JP2001205057A - Hollow fiber membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe hollow fiber membrane which comprises a hydrophobic polymer and a hydrophilic polymer and indicates a very small amount of substances eluted from the dry membrane. SOLUTION: In the hollow fiber membrane to be sterilized by being irradiated with γ rays, the water content of the membrane after the irradiation is 10% or below, and when the membrane is dissolved in a common solvent for both polymers, the content of insoluble components of the membrane is 10 wt.% or below.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a hollow fiber membrane requiring sterilization. In particular, the present invention relates to a medical hollow fiber membrane that is sterilized by gamma ray irradiation, and relates to a hollow fiber membrane in which components eluted from the membrane are reduced.

[0002]

2. Description of the Related Art Many medical films using a hydrophobic polymer as a material have been invented. Among membranes used for medical purposes, a membrane that comes into contact with the blood of a patient has a major problem in controlling adsorption of plasma proteins to the membrane. When formed into a membrane with a hydrophobic polymer alone, plasma proteins are adsorbed in large quantities,
There is a disadvantage that the film performance deteriorates with time. In order to overcome the drawback, medical films in which a hydrophilic polymer is blended with a hydrophobic polymer have been developed. By blending a hydrophilic polymer with the membrane, the hydrophilicity of the membrane is improved, and protein adsorption to the membrane is suppressed. As a result, the resulting film has little change over time,
A film having a sharp fractionation characteristic is obtained.

[0003] However, hydrophilic polymers are water-soluble and may elute into blood when they come into contact with blood. It has been suggested that the eluted hydrophilic polymer may cause an anaphylactic reaction or the like, and the smaller the amount of the hydrophilic polymer eluted from the membrane into the blood, the better. Therefore, as described in JP-A-61-238306, a system prepared by adding a non-solvent or an additive as a swelling agent to a solution in which a polysulfone-based resin and a hydrophilic polymer are mixed and dissolved is used as a stock solution for film formation. A method is shown in which the coated membrane is kept moist and crosslinked by gamma radiation.

In this method, a hollow fiber membrane is filled in a module, and after bonding, the module is filled with water, and the module is irradiated with gamma rays while being filled with water to insolubilize the hydrophilic polymer by cross-linking. The effect of reducing the amount of elution has been observed. However, in this method, it is necessary to irradiate the film with gamma rays while keeping the film in a wet state, and the module is filled with water in the shipping mode. In this case, since the weight increases at the time of shipment, energy consumption during transportation is large, and generation of global warming gas is promoted. In addition, the number of packing units is about 12, and the consumption of packing materials increases. Further, since the filled water may freeze in a cold region, it is not preferable to ship the module filled with water, for example, it is necessary to heat the storage, since the energy consumption is large because the module is filled with water. Therefore, a safe membrane, which is a hollow fiber membrane composed of a hydrophobic polymer and a hydrophilic polymer and has a very small amount of elution from the membrane in a dry state, has not been obtained.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a hollow fiber membrane comprising a hydrophobic polymer and a hydrophilic polymer, in which the amount of substances eluted from the dry state membrane is extremely small and the hollow fiber membrane is safe. Is to get

[0006]

The present invention is as follows. (1) In a hollow fiber membrane composed of a hydrophobic polymer and a hydrophilic polymer and sterilized by gamma ray irradiation, the moisture content of the hollow fiber membrane after gamma ray irradiation is 10 wt% or less, and the hollow fiber membrane is hydrophobic. A hollow fiber membrane characterized in that when dissolved in a common solvent of a polymer and a hydrophilic polymer, an insolubilizing component of the membrane is 10% by weight or less. (2) The amount of the hydrophilic polymer per 1 m ^{2 of the} membrane area of the membrane extracted with a 40% aqueous ethanol solution on the liquid contact side of the membrane is 2.0
mg / m ² or less.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The hollow fiber membrane of the present invention comprises a hydrophobic polymer and a hydrophilic polymer. Examples of the hydrophobic polymer include polyacrylonitrile, polysulfone-based polymer, polymethyl methacrylate, and polyamide. Among them, a polysulfone-based polymer is preferable, and polyether sulfone is particularly preferable in that it can be controlled to a preferable moisture content. Examples of the hydrophilic polymer include polyvinyl pyrrolidone, polyvinyl alcohol, and polyethylene glycol, and polyvinyl pyrrolidone (PVP) is preferable. When a hydrophobic polymer is used for a hemodialysis membrane, a hydrophilic polymer such as PVP is often used as a hydrophilic agent for the membrane in order to suppress the adhesion of plasma proteins to the membrane. The ability as a hemodialysis membrane can be exhibited by including PVP in the membrane and making it hydrophilic.

