher and within a range that does not allow albumin to pass through.

In the semipermeable membrane made from the polyester copolymer of the present invention, by changing the composition of the copolymer, the type of solvent when preparing the membrane forming stock solution, the coagulation bath temperature during membrane forming, etc. Various semipermeable membranes can be obtained that satisfy these required permeation performance.

The acid component of the polyester copolymer of the present invention includes terephthalic acid as an essential component, and 20 to 60 mol%, preferably 30 to 50 mol% of acid components other than terephthalic acid. The acid component other than terephthalic acid is preferably a dicarboxylic acid such as an aromatic dicarboxylic acid other than terephthalic acid or an aliphatic dicarboxylic acid. Examples of aromatic dicarboxylic acids other than terephthalic acid include isophthalic acid, naphthalene dicarboxylic acid, diphenyl dicarboxylic acid, diphenyl ether dicarboxylic acid, methyl terephthalic acid, and methyl isophthalic acid.

Among these, isophthalic acid is particularly preferred.

It is also possible to use a small amount (usually 2 mol % or less) of a dicarboxylic acid containing a group represented by -So or M (M is an alkali metal) in the molecule, such as sodium 5-sulfoisophthalate.

Aliphatic dicarboxylic acids include malonic acid, glutaric acid,
Adipic acid, sebacic acid, dodecanedioic acid, succinic acid, 1
, 3-cyclopentadicarboxylic acid, and 1°4-cyclohexanedicarboxylic acid.

Among these, adipic acid is particularly preferably used.

By adding these aromatic dicarboxylic acids and aliphatic dicarboxylic acids other than terephthalic acid, it becomes possible to increase the solubility in polar organic solvents without significantly reducing the film strength.

Next, as the glycol component used in the present invention,
In addition to pre-distorted glycols such as 1,4-butanediol and ethylene glycol, glycols with a molecular weight of 250 or less are used as Yabuhira, such as ethylene glycol, trimethylene glycol, 1,4-butanediol,
Compounds such as 1.4-cyclohexane dimetatool, neopentyl glycol, and 2°2-bis(4-hydroxyphenyl)propane can be used.

Among these, 1,4-butanediol is particularly preferred.

As polyethylene glycol, the number average molecular weight is approximately 1
,000 to 60,000 are used.

Among them, the number average molecular weight is approximately 2,000 to 20.00 due to solute permeability balance, blood compatibility, and eluate limitations.
A value of 0 is preferred, and a value of about 4,000 to 1 ooo is particularly preferred.

The content of these polyethylene glycols in the polyester copolymer depends on its molecular weight and the content of acid components other than terephthalic acid, but is generally 5 to 30% by weight, and may be reduced by 10 to 25% by weight. This is undesirable as the amount of eluate increases.

Note that it is also a preferable method to use a polyalkylene glycol other than polyethylene glycol in combination with polyethylene glycol. That is, a polyalkylene glycol having a number average molecular weight of about 300 to 60,000, such as polypropylene glycol, polytetramethylene glycol, a copolymer of ethylene oxide and propylene oxide, a copolymer of ethylene oxide and tetrahydrofuran, etc., is combined with the above-mentioned polyethylene glycol. It can be used as In this case, the content of polyalkylene glycol containing ethylene glycol based on the polyester copolymer is generally 10 to 60% by weight, preferably 15 to 40% by weight.

The degree of polymerization of the polyester copolymer is preferably 15 or more, more preferably 22 or more when expressed in terms of relative viscosity.

The value of relative viscosity is calculated by crushing polyester cooled with dry ice, placing 8 g of it in 100 mβ of O-chlorophenol at 100°C, and melting it for 30 minutes. and,
It is expressed as a ratio of values measured in the same unit at 25°C.

The method for polymerizing the polyester copolymer is, for example: The transesterification reaction is carried out by heating at 140 to 240°C in the presence of a transesterification catalyst and distilling off the methanol produced, and then antimony dioxide, germanium dioxide, and tetrab'
Polyalkylene glycol is added in the presence of a known polymerization catalyst such as til titanate and, if necessary, a phosphorus compound such as phosphorous acid or phosphoric acid (and/or an ester thereof) at 200 to 290°C. 0.
A method of polycondensation by distilling off glycol under vacuum at a high temperature of 01 to 50 mmHH; (2) Producing dicarboxylic acid and glycol at 150 to 250°C under normal pressure or reduced pressure, in some cases under pressure, in the presence of an esterification catalyst if necessary. It is obtained by esterifying while distilling off water, and then polycondensing by adding polyalkylene glycol in the presence of a polycondensation catalyst and optionally a phosphorus compound.

