JPH07163659A - Blood dialyzer using hollow fiber membrane - Google Patents

Abstract

PURPOSE:To remove unnecessary materials effectively without requiring any complex apparatus by satisfying a specific formula when the screening factor against inulin in the hollow fiber membrane of a blood dialyzer is made a specific value, and a pressure less on the dialyzer solution side is made zero and a load pressure at the outlet on the dialyzer side is equal to the outlet on the blood side. CONSTITUTION:In a blood dialyzer using hollow fiber membrane whose membrane area defined on the basis of inside diameter reference is 0.5m<2> or more, screening factor of the hollow fiber membrane against inulin is 0.5 or more and a pressure loss is made zero on the dialyzing solution side of a blood dialyzer, and such a formula may be satisfied as UFR(B)XL<2>/D<3>>=6X10<-3> when the load pressure at the outlet on the dialyzing solution side is equal to that at the outlet on the blood side. Here UFR(B) is an ultrafiltration coefficient (ml/hour.m<2>.mmHg) of the hollow fiber membrane against blood when blood with viscosity of 2.5cp at a temperature of 37 deg.C flows into the blood dialyzer at 200ml/min, D is the inside diameter (mum) of hollow fiber membrane, at L is the length (cm) of the hollow fiber membrane.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hemodialyzer using a hollow fiber membrane used for treating renal failure, and more specifically, for use in treating renal failure, hemodialysis without requiring a complicated device. The present invention relates to a hemodialyzer using a hollow fiber membrane capable of performing filtration.

[0002]

2. Description of the Related Art Due to chronic renal failure, hemodialysis or C
199 patients are being treated for APD (peritoneal dialysis)
At the end of two years, 123,926 people are increasing at a rate of less than 10,000 per year (Kenshi Maeda, Current status of chronic dialysis therapy in Japan, Japan Society for Dialysis Therapy, 1993). In the United States, 101,763 people at the end of 1990 (JITokars et al., ASAIO
Journal, 39, 71-80 (1993)), there is almost the same number of patients in Europe, and it is expected that the number of patients will increase at a pace of less than 10% per year. One of the reasons why the number of patients continues to increase worldwide is the progress of hemodialysis treatment methods including hemodialysis machines.

Hemodialysis treatment was first performed by Abel in 1914 using animals, and after many trials and errors, it was used by Corfu in 1945 for patients with acute renal failure and succeeded in lifesaving. Hemodialysis came to be used for patients with chronic renal failure by Scrivna 1960
This is after the development of the shunt (a blood sampling unit for extracorporeal circulation) in 1945. Up to about 1970, hemodialyzers used for treatment were mainly made of sheet type dialysis membranes called keel type and coil type, but were manufactured by melt spinning using cellulose acetate as a material in the latter half of the 1960s. Since the hollow fiber dialysis membrane was developed in the United States, the hollow fiber type has rapidly spread, and now 90% or more of the hemodialyzer usage in the world is the hollow fiber type.

Membrane materials have been actively developed, and regenerated cellulose and cellulose acetate derived from natural materials, synthetic polymers such as polyacrylonitrile, polymethylmethacrylate, ethylene vinyl alcohol copolymer, polysulfone, polyamide, polycarbonate, etc. Is on the market.

When hemodialysis treatment began to spread, the substances to be removed were mainly excess water, electrolytes, and small molecular weight substances having a molecular weight of 1000 or less, such as urea and creatinine. Emphasis was placed on enhancing the removal of substances, and cellulosic membranes having high strength and capable of being thinned were mainly used. Subsequently, when it was announced that uremic substances were present in medium- and high-molecular-weight substances having a molecular weight of 1000 or more, synthetic polymer dialysis membranes with easy pore size development were developed. The molecular weight of the causative agent of carpal tunnel syndrome, which is a complication observed in long-term dialysis patients in 1985, was 1180.
Since it was identified as a low molecular weight protein β2 microglobulin of 0, the pore size of the dialysis membrane was further accelerated,
Many dialysis machines have been developed that use a type of membrane generally called a high performance membrane.

