JPS5892423A - Hydrophobic semi-permeable membrane and module using same - Google Patents

Abstract

PURPOSE:To enhance the removal ratio of a low molecular substance such as urea or creatinine, by using a hydrophobic semi-permeable membrane to which specific coefficient of mass transfer and water permeability are imparted by water containing treatment in a module form. CONSTITUTION:A membrane comprising hydrophobic material is immersed in a solution with low surface tension to penetrate the same into the fine structure of said membrane and the penetrated solution is replaced with water to hydrate said membrane. In this water containing state, the membrane has coefficient of mass transfer of urea of 4X10<-4>cm/sec or more and the water permeability thereof is brought to 50m/m<2>.hr.mm.Hg or more. Thus obtained membrane is accommodated in a cylindrical container 7 having an inlet 3 and an outlet 4 in a hollow yarn like form and, after both terminal ends thereof are subjected to centrifugal molding by using an adhesive such as polyurethane resin, the adhered terminal ends are cut to form a module having opening parts at both terminal ends thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a semipermeable membrane made of a hydrophobic material, and more specifically to a hydrophobic semipermeable membrane that can maintain high ultrafiltration performance and dialysis performance when removing solutes by dialysis or dialysis. The membrane and the module containing the semipermeable membrane I%! Regarding.

Dialysis, which is based on the principle of diffusion of substances using semipermeable membranes, and ultrafiltration, which is based on the principle of sieving based on the pore size of the membrane, are used as means to efficiently separate and remove substances in a solution easily and in a short time. ing. Examples include hemodialysis therapy for renal failure patients, and ultra-P membranes for the purpose of removing medium-high molecular weight toxins estimated to have so-called molecular weights i, ooo to to, ooo, which are difficult to remove by hemodialysis. Treatment is being performed using a filtration type artificial kidney.

However, such a filtration type artificial kidney is excellent in removing these medium and high molecular weight toxins.

This method has problems such as being inferior to the efficient removal of low-molecular-weight toxins that can be removed by spontaneous dialysis of urea or creatinine, and requiring a large amount of sterile fluid.

By the way, filtration dialysis therapy, which simultaneously removes medium- and high-molecular weight substances as well as low-molecular weight substances, is being widely adopted as a new means to solve the problems with dialysis therapy.

Semipermeable membranes used in such filtration dialysis therapy not only have high dialysis performance and ultra-P membrane performance, but also have the ability to prevent plasma proteins in the blood from depositing on the membrane surface when they come into contact with blood. This may result in denaturation of adsorbed proteins, platelet adhesion, and aggregation, resulting in a small deterioration of membrane performance, a decrease in leukocytes due to activation of the tank body in contact with the membrane surface, activation of coagulation factors, and red blood cells. It is preferable to use a material that is so-called excellent in biocompatibility and does not easily cause membrane destruction. Examples of such membranes with excellent biocompatibility include Risulfone.

Polycarbonate, l-propylene, polyethylene, polyethylene terephthalate, polyvinylidene heptadide, ethylene tetrafluoride, meliacrylonitrile-vinylidene chloride copolymer, ethylene-vinyl acetate copolymer, etc. - Hydrophobic materials that are difficult to wet with blood It is becoming clear from various research results that materials made of flexible materials are preferable. However, as a result of various studies on membranes made of such hydrophobic materials, the present inventors found that although they have properties necessary for use in, for example, dialysis-type or filtration-type artificial kidneys, such as ultrafiltration performance. , *Dialysis performance to efficiently remove low molecular weight substances such as creatinine and creatinine, that is, the mass transfer coefficient of low molecular weight substances is inferior, and therefore it is insufficient as a membrane for dialysis and Kl'l permeation. I came to understand. Unfortunately, for these reasons, membranes made of these hydrophobic materials, despite their excellent compatibility with blood, cannot be put to practical use in substance separation applications that partially utilize the diffusion principle, such as hemodialysis and filtration dialysis. It had a long time difference, and was far from being put into practical use as a minute hand. Nevertheless, the present inventors have conducted intensive research to improve the dialysis performance of membranes using such hydrophobic materials, and as a result, we have developed a method that has been tried by many researchers in the past, namely, adding hydrophilic groups to membrane-constituting polymers. The fine structure of the film can be changed by making the film material itself hydrophilic or by changing the three-dimensional structure of the polymer, and by examining various film-forming conditions including the solvent for the polymer. It was discovered that the dialysis performance of the membrane could be dramatically improved by an unexpectedly simple method, without using extremely complicated measures such as making it wettable and easy for low-molecular-weight substances to diffuse. ◇ That is, the present inventors have succeeded in producing low-molecular-weight substances in membranes made of these hydrophobic materials, which was thought to be impossible in the past, by simply subjecting conventional membranes made of such hydrophobic materials to a hydrous treatment. It was found that the mass transfer coefficient of Yet again.