Although the polyalkylene glycol can be added at any stage before the transesterification reaction, before the esterification reaction, or during the polycondensation reaction, it is generally preferable to add it after the transesterification reaction or after the esterification reaction.

The solvent used to form a film or to prepare a spinning dope needs to be one that can dissolve the polyester copolymer and can ultimately be replaced with water.

Preferred examples of the solvent include polar organic solvents such as 1,3-dioxolane, dimethylsulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, and 1,4-dioxane.

Among these, 1,3-dioxolane is a particularly preferred solvent because it can dissolve the polyester copolymer used in the present invention at an easy-to-handle temperature of 40 to 75 DEG C. and provides a semipermeable membrane with great strength.

Note that the solvent may also be a mixture of 1,3-dioxolane or dimethyl sulfoxide and other solvents, or a mixture of these solvents and other non-solvents (e.g. ethylene glycol monoethyl ether, polyethylene glycol, glycerin, etc.). , is preferable as a method of adjusting the permeability performance of the membrane.

The concentration of the raw material polymer in the membrane forming stock solution is a major factor in controlling water permeability. The value varies greatly depending on the solvent, and is 1,
When using 3-dioxolane as a solvent, 15 to 30% by weight is appropriate, and when using ditinyl sulfoxide as a solvent, 30 to 50% by weight is appropriate, and usually 15 to 5% by weight.
It is selected from around 0fi amount%.

In addition, in the case of a polymer that is difficult to melt, it may be handled at a temperature above the boiling point of the solvent by applying pressure.

The membrane-forming stock solution obtained in this manner can be formed into a membrane or spun into aerial fibers by various known methods. For example, the stock solution can be cast onto a flat plate such as a glass plate or a metal plate, and then immersed in a coagulation bath to solidify it, or it can be extruded into a coagulation bath through a nozzle with long and narrow holes to form a film.

In this case, it is also possible to apply it onto a supporting fabric such as polyester taffeta. In addition to flat membranes, membranes of various shapes can be formed by spinning from a spinneret with concentric circular holes to form a cylindrical or hollow fiber shape, or by spreading them on convex, concave, or other irregularly shaped surfaces and solidifying them. can be obtained.

Among these various shapes, hollow fiber molded products are most suitable for medical applications and the like because they have a small filling liquid volume (priming volume) and a high linear velocity when modularized.

Depending on the composition of the film-forming stock solution made from the material of the present invention (mainly due to the solvent), it may gel in a low temperature range, so heating may be required when preparing the stock solution.

Especially when dimethyl sulfoxide is used as a solvent, 110
It becomes gel-like and solidifies at temperatures between 1.3 and 50 degrees Celsius.
When dioxolane is used as a solvent, it often becomes gelatinous and solidifies at temperatures below around 65°C to 40°C. Therefore, when forming membranes onto hollow fibers, it is necessary to use the internal coagulation liquid as a core liquid in the so-called dry-wet spinning method. It is also possible to form a film by the gas injection method without using it.

It goes without saying that a core liquid can be used in the same manner as in the usual dry-wet spinning or wet spinning method.

As the coagulation bath, water, aliphatic lower alcohols, or a mixture thereof is generally used.

Furthermore, in order to adjust the coagulation ability, it is also possible to use a mixture of water or alcohol to which the solvent used in the stock solution or inorganic salts is added.

However, in general, when a solvent such as 1,3-dioxolane or dimethyl sulfoxide is used, it is preferable to use a mixture of the solvent and water as the coagulation bath.

Moreover, the temperature of the coagulation bath at that time is 0°C to around 95°C, usually around 4°C to 40°C.

In the case of obtaining a semipermeable membrane in the form of hollow fibers, any spinneret used for spinning ordinary hollow fibers can be used, but a spinneret consisting of an annular orifice with a hollow capillary in the spinneret hole is preferably used. .

When spinning hollow fibers using such a spinneret, spinning is performed while quantitatively injecting gas or liquid as a core liquid from a hollow tube located in the center of the spinneret.

