JPH04348757A - Dialysate treatment method and treatment device - Google Patents

Abstract

PURPOSE:To obtain the method and device for treating a dialyzate which allow easy handling and decrease pressure drops by passing the dialyzate through the inside of an adsorption layer consisting of many porous materials having many pores to adsorb and remove the low mol. wt. protein contained in the dialyzate. CONSTITUTION:A pipe 8 is liquicltightly connected to an outlet 3 side of the device for treating the dialyzate and is connected to a dialysis device 9. The dialysis device 9 has many dialyzing tubes 10 consisting of semipermeable membranes, an outside pipe 11, a blood supply pipe 12, a blood discharge pipe 13, and a dialyzate outlet 14. Blood flows in the inside of the dialyzing tubes 10 and the dialyzate flows on the outside of the dialyzing tubes 10, respectively like arrows. The dialysis is executed through the semipermeable membranes constituting the dialyzing tubes 10. The harmful components in the dialyzate migrate into the dialyzate during this time and the dialyzate contg. the harmful components is discarded by a pump, etc., from an outlet 14. The adsorption layer is adequately packed with the powdery porous materials, such as porous glass powder and active carbon.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and apparatus for treating dialysate used for dialysis of blood.

0002

BACKGROUND OF THE INVENTION It is known to remove bacteria, pyrogens, etc. contained in a dialysate using a sterilizing filter, a polyamide membrane, or the like.

0003

[Problem to be solved by the invention] By improving the dialysis membrane,
Even low molecular weight proteins such as β2-microglobulin (hereinafter abbreviated as β2-MG), which was thought to be impossible in the past, can now be removed by diffusion. Depending on the membrane, the clearance of β2-MG in normal dialysis is 40ml/
Some reach close to min. On the other hand, there is also a type that removes proteins by adsorbing them to the membrane itself, and it is expected that the ability to remove low-molecular-weight proteins will continue to improve to meet clinical demands. However, in the case of removal by diffusion, it is possible to remove from the blood side to the dialysate side, and at the same time, proteins having similar molecular weights on the dialysate side also enter the blood side if there is a difference in concentration. The extent of its invasion is not significantly reduced by increased ultrafiltration and cannot be prevented under normal dialysis conditions. Some of these low-molecular-weight proteins in the dialysate are considered to be sufficiently toxic and antigenic to living organisms, and not only can they cause various symptoms such as fever during dialysis, but if continued over a long period of time, they may lead to abnormalities in the immune system. be. Therefore, in order to use a dialyzer with a highly permeable membrane,
Antigenic substances, etc. in the dialysate must be removed as much as possible.

Bacterial cells can be removed from the dialysate by frequently cleaning the dialysate line and installing a sterilization filter, but even if the bacterium is trapped just before the dialyzer, low-molecular proteins that may come out from it may be removed. etc. cannot be trapped. Cutoff point is 20,00
There is also a method of removing pyrogens along with bacterial cells immediately before the dialyzer by using a polyamide membrane of about 0.0 mm, but this method requires a membrane area of 2 m2, and it is thought that it will be difficult to popularize it due to cleaning and cost considerations.

The present invention solves the above-mentioned problems of the prior art, is easy to handle, has little pressure loss, and provides treatment for dialysate to effectively remove low-molecular-weight proteins and the like contained in the dialysate. An object of the present invention is to provide a method and a processing apparatus.

[0006]

[Means for Solving the Problem] Considering various conditions such as dialysate flow rate, pressure loss, and ease of handling, the present inventor believes that adsorption immediately before the dialyzer is the best way to remove them. Based on this viewpoint, we conducted studies and completed the present invention. They then focused on porous glass, synthetic polymers, cellulose, and activated carbon as adsorbents, and investigated the degree of adsorption of several proteins.

The present invention is a new proposal based on the above-mentioned research results, in which a dialysate used for dialysis treatment of blood is passed through an adsorption layer made of a porous material having a large number of pores. A dialysate treatment method characterized by adsorbing and removing low molecular weight proteins contained in the solution in an adsorption layer, and an adsorption layer comprising a dialysate feed hole and a porous material having a large number of small pores. The present invention relates to a dialysate treatment device having a dialysate discharge hole. In a preferred embodiment of the treatment apparatus of the present invention, porous glass, synthetic polymers, cellulose or activated carbon is used as the porous adsorbent.

[0008] The present inventor first conducted a batch test using a beaker in order to obtain specifications for embodying the method and apparatus of the present invention. In this batch test, porous glass (trade name MPG) manufactured by Ise Chemical Industry Co., Ltd.
Fine powder (particle size 100 to 200 μm) was used, and the proteins listed in Table 1 were used as proteins.

