WO2010073320A1

WO2010073320A1 - Blood purification device

Info

Publication number: WO2010073320A1
Application number: PCT/JP2008/073421
Authority: WO
Inventors: 一本松　正道; 鴻志白; 知恵來栖; 利一宮本; 有希向田
Original assignee: 株式会社Ｒｅｉメディカル
Priority date: 2008-12-24
Filing date: 2008-12-24
Publication date: 2010-07-01

Abstract

A blood purification device whereby the restriction on the removal rate of harmful components imposed by the plasma separation rate of a plasma separation unit in the existing blood purification devices with the use of a plasma separation membrane is overcome and thus the removal rate of harmful components is increased, thereby shortening the treatment time required for achieving a definite level of the removal rate of harmful components or increasing the removal rate of harmful components within a definite treatment time required. The removal rate of harmful components of a blood purification device is increased without any restriction imposed by the plasma separation rate of a plasma separation unit by circulating plasma, from which harmful components have been removed by using a harmful component-removing unit such as an adsorption column, in the inlet of the plasma separation unit and thus mixing plasma with blood collected from the human body so as to pass the blood before the removal of the harmful components, which is to be treated, in the diluted state through the plasma separation unit.

Description

Blood purification treatment equipment

The present invention relates to a blood purification treatment apparatus for apheresis treatment that removes harmful components in plasma separated by a plasma separator using an adsorption column or a double membrane filter.

Apheresis treatment involves humoral factors that cause disease from the blood through extracorporeal circulation (proteins and pathogenic substances (immune-related substances such as antibodies and cytokines) present in the blood) and cells (lymphocytes) , Granulocytes, viruses, etc.) to improve the pathological condition.

In the apheresis treatment of the adsorption system, the patient's blood or plasma is perfused through an adsorption column formed by immobilizing a functional group having affinity for the substance to be adsorbed on the surface of the carrier, so that the patient's blood circulated extracorporeally. It is a treatment method that adsorbs and removes a substance to be adsorbed from inside. A method for directly removing the substance to be adsorbed from the blood is called a blood adsorption method, and a method for removing the substance to be adsorbed from the plasma separated from the blood by a plasma separator is called a plasma adsorption method. The present invention belongs to the latter plasma adsorption method.

As shown in FIG. 12, a conventional blood purification apparatus using a plasma adsorption method for apheresis treatment includes a plasma separator 1, a blood inlet T <b> 1 for feeding blood collected from a human body to the plasma separator 1, and a blood feed. The blood pump P1 interposed in the entrance T1, the adsorption column 2 for adsorbing and removing harmful components in the plasma separated by the plasma separator 1, and the blood after plasma separation from the blood outlet 1b of the plasma separator 1 The blood delivery path T2 for returning to the plasma, the plasma bypass T4 from the plasma outlet 1c of the plasma separator 1 via the adsorption column 2 to the blood delivery path T2 downstream from the blood outlet 1b of the plasma separator, and And a plasma pump P3 interposed in the plasma bypass T4 (see, for example, FIG. 30 of Non-Patent Document 1 and FIG. 2 of Non-Patent Document 2 below). That is, in the conventional blood purification apparatus shown in FIG. 12, the plasma separated by the plasma separator 1 and adsorbed and removed by the adsorption column 2 is the residual plasma separated on the downstream side of the plasma separator. It joins with blood (blood cell components and residual plasma that has not been plasma-separated) and returned to the human body.

However, the conventional blood purification treatment apparatus using the plasma adsorption method for apheresis treatment has the following problems.

Blood usually consists of about 40 to 45% blood cell components and the remaining plasma. Even if plasma separation is performed, plasma remains on the blood side and cannot be completely separated. The ratio of plasma that can be separated to the total plasma (plasma separation rate) is about 50% for a plasma separator using a plasma separation membrane and about 60 to 70% for a plasma separator using a centrifuge. The reason why the plasma in the blood cannot be completely separated and the separation rate is limited to 50 to 70% is that if the blood cell components are concentrated too much, the viscosity increases too much to flow through the blood circuit. This is because shear stress is applied to cause hemolysis. In a membrane type plasma separator, if the blood cell component is concentrated too much, the viscosity increases too much, and the pores of the separation membrane are clogged with blood cells, making separation difficult. Obviously, this cannot be solved even if the membrane area of the separation membrane is increased in the membrane plasma separator. In the case of a membrane-type plasma separator, the blood after plasma separation contains about 27.5% to 30% of plasma relative to the whole blood, and the blood cell component is concentrated to about 57% to 62%. Become.

Therefore, even if all the harmful components are removed by the adsorption column, the removal rate of the harmful components with respect to the whole plasma is limited by the plasma separation rate of the plasma separator, and is only about 50% in the case of the membrane type plasma separator. If the removal rate of harmful components relative to the whole plasma is low, the required treatment time until the removal amount of harmful components with respect to the patient's total blood volume reaches the specified achievement rate of harmful component removal (standard treatment 60%, advanced treatment 80%) There was a problem of becoming longer.

Hereinafter, the relationship between the harmful component removal achievement rate and the required treatment time will be explained in detail. When the heart's pumping capacity (blood circulation rate in the human body) is about two orders of magnitude greater than the amount of blood collected per unit time (blood pump flow rate) in apheresis treatment, and blood after removing harmful components is returned to the human body Because the amount of blood returned every unit time is very small compared to the amount of blood circulating in the human body, the blood from which harmful components have been removed is immediately and completely mixed with the blood in the human body. A "complete mixing model" can be used in which the concentration of harmful components in the water is reduced evenly. In the complete mixing model, A is the total blood volume of the human body, C is the concentration of harmful components relative to the total blood volume A, Q is the volume of blood to be processed (blood flow rate) per unit time in the blood purification apparatus, and R is the blood purification. If it is set as the harmful component removal rate of a processing apparatus, the relational expression (differential equation) shown in the following Numerical formula 1 will be established.

[Formula 1]
d (A × C) / dt = −Q × C × R

Here, it is assumed that the total blood volume A, the blood volume Q to be processed, and the harmful component removal rate R are constant over time, and the harmful component concentration C decreases with the treatment time t (elapsed time of blood purification treatment). When the differential equation shown in Equation 1 is solved, the harmful component concentration C is expressed by an exponential function as shown in Equation 2 below. The constant C0 is the initial harmful component concentration (t = 0). Then, when taking the logarithm of both sides of Formula 2, the treatment time t is expressed by Formula 3 below.