There are no particular restrictions on the gas, but air, nitrogen, or the like is usually used. The core liquid can be the solvent used in the spinning stock solution or a mixture of the solvent and water, alcohols such as isopropyl alcohol, polyhydric alcohols such as ethylene glycol and glycerin, higher fatty acid esters such as isopropyl myristate, higher fatty acids. A mixture of alcohol and alcohol is used.

Even when the membrane of the present invention is dried, the mechanical properties do not change significantly, but there are cases where the permeation performance changes.

In that case, by attaching a wetting agent such as hydrous glycerin or ethylene glycol, there will be no major change in permeation performance or mechanical properties over a long period of time.

Furthermore, it is also possible to change the permeation performance and mechanical properties (strength, dimensional stability, etc.) of the membrane by heat treatment or stretching treatment after membrane formation.

The semipermeable membrane of the present invention is most suitable as a medical material for artificial kidneys and the like, but it can of course also be applied as a separation membrane in fields such as the food industry and wastewater treatment.

Various biological components can be attached to the semipermeable membrane made of a polyester copolymer of the present invention using methods such as scanning or transmission electron microscopy, amino acid analysis, electrophoresis, and Fourier exchange infrared absorption spectroscopy. It can be quantified by measuring blood cell components and adherent protein components.

On the other hand, regarding evaluation of medical applications, such as antithrombotic properties, various in vitro and ex vivo methods such as l, ee-White method, body bowl bypass circulation method, intravascular indwelling method, etc.
Alternatively, it can be evaluated by in vivo testing.

As a result of evaluation using such a method, the semipermeable membrane made of the polyester copolymer of the present invention was found to be effective against human and animal cells,
In other words, it suppresses the adhesion of platelets, white blood cells, lymphocytes, and tissue cells, and also has low adsorption of body fluid components such as proteins, and has practical mechanical properties such as strength, elongation, and flexibility. , was found to be suitable for medical applications.

〔Effect of the invention〕

The semipermeable membrane made of the polyester copolymer of the present invention has the following characteristics and is extremely preferable as a medical semipermeable membrane.

(Albumin 11 is not substantially permeable, and the water permeation rate can be adjusted over a wide range. Furthermore, it has higher permeability to solutes such as urea than other membranes with the same water permeation rate.

(2) It has great strength in both dry and hydrated states.

(3) When it comes into contact with blood, there is almost no adhesion or degeneration of platelets, which can trigger thrombus formation, and it has excellent antithrombotic properties.

(4) When it comes into contact with blood, there is less adhesion of plasma proteins,
Deterioration of membrane permeability over time is small.

(5) Polyester copolymers are easily prepared from high-purity industrial monomers that are used in large quantities for clothing, and can be supplied at a lower cost than blood-compatible polymers that have been studied in the past.

Examples of the present invention are shown below, but the present invention is not limited to these Examples.

Note that parts in the examples indicate parts by weight.

Example 1 77.5 parts of dimethyl terephthalate, 23.2 parts of dimethyl adipate, 25.8 parts of dimethyl isophthalate, 108 parts of butanediol, 0.1 part of tetra n-butyl titanate
18 parts were mixed and transesterification was carried out at 170 to 210° C. while distilling methanol off.

Thereafter, 0.324 parts of tetra n-butyl titanate) and 35.9 parts of polyethylene glycol having an average molecular weight of 6,000 were added.
A polycondensation reaction was carried out at 245° C. and 0.2 mmHg to obtain a pro7 ester ester copolymer ①.

The approximate composition of the obtained copolymer I is terephthalic acid component 6
The adipic acid component was 20 mol%, the isophthalic acid component was 20 mol%, and the polyethylene glycol content was 20% by weight. Note that the glycol component other than polyethylene glycol is a butanediol component.

7 so that the concentration of copolymer ■ in the solution is 25% by weight.
It was dissolved in 1,3-dioxolane at 2°C to obtain a film-forming stock solution.

The solution was poured at 70°C by placing a 100μ spacer between glass plates, cooled to room temperature and gelled, then one of the glass plates was removed and placed in water to replace the solvent with water, resulting in a film with a thickness of 113μ and water content. A transparent film A with a yield of 55% was obtained.