Further, in the case of dialysis in which blood and dialysate are flown to both sides across a membrane and the uremic substance is removed by the principle of diffusion using the difference in concentration between the two liquids as a driving force, as the molecular weight of the target substance increases, The diffusion rate becomes low and the removal rate becomes low. For this reason, an attempt has been made to remove substances together with water by filtration (hemofiltration), and a treatment method called hemodiafiltration in which hemofiltration and hemodialysis are simultaneously performed. By using these methods, a molecular weight of 10 which is difficult to remove by dialysis
It has become possible to efficiently remove substances from 00 or more to low molecular weight proteins from blood together with filtered water. Even in normal hemodialysis, 2-3 liters of body fluid is filtered by one treatment to remove excess water, but in the case of hemofiltration or hemodiafiltration, it is 5-20 per time.
Filter 1 liter of body fluid. Therefore, in hemofiltration and hemodiafiltration, it is known that the amount of low-molecular-weight protein removed by one treatment reaches 1.5 times to several times that in normal hemodialysis. However, hemofiltration and hemodiafiltration require an operation of replacement fluid to supplement water, and the work is complicated and expensive, so that it is currently applied only to some patients.

In recent years, a treatment method called biofiltration using a dialysate as a replacement fluid has been developed. This is to perform filtration from blood to dialysate or from dialysate to blood at regular time intervals while performing hemodialysis. By using a dialysate as a replacement fluid while performing hemodiafiltration as described above, it is not necessary to prepare a replacement fluid, and the operation of hemodiafiltration is simplified to the same level as that of general hemodialysis. However, since a special machine is required to perform the filtration alternately at regular intervals, this biofiltration has not become widespread.

[0008] As described above, the reality is that an inexpensive and simple treatment method by hemofiltration or hemodiafiltration, which does not require a special machine, has not yet been obtained.

[0009]

When a fluid flows inside the hollow fiber, a pressure loss occurs and the pressure at the inlet becomes higher than the pressure at the outlet. In the case of hemodialysis using a hollow fiber dialysis membrane, this pressure loss is proportional to the blood flow rate, viscosity, and the length of the hollow fiber, and is inversely proportional to the fourth power of the hollow fiber inner diameter and the number of hollow fibers (Hagen Poiseuille's). formula). ΔP = 128ηLQ / nπD ⁴ × 10 ¹⁶ However, ΔP: pressure loss [mmHg] η: blood viscosity [mmHg · time] Q: blood flow rate [ml / hour] n: number of hollow fibers D: inner diameter of hollow fibers [Μm] L: Length of hollow fiber [cm] π: Circular ratio Based on the above principle, pressure loss causes a pressure difference between the inlet and outlet on the blood side of the dialyzer. By adjusting, the blood has a higher pressure than the dialysate near the blood inlet, and conversely, the dialysate has a higher pressure than the blood near the blood outlet. Therefore, due to the transmembrane pressure difference between the blood and the dialysate generated above, blood flows from the blood to the dialysate near the inlet on the blood side and reverse filtration occurs near the outlet on the blood side. It is possible to supplement the water to be filtered and at the same time filter unwanted solutes in the blood to the dialysate side.

We do not require any special equipment,
In order to obtain a hollow fiber hemodialyzer that can easily perform biofiltration, we actively use the movement of water due to the above pressure loss during hemodialysis using a hollow fiber hemodialyzer. As a result of diligent studies, the greater the above pressure loss, the greater the amount of water transfer in both directions (from blood to dialysate and from dialysate to blood). It has been found that the efficiency is improved, at the same time, water in the filtered blood can be easily replenished, and the same effect as biofiltration can be obtained without using a special device. Also,
When it is necessary to discharge the accumulated urine as in normal hemodialysis, it was found that the water removal amount can be easily adjusted by adjusting the pressure on the dialysate side in accordance with the discharged amount.

The present inventors have completed the present invention as a result of further studies based on such findings.