[Formula 2]
C / C0 = exp (−Q × R / A × t)
[Formula 3]
t = −log (C / C0) × A / (Q × R)

Here, when t = tx (necessary treatment time) and C = Cx (target harmful component concentration after removal with harmful component removal achievement rate Ta), the harmful component removal achievement rate Ta and target harmful component concentration Cx are as follows. Since t = tx, C = Cx, and Equation 4 are substituted into Equation 3, the required treatment time tx is represented by Equation 5 below using the harmful component removal achievement rate Ta. .

[Formula 4]
Cx / C0 = 1-Ta
[Formula 5]
tx = −log (1-Ta) × A / (Q × R)

Here, when the total blood volume A of the patient is 6 L, the blood volume to be treated Q (blood collection volume) is 0.1 L per minute, the plasma separation rate is 50%, and the harmful component adsorption rate of the adsorption column is 100%. As described above, the harmful component removal rate R of the purification apparatus is limited by the plasma separation rate of the plasma separator, and thus is 50%, which is the same as the plasma separation rate. In order to achieve the harmful component removal achievement rate Ta of 60%, substituting Ta = 0.6, A = 6L, Q = 0.1 L / min, and R = 0.5 into Equation 5, the required treatment time tx is 110 minutes, and a net treatment time of about 2 hours excluding preparation time is required. Moreover, in order to achieve 80% of the harmful component removal achievement rate Ta, it is necessary to substitute Ta = 0.8, A = 6L, Q = 0.1 L / min, and R = 0.5 into Equation 5. The treatment time tx is 193 minutes, and a treatment time of about 3 hours or more excluding the preparation time is required. Furthermore, in order to achieve a harmful component removal achievement rate Ta of 90%, it is necessary to substitute Ta = 0.9, A = 6L, Q = 0.1 L / min, and R = 0.5 into Equation 5. The treatment time tx is 276 minutes, and a treatment time of about 4 hours 30 minutes or more excluding the preparation time is required. As described above, in the blood purification treatment apparatus using the conventional plasma adsorption method, the harmful component removal rate of the blood purification treatment apparatus is limited by the plasma separation rate of the plasma separator. Even at 60%, it took a long time of about 2 hours, and the physical burden on the patient was very large.

The present invention has been made in view of the above-described problems, and its purpose is to increase the harmful component removal rate of a blood purification treatment apparatus using a plasma separation membrane such as a plasma adsorption method, thereby removing certain harmful components. Providing a blood purification treatment device that can shorten the required treatment time with respect to the achievement rate, or improve the achievement rate of harmful component removal for a certain required treatment time, greatly increasing the physical burden on the patient in apheresis treatment It is to reduce.

The inventors of the present application, as a result of diligent investigation focusing on the fact that the harmful component removal rate of the blood purification treatment apparatus by the current plasma adsorption method is limited by the plasma separation rate of the plasma separator, The plasma after the removal is circulated to the inlet of the plasma separator and mixed with the blood collected from the human body, and the collected blood before removal of harmful components is passed through the plasma separator in a diluted state. It has been found that the harmful component removal rate of the blood purification apparatus can be improved without being limited by the plasma separation rate. In addition, it has been found that the removal rate of harmful components can also be improved in the apheresis treatment in which harmful components in plasma are removed not with an adsorption column but with a double membrane filter.

That is, a blood purification treatment apparatus for apheresis treatment according to the present invention for achieving the above object includes a plasma separator, a blood delivery path for delivering blood collected from a human body to the plasma separator, and the blood A blood pump intervened in the delivery path, a harmful component remover for removing harmful components in the plasma separated by the plasma separator by adsorption or filtration, and the harmful components from the plasma outlet of the plasma separator A plasma circulation path that returns to the blood inlet path upstream from the blood inlet of the plasma separator via a remover, a plasma pump that is interposed in the plasma circulation path, and blood in the plasma separator A first feature is that it comprises a blood delivery path for returning blood after plasma separation from the outlet to the human body.

Furthermore, in the blood purification treatment apparatus according to the present invention, the ratio of the plasma flow rate sent from the plasma circulation path to the blood flow rate sent from the blood pump per unit time exceeds 0.6, and the harmful The second feature is that the value is not less than a predetermined upper limit value of 1.0 or more, which is limited by the processing capability of the component remover.

Furthermore, the blood purification processing apparatus according to the present invention branches downstream from the outlet of the harmful component remover in the plasma circulation path and reaches the blood delivery path downstream from the blood outlet of the plasma separator. According to a third aspect of the present invention, a plasma bypass route and a second plasma pump interposed in the plasma bypass route are further provided.

Furthermore, in the blood purification processing apparatus according to the present invention, the plasma separator is a membrane type plasma separator, and the blood pump is disposed between the blood pump in the blood inlet and the blood inlet of the plasma separator. A fourth feature is that a mixer for uniformly mixing the blood fed from the blood and the plasma fed from the plasma circulation path is provided.

Furthermore, in the blood purification apparatus according to the present invention, the harmful component remover adsorbs and removes the harmful component in the plasma by fixing a functional group that specifically binds to the substance to be adsorbed on the surface of the porous carrier. A porous carrier comprising a skeleton body made of silica gel or silica glass having a three-dimensional network structure, and a three-dimensional network-like through-hole is formed in a gap between the skeleton bodies; A fifth feature is that the pores penetrating to the inside are dispersedly formed. Here, the surface of the porous carrier corresponds to the inner wall surfaces of the through holes and pores of the porous carrier, and the surface of the skeleton body agrees with the inner wall surfaces of the through holes.

According to the blood purification processing apparatus of the first feature, the plasma separated by the plasma separator is sent from the plasma outlet of the plasma separator to the harmful component remover, and the harmful component remover is harmful in the plasma. After the components are removed, the sample is collected from the human body that returns to the blood inlet path upstream from the blood inlet of the plasma separator through the plasma circuit and is sent from the blood inlet path to the plasma separator. Since it is mixed with blood, the blood to be treated is diluted with plasma after removal of harmful components, and the diluted blood is sent to a plasma separator. In the plasma separator, the diluted blood is separated into plasma, so that the same amount of plasma as the plasma mixed upstream of the blood inlet of the plasma separator is separated without concentrating blood cell components and increasing the viscosity. Is possible. Therefore, in the conventional blood purification processing apparatus, the harmful component removal rate is limited to about 50% by the plasma separation rate of the plasma separator, but in the blood purification processing device of the first feature, the harmful component removal rate. However, without being limited by the plasma separation rate of the plasma separator, it is determined by the mixing ratio of the plasma volume in the blood to be treated and the plasma volume after removal of harmful components. Therefore, in the conventional blood purification treatment apparatus, the amount of plasma sent to the harmful component remover is limited by the plasma separation rate of the plasma separator, but the restriction is removed. The amount of plasma that can be delivered to the blood vessel can be increased to the upper limit of the processing capacity of the harmful component remover, and the harmful component removal rate of the blood purification apparatus is improved accordingly. As a result of the improvement in the harmful component removal rate of the blood purification treatment apparatus, as is apparent from Equation 5, the necessary treatment time is shortened in inverse proportion to the increase in the harmful component removal rate.

