JP2000126287A - Hollow fiber type blood purifying device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve a blood remaining characteristic by passing a model blood which exhibits the behavior similar to the behavior of the human total blood of a specific temperature in a relation between a viscosity and a shear rate in a specific amount in such a manner that the residual amount of the model blood at the time of washing with a specified amount of a phosphoric acid buffer solution of a specific pH and specific formulation attains a specific value or below. SOLUTION: The model blood which exhibits the behavior similar to the behavior of the human total blood of 37 deg.C in the relation between the viscosity and the shear rate is introduced into the hollow fiber type blood purifying device at a flow rate of 1.28 times the volume of the flow passage of this device. The hollow fiber membranes are then washed by passing the phosphoric acid buffer solution of pH 7.5 at 125 ml/m2 per unit inside surface area of the hollow fiber membranes and at a flow rate of 100 ml/min. The human total blood is hematocrit(ht) 40%.total protein(TP) 8. The phosphoric acid buffer solution is 5.33 mmol disodium hydrogenphoshate dodecahydrate, 1.34 mmol potassium dihydrogenphoshate and 154 mmol sodium chloride. The remaining of the blood after washing is confined to <=1.5 ml/m2 per hollow fiber unit area. The blood remaining characteristic is thus improved.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hollow fiber type blood purifier suitably used for blood purification, hemodialysis or ultrafiltration.

[0002]

2. Description of the Related Art Conventionally, blood purification and separation of specific components in blood have been performed using a blood purifier using a hollow fiber as a separation membrane. Examples of such a blood purifier include a hemodialyzer, a hemofilter, a plasma separator, and an artificial lung. In the hollow fiber type blood purifier, it is desirable that blood flow in the header part and the hollow fiber part of the purifier be performed smoothly. If the flow is not disturbed and uniform, blood replacement efficiency will increase and purification efficiency will improve. At the same time, this will prevent the activation of blood and the formation of blood clots during the blood purification process.

[0003] Further, the improvement of the fluidity in the purifier can drastically reduce the amount of blood remaining in the purifier after use, that is, the so-called residual blood volume.

However, in the conventional blood purifier, the amount of residual blood is large, and it has been desired to reduce the amount of residual blood. The present inventors have conducted intensive studies in order to solve such a problem, and as a result, have found that the remaining blood tends to be generated more frequently in the yarn arranged on the outer peripheral portion of the blood purifier, and the purifier having a small residual blood amount has been found. I came to find.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems in the prior art and to provide a hollow fiber type blood purifier having excellent residual blood characteristics.

[0006]

The present invention has the following configuration to achieve the above object.

[0007] A model blood exhibiting the same behavior as that of human whole blood (hematocrit (ht) 40%, total protein (Tp) 8) having a relationship between viscosity and shear rate of 37 ° C. was introduced into a hollow fiber blood purifier. The blood was sent from the mouth, and the model blood having a volume 1.28 times the blood flow volume of the hollow fiber blood purifier was allowed to flow. (5.33 mmol), potassium dihydrogen phosphate (1.34 mmol), sodium chloride (154 mmol) were washed at a flow rate of 100 ml / min at a flow rate of 125 ml / m ² per unit area of the inner surface of the hollow fiber membrane. The amount of model blood remaining in the hollow fiber membrane is 1.5 per unit area.
A hollow fiber type blood purifier characterized by having a concentration of not more than ml / m ² . As described above, the present invention is characterized in that it is a hollow fiber blood purifier having a small residual blood volume generated in the blood return model system and having excellent residual blood characteristics. To construct a hollow fiber blood purifier with little residual blood and excellent blood fluidity in the purifier,
The structure of the purifier was studied.

First, in the present invention, the relationship between the viscosity and the shear rate is that of human whole blood (hematocrit (ht) 40 at 37 ° C.).
% ・ Total protein (Tp) 8) A fluid having the same behavior as that of the hollow fiber type blood purifier is sent from the blood inlet. The relationship between the viscosity and the shear rate here means that the viscosity obtained by changing the rotational speed of the conical rotor with an E-type viscometer (manufactured by Tokimec Co., Ltd.) is the viscosity obtained by the following equation. This refers to the correlation obtained when plotting.

