Object liquid purifier

Abstract

To provide an object liquid purifier that allows dialysis to be performed in a reliable manner, and allows a substance to be discarded during dialysis to be removed without excess or shortage while reducing a total amount of dialysis solution used in the dialysis.SOLUTION: An object liquid purifier includes: a separation device 100; an unpurified object liquid passage 11; a purified object liquid passage 12; a reproduction part 200; a filtration dialysis drainage passage 21; a reproduction liquid passage 22; a drainage passage 24; a first replenishing liquid passage 412; a first flow rate adjusting device 31; a second flow rate adjusting device 32; a measuring device 35 for measuring the concentration of an object substance; a control device 300; and a notification device 400.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a technique for appropriately removing toxins (target substances) such as potassium ions from dialysis effluent and the like during dialysis treatment for patients with chronic renal failure and the like. [Background technology]

[0002] In hemodialysis, potassium ions and other toxins are removed by diffusion based on the difference in concentration between the blood and the dialysate when the blood and dialysate come into contact with each other through a dialysis membrane in a dialyzer. The concentrations of the dialysate components entering the dialyzer are predetermined, and the dialysis effluent, into which toxins such as potassium ions have migrated from the blood, is simply discarded.

[0003] The amount of target substances removed and their post-dialysis blood concentrations, such as potassium ions, vary depending on the blood flow rate and dialysis time, but these are treatment conditions that are primarily determined by other factors. Therefore, to achieve appropriate amounts and concentrations of target substances removed and post-dialysis blood concentrations, the concentration of the target substances in the dialysis fluid is generally varied. For this reason, dialysis fluids with several different concentrations are commercially available.

[0004] It has been reported that a large difference between the concentration of a target substance, such as potassium ions, in the dialysate and the patient's serum increases the incidence of arrhythmia and the risk of hospitalization and death (see Non-Patent Document 1). Therefore, if the concentration of the target substance could be adjusted to reduce the difference between the patient's serum and dialysate concentrations, it would be beneficial for the patient. To reduce the difference between the potassium ion concentration in the dialysate and the patient's serum, a method has been proposed in which the potassium ion concentration in the dialysate is set to 1.5 mEq / L lower than that in the patient's serum at the start of treatment and then exponentially reduced during treatment (see Non-Patent Document 2). However, because there is no device that measures the potassium ion concentration in blood during dialysis and uses the results as feedback to control the dialysate concentration, a method for adjusting the dialysate concentration to an appropriate level has not yet been realized.

[0005] Therefore, the inventors have invented an apparatus that can efficiently remove target substances such as potassium ions from target liquids such as dialysis effluent while maintaining the fluidity of the dialysis effluent and controlling the concentration difference to an appropriate level (Patent Document 1). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent Application No. 2022-132837 [Patent Document 2] U.S. Patent No. 9,302,038

[0007] [Non-Patent Document 1] Steven M. Brunelli1, David M. Spiegel, Charles Du Mond,Nina Oestreicher,Wolfgang C. Winkelmayer and Csaba P. Kovesdy. Serumto-dialysate potassium gradient and its association with short-term outcomes in hemodialysis patients. Nephrol Dial Transplant (2018) 33:1207-1214 [Non-patent document 2] :Redaelli B, Locatelli F, Limido D et al. Effect of a new model of hemodialysis potassium removal on the control of ventricular arrhythmias. Kidney Int (1996) 50: 609-617 Summary of the Invention [Problem to be solved by the invention]

[0008] By using the dialysis method and apparatus disclosed in Patent Document 1, it is possible to remove unnecessary ions such as potassium from target liquids such as dialysis effluent while maintaining the fluidity of the dialysis effluent, and to remove target substances efficiently while controlling the concentration difference to an appropriate level. However, when the dialysis method and apparatus disclosed in Patent Document 1 are used with a normal dialysis machine (e.g., Patent Document 2), a replacement fluid is supplied during dialysis, which results in the problem that the total amount of dialysis is still large and a large amount of replacement fluid is also required, making it insufficient from the perspective of reducing the total amount of dialysis fluid.