For example, if the blood flow rate of the blood to be processed per unit time and the plasma flow rate through the harmful component remover are the same, assuming that the proportion of blood cell components in the blood to be processed is 40%, The mixing ratio of the plasma volume and the plasma volume after removal of harmful components is 0.6: 1, and the harmful component removal rate of the blood purification apparatus is 62.5% (= 1 / (1 + 0.6)). Here, if the total blood volume A of the patient is 6 L, the blood volume Q to be treated (blood collection volume) is 0.1 L per minute, and the harmful component removal rate R is 62.5%, In order to achieve the component removal achievement rate Ta, the necessary treatment time tx is 88 minutes, and the necessary treatment time, which was 110 minutes with the conventional blood purification treatment apparatus, is shortened by 22 minutes and is reduced by 20%.

更に The required treatment time can be further reduced by further increasing the mixing ratio of the plasma volume after removal of harmful components. For example, when the mixing ratio is doubled, the mixing ratio of the plasma volume in the blood to be processed and the plasma volume after removal of harmful components is 0.6: 2, and the harmful component removal rate of the blood purification apparatus is 77%. (= 2 / (2 + 0.6)) Therefore, from Equation 5, the required treatment time tx is 71 minutes, and the required treatment time, which was 110 minutes in the conventional blood purification apparatus, is reduced by 39 minutes. 35% reduction. Furthermore, when the mixing ratio is quadrupled, the mixing ratio of the plasma volume in the blood to be treated and the plasma volume after removal of harmful components is 0.6: 4, and the harmful component removal rate of the blood purification apparatus is 87%. (= 4 / (4 + 0.6)) Therefore, from the above formula 5, the required treatment time tx is 63 minutes, and the required treatment time which was 110 minutes in the conventional blood purification apparatus is reduced by 47 minutes, 43% reduction.

However, if the ratio of the plasma flow rate through the toxic component remover to the blood flow rate of the blood to be processed per unit time is reduced to 0.6, the plasma volume in the blood to be processed and the plasma volume after removal of the toxic component are mixed. The ratio is 0.6: 0.6, and the harmful component removal rate of the blood purification processing apparatus is 50%, which is the same as that of the conventional blood purification processing apparatus. If the flow rate of the plasma pump is controlled so that the ratio of the plasma flow rate through the harmful component remover to the blood flow rate of the blood to be processed exceeds 0.6, it is definitely necessary for the conventional blood purification treatment device Treatment time can be shortened. Furthermore, as described above, by setting the ratio of the plasma flow rate through the harmful component remover to the blood flow rate of the blood to be treated to 1 or more, the required treatment time can be shortened by 20% or more. Therefore, it is preferable to set the upper limit value of the ratio of the plasma flow rate through the harmful component remover to the blood flow rate of the blood to be treated, which is 1 or more, which is limited by the upper limit of the processing capability of the harmful component remover.

Furthermore, according to the blood purification processing apparatus of the third feature, the blood is branched downstream from the outlet of the harmful component remover in the plasma circulation path to reach the blood delivery path downstream from the blood outlet of the plasma separator. Since a plasma bypass is provided, the amount of plasma separated by the plasma separator and flowing through the harmful component remover is larger than the amount of plasma after removal of the harmful component mixed with the blood to be treated. Compared with the case where there is no path, the plasma separation rate in the plasma separator is further improved. In the absence of the plasma bypass, the blood volume delivered from the blood outlet of the plasma separator is the same as the blood volume of the blood to be treated. If there is such a plasma bypass, the plasma in the blood delivered from the blood outlet of the plasma separator will be reduced by the amount of plasma diverted to the plasma bypass, resulting in harmful effects in the reduced plasma. Since the components are additionally removed by the harmful component remover, the harmful component removal rate of the blood purification apparatus is further improved. However, the amount of plasma diverted to the plasma bypass is limited by the upper limit of the plasma separation rate of blood diluted with plasma after removal of harmful components of the plasma separator. It is necessary to limit the flow rate of the plasma pump 2 to 30% or less of the blood flow rate of the blood to be processed.

Furthermore, according to the blood purification apparatus of the fourth feature, since the mixer for uniformly mixing the blood to be processed and the plasma after removal of the harmful components is provided, the blood after the removal of the harmful components is provided. To be diluted evenly. When the dilution is insufficient, the blood cell component concentration is high in some blood sent to the plasma separator, so that a part of the plasma having a high harmful component concentration at a certain ratio to the blood cell component is plasma. Since it is sent to the blood delivery path from the blood outlet of the plasma separator without being separated, the harmful component removal rate will be lower than the expected value. According to the blood purification apparatus of the fourth feature, Therefore, it is possible to prevent a reduction in the harmful component removal rate. Furthermore, in the blood sent to the plasma separator, blood cell components that are not sufficiently diluted with plasma after removal of harmful components are partially concentrated, resulting in excessively high viscosity, and the pores of the plasma separation membrane are blood cells. Since it is possible to prevent clogging and plasma separation from being obstructed, it is possible to prevent a decrease in the harmful component removal rate of the blood purification apparatus due to deterioration in the performance of the plasma separator.

Furthermore, according to the blood purification processing apparatus of the fifth feature, for example, in the plasma adsorption apheresis treatment, the bead-shaped carrier used in the conventional blood purification processing apparatus disclosed in Non-Patent Document 1 is used. Compared with the adsorption column densely packed in the column container, the flow resistance can be kept low, the pressure loss can be kept low compared with the bead-like carrier, and the porous carrier constituting the adsorption column is Since it has a three-dimensional network structure skeleton body and the pores penetrating from the surface to the inside of the skeleton body are dispersed, the pore surface area where the functional group functions effectively can be increased, An adsorption column having a high adsorption rate can be provided. More specifically, by using an integrated porous carrier having a three-dimensional network structure skeleton body and a three-dimensional network-like through hole formed outside the skeleton body, three through-holes serving as plasma passages are formed. Even if the through-hole diameter is the same as the diameter of the flow path that passes through the narrowed portion of the gap between each bead-shaped carrier when the bead-shaped carrier is densely packed in the column container, the flow is not limited. The road resistance can be suppressed low, and the pressure loss can be suppressed lower than that of the bead-shaped carrier. Moreover, in both the bead-like support and the three-dimensional network structure, the movement of the substance to be adsorbed in the pores is caused by diffusion, and the functional groups fixed to the pores near the surface of each support are exclusively effective. Assuming that it functions, the three-dimensional network structure with a larger surface area per unit volume has a pore surface area where the functional group functions more effectively than a bead shape (spherical) with a smaller surface area. You can make it bigger.