Viscosity = shear stress / shear rate Here, a fluid whose viscosity and shear rate show the same behavior as human whole blood at 37 ° C. is defined as a viscosity at a shear rate of 9.6 s ^−1. Is 10 to 14 cP, and the shear rate is 76.
Viscosity at 8s ^-1 is 5～7CP, viscosity at shear rate 192S ^-1 refers to what is 3～6CP.

As human whole blood, hematocrit (ht) indicating the volume% of the formed material in blood is 40%, and total protein (Tp) indicating the total protein weight in 100 ml of serum is 8 g. It was taken.

In the present invention, such a model blood is a fluid composed of, for example, xanthan gum, a phosphate buffer solution, and bovine washed red blood cells, wherein the relationship between viscosity and shear rate is 37.
A fluid characterized by exhibiting the same behavior as human whole blood at ℃ (ht40% · Tp8) can be used.

Next, the model blood having a volume of 1.28 times the volume of the blood channel of the hollow fiber type blood purifier is allowed to flow. Here, the volume of the blood flow channel is obtained by calculating the inner volume of each hollow fiber membrane obtained from the inner diameter of the hollow fiber membrane and the effective length of the fiber, converting this into the number of hollow fibers, and further adding the value obtained by adding the header volume. Say.

Next, a phosphate buffer solution of pH 7.5 (disodium hydrogen phosphate dodecahydrate (5.33 mmol), potassium dihydrogen phosphate (1.34 mmol), sodium chloride (154 mmo)
Using l)), 125 per unit area of the inner surface of the hollow fiber membrane
Wash off at a flow rate of 100 ml / min at a rate of ml / m ² .

In the present invention, it is necessary that the amount of model blood remaining in the purifier after the above operation is not more than 1.5 ml / m ² per unit area of the hollow fiber membrane. Here, the membrane unit area refers to the product of the circumference determined from the inner diameter of the hollow fiber membrane, the effective length, and the number of hollow fibers.

The amount of residual blood is determined by collecting the blood remaining in the header on each of the A and V sides of the blood purifier after returning blood, and measuring the blood volume. After removing the residual model blood in both headers, the polymer solution was flowed from the V side to the A side, and the washing was continued until the outflow of the residual blood from inside the hollow fiber was no longer observed. Measure.
A double volume of RO water was added to several ml of each solution collected from the A side and V side and from the inside of the hollow fiber to cause hemolysis, and ultraviolet / visible light absorption was measured at a detection wavelength of 414 nm, and the hemoglobin concentration in the solution was measured. Is determined by quantifying how many ml of residual blood has occurred in terms of model blood.

According to the present invention, a hollow fiber bundle and a main body case accommodating the hollow fiber bundle, a partition wall in which at least one of the hollow fiber bundles is fixed in an open state, and both ends of the main body case are provided. In a hollow fiber type blood purifier comprising a pair of attached headers, db / da> 0, where da is the major axis of the envelope of the hollow fiber bundle and db is the minor axis of the envelope of the hollow fiber bundle. .90, and db
/Da>0.95, and furthermore, db / da> 0.
97 is desirable. The closer the ratio of the major axis to the minor axis of the envelope of the hollow fiber bundle is to 1, the higher the roundness of the hollow fiber bundle is, which has the effect of reducing the occurrence of turbulence in blood flow on the inner end face of the header. Further, by reducing the ratio of the resin portion on the outer periphery of the hollow fiber bundle having no hollow fiber at the end face, the portion where blood does not easily flow is reduced, and the residual blood at the time of blood return can be reduced. The resin portion of the outer periphery of the hollow fiber bundle without the hollow fiber on the end surface is a value (C value) obtained by subtracting the radius of the hollow fiber bundle portion from the radius (D / 2) of the outer peripheral end of the header inner surface on the partition end surface to which the hollow fiber bundle is fixed. ), The smaller the C value is, the less the blood flow on the end face is reduced,
Residual blood when returning blood is also less likely to occur. This C value is C <2m
m, more preferably C <1 mm.