[0009] Furthermore, Patent Document 1 discloses a dialysis method for removing a single target substance (only potassium ions are disclosed in the embodiment). In order to determine whether dialysis has been performed sufficiently, it is not enough to simply remove a single target substance (a substance that can be adsorbed by a single adsorbent) in the exact amount; it is necessary to determine whether dialysis has been performed sufficiently after removing multiple target substances in the exact amount. However, Patent Document 1 does not disclose a method for performing the exact removal of multiple target substances, which poses a problem in that each of the multiple target substances is not removed in the exact amount during dialysis.

[0010] Therefore, the present invention aims to provide a target fluid purification device that can reliably perform dialysis, reduce the total amount of dialysis fluid used in dialysis, and remove multiple target substances to be discarded during dialysis in the exact amount. [Means for solving the problem]

[0011] In order to achieve the above object, the present invention has the following specific features.

[0012] (1): The target liquid purification device of the present invention is A target liquid purification device for removing at least one target substance from an unpurified target liquid, comprising: a separation device comprising a porous membrane having a pore size that allows the target substance contained in the unpurified target liquid to pass through, and a first portion and a second portion separated by the porous membrane, wherein the unpurified target liquid containing the target substance is passed through the porous membrane from the first portion and introduced into the second portion to produce a diafiltration effluent, and the target substance contained in the unpurified target liquid is removed by the passage, thereby producing a purified target liquid; an unpurified liquid passage for introducing the unpurified liquid into the first portion of the separation device; a liquid to be purified passage for leading the liquid to be purified from the first portion of the separation device; a diafiltration drain passageway for conducting the diafiltration drain from the second portion of the separation device; a drainage passage branching from the dialysis filtration drainage passage, for discarding the first liquid as a drainage liquid, of a first liquid and a second liquid resulting from separation of the dialysis filtration drainage liquid; a regeneration unit including two or more regeneration circuits connected in series, each of which has an adsorbent that adsorbs the target substance, and which removes at least one of the target substances from the second liquid by bringing the second liquid introduced from the dialysis filtration discharge passage into contact with the adsorbent, thereby producing a regeneration liquid having a reduced concentration of the target substance; a regenerant passage for introducing the regenerant from the regeneration section into the second portion of the separation device; a first replenishment liquid passage for directly introducing replenishment liquid into at least one of the unpurified liquid passage and the purification liquid passage; The present invention is characterized by comprising at least one measuring device provided in any one of the unpurified target liquid passage, the separation device, and the diafiltration discharge liquid passage, which measures the concentration of the target substance.

[0013] (2): In the target liquid purification device having the configuration described in (1), one of the regeneration circuits comprises a first circuit that brings the upstream liquid into contact with the adsorbent and then discharges it downstream, a second circuit that introduces the upstream liquid into the downstream without bringing it into contact with the adsorbent, and a flow rate control device that adjusts the flow rates of the upstream liquid introduced into the first circuit and the second circuit, It is preferable that the flow rate control device adjusts the flow rate introduced into the first circuit and the flow rate introduced into the second circuit depending on the concentration of the target substance in the diafiltration effluent measured by the measuring device.

[0014] (3): In the target liquid purification device having the configuration described in (1) or (2), an anomaly detection device that detects an anomaly based on a time-series variation in the concentration of the target substance; It is preferable to further include an alarm device that notifies of an abnormality detected by the abnormality detection device. [Brief explanation of the drawings]