It has also been found that by incorporating such a water-containing hydrophobic membrane into a heat exchanger type module, a dialysis and filtration area capable of fully functioning as a dialysis type artificial kidney can be obtained. As a result of further detailed research into this point, we have created the ninth invention. KJchi The present invention is made of hydrophobic material,
This invention relates to a water-containing hydrophobic membrane having a urea mass transfer coefficient of 4 x 10-'cm/s@e or more and a water permeability of 50-/♂・Ba・MlIH9 or more.
The present invention also relates to a module characterized in that such a hydrophobic semipermeable membrane can be easily accommodated. The mass transfer coefficient of urea of the hydrophobic hydrophobic membrane of the present invention is 4 x 10-'cs+/s@e or more,
Below this value, it is difficult to perform sufficient dialysis removal of low molecular weight substances such as urea and creatinine. In addition, the water permeability is 50 d/l-machi/home HP or more, and if it is lower than this, it is difficult to sufficiently remove medium and high molecular weight substances and remove a large amount of water within a dialysis time of 4 to S hours.

By the way, such hydrophobic membranes are those in which the polymers constituting these membranes have a water absorption rate of about 10% by weight or less at 25° C. and 100% relative humidity.

In general, it has the property of not being easily wetted by water and blood.

Therefore, the filtration is not limited only to the film made of the above-mentioned materials. Such hydrophobic membranes naturally have extremely low water content;
Hydrous treatment of membranes that has been commonly performed in the past.

That is, it is not possible to create a membrane with an excellent mass transfer coefficient by immersing it in water or treating it with a substance that has a high affinity for water, such as glycerin.

However, as is generally well known, the surface of a membrane made of such a hydrophobic material is easily wetted by a 17A solution having a low surface tension. Therefore, when these solutions are used, penetration of the solution into the microstructure of the membrane occurs.

Then, by replacing this solution with water, it becomes possible to make it hydrated. In general, the surface tension of hydrophobic resins is small, but the surface tension of polyolefin resins, such as polyethylene and polypropylene, varies depending on the molecular weight of the resin, but 22 -
It is around 26 dyn·/1, and in the case of tetrafluoroethylene resin, it is 18.5 dyn·/1.

When an ultrafiltration membrane is made using these resins, these values are slightly different from those of a porous membrane made of tetrafluoroethylene resin, for example, due to the surface grooves a of the membrane, that is, the unevenness of the surface, and the formation of a microporous membrane. In this case, the a-rising surface tension is approximately 28.5 dyn/(mKt), although it varies slightly depending on the surface structure of the porous membrane.
It will bring you great luck. The solution that can leak such a membrane is 1
Liquid substances that mix well with water, the surface tension of which is close to the value of the critical surface tension of these membranes, are preferred, such as methanol, ethanol, butanol, isopropyl alcohol.

Examples include ashatsuton, vinegar, etc., especially 1llff before artificial production.
When used in a single-use membrane, a liquid substance that has low toxicity and is easily mixed and replaced with water is preferred. It is preferable to hydrate the membrane by thoroughly soaking the membrane with these liquid substances and then replacing the membrane with water. The hydrated hydrophobic semipermeable membrane of the present invention may be obtained by drying the membrane and treating it with water using the above-mentioned hydration treatment method, or if it is made by a wet film formation method, it can be used as it is. It may be kept in a water-containing state until use.

The form of the membrane may be flat membrane, tubular membrane, or hollow fiber. Such a hydrous-treated membrane exhibits its maximum effect when used in the final 7 joule form. Such a module may be used for example as shown in FIG.
This is a typical example of a heat exchanger module used in blood hyperdialysis, but it is not necessarily limited to the shape shown in Figure 1. To explain its structure with reference to Figure 1, blood flows from inlet 1. Entry/Exit 2 also goes out of the module. The dialysate enters through inlet 3 and exits through outlet 4 <o
5t! The water-containing hydrophobic semipermeable membrane of the present invention is a hollow fiber, and the blood flows through the hollow part of the cylindrical container that fixes the adhesive and the hollow fibers. 9 is a nozzle that guides the blood into the hollow fiber, and 10 is a cap that fixes the nozzle to the container. In this module, hollow fibers are housed in a cylindrical container 7 as shown in the figure.