In order to improve the fluidity in the hollow fiber portion of the purifier, it is preferable to improve the fluidity of each hollow fiber constituting the hollow fiber bundle. When the cross section of the hollow fiber is crushed or flat, the fluidity in the hollow fiber is significantly reduced. Therefore, it is desirable that the minor axis of the hollow fiber is equal to or smaller than the major axis, that is, 70% or less of the diameter when the hollow fiber is a perfect circle, and 1% or less in the whole blood purifier.

Further, the ratio of the area of the hollow fiber opening to the area inside the header on the end face, that is, the blood inflow area ratio on the end face. It goes up. The porosity is 28
% Or more is required, and desirably 30% or more.

The above is the result in the hollow fiber portion.
In addition, it is preferable to improve the fluidity in the header during blood purification. In the present invention, it is preferable that the angle θ formed between the header inner ceiling surface and the partition wall satisfies 5 ° <θ <10 °. In the case of θ ≦ 5 °, air bubbles that have entered the header tend to be difficult to escape. Conversely, 10 ° ≦ θ
In the case of, the internal capacity of the header is unnecessarily increased, and there is a possibility that a fluid retaining portion may be generated.

Further, the intersection point of an imaginary line passing through the outer peripheral edge of the header inner surface and orthogonal to the partition wall and a virtual extension line of the header inner ceiling surface is P, the distance between the partition wall and the intersection point P is h, When the diameter of the outer peripheral end portion of the header inner surface is D, it is preferable that 0.08 Dmm ≦ h ≦ 0.13 Dmm. This is for increasing the volume of the outer peripheral portion according to the diameter to keep the flow well. FIG. 3 shows this mode.

As described above, for example, by defining the hollow fiber portion of the hollow fiber type blood purifier and the inner shape of the header, a hollow fiber type blood purifier having good blood fluidity and a small amount of residual blood can be obtained. it can.

[0022]

Example 1 An experiment was conducted using the following model system for quantifying residual blood volume.

First, human whole blood at 37 ° C. (ht40%
-Two kinds of liquids were prepared as fluids having the same flow characteristics as Tp8). One is a 0.75 g / L xanthan gum / phosphate buffer solution which has similar flow characteristics at 25 ° C to 37 ° C human whole blood. The other is a washed erythrocyte + xanthan gum / phosphate buffer solution containing 20% hematocrit and 500 mg / xanthan gum, and also has a flow property similar to that of human whole blood at 25 ° C. and 37 ° C. Here, the former is called a model polymer solution, and the latter is called a model blood. The relationship between the shear rate and the viscosity of each solution is as shown in FIG. As shown in FIG. 4, the shear rate is 9.6 s ^-1.
At a shear rate of 76.8 s ^-1 and a viscosity at a shear rate of 192 s ^-1
It was 6 cP.

In order to observe the flow of blood when flowing into the blood purifier and the flow when returning blood, an apparatus as shown in FIG. 1 was prepared, and the blood return performance of the blood purifier was examined based on the residual blood volume after returning blood. did.
All experiments were performed at 25 ° C.

The main operation procedure is as follows.

(1) The model polymer solution heated to 25 ° C. was used until the internal temperature of the blood purifier was stabilized at 25 ° C.
For 20 minutes. This is because the temperature environment is kept constant at 25 ° C. because the viscosity characteristics are easily affected by the temperature.

(2) The reflux of the model polymer solution was stopped, the circuit was switched to Line 2, and the model blood was filled in the circuit and connected to the A-side header. This is because the amount of residual blood after return is quantified by introducing model blood containing red blood cells. By switching the circuit, the amount of red blood cells used can be suppressed to a small amount.

(3) At a flow rate of 100 ml / min, the model blood was fed 1.28 times the volume of the blood flow channel of the hollow fiber blood purifier. After a lapse of about 1.28 minutes, the phosphate buffer solution heated to 25 ° C. flowed into the module, and blood returned. The liquid supply was stopped when 200 ml of blood was returned. In clinical practice, the flow rate is 100 ml / min and the physiological saline is 200 ml.
In this system, the flow rate is 1
00 ml / min, and the blood returned was phosphate buffered solution 200m
1 was used.