However, when PVP elutes from the membrane and enters the blood of a dialysis patient, there is a risk of causing an anaphylactic shock reaction. That is, although PVP is very important in terms of performance, PVP more than necessary has a problem in safety.

[0009] Techniques for reducing the eluate by cross-linking and insolubilizing PVP in the wet state by gamma rays are known, but no attempt has been made in the dry state.
The authors modified the hollow fiber membrane composed of a hydrophobic polymer and a hydrophilic polymer by irradiating it with gamma rays in a dry state,
It has been found that the eluate can be reduced. This is presumably because some of the polymer substances constituting the film are clustered.

[0010] When the moisture content of the hollow fiber membrane is 10 wt% or less, the module becomes lighter and the transport becomes easier.
It is preferable because it does not freeze even when used in cold regions or when transported by air. More preferably, the water content is 5 wt% or less. The dose of gamma rays is preferably 20 kGy or more. The reason is that unless it is 20 kGy or more, the sterilization effect is not reliable and the effect of reducing the eluted material is not sufficient. In order to maintain the performance of the film, it is preferably 50 kGy or less.

It is desirable that the irradiation of gamma rays be performed in an atmosphere containing substantially no oxygen gas. When oxygen gas is included, a large amount of radicals are generated during gamma ray irradiation, the polymer forming the film is decomposed, and the amount of eluted material increases. The amount of oxygen gas can be easily known by gas chromatography. The present invention can be carried out in a state where oxygen gas cannot be detected and substantially does not contain oxygen gas. At the time of gamma ray irradiation, the moisture content of the hollow fiber membrane is preferably 10 wt% or less, more preferably 5 wt% or less.

[0012] It is preferable that the amount of eluted material is small. In particular, it has been suggested that an anaphylactic reaction occurs when a hydrophilic polymer necessary for expressing the performance of the membrane is eluted from the membrane into the blood. However, the hydrophilic polymer is an indispensable element, and it is technically impossible to completely elute the amount eluted. By applying the present invention, the amount of the hydrophilic polymer eluted from the hollow fiber membrane composed of a hydrophobic polymer and a hydrophilic polymer in a substantially dry state is 2. per unit membrane area of the hollow fiber membrane. It was very easy to achieve 0 mg / m ² or less.

The fact that the means in the present invention does not insolubilize the membrane can be easily confirmed by dissolving the membrane in a common solvent of a hydrophobic polymer and a hydrophilic polymer. When the gamma ray-irradiated film is immersed in a common solvent in a wet state, a cloudy portion is observed, or a gel in which the shape of the hollow fiber membrane is maintained is observed. On the other hand, when the film irradiated with gamma rays in a dry state is immersed in a common solvent, it is dissolved without becoming cloudy. Although it cannot be said that a gel is generated by the cross-linking, it can be considered that the polymer is partially bonded to form a cluster.

In this method, the weight of the insolubilized component is measured. A common solvent for the hollow fiber membrane is placed in a test tube, and the membrane whose weight has been measured is immersed. And then centrifuged to precipitate the insoluble components, washed with water, freeze-dried, and weighs the insoluble components, which can be determined by the ratio to the original hollow fiber membrane. In the present invention, the insolubilizing component of the membrane was 10 wt% or less, and almost no insolubilizing component was found.

