JPS61290960A - Blood dialyser - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] [Field of use].

The present invention relates to a hollow fiber type hemodialyzer. More specifically, the present invention relates to a hollow fiber hemodialyzer having a built-in irregularly shaped hollow membrane having protrusions on its outer periphery.

[Prior Art] Hemodialyzers are used to purify the blood of renal failure patients and remove excess water. In this system, a large number of dialysis membranes, such as hollow fiber membranes, are housed in a container, and the patient's blood is poured into the hollow interior of the container, and the dialysate is poured outside, that is, between the hollow fiber membranes, and the blood is dialyzed through the hollow fiber membranes. In addition to removing waste products and adjusting the electrolyte concentration, a pressure difference is applied between the inside and outside of the hollow fiber membrane, and excess water in the blood is removed by ultrafiltration.

Various efforts have been made to improve the dialysis performance, which is the most important performance of a dialyzer. For example, methods such as reducing the thickness of the hollow fiber membrane or increasing the effective membrane area have been taken.

In particular, reducing the thickness of the hollow fiber membrane has the advantage of improving dialysis performance per unit area and making it possible to downsize the dialyzer. The basic performance of a dialyzer is clearance, or waste removal (hereinafter referred to as C), and ultrafiltration, or water removal (
(hereinafter referred to as F). When the thickness of the dialysis membrane is reduced, F per unit area increases at an accelerated rate, whereas C increases only gradually. As a result, if we try to keep C within a practically appropriate range, F will exceed the appropriate range, and dialyzers containing such hollow fiber membranes are difficult to use as they are, and, for example, water removal performance may be affected. It is necessary to devise measures such as using other control devices together. Furthermore, if an attempt is made to improve the performance of a dialyzer by increasing the effective membrane area, F will increase almost in proportion to the area, while C will gradually increase and converge to a constant value, A similar problem occurs when the thickness is reduced. In any case, it is often difficult to keep the balance between F and C within an appropriate range for practical use in dialyzers in which the hollow fiber membrane has a certain thin thickness and a certain large membrane area. Ta.

[Object of the Invention] An object of the present invention is to solve the above problems and provide a hemodialyzer with excellent dialysis performance and particularly a good balance between waste removal performance and water removal performance. Another object of the present invention is to provide a high-performance, small-sized hemodialyzer housing a hollow fiber membrane with protrusions that can be stably and easily manufactured.

[Structure of the Invention] The present invention provides a hollow fiber type hemodialyzer in which a bundle of permselective hollow fibers, Ill, is housed in a container, in which most of the hollow fiber membranes extend along the longitudinal direction on the outer periphery. It is a hollow fiber membrane with an irregular cross section having two or more protrusions, and the total effective area of the dialyzer S [Tdl, ultrafiltration performance UFR [ae/
m-hr・zen Hg] and urea clearance CLLI [
se/sin ] satisfies any of the following formulas (1) to ([[)] When 0.5≦S≦1.0, tJFR/S≦6. CLtJ/UFR≧30...(I
)1.0<S≦1.6, LIFR/S≦5. CLU/UFR≧30...(II
) When 1.6<S≦2.5, UFR/S≦4. CLLJ/LJFR≧25...(I
II).

More preferably, it is made of cellulose, has a film thickness of 30μ or less excluding the protrusions, and has an effective film area of 0.57.
The above-mentioned hemodialyzer and cellulose ester or polymethyl methacrylate which is F1 or higher.

Polyethylene polyvinyl alcohol copolymer, polyacrylonitrile, polycarbonate.

The present invention provides the above-mentioned hemodialyzer, which is made of semi-synthetic or synthetic polymer such as polysulfone, has a membrane thickness of 50 μm or less excluding protrusions, and has an effective membrane area of 0.71 d or more.

The present invention will be explained in detail below. The main feature of the present invention is to use an atypical hollow fiber membrane having continuous protrusions along its length on the outer periphery, and to obtain a dialyzer with superior performance based on this. The protrusions on the hollow outer periphery prevent the hollow fibers from coming into close contact with each other, improve the perfusion efficiency of the dialysate flowing between the hollow fibers, and reduce membrane resistance on the dialysate side.

C is related to the difference between the concentration of the substance in the blood and the i3m degree in the dialysate, so if the membrane resistance on the dialysate side, that is, the concentration near the dialysis membrane, decreases, C will increase accordingly. Become. On the other hand, F is proportional to the membrane area.

The membrane area is substantially smaller than that of a normal hollow fiber membrane in the area where the protrusions are present. The presence of the protrusions also reduces the number of hollow fibers that can be accommodated in a hemodialyzer container, and thus the membrane area. That is, by providing protrusions on the outer periphery of the hollow fiber membrane, C, which is affected by the perfusion efficiency of dialysate, cancels out these hump caps and increases;
On the contrary, it decreases. An increase in blood velocity due to a decrease in the number of hollow fibers also works in the direction of increasing C. As a result, the inventor of the present invention discovered through intensive research that it is extremely easy to balance C and F within a practically preferable range, and arrived at the present invention.