By the above operation, the blood flow in the outer peripheral portion of the blood purifier at the time of blood inflow, the flow in the header at the time of blood return, and the blood return state of the outer peripheral portion can be observed. Next, a method of quantifying the amount of blood remaining in the blood purifier after returning blood will be described.

After the blood return, the blood remaining in each of the headers on the A and V sides of the blood purifier was collected, and the blood volume was measured. After removing the residual model blood in both headers, the model polymer solution was flowed from the V side to the A side, and the washing was continued until the residual blood from the hollow fiber did not flow out. Was measured (FIG. 2). A double volume of RO water is added to several ml of each solution to cause hemolysis, and ultraviolet / visible light absorption measurement is performed at a detection wavelength of 414 nm to determine the hemoglobin concentration in the solution. The amount of residual blood per unit area of the hollow fiber membrane was determined.

The blood purifier used is as follows.

When the major axis of the envelope of the hollow fiber bundle is da and the minor axis of the envelope of the hollow fiber bundle is db, db / da = 0.
97, the C value = 0.25 mm, the porosity = 33%, and the minor diameter of the hollow fiber is 70% or less of the value in the case of minor axis = major axis, but 1% or less in the whole blood purifier. And θ = 6 ゜, h
Using a blood purifier that satisfies the condition of = 4 mm, the residual blood volume by the above operation was measured, and the residual blood volume per unit area of the hollow fiber membrane was 0.56 ml / m ² .

Example 2 An experiment was conducted in the same manner as in Example 1 except that the blood purifier used was as follows.

When the major axis of the envelope of the hollow fiber bundle is da and the minor axis of the envelope of the hollow fiber bundle is db, db / da = 0.
96, the C value = 0.25 mm, the porosity = 33%, and the minor diameter of the hollow fiber is 70% or less of the value in the case of minor axis = major axis, but 1% or less in the whole blood purifier. And θ = 6 ゜, h
= 4 mm. As a result of a residual blood amount quantification experiment, the residual blood amount per unit area of the hollow fiber membrane was 1.03 ml / m ² .

Example 3 An experiment was conducted in the same manner as in Example 1 except that the blood purifier used was as follows.

When the major axis of the envelope of the hollow fiber bundle is da and the minor axis of the envelope of the hollow fiber bundle is db, db / da = 0.
96, the C value = 1.25 mm, the porosity = 29%, and the minor diameter of the hollow fiber is 70% or less of the value in the case of minor axis = major axis, but 1% or less in the whole blood purifier. And θ = 10 ゜
A blood purifier satisfying the condition of h = 2 mm was used. As a result of a residual blood amount quantification experiment, the residual blood amount per unit area of the hollow fiber membrane was 1.03 ml / m ² .

Comparative Example 1 An experiment was performed in the same manner as in Example 1 except that the blood purifier used was as follows.

When the major axis of the envelope of the hollow fiber bundle is da and the minor axis of the envelope of the hollow fiber bundle is db, db / da = 0.
92, the C value = 1.25 mm, the porosity = 29%, and the short diameter of the hollow fiber is 70% or less of the value when the short diameter = the long diameter is 1% or less in the whole blood purifier. And θ = 10
゜, h = 2 mm The blood purifier that satisfies the condition of 2 mm was subjected to a residual blood volume quantification experiment using a model system. As a result, the residual blood volume per unit area of the hollow fiber membrane was 1.69 ml / m ² .

Comparative Example 2 An experiment was performed in the same manner as in Example 1 except that the blood purifier used was as follows.

When the major axis of the envelope of the hollow fiber bundle is da and the minor axis of the envelope of the hollow fiber bundle is db, db / da = 0.
92, the C value = 1.25 mm, the porosity = 29%, and the minor diameter of the hollow fiber is 70% or less of the value in the case of minor axis = major axis. Yes, θ = 10
As a result of performing a residual blood amount quantification experiment using a model system for a blood purifier satisfying the conditions of ゜ and h = 2 mm, the residual blood amount per unit area of the hollow fiber membrane was 8.13 ml / m ² .