Centrifugally mold both ends with an adhesive such as meliurethane resin,
By cutting the glued ends, a module having openings 9 at both ends is made into a module.

However, if the module of the present invention contains a water-containing hydrophobic semipermeable membrane, then the above-mentioned module can be used. Not done.

By performing hemodialysis or hyperdialysis using such a hydrophobic semipermeable membrane containing water, it is possible to achieve excellent biocompatibility and to exert a significant therapeutic effect. Note that the hydrophobic hollow fiber #i housed in the module of the present invention may be assembled in a state where it is hydrated from the time of membrane formation, or it may be one that is subjected to hydration treatment after the module is assembled.

In addition, in the assembled state of the module, it is better to sterilize it with Ill0G gas, high-pressure steam, radiation, etc., and then store it in a sealed state to prevent the water content in the membrane from evaporating. Also, fill both sides of the module for blood and dialysate with formalin aqueous solution or saline.

The water-containing state may be preserved by enclosing pure water or the like and performing sterilization using 14III or high-pressure steam sterilization. In such a water-containing state, a semipermeable membrane made of a hydrophobic material has a mass transfer coefficient of urea of 4
10-'cm/s@a or more and water permeability is 501/d-
) tr-uH9 or higher If a hydrophobic semipermeable membrane is incorporated into the module, a dialysis and filtration artificial kidney with excellent performance and blood compatibility can be obtained. Although the above description has mainly focused on blood dialysis and ultrafiltration applications, the present invention is not limited to blood applications, but can be applied to other industrial applications as well.

It can also be applied to pharmaceutical applications.

The effects of the present invention will be explained below using examples.

4. Examples Example-1 i9 sulfone (union carbide nkllip-1
700) A stock solution consisting of 23% by weight, dimethylacetoacetate by 72% by weight, and triethylene glycol by 5% by weight is extruded from an annular spinneret for hollow fiber m speed, and water is used in the hollow part and coagulation bath from the inside and outside of the hollow fiber. Solidification, inner diameter 2
A hollow fiber with a membrane thickness of 50μ and a thickness of 50μ was obtained. After sufficiently washing the hollow fiber with water, it was immersed in a 30° C. SOS glycerin aqueous solution for 3 hours, centrifugally dehydrated, and vacuum-dried at room temperature for 48 hours. A bundle of 10,000 hollow fibers thus obtained was made of polycarbonate resin with an effective length of 160 mm.
! It was housed in an IK, and both ends were centrifugally glued with a polyurethane resin adhesive to create a heat exchanger type module shown in Fig. 1 with an effective membrane surface of 1i horizontally. One of the modules was pried with 1 ton of pure water on the blood side and the dialysate side, and this was used as a blank. 0 and 2* were respectively heated to 18°C, and 40% and 100% methanol aqueous solutions 500 - were poured downward at a flow rate of SOd/min. From the blood inlet to the dialysate side Kl! The inside of the module was filled with blood and dialysate while being filtered, and after being left for 10 minutes, the methanol was subsequently washed and replaced with 11 pure water to hydrate the hollow fibers, and these modules were designated as A and B, respectively. Next is urea 10011F/d! , prepare an aqueous solution of Vitanon Il+t10 cape/dl, and place it 200 m from the blood side of the module.
On the other hand, pure water was flowed on the dialysate side at a flow rate of 500 d/min, and dialysis was performed at 37°C. The clearance of urea and vitamin Bll was determined from the following formula. Next, pressure was applied to the blood side of the module to determine the water permeability.

0 set However, OL: Clearance -/min Qs++ Ih Liquid side solution flow rate -/min C group: Blood inlet solute concentration f17d 1OB0; Blood outlet solute concentration 9/d 1The concentration of urea solution is determined by diacetyl monooxime direct method, vitamin "I" * Fl 382 m
The absorbance was measured in μ.

Separately, 50 such hollow fibers were bundled together and both ends were glued together to make the effective length 181. It is dangerous to make a loincloth with an effective membrane area of 34 mm and a blood inlet/outlet communicating with the hollow part of the thread. One of them was left as is, and the other two were subjected to the above-mentioned water treatment, 11-40'l and 100% methanol aqueous solution treatment, and were designated as KA and B in the same manner. 8 such mini modules in diameter,
Stored in a U-shape in a plastic container with a height of 13ai and a volume of S+SO- of circles*m.