[0012]

[Means for Solving the Problems] That is, the present invention is a hemodialyzer using a hollow fiber membrane having an inner diameter-based membrane area of 0.5 m ² or more, and has the following requirements (a) and (b): The present invention provides a hemodialyzer using a hollow fiber membrane, which satisfies the requirement. (A) The sieving coefficient of the hollow fiber membrane with respect to inulin is 0.5 or more, (b) the pressure loss on the dialysate side of the hemodialyzer is zero, and the load on the outlets on the dialysate side and the blood side is zero. When the pressures are equalized, the following expression (1) is satisfied. UFR (B) × L ² / D ³ ≧ 6 × 10 ⁻² (1) where UFR (B): when blood of 37 ° C. having a viscosity of 2.5 cP was flowed through the hemodialyzer at 200 ml / min. , Ultrafiltration coefficient of the hollow fiber membrane with respect to the blood [ml / (time · m ² · mmHg)] D: inner diameter of the hollow fiber membrane [μm] L: length of the hollow fiber membrane [cm]

The material of the hollow fiber membrane used in the present invention is not limited in any way. For example, copper ammonia cellulose, saponified cellulose, cellulose diacetate, cellulose triacetate, polyacrylonitrile copolymer, polymethyl methacrylate, polyethylene vinyl. Examples thereof include alcohol copolymers, polyethylene carbonate copolymers, polysulfones, polyether sulfones and polyamides.

The method for producing the hollow fiber membrane used in the present invention is not limited in any way. For example, a three-component system membrane-forming stock solution prepared by dissolving a polymer in a solvent and simultaneously adding a non-solvent is used as a tube-in-orifice type mouthpiece. It is obtained by extruding with a hollow part forming agent and passing through steps such as coagulation, post-treatment, drying and winding under appropriate conditions. The hollow portion forming agent used in the production is more preferably a gas that does not need to be removed after forming the hollow fibers.

The membrane area based on the inner diameter of the hemodialyzer of the present invention must be 0.5 m ² or more. When the membrane area based on the inner diameter is smaller than 0.5 m ^2, even if a pressure loss is applied, the membrane area is small and moisture does not move sufficiently.
In addition, the removal rate of small molecular weight substances becomes low.

The sieving coefficient for the inulin of the hollow fiber membrane used in the present invention must be 0.5 or more. This is because when the sieving coefficient for inulin is less than 0.5, the permeability of the membrane for substances having a medium molecular weight or higher is low, and the removal rate of these substances is low. A so-called high-performance membrane has high water permeability and is excellent in removing low molecular weight proteins, and is more preferably applied to the present invention. There is no precise definition for high performance membranes, but their performance is
UFR in pure water (hereinafter, UFR (W)) is 20 ml /
Membranes having a sieving coefficient of β 2 microglobulin of 0.2 or more for (time · m ² · mmHg) or more are considered generically. As materials for such membranes, regenerated cellulose, cellulose triacetate, polymethylmethacrylate, ethylene vinyl alcohol copolymer, polyacrylonitrile, polysulfone, polyamide, polymer alloy membranes and the like have already been put on the market.

The hollow fiber membrane used in the present invention, when the pressure loss on the dialysate side of the hemodialyzer of the present invention is zero and the load pressures on the dialysate side and the blood side are equal,
It is necessary to satisfy the formula (1). Here, "zero pressure loss on the dialysate side" means, for example, that the dialysate side of the hemodialyzer of the present invention is filled with water, and that the inlet on the dialyzer side is plugged. "Equalizing the load pressures on the dialysate side and blood side outlets" means, for example, in the above case,
It means opening the outlet on the dialysate side and the outlet on the blood side to the atmosphere to bring the pressure to atmospheric pressure. In addition, in the equation (1), when blood having an average property is flowed at 200 ml / min under the above conditions, the amount of water transferred from the blood side to the dialysate side is 4
It means 0 ml / min or more. The details will be described below. It should be noted that blood with an average property has a viscosity of 2.5c.
P, blood at 37 ° C., for example, its hematocrit is about 30%, and plasma total protein concentration is about 6 g / dl.