When the blood purification treatment apparatus of the present invention is applied to adsorption-type apheresis treatment, the plasma flow rate flowing through the adsorption column needs to be increased as compared with the conventional blood purification treatment apparatus. When the blood flow rate of the blood to be processed and the plasma flow rate through the adsorption column are the same, the flow rate is about 3.3 times. According to the blood purification treatment device of the fifth feature, the adsorption column It is possible to cope with a processing capacity required for a smaller column volume.

The circuit block diagram which shows typically the schematic circuit structure in 1st Embodiment of the blood purification processing apparatus which concerns on this invention. The block diagram which shows typically the structure of the outline of the adsorption column used with the blood purification processing apparatus which concerns on this invention Sectional drawing which shows the principal part which shows typically the structure of the adsorption body of the adsorption column used with the blood purification processing apparatus which concerns on this invention Sectional drawing which shows the principal part which shows typically the structure of the porous support | carrier which comprises the adsorbent of the adsorption column used with the blood purification processing apparatus which concerns on this invention SEM photograph of the porous carrier constituting the adsorbent of the adsorption column used in the blood purification apparatus according to the present invention The block diagram which shows typically the structure of the outline of the mixer used with the blood purification processing apparatus which concerns on this invention The top view and sectional drawing which show typically the structure of the static mixing element of the mixer used with the blood purification processing apparatus which concerns on this invention Table showing calculation results of harmful component removal rate and required treatment time in the first embodiment of the blood purification apparatus according to the present invention The circuit block diagram which shows typically the schematic circuit structure in 2nd Embodiment of the blood purification processing apparatus which concerns on this invention. Table showing calculation results of harmful component removal rate and required treatment time in the second embodiment of the blood purification apparatus according to the present invention The figure which compares and shows the calculation result of the required treatment time in 1st Embodiment and 2nd Embodiment of the blood purification processing apparatus which concerns on this invention, and the conventional blood purification processing apparatus. Circuit configuration diagram schematically showing a schematic circuit configuration of a conventional blood purification treatment apparatus

Explanation of symbols

1: Plasma separator 1a: Blood inlet 1b: Blood outlet 1c: Plasma outlet 2: Adsorption column 3: Mixer 3a: Plasma inlet 4: Anticoagulant injector 5: Drip chamber 6: Pressure monitor 10, 11: Blood purification apparatus according to the present invention 20: Adsorbent 21: Cylindrical container 22, 23: Opening 24: Porous carrier 25: Functional group 26: Skeletal body 27: Through hole 28: Pore 30: Cylindrical container 31 32: Static mixing element 33: Through hole P1: Blood pump P1
P2, P3: Plasma pump T1: Blood delivery route T2: Blood delivery route T3: Plasma circulation route T4: Plasma bypass route

Embodiments of a blood purification apparatus according to the present invention (hereinafter referred to as “the present apparatus” as appropriate) will be described with reference to the drawings. In order to facilitate understanding of the present invention, in the following description, the same components as those in the conventional blood purification apparatus using the plasma adsorption method for apheresis treatment shown in FIG. . In the following description, the apparatus of the present invention will be described on the assumption that it is applied to apheresis treatment by the plasma adsorption method.

<First Embodiment>
As shown in FIG. 1, the device 10 of the present invention in the first embodiment includes a blood separator T1, a blood inlet T1 for feeding blood collected from a human body to a blood inlet 1a of the plasma separator 1, and a blood feeder. Adsorption and removal of harmful components in plasma separated by blood pump P1 interposed in inlet T1, mixer 3 interposed downstream of blood pump P1 in blood inlet T1, and plasma separator 1 An adsorption column 2 (corresponding to a harmful component remover), a blood delivery path T2 for returning blood after plasma separation from the blood outlet 1b of the plasma separator 1 to the human body, an adsorption column from the plasma outlet 1c of the plasma separator 1 2 and the plasma circulation path T3 returning to the plasma intake port 3a of the mixer 3 and the plasma pump P2 interposed in the plasma circulation path T3. In addition, an access port for the anticoagulant injector 4 is provided between the blood pump P1 and the mixer 3 in the blood delivery path T1, and the anticoagulant injector 4 is connected thereto. Further, drip chambers 5 are respectively provided downstream of the blood pumping path T2 and the plasma pump P2 of the plasma circulation path T3, and the pressure monitor 6 is provided in each of the plasma separator 1, the mixer 3, and each drip chamber 5. Is provided. In FIG. 1, the particulate removal filter, the adsorption column activation circuit, and the like illustrated in the circuit diagram of the conventional blood purification processing apparatus exemplified in

Non-Patent Documents

1 and 2 are not shown. Depending on the situation, it may be inserted at a predetermined location. In the present embodiment, the plasma pump P2 is provided on the upstream side of the adsorption column 2 of the plasma circulation path T3, but may be provided on the downstream side.

In the conventional blood purification apparatus, as shown in FIG. 12, the plasma after the harmful components are adsorbed and removed by the adsorption column 2 is downstream from the blood outlet 1b of the plasma separator 1 via the plasma bypass T4. The circuit configuration is such that the concentrated blood after plasma separation sent from the blood outlet 1b of the plasma separator 1 merges with the downstream side of the plasma separator 1 by returning to the blood delivery path T2 on the side. In the device 10 of the present invention, plasma after removal of harmful components by the adsorption column 2 returns to the mixer 3 upstream of the plasma separator 1 via the plasma circulation path T3, and is collected from the human body and blood pump P1. The two are greatly different from each other in that the circuit configuration merges with the blood to be treated.

Since the blood purification process of the apheresis treatment by the apparatus 10 of the present invention is a continuous process in which blood collected from the human body is adsorbed and removed by the apparatus 10 of the present invention and returned to the human body, the plasma separator 1 is subjected to the continuous process. Use a membrane plasma separator suitable for As the membrane type plasma separator, an existing one already approved for medical use in blood purification treatment by the plasma adsorption method such as a hollow fiber type plasma separator in which a hollow fiber membrane bundle is accommodated in a cylindrical container can be used.