Next, fill it with water and close the top lid to make sure it is sealed. At this time, the blood inlet and outlet of the module was set in such a way that it could communicate with the outside through one jar of the container. The above-mentioned aqueous urea and creatinine solution was flowed from the blood inlet of the scissors Il module at a flow rate of 9-7 min from a sealed reservoir of 100-m, while
The aqueous solution inside the plastic container is kept at 37°C in a sealed state as the dialysate side.

Dialysis was performed for 1 hour while stirring with a magnetic stirrer without ultrafiltration, and the mass transfer coefficients of urea and vitamin Blt were determined from the quintic equation.

8 (1/VB + 1/VD) x 3600 However, Kl mass transfer section Wk / s@eSat two module effective membrane area - vB + blood side solution volume - ■ D: dialysate side aqueous solution volume d t: dialysis time 8.C C,+Solute concentration on the blood side 97d IQD+Solute concentration on the dialysate side 97d The 1st subscript indicates the obtained result indicating the concentration at that time. As is clear from these results, the clearance and mass transfer coefficient of blank urea and Vitataka B1m are low, and the S analysis and t! All of the products subjected to the hydration treatment of the present invention showed high values, although they were not suitable for dialysis. Showing excellent performance as a hollow fiber for dialysis and dialysis 0 Table 1

[Brief explanation of the drawing]

FIG. 1 shows a module in which the hydrated hydrophobic semi-escape membrane of the present invention is housed in a container. 1...Blood inlet 2...Blood outlet 3...Dysate inlet 4...
... Dialysate outlet 5 ... Hydrophobic semipermeable @6 ... Adhesive 7 ...
...Cylindrical container End ...Hollow fiber opening 9 ...Nozzle 10 ... - Cap drawing procedure amendment May 27, 1980% approval Director Haruki Shimada 1 Indication of the case Patent application No. 190677/1983 2 Name of the invention Hydrophobic semipermeable membrane and module using the same 5 Person making the amendment Relationship with the case / Patent applicant Asahi Medical Co., Ltd. 4 Agent 5th Floor, Toranomon Industrial Building, 2-29 Toranomon, Minato-ku, Tokyo The description in the document will be amended as follows. ms! The statement of the scope of claims is amended as follows. 1 (made of 11 hydrophobic materials, with a urea mass transfer coefficient of 4 x 10-'01/sec or more and a water permeability of 50
-Re'7jlLl (y
x 10-'011/equation or more, and the water permeability is 50-'
- A module in which a hydrophobic semipermeable membrane containing water with a temperature of Hr·lllHg or more is poured into a liquid. 121, page 5, line 12, "Hydrophobic semipermeable membrane is easily accommodated" is amended as follows. "Stored in a container with a hydrophobic semipermeable membrane having a liquid inlet and an outlet, and a fluid communication cap on the other side that is liquid-tightly separated by the semipermeable membrane" (31, page 5, line 17, "It is difficult. Insert the following description after "1. Also, the urea substance transfer body 91 is added to the hydrophobic semipermeable membrane.
4
The water content must be 90% or more, preferably 95 to 100%. The water content referred to herein is the ratio of the volume of water that permeates into the internal void area of the membrane, and is expressed by the following formula. vo: void volume per unit volume of membrane (-) vW: water-containing volume per unit volume of membrane (-) Vo and Vv can be determined by polymer specific gravity, membrane volume, and weight measurement. (41, page 6, line S, ``@water-based'' is corrected to ``r9BL water-based, and the surface tension of the membrane-constituting resin at 20C is about 40 dyn·/wound or less.''). (51, On page 8, line 7, insert ``For example, processing liquid 1'' after ``To explain.''). (61, On page 8, line 9, insert ``Processing liquid 1, for example.'' (7) Delete "4. Examples" on page 10, line 7. (8) Insert the following statement between lines 8 and 7 from the bottom of page 15. ``Also, the hollow fiber tubes of three similar mini-modules were taken out, and the moisture content was determined by gravimetric method.'' (9), ``Table 1 on page 14 has been amended as follows. ``Table 1 Xl (1. ``50 Brief explanation of the drawings'' in the 8th line from the bottom of the 14th negative is corrected to ``4. Brief explanation of the drawings.''

Claims (1)

[Claims] (1) A hydrated hydrophobic half made of a hydrophobic material and having a urea mass transfer coefficient of 4 X 10-'C1l/I@(1 or more and a water permeability of 50d/I/·)tr-11JIHf or more. Permeable membrane. (It is made of 21 hydrophobic material, and the mass transfer coefficient of urea is 4.
X 10-'m/s@a or more and water permeability is 50d/l
/・7・A gel made of a hydrophobic semipermeable membrane containing water with an MH of 9 or more housed in a container.