[0015] [Figure 1] 1 is a diagram illustrating the configuration of a target liquid purification device according to a first embodiment of the present invention; [Figure 2] FIG. 2 is a diagram illustrating the configuration of a regeneration unit in the target liquid purification device according to the first embodiment of the present invention. [Figure 3] 3 is a flowchart showing a method for adjusting the flow rate of a replenishment liquid in the target liquid purification device according to the first embodiment of the present invention. [Figure 4] 3 is a flowchart showing a method for adjusting a flow rate in a regeneration circuit in the target liquid purification device according to the first embodiment of the present invention. [Figure 5] FIG. 4 is a diagram illustrating the configuration of a target liquid purification device according to a second embodiment of the present invention. [Figure 6] FIG. 10 is a diagram illustrating the configuration of a target liquid purification device according to a third embodiment of the present invention. [Figure 7] FIG. 10 is a diagram illustrating the configuration of a target liquid purification device according to a fourth embodiment of the present invention. [Figure 8] FIG. 10 is a diagram illustrating the configuration of a target liquid purification device according to a fifth embodiment of the present invention. [Figure 9] FIG. 10 is a diagram illustrating the configuration of a target liquid purification device according to a sixth embodiment of the present invention. [Figure 10] FIG. 10 is a diagram showing the concentration of urea nitrogen in the unpurified target liquid and the concentration of urea nitrogen in the first liquid for each flow rate of the replenisher liquid F41 in the target liquid purification device according to the embodiment of the present invention. [Figure 11] FIG. 10 is a diagram showing the relationship between QD (flow rate of replenishment liquid) and CDO (urea nitrogen concentration in the first liquid) in the subject liquid purification device according to the embodiment of the present invention. [Figure 12A] 10 is a diagram showing the relationship between the urea nitrogen concentration and the position of the separation device as seen from the unpurified object liquid passage when the flow rate of the replenisher liquid is 500 mL / min in the object liquid purification device according to the embodiment of the present invention. FIG. [Figure 12B] 10 is a diagram showing the relationship between the urea nitrogen concentration and the position of the separation device as seen from the unpurified object liquid passage when the flow rate of the replenisher liquid is 230 mL / min in the object liquid purification device according to the embodiment of the present invention. FIG. [Figure 12C] 10 is a diagram showing the relationship between the urea nitrogen concentration and the position of the separation device as seen from the unpurified object liquid passage when the flow rate of the replenisher liquid is 150 mL / min in the object liquid purification device according to the embodiment of the present invention. FIG. DETAILED DESCRIPTION OF THE INVENTION

[0016] (First embodiment) 1 includes a separation device 100, an unpurified target liquid passage 11, a purification target liquid passage 12, a regeneration unit 200, a diafiltration drainage passage 21, a regenerated liquid passage 22, a drainage passage 24, a first replenishment liquid passage 412, a first flow control device 31, a second flow control device 32, a measuring device 35 for measuring the concentration of a target substance, a control device 300, and an alarm device 400. Note that the first flow control device 31 and the second flow control device 32 can be omitted.

[0017] The separation device 100 is separated into a first portion 110 and a second portion 120 by a porous membrane 102. The porous membrane 102 has a pore size that allows passage of target substances contained in the unpurified target fluid F11 (e.g., blood, plasma, dialysis effluent, hemofiltrate). The "target substance" refers to, for example, at least one ion selected from potassium ions, ammonium ions, calcium ions, magnesium ions, phosphate ions, bicarbonate ions, and organic acid ions, as well as pathogenic substances that accumulate in the body when a disease occurs, such as urea, creatinine, uric acid, peptides, and proteins. The separation device 100 is configured to pass the unpurified target fluid F11 containing the target substance from the first portion 110 through the porous membrane 102 and introduce it into the second portion 120 to generate a diafiltration effluent F21 (filtrate and / or dialysis effluent), and to remove the target substances contained in the unpurified target fluid F11 during this passage, thereby generating a purified target fluid F12.

[0018] The unpurified target liquid passage 11 is configured to introduce the unpurified target liquid F11 drawn from the patient's body into the first section 110 of the separation device 100. The unpurified target liquid passage 11 may be provided with a flow rate adjustment device (e.g., a pump, a flow rate adjustment valve, or a mass flow controller, not shown) to adjust the flow rate of the unpurified target liquid F11. The purification target liquid passage 12 is configured to introduce the purification target liquid F12 from the first section 110 of the separation device 100 into the patient's body. The purification target liquid passage 12 may be provided with a flow rate adjustment device (e.g., a pump, a flow rate adjustment valve, or a mass flow controller, not shown) to adjust the flow rate of the purification target liquid F12. The separation device 100 is configured, for example, by a dialyzer, with the first section 110 being the internal space of hollow fibers made of dialysis membranes and the second section 120 being the space around the hollow fibers through which the dialysate and / or regenerated liquid flows.