In the present embodiment, as schematically shown in FIG. 2, the adsorption column 2 includes an adsorbent 20 formed by fixing a functional group that specifically binds to a substance to be adsorbed on the surface of a porous carrier in a cylindrical container 21. Each of the end surfaces of the cylindrical container 21 is formed with

openings

22 and 23. One opening 22 serves as a plasma inlet for processing and the other opening 23 removes harmful components. It becomes the outlet for plasma later.

As schematically shown in FIG. 3, the adsorbent 20 is immobilized by surface-modifying a functional group 25 that specifically binds to the substance to be adsorbed on the surface of an inorganic porous carrier 24 formed into a cylindrical shape. It is a thing. When the substance to be adsorbed is, for example, LDL (low density lipoprotein) in blood, the functional group 25 includes dextran sulfate or a salt thereof having affinity for LDL, polyacrylic acid or a salt thereof, or other A chain polyvalent acid or a salt thereof is used. In addition to the LDL, β2 microglobulin, immunoglobulin, endotoxin, and the like are listed as target substances to be adsorbed and removed by the apparatus 10 of the present invention, and the adsorbent 20 has a structure suitable for the target substance to be adsorbed. It will be.

As shown schematically in FIG. 4, the inorganic porous carrier 24 constituting the adsorbent 20 has a three-dimensional network-like skeleton body 26 and an average pore diameter formed in the gap between the skeleton bodies 26. It has a three-dimensional network-like through-hole 27 in the range of 1 μm or more and less than 4 μm, and the surface of the skeleton body 26 has an average pore diameter of the diameter of LDL (corresponding to the maximum length) as the adsorption target substance. The pores 28 in the range of 27 nm to 200 nm in the range of 26 to 27 nm or more are dispersedly formed. Therefore, the porous carrier 24 of the adsorption column 2 used in this embodiment has a double pore structure composed of two types of pores (through holes 27 and pores 28) having different average pore diameters. FIG. 5 shows an example of an SEM (scanning electron microscope) photograph of the porous carrier 24. Note that the double pore structure of the porous carrier 24 and the pore diameter thereof are also appropriately changed according to the substance to be adsorbed.

The method for synthesizing the porous carrier 24 uses, for example, a spinodal decomposition sol-gel method based on the principle disclosed in “Manufacturing Method of Inorganic Porous Material” in JP-A-7-41374. The synthesis method is described in detail in the publication, and since it is not the gist of the present invention, the description is omitted. Further, the method of immobilizing the functional group 25 on the porous carrier 24 by modifying the surface is not the gist of the present invention and will not be described.

Further, in the present embodiment, it is assumed that the adsorption column 2 in which the integrated adsorbent body 20 in which the functional group 25 is surface-modified and immobilized on the porous carrier 24 having a double pore structure is accommodated in the cylindrical container 21 is assumed. However, the reason is that, compared with an adsorption column in which a bead-shaped carrier is packed tightly in a column container as a porous carrier like the conventional blood purification treatment device disclosed in Non-Patent Document 1, the flow rate is higher. This is because the road resistance and pressure loss can be suppressed low, and the porous carrier 24 includes a skeleton body 26 having a three-dimensional network structure, and pores 28 penetrating from the surface to the inside of the skeleton body 26 are formed in a dispersed manner. This is because, due to the double pore structure, the pore surface area where the functional group 25 functions effectively can be increased, and an adsorption column having a high adsorption rate of harmful components can be provided.

As will be described later, the plasma flow rate per unit time flowing through the adsorption column 2 of the device 10 of the present invention is different from that of the conventional blood due to the difference in circuit configuration between the device 10 of the present invention and the conventional blood purification treatment device. Since it is about 3 to 16 times or more as compared with the purification processing apparatus, a large capacity is required as the processing capacity (processing amount and processing speed) of the adsorption column 2, but the porous support having the above-mentioned double pore structure is required. In the case of the adsorption column 2 using 24, a large processing capacity can be obtained with a smaller volume. However, since the processing capacity of the adsorption column 2 can be solved by providing a plurality of adsorption columns in parallel, an existing adsorption column that has already been approved for medical use according to the substance to be adsorbed may be used.

In this embodiment, the plasma after removal of harmful components by the adsorption column 2 and the blood to be processed collected from the human body and fed by the blood pump P1 are mixed uniformly by the mixer 3 and then sent to the plasma separator 1. The composition to enter is adopted. The mixture of plasma and blood to be processed after removal of harmful components can be replaced with a drip chamber, but in a drip chamber, the plasma and blood to be processed are not necessarily mixed uniformly. May be diluted with plasma after removal of harmful components, and blood containing a large amount of harmful components may be returned to the human body via the blood delivery path T2 without being separated by the plasma separator 1. Since the harmful component removal rate of the device 10 of the present invention varies, it is preferable to use the mixer 3 as in this embodiment. Even when the plasma after removal of harmful components is mixed with a drip chamber or the like without using the mixer 3, the blood to be processed is compared with the circuit configuration of a conventional blood purification apparatus. Thus, since the more diluted blood is separated into plasma by the plasma separator 1, the possibility of clogging the plasma separation membrane and lowering the performance is low, but by using the mixer 3, The clogging of the plasma separation membrane is less likely to occur, and a reduction in the harmful component removal rate of the device 10 of the present invention due to a change with time can be suppressed.

The mixer 3 is a dynamic structure in which a mixer having a static structure that promotes mixing by, for example, applying a swirling flow using the pressure of the plasma pump P2 or a stirring device driven by external power in a chamber. Can be used. As the mixer 3 having a static structure, in addition to a structure in which a swirl flow is applied to promote mixing, as shown in FIG. 6, two kinds of disk-shaped PVC (polyvinyl chloride) or the like are provided in the cylindrical container 30. Insert plastic

plastic mixing elements

31 and 32 alternately stacked in several stages (for example, 10 stages), and after removing the blood to be treated and harmful components before removing harmful components from one end of the cylindrical container 30 The blood to be processed and the plasma are stirred and mixed in order by passing the plasma separately and passing through the through holes provided in the two types of

static mixing elements

31 and 32 in order. it can. As shown in FIG. 7, the two types of

static mixing elements

31 and 32 have four through-holes 33 penetrating front and back on one side and five on the other side, and any of the through-holes 33. Also, the diameter is reduced in a funnel shape from the front and back sides toward the inside (center) in the thickness direction (through direction), and the inclination angle of the tapered surface is 45 ° with respect to the central axis of the through hole 33. The dimensions of each part are, for example, the diameters D of the