As described above, the equation (1) is satisfied under the condition that "the pressure loss on the dialysate side is zero and the load pressures on the outlets on the dialysate side and the blood side are equal". Therefore, regarding the filtration that occurs in the hemodialyzer under the conditions, only the filtration from the blood side to the dialysate side occurs due to the pressure loss on the blood side. Here, regarding the above-mentioned filtration, the moving speed M [ml / hour] of water on the blood side to the dialysate side is expressed by the equation (2). M = UFR (B) × A × 1 / 2ΔP = 1/2 × UFR (B) × A × ΔP (2) where UFR (B) is the ultrafiltration coefficient of the hollow fiber membrane against blood [ml / (time .M ² · mmHg)] A: Membrane area based on inner diameter of hemodialyzer [m ² ] ΔP: Pressure loss on blood side [mmHg] Also, the above-mentioned inner diameter based membrane area A [m ² ] is (3) It is represented by a formula. A = n × π × D × L × 10 ⁻⁸ (3) where n: number of hollow fibers D: inner diameter of hollow fiber [μm] L: length of hollow fiber [cm] Meanwhile, ΔP is the above-mentioned Hagen Since it is calculated from the Poiseuille's formula, substituting the formula (3) and Hagen-Poiseuille's formula into A and ΔP of the formula (2) can be rewritten as the formula (4). M = 1/2 × UFR (B) × nπDL × 10 ^-8 × 128 ηLQ / nπD ⁴ × 10 ¹⁶ = 6.4 × 10 ⁹ × UFR (B) × η × Q × L ² / D ³ (4) , Η: viscosity of blood [mmHg · time] Q: flow rate of blood [ml / hour] where η = 2.5 cP (= 5.2 × 10 ⁻⁹ mmHg ·
Time), Q = 200 ml / min (= 1.2 × 10 ⁴ ml /
As time), further conversion into units and rearranging gives the following formula. M = 3.99 × 10 ⁵ × UFR (B) × L ² / D ³ Therefore, in order to satisfy M ≧ 2400 ml / hour (40 ml / min), it is necessary to satisfy the following expression (1). UFR (B) × L ² / D ³ ≧ 6 × 10 ⁻³ (1)

The reason why M needs to be 2400 ml / hour (2.4 liters / hour) or more will be described below. In the above, M means the moving speed of water moving from the blood side to the dialysate side based on the pressure loss on the blood side. However, in the actual hemodialysis treatment, since the urine accumulated in the body needs to be discharged, the load pressure on the dialysate side is not zero, but is adjusted by the extra water content in the blood. Here, in normal hemodialysis, 2 to 4 hours are required.
Since 3 liters of water are removed (in normal hemodiafiltration, the amount of water removed is 5 liters or more in 4 hours, but due to the replacement fluid, the difference is 2-3 liters as in hemodialysis). The effect of removing unnecessary substances in blood in the present invention when the water velocity is 0.6 liter per hour is estimated. First, the dialysate side pressure loss is the blood side pressure loss ΔP.
In comparison with the present invention, since it is very small in the present invention, it is regarded as zero, and when the load pressure on the dialysate side is P _T , the amount of water movement due to filtration generated in the hemodialyzer as shown in FIG. The liquid side is M _B , and the dialysate side to the blood side is M _T. As described above, since (M _B −M _T ) is 0.6 liter / hour, P _T / ΔP,
M _B and M _T are calculated as follows. M _B −M _T = {(1- (P _T / ΔP)) ² − (P _T / ΔP) ² } × M ∴0.6 = {(1- (P _T / ΔP)) ² − (P _T ^{/ ΔP) 2} × 2.4 ∴P} T /ΔP=0.414 M B = (1- (P T / ΔP)) 2 × M = (1-0.414) 2 × 2.4 = 1. 2 [liter / hour] M _T = (P _T / ΔP) ² × M = (0.414) ² × 2.4 = 0.6 [liter / hour] That is, when M is 2.4 liter / hour , M _B is 1.2
Liter / hour, M _T becomes 0.6 liter / hour,
If converted into 4 hours, M _B is 4.8 liters, M
_T will be 2.4 liters. Therefore, if M is 2.4 liters / hour or more, about 5 liters or more of water can be removed similarly to normal hemodiafiltration, and the same water removal effect as hemodiafiltration can be obtained. . As for the replacement fluid, as is clear from FIG. 1, it is possible to easily set an appropriate M _T (corresponding to the replacement fluid amount) by adjusting P _T. Hereinafter, β2 microglobulin, which is a low molecular weight protein, will be described as an example of unnecessary substances in blood. Assuming that the sieving coefficient of β2 microglobulin is 0.6, M _B = 20 ml / min as described above, and therefore the increase in clearance is 12 ml / min (20 ml / min ×
0.6). Further, the clearance of β2 microglobulin when a high performance membrane is used in ordinary hemodialysis is about 20 to 40 ml / min. Therefore, when M is 2.4 liters / hour, the clearance of β2 microglobulin increases by 30 to 60%. Since M ≧ 2.4 liters / hour in the requirements of the present invention, the application of the present invention increases the clearance of β2 microglobulin by several tens of percent or more as compared with ordinary hemodialysis. As described above, in the present invention, it is possible to obtain the amount of water removed corresponding to normal hemodiafiltration, and about 1.5 times to normal hemodialysis.
In order to be able to obtain several times higher removal rates of unwanted substances, M is required to be above 2.4 liters / hour.

