JPH01300960A - Preparation of membrane type medical filter device - Google Patents

Abstract

PURPOSE:To obtain a device capable of being used simply and safely and excellent in water permeability and filterability, by allowing aseptic water to fill and subsequently performing high pressure steam sterilization. CONSTITUTION:A membrane type medical filter apparatus having a porous membrane, which is composed of a hydrophobic polymer and provided with pores having an average pore size of 0.01-10mum, mounted therein and also having a blood introducing port, a blood lead-out port and a filtrate lead-out port is prepared. Each of the spaces partitioned by the porous membrane of this apparatus a filled with aseptic water and, subsequently, the introducing port and the lead-out ports are closed. Thereafter, high pressure steam sterilization is performed and aseptic water is allowed to penetrate in the pores of the porous membrane simultaneously with sterilization.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for manufacturing a membrane-type medical filtration device, and more specifically, to a method for manufacturing a membrane-type medical filtration device. The present invention relates to a method of manufacturing a medical filtration device incorporating a membrane.

The membrane-type medical filtration devices mentioned here include plasma separators that separate blood cell components and plasma components from blood, plasma component separators that further fractionate plasma components based on molecular weight, and hemoconcentrators that separate only water from blood. A blood vessel, a plasma component collector for donating and collecting plasma components from blood from a donor, etc.

[Prior art] In porous membranes made of hydrophobic polymers, aqueous liquids such as blood do not wet the hydrophobic polymers, so it is difficult for aqueous liquids to penetrate into the micropores of the porous membrane. Medical filtration devices incorporating porous membranes made of hydrophobic polymers cannot be used as is. Therefore, it has been proposed to preliminarily treat porous membranes made of hydrophobic polymers, and these hydrophilic treatment methods include: ■ Infiltrating water-soluble, low interfacial tension organic solvents into the micropores. (Refer to Japanese Patent Publication No. 61-13824), (1) treating the porous membrane with a surfactant, (2) chemically introducing hydrophilic groups onto the surface of the porous membrane, (2) A method of coating the surface of a porous membrane with a hydrophilic polymer, and a method of infiltrating water into micropores under a pressure of 5 kg/cm2 or more (Japanese Patent Application Laid-open Nos. 61-92675 and 61-946).
No. 62 and No. 61-109573) are known.

[Problems to be Solved by the Invention] However, in the method (2) above, in which the low interfacial tension organic solvent is infiltrated into micropores and replaced with water removal, a large amount of water is required to wash and remove the low interfacial tension organic solvent. There are drawbacks that require it. In addition, in the method (3) of treatment with a surfactant, the surfactant is eluted into the blood and plasma, which poses a safety problem.

In addition, the method (2) of chemically introducing lignophilic groups onto the surface of the porous membrane has safety problems as it tends to leave reaction residue, solvent, etc., and the method (2) of coating with a hydrophilic polymer also
Not only does the solvent used in Coach Inter easily remain, which poses a safety problem, but also the hydrophobic porous membrane generally has good biocompatibility and low compatibility with blood, such as low activation of complement and platelets. The drawback is that the hydrophobic properties are lost by coating the surface of the hydrophobic membrane with another polymer.

Furthermore, the above method of injecting water into the micropores at a pressure of 5 kg/cm2 or more does not have the above problem, but if a high pressure of 5 kg/cm2 or more is applied, there is a possibility that the membrane or container will be damaged. The disadvantage was that it became large.

[Means for Solving the Problems] Therefore, the present inventors conducted extensive studies to solve the drawbacks of medical filtration devices incorporating porous membranes made of these hydrophobic polymers, and as a result, they arrived at the present invention.

That is, the present invention provides a model medical filtration system that is made of a hydrophobic polymer, has a built-in porous membrane with an average pore diameter of 0.01 to 10 microns, and has a blood inlet and outlet and a filtrate outlet. After preparing an apparatus and filling each space separated by the porous membrane with sterile water, then sealing each of the inlets and outlets, high-pressure steam sterilization is performed, and at the same time, the sterile water is poured into the porous membrane. The present invention provides a method for manufacturing a model medical filtration device, which is characterized by infiltrating into the micropores of a membrane.

The present invention is characterized in that high-pressure steam sterilization is performed after filling the inside of the device with sterile water. The above-mentioned special public service 1986
Publication No. 13,824 (conventional method (2)) also states that high-pressure steam sterilization is performed after replacing the water with water, but this method is based on the premise that a low interfacial tension organic solvent is used. It is something. Therefore, it is essential to wash and remove the organic solvent, which still poses problems in terms of labor and complication of the process.