elements

31 and 32 are 18 mm, the thickness d is 5 mm, the minimum diameter a of the through hole 33 is 2 mm or 5 mm, and the maximum diameter of the inlet and outlet portions of the through hole 33. There are two types of b, 4 mm or 6 mm, and a combination of the minimum diameter a and the maximum diameter b employs any of three types of 2 mm / 4 mm, 2 mm / 6 mm, and 5 mm / 6 mm. In FIG. 6, among the two types of

elements

31, 32, the through-hole 33 distinguishes the four elements 31 in gray, and in FIG. 7, the disk surface of the element 31 is displayed in gray. This is a display for easy explanation, and is not related to actual coloring. The number and dimensions of the through holes 33, the shapes of the

elements

31, 32, the number of steps, and the dimensions of each part are examples and can be changed as appropriate.

In the two types of

elements

31 and 32 having the structure shown in FIG. 7, the two types of one element are divided into four or five through holes 33, and the diameter of each through hole 33 is narrowed from the inlet side. Since the structure spreads toward the outlet, a sudden speed change and pressure change occur with respect to the fluid passing through each through-hole 33, and the fluid is stirred and mixed. Since the fluid divided into four flows further in a distributed manner in the five through holes 33, a speed change and a pressure change occur. Similarly, the fluid divided into five is further dispersed in the four through holes 33. Therefore, a speed change and a pressure change are further generated, and the fluid is alternately passed through the two types of

elements

31 and 32, whereby the fluid is stirred and mixed gradually.

At the start of the operation of the device 10 of the present invention, the blood circuits such as the plasma separator 1, the adsorption column 2, and the mixer 3 are filled with physiological saline, and the basic operation at the start of the operation will be described later. This is the same as the conventional blood purification apparatus except for controlling the plasma flow rate after the harmful components are removed by the adsorption column 2 delivered from the plasma pump P2.

Next, the harmful component removal rate of the device 10 of the present invention having the circuit configuration shown in FIG. 1 and the relationship between the harmful component removal achievement rate and the required treatment time when the device 10 of the present invention is used will be described in detail.

As described above, the apparatus 10 of the present invention collects plasma from the human body after the harmful components have been removed by the adsorption column 2 and returns to the mixer 3 upstream of the plasma separator 1 via the plasma circuit T3. In this way, the harmful components in the blood to be treated are diluted with the plasma after the harmful components are removed, and a part of the blood in the plasma separator 1 is used. Since the harmful component in the blood to be treated is returned to the human body from the outlet 1b via the blood delivery path T2, the ratio of the plasma after removal of the harmful component to the total plasma in the diluted blood after being mixed by the mixer 3 It will be removed according to. That is, the harmful component removal rate R is determined by the blood flow rate Q of the blood to be processed per unit time and the plasma flow rate S flowing into the mixer 3 via the plasma circulation path T3, and the flow rate Q ( L / min) and the flow rate S (L / min) of the plasma pump P2, the relationship shown by the following formula 6 is established. However, the ratio of plasma in the blood to be treated is 60%, and the adsorption rate of harmful components of the adsorption column 2 is 100%. Further, when the ratio (S / Q) of the plasma flow rate S to the blood flow rate Q is x, Equation 6 is given by Equation 7.

[Formula 6]
R = S / (S + Q × 0.6)
[Formula 7]
R = x / (x + 0.6) = 1-0.6 / (x + 0.6)

From Equation 7, it can be seen that the harmful component removal rate R increases as the ratio x increases. Thus, in the conventional blood purification treatment apparatus, the harmful component removal rate R is limited by the plasma separation rate of the plasma separator 2 and is about 50%, but in the case of the device 10 of the present invention, the ratio x It can be seen that the harmful component removal rate R can be set to exceed 50%.

Moreover, since the harmful component removal rate R is 50% or less when the ratio x is 0.6 or less, the ratio x is less than 0.6 because the conventional harmful component removal rate is 50% or less. Set a large value, for example, about 1 to 5. Even if the ratio x is increased to increase the plasma flow rate S, the blood flow after removal of harmful components sent from the blood outlet 1b of the plasma separator 1 is the blood to be processed sent to the mixer 3. It is the same as the blood flow rate Q.

The relationship between the harmful component removal achievement rate Ta and the necessary treatment time tx when the device 10 of the present invention is used is given by the relational expression of the above formula 5, similarly to the conventional blood purification treatment apparatus. The total blood volume A of the patient is 6L, the flow rate Q of the blood to be processed is two types of 0.1L / min (high speed processing) and 0.05L / min (normal processing), and the harmful component removal achievement rate Ta is 60% (standard) The calculation results of the required treatment time tx when the ratio x is 1, 2, 3, 4 and 5 are summarized in the table of FIG. indicate. Further, the necessary treatment time tx of the conventional blood purification processing apparatus under the same conditions is also displayed in accordance with the list of FIG. 8 for comparison. Further, in the two columns on the right side of the necessary treatment time tx by the apparatus 10 of the present invention, the shortened time and the time reduction rate from the necessary treatment time tx by the conventional blood purification processing apparatus of the same treatment type are also shown. In the conventional blood purification apparatus, it is assumed that plasma having a flow rate corresponding to 30% of the blood flow rate Q is separated and harmful components are removed by the adsorption column, and the harmful component removal rate is 50%.

As is clear from the calculation results shown in FIG. 8, when the blood flow rate Q of the blood to be treated and the plasma flow rate S after removal of harmful components are the same amount (x = 1), the necessary treatment time tx is reduced by 20%, As the ratio x increases from 2 to 5, the reduction rate of the required treatment time tx also increases to 35%, 40%, 42.5%, and 44%. For example, in the case of advanced treatment (Ta = 80%) with normal treatment (Q = 0.05 L / min), the required treatment time tx was 386 minutes (6 hours 26 minutes) in the conventional blood purification treatment apparatus. In the device 10 of the present invention with the ratio x = 4, the time is shortened to 222 minutes (3 hours 42 minutes), and it can be seen that the physical burden on the patient is greatly reduced. Further, when the flow rate Q of the blood to be treated is set to 80% or higher in the harmful component removal achievement rate Ta in the normal processing, the necessary treatment time tx becomes longer than 6 hours, but by using the device 10 of the present invention. Since the absolute value of the necessary treatment time tx can be significantly shortened without increasing the flow rate Q of the blood to be treated, the effect of shortening the necessary treatment time is particularly great during normal treatment and advanced treatment.