In this method, 500 ml of a 40% aqueous ethanol solution is refluxed for 1 hour at 37 ° C. on the blood contact side of the hollow fiber, and an aqueous ethanol solution containing the eluted material from the membrane is measured. Can be quantified by a colorimetric method using iodine (Method 1968 by K. Mueller et al.).
Year).

[0016]

The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

Example 1 Polyether sulfone (PE
S) is 17.0% by weight, polyvinylpyrrolidone (K-90) is 3.0% by weight as a hydrophilizing agent, and water is used as a non-solvent.
0% by weight, dimethylacetamide (DMAC) 7
5.0%, the internal solution concentration (DMAC + water) is 51%,
The inner solution is discharged from the inside of the double spinneret from outside the double spinneret holding the spinning stock solution at 40 ° C., and after passing through the air gap at an air gap length of 600 mm and a spinning speed of 60 m / min, Coagulation bath concentration at 70 ° C (DMAC + water) 10
%, Washed with pure water at 45 ° C. for 1 minute and pure water at 80 ° C. for 90 seconds, wound up in a scalpel, and hollow fiber membrane having an inner diameter of 199.7 μm and a film thickness of 29.6 μm. I got
10098 of these hollow fiber membranes were inserted into a polyethylene pipe and cut into a predetermined length.
The dried bundle was dried for 2 hours.
The case was filled with the bundle at a filling rate of 59.8%, the ends were bonded with urethane resin, and the resin was cut out to form a module. When the moisture content of this hollow fiber membrane was measured,
It was 2.4 wt%. The moisture content was determined by heating the hollow fiber at 120 ° C. for 2 hours and measuring the weight in a completely dried state, calculating the difference from the weight before drying, and calculating the ratio to the weight before drying.

The dry module thus obtained was
The finished product was sterilized by gamma irradiation at 0 kGy. There is no insolubilizing component in the membrane of this module,
%. 0.8 mg of eluate from this membrane
A / m ^2, 65.7 as compared to 2.3 mg / m ² of non-irradiated product
% And 2.0 mg / m ² or less. When these hollow fiber membranes were dissolved in dimethyl sulfoxide and the molecular weight distribution was measured by gel permeation chromatography, there was almost no difference between non-irradiated and gamma-ray irradiated, almost no cross-linking, and partial cross-linking. It is considered that only the cluster was formed and was not detected in the GPC curve (FIG. 1).

Comparative Example 1 The dry module obtained in Example 1 was subjected to 12 g
Autoclave sterilization was performed at 1 ° C. for 20 minutes. There is no insolubilizing component in the membrane of this module, 0 wt%
Was considered. The amount of eluate from this membrane was 3.6 mg /
m ^2, and elution compared to 2.3 mg / m ² of non-sterile products had increased rather without reduction.

[0020]

[Table 1]

[Brief description of the drawings]

FIG. 1 shows the molecular weight distribution of a polymer forming a hollow fiber as measured by gel permeation chromatography.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C077 AA01 KK01 LL05 PP07 PP09 PP10 PP13 PP15 4D006 GA13 HA02 MA01 MA31 MA33 MA40 MC32 MC33 MC37 MC39 MC40X MC54 MC62 MC63X MC85 MC86 MC88 NA04 NA32 NA71 PA01 PB09 PB42 PC41 PC47 4L03 AB DA00

Claims (2)

[Claims] 1. A method comprising: a hydrophobic polymer and a hydrophilic polymer;
In a hollow fiber membrane sterilized by gamma ray irradiation, when the moisture content of the hollow fiber membrane after gamma ray irradiation is 10 wt% or less and the hollow fiber membrane is dissolved in a common solvent of a hydrophobic polymer and a hydrophilic polymer, 10% by weight of insolubilized component
A hollow fiber membrane characterized by the following. 2. The hollow fiber membrane according to claim 1, wherein the amount of the hydrophilic polymer per 1 m ^{2 of the} membrane area of the membrane extracted with the 40% aqueous ethanol solution is 2.0 mg / m ² or less. .