Comparative Example 3 An experiment was performed in the same manner as in Example 1 except that the blood purifier used was FB-150U manufactured by Nipro Corporation.

When the major axis of the envelope of the hollow fiber bundle is da and the minor axis of the envelope of the hollow fiber bundle is db, db / da = 0.
95, C value = 1.5 mm, aperture ratio = 28%, θ =
As a result of an experiment for determining the amount of residual blood in a model system for a blood purifier satisfying the conditions of 9 ° and h = 4 mm, the amount of residual blood per unit area of the hollow fiber membrane was 1.52 ml / m ² .

As can be seen from the above results, by making the hollow fiber bundle close to a perfect circle and decreasing the C value, the uniformity of the flow and the efficiency of liquid replacement are improved, and the residual blood is reduced.

[0044]

As described above, according to the present invention, in the hollow fiber type blood purifier, there is an effect that the roundness of the hollow fiber bundle is improved, thereby greatly reducing the amount of residual blood. Furthermore, by defining the inner shape of the header so that the fluid reaches the outer periphery and there is no drift, the blood fluidity in the purifier is improved, and the effect of increasing the replacement efficiency and decreasing the residual blood volume is achieved. is there.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of a model experiment system in the present invention.

FIG. 2 is a schematic diagram of a model experiment system (residual blood amount quantification method) in the present invention.

FIG. 3 is a schematic sectional view of the inner shape of the header of the present invention.

FIG. 4 is a graph showing viscosity characteristics of model blood used in Examples of the present invention.

Claims (5)

[Claims] 1. A hollow fiber type blood purifier comprising a model blood having a behavior similar to that of human whole blood (hematocrit (ht) 40% / total protein (Tp) 8) whose viscosity and shear rate are 37 ° C. The blood was sent from the inlet, and the model blood having a volume of 1.28 times the volume of the blood flow channel of the hollow fiber blood purifier was allowed to flow. Purification when salt (5.33 mmol), potassium dihydrogen phosphate (1.34 mmol), sodium chloride (154 mmol) is washed off at a flow rate of 100 ml / min at a rate of 125 ml / m ² per unit area of the inner surface of the hollow fiber membrane. The amount of model blood remaining in the vessel is 1.5 m per unit area of the hollow fiber membrane
1 / m ² or less, a hollow fiber type blood purifier characterized by the following: 2. A fluid comprising washed red blood cells obtained by separating erythrocytes from xanthan gum, said phosphate buffer solution and bovine whole blood and washing with said phosphate buffer solution as said model blood. The hollow fiber type blood purifier according to claim 1. 3. A hollow fiber bundle, a main body case accommodating the hollow fiber bundle, a partition wall in which at least one of the hollow fiber bundles is fixed in an open state, and mounted on both ends of the main body case. In a hollow fiber type blood purifier comprising a pair of headers, when the major axis of the hollow fiber bundle is da and the minor axis of the hollow fiber bundle is db, db / da> 0.
The hollow fiber type blood purifier according to claim 2, wherein the number is 95. 4. A hollow fiber bundle, a main body case accommodating the hollow fiber bundle, a partition wall in which at least one of the hollow fiber bundles is fixed in an open state, and mounted on both ends of the main body case. In a hollow fiber type blood purifier comprising a pair of headers, a value (C value) obtained by removing a radius of a hollow fiber bundle portion from a radius (D / 2) of an inner peripheral end portion of a header on a partition end surface to which the hollow fiber bundle is fixed. The hollow fiber type blood purifier according to claim 2, wherein C is less than 2 mm. 5. The method according to claim 1, wherein the probability that the short diameter of the hollow fiber is 70% or less of the diameter of a perfect circle is 1% or less of the entire hollow fiber incorporated in the blood purifier. Claim 1
The hollow fiber blood purifier according to any one of claims 1 to 3.