In FIG. 1, the UFRs relating to the filtration from the blood side to the dialysate side and the UFR relating to the filtration from the dialysate side to the blood side are calculated as the same value. Since UFR in filtration to the
The value of _B becomes larger than the calculated value above, and it is expected that a larger effect of removing water and removing unnecessary substances will be obtained. Here, since M _B is actually larger than the calculated value and it is difficult to accurately calculate the value of M _B , it was obtained by the calculation as described above. In addition, pressure loss actually occurs on the dialysate side as well, but since the dialysate flows countercurrent to the blood, the pressure on the dialysate side is high on the outlet side and low on the inlet side. Therefore, the movement of water caused by the pressure loss is in the same direction as the movement of water caused by the pressure loss of blood (blood inlet side, blood → dialysis fluid, blood outlet side, dialysate → blood). When blood and dialysate are caused to flow through the dialyzer in this way, water moves due to the pressure loss of both, and thus the value of M _B actually becomes larger than the above calculated value as in the above case.
Here, since M _B actually becomes larger than the calculated value, the pressure loss of the dialysate is several to 20 mmHg in a normal dialyzer, and it is difficult to accurately calculate the value of M _B. It was calculated.

In the present invention, the parameters (UFR (B), L, D) included in the equation (1) need to satisfy the equation (1). The smaller the inner diameter of the thread film, and / or
The longer L (the length of the hollow fiber membrane) and / or the UFR
The larger (B) (the ultrafiltration coefficient of the hollow fiber membrane for blood under the conditions described in the claims), the more preferable. However, regarding D, 100 μm is used to prevent the blood from being destroyed or coagulated when the blood flows through the hollow fiber membrane.
m or more is preferable. Also, if L is made longer, the length of the dialyzer inevitably becomes longer, and if inconveniences such as carrying and handling occur, make the dialyzer into a donut shape or wind the hollow fiber spirally. It is preferably applied. Generally, UFR is used to objectively express the water permeability of the membrane.
(W) is often used, but in the present invention, U is used for the purpose of guaranteeing the performance of the hemodialyzer in a more clinically appropriate manner.
FR (B) was used. That is, UFR (W) indicates the water permeation resistance of only the membrane, but UFR (B) includes the resistance due to the protein adhering to the membrane and the concentration polarization layer, so that the properties and flow state of blood other than the membrane itself are included. It is considered that it is affected by the transmembrane pressure difference. According to the investigations by the present inventors, the UFR (W) is several to several hundreds in the commercially available dialyzer, while the UFR (B) is about 1 to 40. Further, as described above, satisfying the equation (1) is equivalent to the right side of the equation (2) being 2.4 liters / hour or more. Therefore, in other words, the requirement of the present invention regarding the equation (1) is The larger the pressure loss on the side,
And / or the larger the membrane area of the hemodialyzer based on the inner diameter, and / or the larger the UFR (B), the more preferable. Here, with respect to the inner diameter-based membrane area of the hemodialyzer, in order to ensure the minimum amount of water and the movement amount of the low molecular weight compound between the membranes in order to achieve the object of the present invention, another 0.5 m is used. ^Although a requirement of ² or more is provided, in order to suppress an increase in extracorporeal blood circulation and an increase in the cost of a dialyzer due to an increase in the amount of hollow fiber membranes,
The membrane area based on the inner diameter is preferably 3 m ² or less.
In addition, UFR (B) is 5% in order to guarantee the minimum amount of transmembrane water content for achieving the object of the present invention.
It is preferably at least ml / (m ² · hour · mmHg). Further, it is an important requirement of the present invention to increase the pressure loss on the blood side, but in order to avoid the risk of leakage of the adhesion part of the inlet of the hemodialyzer, tube damage, etc., the pressure loss on the blood side is reduced. Is preferably 760 mmHg or less.