As is apparent from FIG. 8, even if the ratio x is set to a value larger than 4, the time reduction width of the necessary treatment time tx is reduced, and the treatment of the adsorption column as the plasma flow rate S increases. It is considered that the upper limit of the ratio x is preferably about 4 to 6 if the capability needs to be increased and the harmful component removal achievement rate Ta is about 80% or less. This is because when the ratio x is somewhat large, the increment of the harmful component removal rate R with respect to the increment of the ratio x is compressed, and the harmful component removal rate R and the necessary treatment time tx are inversely proportional to each other. This is because the time reduction width is suppressed.

Second Embodiment
A second embodiment of the device of the present invention will be described. As shown in FIG. 9, the device 11 of the present invention in the second embodiment is different from the circuit detour T4 downstream of the adsorption column 2 with respect to the circuit configuration of the device 10 of the first embodiment shown in FIG. A plasma bypass T4 that branches and reaches the blood delivery path T2 downstream from the blood outlet 1b of the plasma separator is added, and the second plasma pump P3 is interposed in the plasma bypass T4. . A drip chamber 5 is interposed downstream of the plasma pump P3 in the plasma bypass T4, and a pressure monitor 6 is provided. In the second embodiment, unlike the first embodiment, the plasma pump P2 is provided downstream of the branch point of the plasma circulation path T3 with the plasma bypass T4. The inventive device 11 in the second embodiment has a mixed circuit configuration in which the inventive device 10 of the first embodiment and the conventional blood purification treatment device shown in FIG. In FIG. 9, the particulate removal filter, the adsorption column activation circuit, and the like shown in the circuit diagram of the conventional blood purification processing apparatus exemplified in

Non-Patent Documents

1 and 2 are not shown. Depending on the situation, it may be inserted at a predetermined location. The plasma separator 1, the adsorption column 2, and the mixer 3 used in the device 11 of the present invention can be the same as those used in the device 10 of the first embodiment. To do.

Next, the harmful component removal rate of the device 11 of the present invention having the circuit configuration shown in FIG. 9 and the relationship between the harmful component removal achievement rate and the required treatment time when the device 11 of the present invention is used will be described in detail.

As described above, the device 11 of the present invention is configured so that a part of plasma after removal of harmful components by the adsorption column 2 is upstream of the plasma separator 1 via the plasma circuit T3 at the plasma flow rate S1 by the plasma pump P2. And the blood to be processed which is collected from the human body and sent by the blood pump P1 at the blood flow rate Q, and the remaining part of the plasma after the harmful components are removed by the adsorption column 2, The plasma pump P3 returns to the blood delivery path T2 downstream from the blood outlet 1b of the plasma separator 1 via the plasma bypass T4 at the plasma flow rate S2, is diluted by the mixer 3, and is separated by the plasma separator 1. The circuit configuration merges with blood.

Here, in the device 10 of the present invention of the first embodiment, the blood flow rate Qx delivered from the plasma separator 1 to the blood delivery path T2 is the same as the blood flow rate Q of the blood to be processed, and 60% of it is a plasma component. However, in the device 11 of the present invention of the second embodiment, the blood flow after mixing in the mixer 3 flowing into the plasma separator 1 is (Q + S1) and is sent from the plasma separator 1 to the adsorption column 2. Since the plasma flow rate is (S1 + S2), the blood flow rate sent from the plasma separator 1 to the blood delivery path T2 is (Q−S2), and the dilution containing harmful components per unit time into which the plasma separator 1 flows The ratio of the plasma volume containing harmful components per unit time returning from the plasma separator 1 to the human body via the blood delivery path T2 with respect to the obtained plasma volume is compared with the circuit configuration of the device 10 of the present invention of the first embodiment. Reduced. In addition, since blood with a blood flow rate (Q-S2) joins with plasma with a plasma flow rate S2 that returns to the blood delivery path T2 via the plasma bypass T4 and is returned to the human body, the blood to be processed collected from the human body It becomes the same as the blood flow rate Q.

From the above, the harmful component removal rate R of the device 11 of the present invention is as follows: the flow rate Q (L / min) of the blood pump P1, the flow rate S1 (L / min) of the plasma pump P2, and the flow rate S2 (L / min) of the plasma pump P3. Is given by Equation 8 below. However, the ratio of plasma in the blood to be treated is 60%, and the adsorption rate of harmful components of the adsorption column 2 is 100%. Here, when the ratio (S1 / Q) of the plasma flow rate S1 to the blood flow rate Q is x and the ratio (S2 / Q) of the plasma flow rate S2 to the blood flow rate Q is 30%, Equation 8 is expressed by Equation 9. become. Here, as explained in “Problems to be Solved by the Invention”, in the membrane type plasma separator, if the blood cell component is concentrated too much, the viscosity increases too much, and the pores of the separation membrane are clogged with blood cells and the plasma separation is not performed. The blood cell component and the plasma component are not completely separated from each other because of inhibition, and in the blood after plasma separation, 30% of the plasma component remains with respect to the blood cell component of 40% of the blood volume of the blood to be treated. The upper limit of the latter ratio (S2 / Q) is about 30%.

[Formula 8]
R = (S1 + S2) / (S1 + Q × 0.6)
[Formula 9]
R = (x + 0.3) / (x + 0.6) = 1-0.3 / (x + 0.6)

From Formula 9, it can be seen that the harmful component removal rate R increases as the ratio x increases. Thus, in the conventional blood purification treatment apparatus, the harmful component removal rate R is limited by the plasma separation rate of the plasma separator 2 and is about 50%, but in the case of the device 11 of the present invention, the ratio x It can be seen that the harmful component removal rate R can be set to exceed 50%. In the device 11 of the present invention of the second embodiment, when the ratio x is 0, the circuit configuration is the same as that of the conventional blood purification apparatus, so the ratio x is larger than 0. If x is greater than 0, the harmful component removal rate R is greater than 50%, so the harmful component removal rate R is always higher than the conventional harmful component removal rate of 50%. Furthermore, when the ratio x is the same, the harmful component removal rate R of the device 11 of the present invention shown in Equation 9 may be larger than the harmful component removal rate R of the device 10 of the first embodiment shown in Equation 7. As can be seen, the harmful component removal rate R is improved by the inventive device 10 of the first embodiment.