On the other hand, the present inventor conducted experiments and studies from various angles, and surprisingly found that by filling sterile water without using an organic solvent and then performing high-pressure steam sterilization, sterile water could be made into porous pores at low pressure. They discovered that it is possible to penetrate into the fine pores of the membrane.

The model medical filtration device manufactured by the present invention does not use organic solvents or surfactants as wood-filtering treatment agents, and the fine pores of the porous membrane are filled with water. In addition to being safe as there is no residual sterilization agent, the filtration device is sterilized using high-pressure steam, eliminating the safety issues caused by residual gas caused by conventional ethylene oxide gas (EOG) sterilization, as well as gamma ray sterilization. There is no problem of toxicity due to decomposition products of the porous membrane, housing, botting material, etc., resulting in a very safe medical filtration device. Furthermore, since the medical filtration device of the present invention is already filled with sterile water before use, water, plasma, etc. can flow in and out of the porous membrane at very low pressure (for example, a pressure of 50 mmHg or less) during use. In addition, it is easy to degas the inside of the filtration device, and it does not require washing with large amounts of physiological saline, making it easy to use.

The porous membrane made of a hydrophobic polymer used in the present invention is made of a material that can withstand high-pressure steam sterilization.
For example, polypropylene, poly4-methylpentene-1,
Preferred examples include polysulfone, polyethersulfone, polyhynylidene fluoride, polytetrafluoroethylene, polydimethylsiloxane, polyethylene terephthalate, and nylon.

The form of the porous membrane used in the present invention is not particularly limited, and for example, a hollow fiber or a flat membrane may be used.

Further, there are no particular limitations on the method for producing the porous membrane, and any known production method such as a stretching method, a wet phase separation method, a melt phase separation method, a solvent extraction method, etc. may be employed.

The sterile water used in the present invention may be water that has been subjected to normal sterilization treatment, or water that is mainly composed of water and contains solutes that are not harmful for medical purposes. These include distilled water for injection, pyrogen-free water, physiological saline, and the like.

Further, the present invention targets porous membranes having an average pore diameter of 0.01 to 10 microns (gm) (measured by bubble point method). In porous membranes with an average pore size smaller than 0.01 microns, sterile water does not easily penetrate into the micropores, and in porous membranes with an average pore diameter larger than 10 microns, water can be poured into the micropores of the porous membrane using a normal method. This is because it can be caused to flow in.

The method of the present invention will be compared with the conventionally known method of infiltrating water into the micropores of a porous membrane by applying a pressure of 5 kg/cm2 or more. The method of mercury porosimetry used for measurements, etc. is applied to water, but in the present invention, sterile water is infiltrated into micropores under high-pressure steam sterilization conditions. Not only does it actively utilize the decrease in interfacial tension of water that accompanies a rise in temperature, but it also utilizes the flow of water vapor into the micropores, making it ideal for use in porous membranes, botting areas (adhesive areas), etc. On the other hand, it becomes possible for water to penetrate into the micropores of the porous membrane without applying a severe pressure of 5 kg/cm2 or more.

The autoclave sterilization of the present invention is preferably carried out at a gauge pressure of 0,
7 kg/cm2 or more, particularly preferably 1.0 to 1,
4 kg/c+m''. If autoclaving is carried out at a gauge pressure of 0.7 kg/cI112 or less, water penetration into the micropores of the porous membrane is insufficient.

Further, according to the present invention, the membrane type medical filtration device can be sterilized at the same time, and the manufacturing process is not only safe against contamination but also efficient.

Depending on the pore size of the porous membrane, in addition to the pressure of high-pressure steam sterilization, the inside of the high-pressure steam sterilization tank may be further pressurized with an inert gas (for example, nitrogen gas). Closing gates provided at the blood inlet and outlet as well as the filtrate outlet 11
It is also possible to adopt a method of ensuring that sterile water enters the micropores, such as by pressing a knob or plug. In this case, the pressure may also be lower than the conventional method mentioned above, in the pressure range of 1.0 kg/cm2 to 5.0 kg/cm2, preferably 1.6 kg/cm2 to 3.
It can be used in a pressure range of 0 kg/c+m2.