[0022]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. In particular, in the examples, β2 microglobulin (molecular weight:
However, as described above, the present invention is not intended to remove only β2 microglobulin, but blood that utilizes the movement of water between membranes caused by the pressure loss that occurs during dialysis. The main purpose is to remove unnecessary substances having a medium or higher molecular weight (molecular weight: about 1000 daltons). Therefore, many hemodialysis membranes currently on the market hardly permeate β2 microglobulin, but even if this type of membrane is used and the requirements of the present invention are satisfied, the object of the present invention is sufficient. It can be reached.

In the examples, a dialyzer consisting of a cellulose triacetate (hereinafter referred to as CTA) hollow fiber membrane (inulin sieving coefficient: 0.8) obtained by a conventional method is used, and a hollow dialyzer is used like a normal hemodialyzer. A dialyzer was constructed so that blood flows inside the thread and dialysate flows outside. The thickness and length of the dialyzer were adjusted so that the filling rate of the hollow fiber was 45 to 50% in order to prevent uneven flow of the dialysate. 1. How to obtain UFR (B) Inside the hollow fiber of the above dialyzer, hematocrit 30
%, Total protein 6 g / dl, ACD-added fresh bovine blood adjusted to a viscosity of about 2.5 cP at a shear rate of 400 s-1 urea 100 mg / dl, β2 microglobulin 3 mg / dl
(To be referred to as model blood below) was kept at 37 ° C and flowed inside the hollow fiber at a rate of 200 ml / min. Outside the hollow fiber, a commercially available dialysate (Kindery solution GF, Fuso Yakuhin Kogyo Co., Ltd.) (Company), the dialysate inlet of the dialyzer was capped. Next, the blood outlet and the dialysate outlet of the dialyzer are released to the atmosphere, that is, these pressures are made zero, and the pressure at the blood inlet and the amount of water transferred from the blood to the dialysate side are measured, and the UFR is calculated according to the following formula. (B) was determined. UFR (B) = M / (PBi / 2 × A) where M is the moving speed of water [ml / Hr], PBi is the blood inlet pressure [mmHg], and A is the inner diameter-based membrane area [m
² ]. 2. Method of measuring clearance and pressure loss Model blood is 200 ml / min inside the hollow fiber of the above-mentioned dialyzer and 500 ml / min of commercially available dialysate (same as above) as a dialysate outside the hollow fiber. The clearance of urea and β2 microglobulin was determined using the formula shown below with the apparent ultrafiltration amount set to zero by adjusting the load pressure on the dialysate side. Clearance = (Xi−Xo) / Xi × 200 where Xi: solute concentration at the blood side inlet, Xo: solute concentration at the blood side outlet, and pressures at the model blood inlet and outlet and dialysate inlet and outlet at this time Was measured and the pressure loss was calculated. All temperatures were 37 ° C.

[0024]

Example 1 3000 CTA hollow fiber membranes having an inner diameter of 200 μm and a film thickness of 15 μm were bundled into a dialyzer with a length of 100 cm. Therefore, the effective membrane area of this dialyzer is 1.89 m ² based on the inner diameter. PBi and M of this dialyzer
Is measured at 405 mmHg and 5700 ml / hour respectively, and UFR (B) is 15.0 ml / (hour · m ² · m
mHg). In addition, UFR (B) ・ L ² / D
The value of ³ was calculated to be 1.9 × 10 ^-2 . When model blood and dialysate were flowed through this dialyzer and clearance and pressure loss were measured, the pressure loss was 610 mmHg on the blood side,
It is 30 mmHg on the dialysate side, the clearance of urea is 185 ml, and the clearance of β2 microglobulin is 6
It was 4 ml.

[0025]

Comparative Example 1 A dialyzer was prepared by bundling 12,000 hollow fiber membranes the same as in Example 1 and setting the length to 25 cm. Therefore,
The effective membrane area of this dialyzer is 1.89 m ² as in Example 1, based on the inner diameter. The PBi and M of this dialyzer were measured as 30 mmHg and 780 ml / hour, respectively.
R (B) was calculated to be 27.5 ml / (Hr · m ² · mmHg). The value of UFR (B) · L ² / D ³ was calculated to be 2.1 × 10 ⁻³ . When model blood and dialysate were flowed through this dialyzer and the clearance and pressure loss were measured, the pressure loss was 30 mmHg on the blood side and 18 mmHg on the dialysate side, and the urea clearance was 183 m.
1, clearance of β2 microglobulin was 34 ml. Compared with Example 1, the clearance of urea showed almost no difference, but the clearance of β2 microglobulin was about 60%. This difference was considered to be a difference in the amount of filtered water due to the difference in blood-side pressure loss between the two dialyzers.