That is, the present invention is a hemodialyzer that is formed by filling a bundle consisting mainly of hollow fiber membranes with irregular cross-sections having two or more protrusions, preferably consisting only of hollow fiber membranes with protrusions. Provided is a dialyzer, which uses the hollow fiber membrane with protrusions and has water permeability corresponding to the total effective membrane area of the device, and which satisfies any of the relationships (I) to (III) above. It is something to do. In addition, the total effective membrane area S used in the above formulas (I) to (II) is the sum of the inner surface of the hollow fiber membrane that is effective for dialysis, excluding the part that is not effective for dialysis and corresponds to the base of the protrusion. The ultrafiltration performance UFR and urea clearance CLU mean values obtained by measurement according to the dialyzer performance evaluation standards of the Japan Society for Artificial Organs dated September 1980. That is, UFR is measured by a circulation method, in which liquid B and liquid D are circulated, and the filtration flow rate is determined from the reduced volume of liquid B over 10 minutes. B liquid.

The temperature of liquid D is 31±1℃, and the inlet flow rate is 200±
This value is measured under the conditions of 41d/Sin and 500±10d/win. In addition, CLU allows a 0.1% by weight aqueous urea solution to flow inside the hollow fiber at an average flow rate of about 1.2 n/sea at about 37°C and out of the hollow fiber at an average flow rate of about 1.
．． Means the value measured by flowing water at 8ax/sec.

With conventional hollow fiber membranes, it was difficult to satisfy the above conditions when improving dialysis performance by simply reducing the membrane thickness or increasing the membrane area. It is extremely easy to design a dialyzer to meet the above conditions using threads with such irregular cross-sections.

The hemodialyzer of the present invention has S, UFR, and CLU of the above formula (
I) to (III), and UF
When R/S exceeds the upper limit of each formula, especially when it exceeds 6, it becomes difficult to control water removal during dialysis, often resulting in excessive water removal. Also CLU/UF
When R is smaller than each lower limit of formulas (I) to (1), especially when it is less than 25, the effect of dialysis cannot be fully demonstrated, and waste products gradually accumulate in the body, resulting in so-called underdialysis. It causes

The present invention is particularly effective when the hollow fiber membrane is thin and the effective membrane area is large, where C and F tend to be unbalanced.

That is, when the hollow fiber membrane material is (A) t-fluulose,
The film thickness at the part excluding the protrusions is 30μ or less. (B) Semi-synthetic or synthetic material such as cellulose, ester or polymethyl methacrylate, polyethylene/polyvinyl alcohol copolymer, polyacrylonitrile, polycarbonate, polysulfone (including polynylon) In the case of polymers, it is desirable that the film thickness of the portion excluding the protrusions is 50 μm or less. If it is thicker than this, from the point of view of performance balance, there is no need to provide protrusions as in the present invention, but the dialysis performance will be low and the size of the dialyzer will be extremely large. Furthermore, the membrane area is preferably 0.5 Td or more in the case of (A) above, and 0.1 d or more in the case of (B).

Further, in the hemodialyzer of the present invention that satisfies the above formulas (I) to (DI), it is preferable that the UFR is 3.5 or more because water removal performance can be maintained at a high level while maintaining waste product removal performance; tJ F,, R is preferably 4.0 or more, particularly preferably 5.0 or more. Mab
If the hemodialyzer has a CLU of 160 or more, it is easy to maintain water removal properties and the removal rate of waste products represented by urea at a high level.
It is desirable that LtJ is 170 or more.

The number of protrusions on the hollow fiber membrane used in the dialyzer of the present invention is 2.
-10 articles are preferred, and 2-8 articles are more appropriate. 11
If this is the case, the effective membrane area at the base of the protrusion will be significantly reduced (1), and the ability to remove waste products and water will be reduced, making it impractical. A particularly effective range of the number of protrusions is 3 to 8,
Ru. Further, the outer diameter of the hollow fiber membrane is preferably 100 to 400μ, and the thickness of the membrane excluding the protrusions is preferably 5 to 30μ in the case of (A) and 10 to 50μ in the case of (B). In addition, the height of the protrusion is 5 to 80 μm, and even 10 μm.
~50μ is preferable, and the width of the protrusion is preferably 15~50μ.
A suitable value is 0μ, preferably 20 to 40μ. Hollow fibers within this range are preferable because they have good circularity and are less likely to cause blood coagulation or residual blood within the hollow fibers.