The water permeability (UFR of water) of this membrane, the permeability of urea, phosphate ions, and vitamin B1
Measured at 5°C. The permeability of albumin is calculated from bovine albumin (
Fr, V) (e.g. Seikagaku Kogyo ■, Sigma) to 0
．． The measurement was performed using a solution dissolved in distilled water to a concentration of 2 g/di.

Here, water permeability P+ (g-'・cm'-5ec)
is the pressure permeation constant, which represents the unit area of the membrane, the unit pressure difference per unit membrane thickness, and the volume of permeated liquid per unit time, and Pz (cJ/5ec) is the permeation constant of the membrane when there is no volumetric flow of liquid. represents the permeation constant of a solute due to the concentration gradient per unit area and unit film thickness of light.

Further, after membrane A was immersed in a 70% glycerin solution for 5 minutes, the membrane B was left indoors for 3 weeks, and the resulting membrane B was washed with water and its transmittance was measured.

Furthermore, as a comparative example, flat membrane C (actic PMMA 5 parts and isotactic PMM^1) corresponding to polymethyl methacrylate hollow fibers commercially available as artificial kidneys was
The transmittance of a transparent film (149 μm in thickness and 53% water content) obtained in the same manner from a dimethyl sulfoxide solution was measured.

The strength and elongation of these films were measured using a tensile strength tester (Shimadzu IM-100 model autograph) using the usual method.
Measurements were made in water using a

Table 1 shows the measurement results for these films.

Although the semipermeable membranes A and B of the present invention have similar water permeability, they have extremely good permeability to solutes such as urea, and are more suitable for artificial kidneys. Furthermore, it has shown that it is possible to create a membrane with extremely high strength and thinner membranes, making it possible to create a small-sized dialyzer with high removal efficiency.

Table 1 Example 2 When forming the membrane A obtained in Example 1, the membrane was placed in water for 10 seconds, then stretched to about 3 times the thickness and placed in water again to obtain a film thickness of 44.
A transparent film with a water content of 50% was obtained.

Furthermore, as a comparative example, Pro Co., Ltd. NC-
Cuprophane membrane E (film thickness 40μ, water content 5) for
1%) was prepared.

Table 2 shows the permeation characteristics of these membranes.

Table 2 In other words, the semipermeable membrane of the present invention can be made into a membrane with greater strength by stretching, and has a greater ability to remove large molecular weight solutes than the cuprophane membrane, which is most commonly used in artificial kidneys. It has a wide membrane, making it suitable for artificial kidneys.

Example 3 Using a method similar to the polymerization method of the raw material polymer in Example 1, polytetramethylene glycol (average molecular weight 1,40') was added to polyethylene glycol (average molecular weight 6,000').
Copolymer ■ was obtained using Copolymer 0).

The approximate composition of Copolymer H is 58 mol% of terephthalic acid component.
, adipic acid component: 21 mol%, isophthalic acid component: 21 mol%, polyethylene glycol: 15% by weight, and polytetramethylene glycol: 5% by weight. Note that the glycol component other than polyalkylene glycol is a butanediol component.

1, so that the concentration of copolymer ■ in the solution is 25% by weight.
A transparent film F having a film thickness of 124 μm and a water content of 44% was obtained by dissolving in 3-dioxolane and using the same method as in Example 1.

The water permeability UFR of this membrane is 0.68 m1/hr -rd
-mmHg, converted to Pl is 1.77X10
-"g-' ・crA・sec.The permeability P2 of urea is 2.95 X 1O-bctA/sec, and the permeability P2 of vitamin BI2 is 0.35X10-6cj/
sec, its strength was 510Kg/crA, and its elongation was 2100%.

Example 4 Copolymer ■ prepared in Example 3 was mixed with 75% dimethyl sulfoxide and 25% ethylene glycol monoethyl ether.
A film-forming stock solution was prepared by dissolving the solution in a mixed solvent with a concentration of 40% by weight at 120°C at 120°C, and a film was formed using a glass plate at 110°C in the same manner as in Example 1, with a film thickness of 125μ and a water content of 47%.
A film G was obtained.

The water permeability UFR of this membrane is 68.5 ml/m2・hr-
mmHg, converted to P, 1.78xlO-”
g-'cJ·sec. Urea permeability P2 is 3.
4 Xl0-'an! /sec, and albumin did not permeate at all.

This membrane has suitable performance for hemofiltration.