Further, in the present invention, it is preferable to remove air from each space separated by a porous membrane in the demolding filtration device under reduced pressure, and then fill the space with sterile water. After each space separated by a porous membrane in the mold filtration device is filled with carbon dioxide gas, when the spaces are filled with sterile water, carbon dioxide gas has a high solubility in sterile water, so It is easy to replace and does not leave bubbles, which is preferable.

[Examples] The present invention will be explained in more detail based on Examples below.
The present invention is not limited to these examples.

(Example 1) Polypropylene (UBE-PP-F 109K, trade name: manufactured by Ube Industries, MFI = 9 g/], 0 minutes),
Spinning was performed at a spinning temperature of 210'C using a nozzle for producing hollow fibers. The obtained polypropylene hollow fibers were heat treated in a heated air bath at 145°C for 30 minutes, and then stretched at a temperature of 135°C to 400% of the initial length and at a strain rate of 8.33%/min. A heat treatment was performed for 15 minutes in a heated air tank at 145° C. to produce porous polypropylene hollow fibers. The porous polypropylene obtained had an inner diameter of 320 gm and a film thickness of 55 lm. In addition, the average pore diameter measured by the Hutzlboind method (using ethanol) was 0.4
The weight was 8 gm and the porosity was 75%.

This porous membrane was housed in a polycarbonate housing, and both ends were fixed with a polyurethane adhesive to produce a polypropylene porous membrane filtration device having a membrane area of 0.5 m2. After reducing the pressure in the internal space of this filtration device with a vacuum pump, each space of the filtration device was filled with sterile water, each outlet and inlet were sealed with a silicone cap, and the temperature was 121°C (1 atm vapor pressure). 1,033 kg/c+++2) (equivalent to gauge pressure)) and high-pressure steam sterilization was performed for 20 minutes. At this time, nitrogen gas is used to reduce the gauge pressure of the high-pressure steam sterilization tank to 2 k
It was made to be g7cm2.

When we measured the water permeability using this filtration device, we found that
It showed a high water permeability of 451/min-m2・kg/cn+2.

Furthermore, when the above filtration device was subjected to a sterility test, no bacteria were observed.

Furthermore, a plasma separation test was conducted using a mongrel adult dog (lo, 1 kg) using a demolding filtration device prepared in the same manner as above, and the plasma filtration rate was 4.81/h in 120 minutes.
It was r/m2. In addition, the transmembrane pressure difference [TMP = (module inlet pressure + module outlet pressure) / 2 - filtration side pressure] was 30 mmt1 throughout the plasma separation test (3 hours).
g or less.

(Example 2) After reducing the pressure inside a filtration device produced in the same manner as in Example 1 using a vacuum pump, sterile water was filled into each space of the filtration device,
Each inlet and outlet were sealed, and high-pressure steam sterilization was performed for 121° C12O minutes.

Next, when the amount of water permeated was measured using this filtration device, the amount of water permeated was 521/min-m2·kg/cm2.

(Comparative example) After reducing the pressure in the internal space of a filtration device produced in the same manner as in Example 1 using a vacuum pump, each space of the filtration device was filled with sterile water, and each space of the filtration device was filled with 4 kg at room temperature using water pressure. /c
Pressure was applied with n2. When the water permeability was measured using this filtration device, it was found to be 2.2 x 10-21/win-m2.
・It showed a water permeation amount of kg/c+s2, and a practically usable water permeation amount was not obtained.

After passing ethanol through this porous membrane, the water was replaced with water and the amount of water permeation was measured; 52 sentences/[Din-112
・It showed a water permeability of kg/c112.

As described above, it can be seen that Examples 1 and 2 are as effective as or more effective than using ethanol for hydrophilization, and do not require a large amount of water to remove ethanol, and have a large effect. .

[Effects of the Invention] As explained above, according to the present invention, a membrane-type medical filtration device is manufactured by filling it with sterile water and then performing high-pressure steam sterilization, so it can be used easily and safely. Moreover, an M-type medical filtration device having excellent water permeability and filtration performance can be obtained.

Claims (1)

[Claims] (1) Made of hydrophobic polymer, the average pore diameter of micropores is 0.
．． A membrane-type medical filtration device incorporating a porous membrane with a size of 0.01 to 10 microns and having an inlet and outlet for blood and an outlet for filtrate is prepared, and each space separated by the porous membrane is filled with sterile water. Then, after sealing each of the inlets and outlets, high-pressure steam sterilization is performed, and at the same time as sterilization, the sterile water is infiltrated into the micropores of the porous membrane. Production method.