The relationship between the harmful component removal achievement rate Ta and the necessary treatment time tx when using the device 11 of the present invention is the relational expression of the above formula 5, as in the case of the conventional blood purification apparatus and the device 10 of the first embodiment. Given in. The total blood volume A of the patient is 6L, the flow rate Q of the blood to be processed is two types of 0.1L / min (high speed processing) and 0.05L / min (normal processing), and the harmful component removal achievement rate Ta is 60% (standard) The calculation results of the required treatment time tx when the ratio x is 1, 2, 3, 4 and 5 are summarized in the table of FIG. indicate. However, the ratio of the plasma flow rate S2 to the blood flow rate Q (S2 / Q) is 30%. In addition, the necessary treatment time tx of the conventional blood purification apparatus under the same conditions is also displayed in accordance with the list of FIG. 10 for comparison.

As is clear from the calculation results shown in FIG. 10, when the blood flow rate Q of the blood to be treated and the plasma flow rate S1 after removal of harmful components are the same amount (x = 1), the required treatment time tx is reduced by 38.5%. As the ratio x increases from 2 to 5, the reduction rate of the required treatment time tx also increases to 43.5%, 45.5%, 46.5%, and 47.2%. For example, in the case of advanced treatment (Ta = 80%) with normal treatment (Q = 0.05 L / min), the required treatment time tx was 386 minutes (6 hours 26 minutes) in the conventional blood purification treatment apparatus. In the device 11 of the present invention with the ratio x = 4, the time is shortened to 207 minutes (3 hours and 27 minutes), and it can be seen that the physical burden on the patient is greatly reduced. Also, compared with the inventive device 10 of the first embodiment, it was 222 minutes (3 hours 42 minutes), but it was shortened to 207 minutes (3 hours 27 minutes). Further, when the flow rate Q of the blood to be treated is set to 80% or higher when the harmful component removal achievement rate Ta is set to be higher than 80% in normal processing, the necessary treatment time tx becomes longer than 6 hours. Since the absolute value of the necessary treatment time tx can be significantly shortened without increasing the flow rate Q of the blood to be treated, the effect of shortening the necessary treatment time is particularly great during normal treatment and advanced treatment.

As is clear from FIG. 10, even if the ratio x is set to a value larger than 2, the time reduction width of the necessary treatment time tx is reduced, and the treatment of the adsorption column as the plasma flow rate S increases. It is necessary to increase the capability, and if the harmful component removal achievement rate Ta is about 80% or less, it is considered that the upper limit of the ratio x is preferably about 2 to 4. This is because when the ratio x is somewhat large, the increment of the harmful component removal rate R with respect to the increment of the ratio x is compressed, and the harmful component removal rate R and the necessary treatment time tx are inversely proportional to each other. This is because the time reduction width is suppressed.

Next, FIG. 11 shows a comparison between the required treatment time tx for each ratio x of the

devices

10 and 11 of the present invention shown in FIGS. 8 and 10 and a conventional blood purification apparatus. In FIG. 11, the necessary treatment time tx of the device of the present invention 10 (with plasma circulation path T3) is connected by a solid line, and the necessary treatment time tx of the device of the present invention 11 (with plasma circulation path T3 and plasma bypass T4) is represented by a broken line. It is connected. 11, the relationship between the necessary treatment time tx and the harmful component removal achievement rate Ta, the relationship between the necessary treatment time tx and the ratio x, and the relationship between the

devices

10 and 11 of the first and second embodiments described above are as follows. Shown more clearly.

As mentioned above, the configuration of the device of the present invention and its performance (relationship between harmful component removal achievement rate and required treatment time) have been described in detail, but blood flow Q, plasma flow S, S1, S2, and harmful component removal used in the performance evaluation are described. The numerical values such as the achievement rate Ta are examples for explanation, and these numerical values are within the range in which the device of the present invention can exhibit the desired performance, the treatment content of the apheresis treatment, the plasma separator used, and the adsorption column It can be appropriately changed according to the processing capacity of the mixer and the like. The apparatus of the present invention can be widely applied to blood purification treatment apparatuses using a plasma adsorption method for apheresis treatment. The harmful components to be adsorbed and removed by the adsorption column are not limited to LDL, and the adsorption column Various types of adsorption columns can be used for the adsorption of harmful components. Furthermore, the method of removing harmful substances in plasma is not limited to the adsorption method using an adsorption column, and may be a filtration method using a double membrane filter or the like. The device of the present invention is used for apheresis treatment. The present invention can be widely applied to a blood purification treatment apparatus using a plasma separation membrane.

The blood purification treatment apparatus according to the present invention can be used for a blood purification treatment apparatus using a plasma separation membrane for apheresis treatment for the purpose of removing pathogenic substances (harmful components) such as LDL in blood.

Claims

A plasma separator;
A blood delivery path for delivering blood collected from the human body to the plasma separator;
A blood pump interposed in the blood delivery path;
A harmful component remover that removes harmful components in the plasma separated by the plasma separator by adsorption or filtration;
A plasma circuit that returns from the plasma outlet of the plasma separator to the blood inlet path upstream of the blood inlet of the plasma separator via the harmful component remover;
A plasma pump interposed in the plasma circuit;
A blood purification treatment apparatus for apheresis treatment, comprising: a blood delivery path for returning blood after plasma separation to a human body from a blood outlet of the plasma separator.
The ratio of the plasma flow rate delivered from the plasma circuit to the blood flow rate delivered from the blood pump per unit time exceeds 0.6 and is limited by the processing capacity of the harmful component remover. The blood purification apparatus according to claim 1, wherein the blood purification apparatus is 0 or more and a predetermined upper limit value or less.
A plasma bypass that branches downstream from the outlet of the harmful component remover in the plasma circulation path and reaches the blood delivery path downstream from the blood outlet of the plasma separator;
The blood purification apparatus according to claim 1, further comprising a second plasma pump interposed in the plasma bypass.
The plasma separator is a membrane plasma separator;
A mixer that uniformly mixes the blood fed from the blood pump and the plasma fed from the plasma circulation path between the blood pump of the blood feeding path and the blood inlet of the plasma separator. The blood purification treatment apparatus according to any one of claims 1 to 3, further comprising:
The harmful component remover is an adsorption column that adsorbs and removes harmful components in plasma by fixing a functional group that specifically binds to an adsorption target substance to the surface of the porous carrier, and the porous carrier includes 3 A skeleton body made of silica gel or silica glass having a three-dimensional network structure is formed, and a three-dimensional network-like through hole is formed in a gap between the skeleton bodies, and pores penetrating from the surface to the inside of the skeleton body are dispersed. The blood purification treatment apparatus according to any one of claims 1 to 3, wherein: