JP7468541B2 - Dialysis Machine - Google Patents

Description

This invention relates to a dialysis device.

Conventional dialysis methods are disclosed in Non-Patent Document 1 (Tumlin, J.A., Costanzo, M.R., Chawla, L.S., et al.: Cardiorenal Syndrome Type 4: Insights on Clinical Presentation and Pathophysiology from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013; 182: 158-173), Non-Patent Document 2 (Eloot, S., Schneditz, D., Cornelis, T., et al.: Protein-bound uremic toxin profiling as a tool to optimize hemodialysis. PLoS One 2016; 11: e0147159.), and Non-Patent Document 3 (Eguchi Kei, et al.: Basic study on protein-bound uremic toxin removal using dilution effect and pH change. Journal of Dialysis 44: 269-271, 2011.).

Tumlin, J.A., Costanzo, M.R., Chawla, L.S., et al.: Cardiorenal Syndrome Type 4: Insights on Clinical Presentation and Pathophysiology from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013; 182: 158-173 Eloot, S., Schneditz, D., Cornelis, T., et al.: Protein-bound uremic toxin profiling as a tool to optimize hemodialysis. PLoS One 2016; 11: e0147159. Kei Eguchi et al.: Basic study on removal of protein-bound uremic toxins using dilution effect and pH change. Journal of Dialysis Society 44: 269-271, 2011.

Conventional technology had the problem of not being able to adequately remove uremic substances from blood.

The inventors have conducted extensive research into methods for removing indoxyl sulfate and have reached the following findings:

Toxicity of protein-bound substances Protein-bound substances are uremic substances that exist in blood in a form partially bound to proteins. There are 25 types of uremic substances that belong to this category. For some uremic substances that belong to protein-bound substances, a significant correlation has been confirmed between serum concentration and life prognosis. For example, it has been reported that indoxyl sulfate concentration is correlated with mortality due to cardiovascular disease. In addition, while the indoxyl sulfate concentration in healthy individuals is 1 to 2.9 mM (mmol/dm ³ ), that in patients with end-stage renal failure exceeds 500 mM, and such high concentrations of indoxyl sulfate have been reported to promote cardiac fibrosis via the synthesis of TGF-β, tissue inhibitor of metalloproteinase 1 (TIMP-1), and α1 collagen (Non-Patent Document 1).

Despite the obvious toxicity of protein-bound substances, there is currently no effective method to remove them.

Kinetics of protein-bound substances One of the indicators of kinetics of protein-bound substances is the protein binding rate. This is the percentage of uremic substances present in plasma that are bound to protein. The protein binding rate of indoxyl sulfate has been reported to be 93% (Non-Patent Document 2). In other words, in an equilibrium state, 93% of indoxyl sulfate exists bound to protein (albumin), and 7% exists in a free form.

During dialysis, only free indoxyl sulfate (molecular weight 213) that is not bound to albumin is removed by the dialyzer. As a result, the concentration of free indoxyl sulfate in plasma decreases. In response to this, indoxyl sulfate bound to albumin is released from albumin to maintain the protein binding rate at 93%. If indoxyl sulfate bound to albumin in the body were to be released from albumin at a rate that matches the removal rate of free indoxyl sulfate in the dialyzer, indoxyl sulfate bound to albumin should be removed extremely easily. However, in reality, indoxyl sulfate bound to albumin is only released slowly.

The currently most effective method for removing indoxyl sulfate would be to release as much indoxyl sulfate as possible from albumin during hemodialysis and then efficiently remove it using a dialyzer. To achieve this, it would be necessary to remove as much free indoxyl sulfate as possible by increasing the extracorporeal blood flow rate, thereby keeping the free indoxyl sulfate concentration in the body as low as possible and ensuring sufficient dialysis time for indoxyl sulfate to be released from albumin. A recent report by Elute et al. supports this prediction. They report that the longer the weekly dialysis time and the higher the extracorporeal blood flow rate, the greater the amount of protein-bound substances removed (Non-Patent Document 2).

However, long-term dialysis places a huge physical burden on patients and a huge financial burden on medical providers.

<Details of the Invention>
At equilibrium, the amount of protein-bound substance actually bound to protein and the concentration of the free-flowing substance exist in a certain ratio. This ratio is called the protein binding rate. For example, 93% of indoxyl sulfate exists bound to protein (albumin) and 7% exists in the free form.

Now, if the concentration of the free substance is reduced by some method, the substance will be released from the protein (Non-Patent Document 3). This release continues until the amount of the protein-bound substance that is actually bound to the protein and the concentration of the eluted substance reach a certain ratio (protein binding rate). However, it takes some time for the substance to be released from the protein and reach a new equilibrium state.

In on-line HDF with pre-replacement, the concentration of free substances in the plasma is reduced by the replacement fluid, but the blood flows into the dialyzer before the substances already bound to proteins are released from the proteins, and only the diluted free substances are removed before the blood is returned to the body. In other words, in on-line HDF with pre-replacement, protein-bound substances are not removed.

In one aspect of this invention, a portion of the blood is directed into a bypass flow path and a replacement fluid is injected into it to reduce the concentration of the free form and to allow the blood to pass through the bypass flow path over a longer period of time, thereby liberating more of the substance from the protein, and the substance that has been liberated from the protein in greater amounts is then removed in a dialyzer into which the bypassed blood flows.

Another aspect of the present invention relates to a dialysis device for removing uremic substances (e.g., indoxyl sulfate) present in blood. A dilution line for introducing blood dilution fluid (dialysis fluid) is provided in the arterial blood circuit. The blood circuit from the dilution line to the dialyzer inlet is made to have a large diameter. The diluted fluid is removed by the dialyzer. The blood pump may be operated at a low speed during dilution.

A dialysis device in one aspect includes a first flow path through which blood extracted from a human body flows, a blood pump provided in the first flow path to send blood, a dialyzer provided downstream of the blood pump to purify the blood supplied from the first flow path with a replacement fluid, and a second flow path that merges with the first flow path downstream of the blood pump and upstream of the dialyzer to supply the replacement fluid to the first flow path. The cross-sectional area of the first flow path downstream of the junction of the first and second flow paths is larger than the cross-sectional area of the first flow path upstream of the junction.

In a dialysis device configured in this manner, the cross-sectional area of the first flow path downstream of the junction is larger than the cross-sectional area of the first flow path upstream of the junction, so the flow rate downstream of the junction can be reduced. As a result, uremic substances in the blood can be easily extracted into the replacement liquid after the junction, and the uremic substances can be reliably extracted into the replacement liquid and removed.

Preferably, the cross-sectional area of the first flow path is selected so that the flow rate downstream of the junction is slower than the flow rate upstream of the junction. In this case, slowing the flow rate from the junction to the dialyzer allows uremic substances to be extracted into the replacement liquid more reliably.

In another aspect, the dialysis device comprises a first flow path through which blood extracted from the human body flows, a blood pump provided in the first flow path and which sends blood, a dialyzer provided downstream of the blood pump and which purifies the blood supplied from the first flow path with a replacement fluid, a bypass flow path provided in parallel to a part of the first flow path, which branches off from the first flow path downstream of the blood pump and merges with the first flow path upstream of the dialyzer, and a second flow path which merges with the bypass flow path and supplies replacement fluid to the bypass flow path.

In a dialysis device configured in this way, a bypass flow path is provided and a substitution fluid is supplied to this bypass flow path, so the concentration of blood in the bypass flow path can be diluted. This makes it easier to extract uremic substances in the blood into the substitution fluid, and ensures that the uremic substances are removed.

Preferably, the flow resistance of the bypass flow path is greater than the flow resistance of the first flow path that is parallel to the bypass flow path. In this case, the flow rate of the mixture of blood and replacement fluid in the bypass flow path is slower because the flow resistance of the bypass flow path is greater than the flow resistance of the first flow path, making it possible to sufficiently extract uremic substances in the blood into the replacement fluid.

Preferably, the volume of the bypass flow path is larger than the volume of the first flow path parallel to the bypass flow path. In this case, a large amount of substitution fluid can be introduced into the bypass flow path, and a large amount of uremic substances can be removed. Furthermore, the flow rate of the mixture of blood and substitution fluid in the bypass flow path is slowed, making it possible to sufficiently extract uremic substances into the substitution fluid.

Preferably, the device further includes a chamber provided in the bypass flow path. In this case, the chamber can slow the flow rate of the mixture of blood and replacement fluid, making it possible to sufficiently extract uremic substances into the replacement fluid.

Preferably, the bypass flow path is provided with an inlet for injecting a drug.
More preferably, the inlet is for injecting a solution of baking soda.

It is possible to provide a dialysis device that can sufficiently remove uremic substances from blood.

FIG. 2 is a circuit diagram of the dialysis device according to the first embodiment. FIG. 11 is a circuit diagram of a dialysis device according to a second embodiment. FIG. 11 is a circuit diagram of a dialysis device according to a third embodiment.

(Embodiment 1)
1 is a circuit diagram of a dialysis device according to embodiment 1. The dialysis device 1 of embodiment 1 includes a first flow path 20, 40, 60, 80, 100 through which blood 22 extracted from a human body 10 flows, a blood pump 30 provided in the first flow path 20 for sending the blood 22, a dialyzer 70 provided downstream of the blood pump 30 for purifying blood supplied from the first flow path 60 with a replacement liquid 111, and a second flow path 110 that merges with the first flow path downstream of the blood pump 30 and upstream of the dialyzer to supply the replacement liquid 111 to the first flow path 60. The cross-sectional area of the first flow path 60 downstream of the junction 50 of the first and second flow paths is larger than the cross-sectional area of the first flow path 40 upstream of the junction 50.

Blood 22 drawn from the human body 10 flows toward the blood pump 30 in the direction indicated by the arrow 11. The blood pump 30 pumps the blood 22 into the first flow path 40. The first flow path 40 enters a chamber provided at the junction 50.

At the junction 50, the replacement fluid 111 supplied from the second flow path 110 is mixed with the blood 22. The replacement fluid 111 flows in the second flow path 110 in the direction indicated by the arrow 113. A replacement fluid pump may be provided in the second flow path 110.

Diluted blood 23, which is composed of blood 22 and replacement liquid 111, flows in the direction indicated by arrow 61 in first flow path 60. The inner diameter of first flow path 60 is larger than the inner diameter of first flow path 40. It is preferable that the flow rate of diluted blood 23 in first flow path 60 is slower than the flow rate of blood 22 in first flow path 40.

The dialyzer 70 has a blood inlet 71, a blood outlet 72, a substitution fluid inlet 73, and a substitution fluid outlet 74. An arterial chamber 76 is provided adjacent to the substitution fluid inlet 73 and the substitution fluid outlet 74.

Diluted blood 23 enters the dialyzer 70 through the blood inlet 71 and is discharged through the blood outlet 72. Uremic substances in the diluted blood are removed in the dialyzer 70. Substitution fluid is removed from the diluted blood 23, and blood 22 flows through the first flow path 80 in the direction indicated by arrow 81. The blood 22 is returned to the human body 10 via the chamber 90 and the first flow path 100.

If indoxyl sulfate remains in the human body 10, it will cause various diseases and increase the mortality rate. It is said that 93% of indoxyl sulfate exists in the blood bound to protein (albumin), and 7% exists in a free form. In dialysis, only free indoxyl sulfate can be removed. When indoxyl sulfate is removed, the indoxyl sulfate bound to albumin is released from albumin so that the indoxyl sulfate remaining in the blood 22 maintains a binding rate of 93%, and removal of indoxyl sulfate from the blood 22 progresses. Therefore, theoretically, if the removal rate of indoxyl sulfate in the dialyzer 70 matches the release rate of indoxyl acid from albumin, indoxyl sulfate can be easily removed from the blood, but since the release of indoxyl sulfate occurs only slowly, it is effective to ensure a dialysis time sufficient for the release of indoxyl sulfate from albumin when the concentration of indoxyl sulfate is diluted, but long-term dialysis is a heavy burden. Therefore, although slowing down the blood flow rate is effective, dialysis is not practical unless a certain flow rate is maintained, as there is a risk of blood clotting (even if heparin is administered).

However, as in this embodiment, even if the flow rate is reduced, the diluted blood 23 contains blood 22 and replacement liquid 111, and the blood 22 itself is diluted, so there is no risk of blood clotting, and the flow rate can be reduced. Furthermore, since the concentration of blood 22 in the diluted blood 23 is low, the amount of indoxyl sulfate that binds to albumin is small, and a large amount of indoxyl sulfate is present in the replacement liquid 111 within the diluted blood 23. This makes it possible to easily remove indoxyl sulfate using the dialyzer 70.

(Embodiment 2)
FIG. 2 is a circuit diagram of a dialysis device according to the second embodiment.

1. Structure of the blood circuit The blood circuit for removing protein-bound substances in the dialysis device 1 is composed of a first flow path 42, which is a conventional blood flow path, and a bypass flow path 41 that bypasses the first flow path 42. A substitution fluid 111 is injected into the bypass flow path 41 that bypasses the first flow path 42. The extracorporeal circulating blood flow rate, which corresponds to the discharge volume of the blood pump 30, and the substitution fluid flow rate, which corresponds to the discharge volume of the substitution fluid pump 112, are both constant during dialysis.

The volume of the first flow path 42 is V0, the flow path resistance is R0, and the blood flow rate flowing through the first flow path 42 in the direction indicated by the arrow 42a is Qb0. Furthermore, the volume of the bypass flow path 41 is V1, the flow path resistance is R1, the flow rate of the diluted blood 23 diluted with the replacement fluid flowing through it in the direction indicated by the arrow 41a is Qbd1, the blood flow rate flowing into the bypass flow path 41 is Qb1, and the flow rate of the replacement fluid 111 flowing into the bypass flow path 41 is Qd. Furthermore, the extracorporeal circulation blood flow rate corresponding to the discharge rate of the blood pump 30 is Qb.

The meaning of each symbol is as follows.
V0: Volume of the first flow path 42 R0: Flow path resistance of the first flow path 42 Qb0: Blood flow rate flowing through the first flow path 42 V1: Volume of the bypass flow path 41 R1: Flow path resistance of the bypass flow path 41 Qbd1: Flow rate of diluted blood diluted with substitution fluid flowing through the bypass flow path 41 Qb1: Blood flow rate flowing into the bypass flow path 41 Qb: Extracorporeal circulation blood flow rate corresponding to the discharge rate of the blood pump 30 Qd: Substitution fluid flow rate 2. Mathematical expression of the blood circuit The amount of indoxyl sulfate bound to albumin released from albumin is determined by both the time required for the diluted blood 23 to pass through the bypass flow path 41 and the degree of dilution. Therefore, first, the time required for the diluted blood 23 to pass through the bypass flow path 41 will be considered, and then the degree of dilution will be considered.

1) Time required for diluted blood 23 to pass through bypass flow path 41 The passing time of blood 22 through first flow path 42 is calculated by dividing the volume of first flow path 42 by the blood flow velocity. Similarly, the passing time of diluted blood 23 through bypass flow path 41 is calculated by dividing the volume of bypass flow path 41 by the flow rate of diluted blood 23.

If the passage time of blood through the first flow path 42 is T0 minutes, the following equation holds true.
T0=V0/Qb0 (1a)
Similarly, if the passage time of the diluted blood 23 through the bypass flow path 41 is T1 minutes, the following formula is established.

T1=V1/Qbd1 (1b)
Assuming that the flow path volume is already given, the target transit time of the blood 22 or the diluted blood 23 is determined by the flow rate of the blood 22 or the diluted blood 23. Therefore, in the next step, an equation for calculating the flow rate of the blood 22 or the diluted blood 23 in each flow path is derived.

If the pressure at the branch point upstream of the first flow path 42 and the bypass flow path 41 is Pu, the pressure at the branch point downstream is Pd, and the difference between the two is dP, then in either flow path, dP can be expressed as the product of the flow rate of the blood 22 or diluted blood 23 and the flow resistance of the flow path. For simplicity, the effect of the viscosity of the blood 22 on the flow resistance is ignored here.

dP = Qb0 x R0 (2a)
dP = Qbd1 × R1 (2b)
where dP = Pu - Pd
On the other hand, the flow rate of the diluted blood 23 in the bypass flow path 41 is equal to the sum of the flow rate of the blood and the flow rate of the replacement fluid flowing into the bypass flow path.

Qbd1=Qb1+Qd (3)
Here, the sum of the flow rates of the blood 22 flowing into each flow path is equal to the extracorporeal circulation blood flow rate, which corresponds to the discharge rate of the blood pump 30 .

Qb=Qb0+Qb1 (4)
The following formula can be derived from formula (2a) and formula (2b).

Qb0×R0=Qbd1×R1 (5a)
By rewriting equation (5a), we obtain equation (5b).

Qb0 = (R1 / R0) × Qbd1 (5b)
For convenience, R1/R0 is defined as follows.

R1/R0=b
As a result, equation (5b) can be rewritten as equation (5c).

Qb0 = b × Qbd1 (5c)
By solving equations (3), (4), and (5c) simultaneously, the following equation is obtained.

Qb1 = (Qb - b x Qd) / (b + 1) (6)
As shown in formula (3), the flow rate Qbd1 of the diluted blood 23 in the bypass flow path 41 is equal to the sum of the flow rate Qb1 of the blood flowing into the bypass flow path 41 and the flow rate Qd of the replacement fluid. Therefore, by substituting formula (6) into formula (3), it is possible to derive a formula for calculating the flow rate Qbd1 of the diluted blood 23 in the bypass flow path 41.

Qbd1 = {(Qb - b x Qd) / (b + 1)} + Qd (7a)
By rearranging equation (7a), equation (7b) is obtained.

Qbd1 = (Qb + Qd) / (b + 1) (7b)
2) Dilution degree of blood flowing through the bypass flow path 41 When the dilution degree of blood flowing through the bypass flow path 41 is D, D is defined by the following formula.

D = Qb1 / (Qb1 + Qd) (8)
3) Volume of bypass flow path 41 determining time T1 required for diluted blood 23 to flow through bypass flow path 41 As already described, if the passage time of diluted blood 23 through bypass flow path 41 is T1 minute, the following equation is established.

T1=V1/Qbd1 (1b)
By rewriting this, an equation for determining the volume of the bypass flow path 41 that determines the time T1 required for the diluted blood 23 to flow through the bypass flow path 41 can be obtained.

V1=T1×Qbd1 (9)
3. Specific method for determining the flow resistance and volume of the bypass flow path 41 1) Substitution fluid flow rate Let us assume that the dilution degree D of the diluted blood 23 flowing through the bypass flow path 41 is preferably about 0.3. Furthermore, since the amount of blood in the body is about ⁵ dm3, the blood flow rate Qb1 flowing into the bypass flow path 41, which is the amount of blood to be processed, may be 30 ^cm3 /min (7.2 dm3 is processed in 4 hours of dialysis). Under these conditions, the substitution fluid flow rate will be 70 ^cm3 /min.

D = Qb1 / Qb1 + Qd (8)
0.3 = 30 / (30 + Qd)
Qd=70
2) Flow Resistance of the Bypass Flow Channel 41 If the blood flow rate Qb1 flowing into the bypass flow channel 41 is 30 cm ³ /min and the replacement fluid flow rate is 70 cm ³ /min, the flow rate Qbd1 of the diluted blood in the bypass flow channel 41 is 100 cm ³ /min.

If the flow rate Qbd1 of diluted blood in the bypass flow path 41 is 100 cm ³ /min and the blood flow rate in the first flow path 42 is 220 cm ³ /min (when the extracorporeal blood flow rate corresponding to the discharge volume of the blood pump 30 is 250 cm ³ /min), the ratio b of the flow resistance of the bypass flow path 41 to the flow resistance of the first flow path 42 can be calculated by substituting these values into equation (5c).

Qb0 = b × Qbd1 (5c)
220 = b x 100
b=2.2
In other words, the flow resistance value of the bypass flow passage 41 is set to 2.2 times the flow resistance value of the first flow passage 42 .

Upstream of the dialyzer 70 the blood circuit branches.
3) Volume of the Bypass Flow Channel 41 The volume of the bypass flow channel 41 can be calculated from the time T1 required for the diluted blood to pass through the bypass flow channel 41 and the flow rate Qbd1 of the diluted blood in the bypass flow channel 41 according to formula (9).

V1=T1×Qbd1 (9)
That is, in order to make the time required for the diluted blood to pass through the bypass flow path 41 3 minutes and to make the flow rate Qbd1 of the diluted blood in the bypass flow path 41 100 cm ³ /min, the volume of the bypass flow path 41 must be 300 cm ³ .

V1 = 3 x 100 = 300
To summarize the above, when the flow resistance value R1 of the bypass flow path 41 is 2.2 times the flow resistance value R0 of the first flow path 42 and the volume of the bypass flow path 41 is 300 ^cm3 /min, if the blood flow rate is 250 ^cm3 /min and the replacement fluid flow rate is 70 ^cm3 /min, ³⁰ cm3 of blood per minute will be maintained at a 3-fold dilution for 3 minutes.

The volume of the bypass flow path 41 can be adjusted by providing a chamber 43 in the bypass flow path 41.

In the dialysis device 1 of the second embodiment, the circuit from the human body to the blood pump 30 and the circuit from the dialyzer 70 to the human body 10 are the same as those in the first embodiment. The dialysis device 1 includes a first flow path 40, 42, 44 through which blood 22 taken from the human body flows, a blood pump 30 provided in the first flow path 40 to send blood, a dialyzer 70 provided downstream of the blood pump 30 to purify the blood supplied from the first flow path 44 with a replacement liquid, a bypass flow path 41 provided in parallel to a part of the first flow path 42, which branches off from the first flow path 40 downstream of the blood pump 30 and merges with the first flow path 42 upstream of the dialyzer 70, and a second flow path 110 that merges with the bypass flow path 41 and supplies the replacement liquid 111 to the bypass flow path 41. A mixture of diluted blood 23 and blood 22 flows in the first flow path 44 in the direction indicated by the arrow 44a.

The flow resistance of the bypass flow path 41 may be greater than the flow resistance of the first flow path 42 parallel to the bypass flow path 41. The volume of the bypass flow path 41 may be greater than the volume of the first flow path 42 parallel to the bypass flow path 41. The bypass flow path 41 may further include a chamber 43 provided therein. The bypass flow path 41 may be provided with an injection port for injecting a drug. The injection port may be an injection port for a solution of baking soda.

(Embodiment 3)
Fig. 3 is a circuit diagram of a dialysis device according to embodiment 3. As shown in Fig. 3, by making the bypass flow path 41 wider overall, the volume of the bypass flow path 41 can be increased without providing a chamber.

This invention is not limited to removing indoxyl sulfate. It also targets other protein-bound substances that accumulate in dialysis patients. Indoxyl sulfate is just one example.

The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. The scope of the present invention is indicated by the claims, not by the above description, and is intended to include all modifications within the meaning and scope of the claims.

10 human body, 20, 40, 42, 44, 60, 80, 100 first flow path, 22 blood, 23 diluted blood, 30 blood pump, 41 bypass flow path, 43, 90 chamber, 50 junction, 70 dialyzer, 71 blood inlet, 72 blood outlet, 73 substitution fluid inlet, 74 substitution fluid outlet, 76 arterial chamber, 110 second flow path, 111 substitution fluid, 112 substitution fluid pump.

Claims (8)

a first flow path through which blood taken from the human body flows;
a blood pump provided in the first flow path to pump blood;
a dialyzer provided downstream of the blood pump for purifying blood supplied from the first flow path with a substitution fluid;
a second flow path that merges with the first flow path downstream of the blood pump and upstream of the dialyzer to supply a replacement fluid to the first flow path;
a cross-sectional area of the first flow path downstream of a junction of the first and second flow paths is larger than a cross-sectional area of the first flow path upstream of the junction. The dialysis device of claim 1, wherein the cross-sectional area of the first flow path is selected such that the flow rate downstream of the junction is slower than the flow rate upstream of the junction. a first flow path through which blood taken from the human body flows;
a blood pump provided in the first flow path to pump blood;
a dialyzer provided downstream of the blood pump for purifying blood supplied from the first flow path with a substitution fluid;
a bypass flow path that branches off from the first flow path downstream of the blood pump and joins the first flow path upstream of the dialyzer, the bypass flow path being provided in parallel to a portion of the first flow path;
a second flow path that merges with the bypass flow path and supplies a substitution fluid to the bypass flow path. The dialysis device according to claim 3, wherein the flow resistance of the bypass flow path is greater than the flow resistance of the first flow path parallel to the bypass flow path. The dialysis device according to claim 3 or 4, wherein the volume of the bypass flow path is greater than the volume of the first flow path parallel to the bypass flow path. The dialysis device of claim 5, further comprising a chamber provided in the bypass flow path. The dialysis device according to any one of claims 3 to 6, wherein the bypass flow path is provided with an inlet for injecting a drug. The dialysis machine of claim 7, wherein the inlet is an inlet for a solution of baking soda.

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