Hollow fiber membrane materials are not particularly limited, but include semi-synthetic or semi-synthetic materials such as cellulose acetate, polymethyl methacrylate, polyethylene polyvinyl alcohol copolymer, polyacrylonitrile, polycarbonate, and polysulfone, which tend to have a large UFR relative to CLLJ. This is particularly effective in the case of synthetic polymer membranes.

The hemodialyzer of the present invention is filled with hollow fiber membranes having such protrusions taking into account the total effective area, but hollow fiber membranes having no protrusions are filled with a small amount of, for example, 10% or less.
1i! It is also possible to fill the tank with at least two people. The filling rate of the hollow fiber membrane in the hemodialyzer is 30 to 80%.
A range of 40 to 70% is preferable, and a range of 40 to 70% is more preferable because products satisfying the above formulas (I) to (II) can be reliably produced.

[Examples] Hereinafter, the content and effects of the present invention will be explained using examples, but the present invention is not limited by these in any way.

Examples 1-9. Comparative Examples 1 to 3 100 parts of cellulose diacetate was mixed with 45 parts of polyethylene glycol (molecular weight: 1400), the mixture was melted at 220°C, and a round mold and a hollow fiber cap with protrusions were used. The material was then spun, then saponified to cellulose with caustic soda, and then wound up.

The film thickness (when wet) of the hollow fiber in the part without projections and the number of projections are as shown in Table 1, and these were adjusted by the type of die and the discharge rate during spinning. The obtained cellulose hollow fibers were stored in containers of various sizes and subjected to UFR at 1nVitrO.
and urea clearance was measured. The results are shown in Table 1. Here, the methods for measuring UFR and clearance CLU are based on the standards of the Society for Artificial Organs. It is clearly seen that in the embodiment according to the present invention, the dialyzer has a small area, a high clearance, and an appropriate LJFR.

In other words, the balance between UFR and clearance is appropriate and high performance is achieved.

Example 10. Comparative Example 4.5 Hollow fibers shown in Table 1 were manufactured in the same manner as in Example 1, and hemodialyzers with effective areas of 0.8 d and 0.4 d were created using each hollow fiber. In v using the dialyzer
When performance was measured using ttro, the results shown in Table 1 were obtained. That is, as shown in Comparative Example 4.5, a hollow fiber without protrusions with a film thickness of 35 μm and a hollow fiber with 6 protrusions also showed zero
．． Dialysis performance after the 4th foot is so low that it is not practical.

Example 11 and Comparative Examples 6 to 7 140 parts of polyethylene glycol and diglycerin were mixed with 100 parts of cellulose diacetate, the mixture was melted at 200°C, and spun using a round and protruded hollow fiber die. Then, after extracting the plasticizer with hot water, hollow fibers were filled into cases of each pole size, and in V+trO performance was measured. The results are shown in Table 1, and the area is 0.6T with a film thickness of 55 μm, a hollow fiber with protrusions, etc., and 6 protrusions.
It is clear that d has low dialysis performance and is not suitable for practical use.

(The following is a blank space) Table 1 [Effects of the Invention] The present invention has made it possible to provide a dialyzer with excellent dialysis performance and particularly a good balance between waste removal performance and water removal performance. At the same time, it is possible to make dialyzers smaller, which is expected to reduce manufacturing costs, simplify use and transportation, and further contribute to short-term dialysis, which is attracting attention as a future trend.

Claims (1)

[Scope of Claims] (1) A hollow hemodialyzer in which a bundle of permselective hollow fiber membranes is housed in a container, in which most of the hollow fiber membranes extend along the longitudinal direction at the outer periphery. It is a hollow fiber membrane with an irregular cross section having protrusions of more than one strip, and the total effective membrane area of the dialyzer S[
m^2], ultrafiltration performance UFR [ml/m^2・hr・
mmHg] and urea clearance CLU [ml/min
] satisfies any of the following formulas (I) to (III). When 0.5≦S≦1.0, UFR/S≦6, CLU/UFR≧30...(I)
When 1.0<S≦1.6, UFR/S≦5, CLU/UFR≧30...(II)1
．． When 6<S≦2.5, UFR/5≦4, CLU/UFR≧25...(III)
(2) The hemodialyzer according to claim 1, wherein the irregular cross-section hollow fiber membrane is mainly made of cellulose and has a thickness of 30 μm or less other than the protruding portions when wet. (3) The irregular cross-section hollow fiber membrane is mainly made of at least one selected from the group consisting of cellulose ester, polymethyl methacrylate, polyethylene/polyvinyl alcohol copolymer, polyacrylonitrile, polycarbonate, and polysulfone, and the protrusions when wetted The hemodialyzer according to claim 1, wherein the other membrane thicknesses are 50 μm or less.