[0026]

[Comparative Example 2] The same dialyzer as in Comparative Example 1 was used, and the amount of water transferred from the blood side to the dialysate side was 2400 m per hour.
Filtration was carried out by applying a load pressure to the inlet on the blood side so as to increase 1 (40 ml / min). The concentrated model blood was diluted by injecting physiological saline into the blood leaving the dialyzer at a rate of 40 ml / min. In this case, PBi and M were measured as 30 mmHg and 780 ml / hour, respectively.
(B) was calculated to be 27.5 ml / (time · m ² · mmHg). The value of UFR (B) · L ² / D ³ is 2.
It was calculated to be 1 × 10 ⁻³ . The pressure loss of the dialyzer was 26 mmHg on the blood side and 19 mmHg on the dialysate side. Regarding the clearance, the solute concentration at the blood side outlet was calculated using the values measured by sampling from blood after being diluted with physiological saline, and as a result, the urea clearance was 185 and the β2 microglobulin clearance was 6
It was 2. Comparative Example 2 performs the same operation as the known hemodiafiltration, and uses the same dialyzer as Comparative Example 1,
The clearance of β2 microglobulin was improved as compared with Comparative Example 1, and the performance equivalent to that of Example 1 was exhibited. However, the amount of blood may change unless a circuit and a pump for injecting physiological saline into the blood leaving the dialyzer are required and the ultrafiltration rate of blood is constantly measured. It took more money and labor than

[0027]

Industrial Applicability As described above, the present invention, when used for treating renal failure and the like, does not require a complicated device,
A hemodialyzer using a hollow fiber membrane capable of performing hemodiafiltration for efficiently removing unnecessary substances from small molecular weight substances to low molecular weight proteins. That is, the present invention, by performing hemodialysis therapy on patients with insufficiency such as kidney, liver and lung, by flowing blood and dialysate into a hemodialyzer,
By positively utilizing the pressure loss generated in the hemodialyzer, unnecessary substances with various molecular weights in blood (from low molecular weight substances such as urea to β2 micro It improves the efficiency of removal of proteins such as globulin) and at the same time replenishes the water in the blood lost by filtration from the dialysate. So-called biofiltration and hemodiafiltration can be performed easily without using a complicated device. The present invention provides a hemodialyzer capable of obtaining the same effect as. As described above, the hemodialyzer of the present invention can be easily handled without using a complicated device and is inexpensive, but has a removal efficiency of unnecessary substances which is several tens% to several times higher than that of a normal hemodialyzer, It is also applicable to all hemodialysis therapies. Therefore, the effect of the present invention in this field is extremely large.

[Brief description of drawings]

FIG. 1 is a diagram showing the amount of water that moves through a membrane due to pressure loss in a dialyzer.

[Explanation of symbols]

ΔP Pressure loss on blood side [mmHg] P _T Pressure loss on dialysate side [mmHg] M _B Moisture amount transferred from blood side to dialysate side [ml] M _T Moisture amount transferred from dialysate side to blood side [ ml] MB [ml] when M PT = 0

Claims (1)

[Claims] 1. A hemodialyzer using a hollow fiber membrane having an inner diameter-based membrane area of 0.5 m ² or more, wherein the following requirement (a) is satisfied:
And a hemodialyzer using a hollow fiber membrane, which satisfies (b). (A) The sieving coefficient of the hollow fiber membrane with respect to inulin is 0.5 or more, (b) the pressure loss on the dialysate side of the hemodialyzer is zero, and the load on the outlets on the dialysate side and the blood side is zero. When the pressures are equalized, the following expression (1) is satisfied. UFR (B) × L ² / D ³ ≧ 6 × 10 ⁻³ (1) However, UFR (B): when blood at 37 ° C. having a viscosity of 2.5 cP is flown through the hemodialyzer at 200 ml / min. , Ultrafiltration coefficient of the hollow fiber membrane with respect to the blood [ml / (time · m ² · mmHg)] D: inner diameter of the hollow fiber membrane [μm] L: length of the hollow fiber membrane [cm]