[Table 1] Next, the specific method of the batch test and its results will be explained. In the experiment, each of these protein solutions was first placed in a beaker, and changes in their concentrations over time were investigated. Acetic acid dialysate was used as the solvent, and the initial concentration of each protein was 1 to 1.
It was set to 10 mg/dl. The amount of porous glass fine powder is 1
g, and the solution volume was 100 ml. Both concentrations were analyzed by a highly sensitive direct colorimetric method based on the same acetic acid dialysate.

FIG. 1 shows the results of an adsorption experiment using a beaker batch. The concentration decreases over time, and the free concentration and adsorption amount reach equilibrium after about 60 minutes. The relationship of this equilibrium state can be summarized as shown in FIG. 2. Lysozyme is the most commonly adsorbed, followed by cytochrome C, ribonuclease A, and α-
It can be seen that lactalbumin is adsorbed in this order. This adsorption tendency is the same as the isoelectric point, and it was found that the adsorption ability of low-molecular proteins is strongly influenced by charge.

[0010] From this figure, the coefficients of Freundlich's adsorption isotherm expressed by Equation 1 were determined, and in the case of lysozyme, k was 0.012 and n was 11. These parameters are indicators of whether the protein is likely to be adsorbed. For α-lactalbumin, k is 0.001 and n is 4. Although there are only a few plots, when these are graphed, they show an upward trend to the right as shown in FIGS. 3 and 4, and it is clear that proteins on the higher electric point side are easily adsorbed to the porous glass fine powder.

[Math 1]

Next, the method and apparatus of the present invention will be explained in more detail with reference to FIGS. 5 and 6. In the present invention, porous materials having a large number of small pores include porous glass,
Synthetic polymers, cellulose, activated carbon, and especially porous glass are preferred. In addition, as porous glass, Vycor glass,
Or SiO245-70wt%, B2O38-30wt%
%, CaO 8-25wt%, Al2O3 5-15w
t%, Na2O 3-8%, K2O 1-5wt%,
Na2O + K2O 4~13wt%, MgO 0~
Glass having a composition of 8wt% (hereinafter referred to as glass A) or SiO245-70wt%, B2O38-30w
t%, CaO 8-25wt%, Al2O3 5-15
A porous glass (hereinafter referred to as porous glass A or ) is appropriate.

[0012] Furthermore, it is preferable to use polysulfone or the like as the synthetic polymer, and ion-exchange cellulose or the like as the cellulose. The activated carbon preferably has a particle size of 8 to 200 mesh, preferably 16 to 32 mesh. In Figures 5 and 6, 1 is a dialysate processing device (column)
and a pipe 4 having a dialysate inlet 2 and a dialysate outlet 3
It includes an adsorption layer 5 filled with porous glass particles and batten plates 6, 6 having a large number of small holes.

A pipe 7 is provided on the inlet 2 side of the dialysate treatment device.
are airtightly connected, the pipe 7 is connected to a dialysate supply device (not shown), a predetermined flow rate of dialysate is supplied from the inlet, and the adsorption layer 5 adsorbs low molecular weight proteins etc. contained in the dialysate. removed.

A pipe 8 is airtightly connected to the outlet 3 side of the dialysate treatment device 1, and the pipe 8 is connected to a dialysis device 9. A dialysis device 9 includes a large number of dialysis tubes 1 made of semipermeable membranes.
0, outer tube 11, blood supply tube 12, blood discharge tube 13,
A dialysate outlet 14 is provided, and blood flows through the inside of the dialysis tube 10.
The dialysate flows on the outside of the dialysis tube 10 as shown by the arrows,
Blood is dialyzed through a semipermeable membrane that constitutes the dialysis tube 10. During this time, harmful components in the blood migrate into the dialysate, and the dialysate containing the harmful components is discarded from the outlet 14 by a pump or the like (not shown).

[0015] The adsorption layer may preferably be one filled with a porous material such as porous glass powder or activated carbon, but a thin porous glass plate may also be used. Furthermore, block-shaped or fibrous synthetic polymers or cellulose can also be used.

The pore diameter of the porous material can be determined experimentally depending on the molecular weight of the protein to be adsorbed or removed.

For example, if the molecular weight is 12,000 to 15,00
In the case of 0, suitable results could be obtained using porous glass with an average pore diameter of 1,500 Å. The thickness of the adsorption layer is experimentally determined depending on the adsorption rate and the flow rate of the dialysate so that the residence time of the dialysate in the adsorption layer is equal to or greater than a predetermined value.

The adsorption rate is influenced by the diffusion coefficient of the protein, that is, the size of the protein molecule, and the solution temperature at the time of adsorption, but factors on the adsorbent side include the flow condition around the powder, that is, the uniformity of the flow and the porosity. It can be broadly divided into the degree of movement through a film formed near a substance, and the ease with which it diffuses to the surface and inside (inside pores) of a porous substance. The flow condition around a porous material depends on the particle size of the porous material and the pipe (
The packing condition of the column (column), pipe shape, and dialysate flow rate have an effect. On the other hand, the state of diffusion into the porous material itself depends on the surface structure of the porous material, the pore radius, and its distribution. Considering the contact area, it is advantageous that the particle size of the porous material is smaller. However, extreme miniaturization is not possible due to the increased pressure loss.

For example, when using a dialysate processing device (column) filled with glass powder having a particle size of 100 to 200 μm and an average pore diameter of 1,500 Å, a packed bed thickness of 10 mm, and an inner diameter of 10 mm, the dialysate When the residence time was 0.1 to 11 seconds, the removal rate remained unchanged at about 100%.

Now, let us assume that an adsorption column is installed immediately before the dialyzer. Since the inner diameter of the dialysate inlet port of the dialyzer is approximately 9 mm, the column length at which the residence time is 0.1 seconds when the dialysate flow rate is 500 ml/min is approximately 3 cm. Note that here, the packing density of the porous material powder was set to 50%. Ideally, it would be disposable like the diasizer. Whether or not sufficient adsorption is achieved is thought to be greatly influenced by the filling state in addition to the shape of the porous material powder. In addition, whether or not it is possible to process dialysate flowing for 5 hours or more depends on the packing volume, and once the protein concentration to be removed in the dialysate is approximately determined, the required volume is automatically determined, and the shape of the column must be determined. Can be done.

As mentioned above, there are still problems to be solved experimentally in order to miniaturize the column, but by using the method and apparatus of the present invention, it is possible to reduce low molecular weight proteins, etc. in the dialysate. It has been found that it can be effectively removed.

[0022]

[Action] The dialysate used for dialysis of blood is passed through an adsorption layer made of a porous material with many small pores, and low molecular weight proteins, etc. contained in the dialysate are adsorbed and removed by the adsorption layer. By doing so, the increase in bacterial cells and pyrogens in the dialysate is effectively prevented.

[0023]

[Example] In a glass tube with an inner diameter of 10 mm, 100 to 20
An acetic acid dialysate containing lysozyme at a concentration of 1,000 ng/ml was passed through a column with an adsorption layer thickness of 10 mm and filled with 1 g of glass powder with a size of 0 μm and a pore diameter of 1,500 Å. Flow rate 0.2-0.55ml
/sec, the average residence time in the column 2
．． The removal rate at 7 sec, 5.6 sec, and 10.8 sec and the change in the removal rate over time were determined. Here, the removal rate is

Calculated by [Equation 2]. Average residence time 0.1 to 10 seconds
There was no difference in the removal rate, and the average residence time was 0.1 sec.
However, it was found that lysozyme can be effectively removed with a removal rate of almost 100%.

Further, even when this operation was continued for 30 minutes, no tendency for the removal rate to decrease was observed. It should be noted that the slight variation in the plot is due to an error due to the low outlet concentration. The fact that the removal rate can be considered constant when the residence time is within this range means that protein adsorption to the porous material occurs extremely quickly, reaching concentration equilibrium at the column outlet within 0.1 seconds. be able to. Note that this result seems to be very different from the beaker batch result, but this is because the protein concentration changes over time in the beaker batch, and the contact conditions between the porous substance powder and the solution are different. , consistent with the adsorption of low-concentration proteins reaching equilibrium within 0.1 seconds.

[0025]

Example 2 A similar experiment was conducted using fine activated carbon powder (average particle size 80 μm) in place of the glass powder of Example 1, and almost the same results were obtained.

[0026]

[Effects of the Invention] Low molecular weight proteins and the like in the dialysate can be efficiently removed in a short time.

[0027]

[Brief explanation of drawings]

FIG. 1 is a graph showing the relationship between contact time and concentration according to a beaker test.

FIG. 2 is a graph showing the relationship between concentration and adsorption amount at equilibrium.

FIG. 3 is a graph showing the relationship between isoelectric point and coefficient K.

FIG. 4 is a graph showing the relationship between isoelectric point and coefficient n.

FIG. 5 is a sectional view of the device of the invention.

FIG. 6 is an enlarged sectional view of FIG. 5;

[Explanation of symbols]

1 Dialysate processing equipment 2 Dialysate inlet 3 Dialysate outlet 4 Pipe 5 Adsorption layer 9 Dialysis machine

Claims (3)

[Claims] Claim 1: A dialysate used for dialysis treatment of blood is passed through an adsorption layer made of a porous material having a large number of pores, and low molecular weight proteins contained in the dialysate are adsorbed to the adsorption layer. A method for treating dialysate characterized by removing 2. A dialysate treatment device comprising a dialysate feed hole, an adsorption layer made of a porous material having a large number of small holes, and a dialysate discharge hole. 3. The processing apparatus according to claim 2, wherein the porous material is porous glass, synthetic polymer, cellulose, or activated carbon.