Example 5 A 1,3-dioxolane solution with a concentration of 27% by weight of the copolymer (1) prepared in Example 1 was used as a spinning stock solution, and 70% dimethyl sulfoxide and water were introduced into the hollow fiber from the annular spinning hole at a spinneret temperature of 67°C. The fibers were spun while injecting a 30% mixed solution and introduced into a coagulation bath consisting of water at about 4° C. to obtain hollow fibers.

The inner diameter of this hollow fiber was about 240μ, and the membrane thickness was about 20μ.

Thirty of these hollow fibers were housed in a small glass case with an effective length of about 12 cm to produce a test module with an effective area of about 28 cm.

The water permeability (UFR) of this module is 2.1ml/
m”・hr-mmHg, and the amount of filtration when a 0.2% albumin aqueous solution is flowed at 25°C under a pressure of 5QmmHg at a linear velocity of 5cm/see at the inlet is 1.9ml.
/m''·hr-mmHg, and no albumin permeation was observed.

Example 6 As one of the safety tests for the polymer used in this application, elution from the polymer was measured.

Copolymer I of Example 1, Copolymer ■ of Example 3 were used as polymers, and as a comparative example, DJ, Lyman et al.
chemistry Vol, 3 No. 7.985 (
Copolymer 1 was used, which was obtained by polymerizing polyethylene terephthalate (Polymer XIV in Japanese) containing 70.7% by weight of polyethylene glycol (Carbowax 1540), which is the most preferred polymer composition in 1964), by the method of Lyman et al.

2 g of the polymer was placed in 100 ml of distilled water and treated in an autoclave at 121° C. for 1 hour, and the value (ml) of 0901N potassium permanganate consumed by 20 mA was used as the eluate to obtain the results in Table 3.

Table 3 PEG: Polyethylene glycol □PT
MG: The low molecular weight glycol component of polytetramethylene glycol I and II is 1,4-butaditol.■ The low molecular weight glycol component of polytetramethylene glycol I and II is ethylene glycol. ,
The amount of platelets and plasma proteins attached to the membrane was measured.

Platelet-rich plasma (Platelet-rich plasma
RP) and platelet poor plasma (PPP) were prepared and contacted with each membrane at 37°C for 3 hours, washed with phosphate buffer, and fixed with 3% glutaraldehyde solution.

The amount of protein was calculated from the amount of amino acids obtained by observing these membranes with an electron microscope and decomposing the deposits with hydrochloric acid.

The amount of platelet adhesion was expressed as the value obtained by subtracting the protein amount in PPP from the protein amount in PPP.

The results are shown in Table 4.

In addition, glass Fi (Pyrex 7
740) was used.

Table 4 In other words, there are very few platelets attached to the semipermeable membrane of the present invention, which can cause thrombus formation, and the attached platelets are hardly deformed; this means that the platelets deform and release internal substances. This is preferable in terms of blood compatibility from the perspective of the coagulation mechanism that begins with release.

Claims (4)

[Claims] (1) The acid component of a polyester copolymer mainly composed of terephthalic acid and low molecular weight glycol with a molecular weight of 250 or less contains 20 to 60 mol% of an acid component other than terephthalic acid, and contains a glycol component other than low molecular weight glycol. A semipermeable membrane made of a polyester copolymer containing 5 to 30% by weight of polyethylene glycol having a number average molecular weight of about 1,000 to 60,000 based on the total amount of the polymer. (2) The semipermeable membrane according to claim (1), wherein the low molecular weight glycol is 1,4-butanediol. (3) The acid component of a polyester copolymer mainly composed of terephthalic acid and a low molecular weight glycol with a molecular weight of 250 or less contains 20 to 60 mol% of an acid component other than terephthalic acid, and contains a glycol component other than a low molecular weight glycol. A polyester copolymer containing 5 to 30% by weight of polyethylene glycol with a number average molecular weight of about 1,000 to 60,000 based on the total amount of the polymer is dissolved in a polar organic solvent at a polymer concentration of 15 to 50% by weight. A method for producing a semipermeable membrane, which comprises forming a membrane or spinning a hollow fiber using the obtained solution as a membrane forming stock solution. (4) The manufacturing method according to claim (3), wherein the polar organic solvent is a solvent containing 1,3-dioxolane as a main component.