[0019] In this embodiment, the separation device 100 is configured as a "countercurrent separation device" in which the flow direction of the unpurified target liquid F11 in the first section 110 and the flow direction of the regenerated liquid F22 in the second section 120 are opposite or in opposite directions, but in other embodiments, the separation device 100 may be configured as a "parallel current separation device" in which the flow direction of the unpurified target liquid F11 in the first section 110 and the flow direction of the regenerated liquid F22 in the second section 120 are parallel or in the same direction.

[0020] The regeneration unit 200 has an adsorbent that adsorbs the target substance. The adsorbent may be activated carbon, an adsorbent based on activated carbon, a porous adsorbent, an adsorbent made of cation exchange resin, anion exchange resin, zirconia ceramics, zeolite, or a mixture thereof. The regeneration unit 200 is configured to remove at least a portion of the target substance by contacting a portion of the diafiltration effluent (second liquid F212) with the adsorbent, thereby generating a regenerated liquid F22 in which the concentration of the target substance has been reduced.

[0021] The diafiltration drainage passage 21 is configured to discharge the diafiltration drainage F21 from the second section 120 of the separation device 100 and introduce a portion of the diafiltration drainage F21, a second liquid F212, into the regeneration section 200. The drainage passage 24 branches off from the diafiltration drainage passage 21 and is configured to discard the first liquid F211 as a drainage, out of the first liquid F211 and the second liquid F212 resulting from separation of the diafiltration drainage F21. The flow rate of the drainage in the drainage passage 24 (the discarded amount of the diafiltration drainage F21) may be appropriately controlled based on the inflow rate of the substitution fluid (fresh dialysate) into the regeneration fluid passage 22 and / or the outflow rate of the regeneration fluid F22 from the regeneration fluid passage, taking into account the flow rate of the regeneration fluid F22 in the second section 120 of the separation device 100. The regeneration fluid passage 22 is configured to introduce the regeneration fluid F22 from the regeneration section 200 into the second section 120 of the separation device 100.

[0022] The first substitution fluid passage 412 is configured to directly introduce the first substitution fluid F41 into the purification target fluid passage 12. The "substitution fluid" means, for example, fresh dialysis fluid.

[0023] The first flow rate adjustment device 31 is, for example, a pump, a flow rate adjustment valve, or a mass flow controller, and is provided in the discharge passage 24. The first flow rate adjustment device 31 adjusts the flow rate of the first liquid F211 discharged from the target liquid purification device during the target liquid purification.

[0024] The second flow rate control device 32 is, for example, a pump, a flow rate control valve, or a mass flow controller, and is provided in the first replacement fluid passage 412. The second flow rate control device 32 adjusts the flow rate of the first replacement fluid passage 412, which is fresh dialysis fluid introduced into the first replacement fluid passage, during purification of the target fluid.

[0025] As will be described later, the first flow control device 31 and the second flow control device 32 adjust the flow rate in accordance with the concentration of the target substance measured by the measuring device 35. At this time, each of the first flow control device 31 and the second flow control device 32 adjusts the flow rate so as to reduce the deviation between the amount of replenishment fluid F41 introduced and the amount of first fluid F211 discharged, or to reduce the deviation between the total amount of replenishment fluid F41 introduced and the amount of water removed and the amount of first fluid F212 discharged.

[0026] Here, the "amount of water removed" refers to excess water contained in the body. This water is preferably excreted during the purification of the target liquid. The amount of water removed typically varies from person to person and is calculated using a predetermined method based on the user's weight, meal frequency, height, etc. According to the guidelines of the Japanese Society for Dialysis Therapy (Journal of the Japanese Society for Dialysis Therapy, Vol. 43, No. 7, pp. 587-632, 2013), the amount of water removed is typically preferably kept within 15 mL per hour per kg of body weight.

[0027] Since it is usually difficult to achieve a uniform flow on the dialysate side, the flow rate of the regenerated fluid F22 is set to about twice the flow rate of the unpurified target fluid F11. On the other hand, in the present invention, it is preferable that the flow rate of the regenerated fluid F22 is the same as or lower than the flow rate of the unpurified target fluid F11. In this case, by making the flow rate of the first replacement fluid F41 and the flow rate of the first fluid F211 the same, the flow rate in the target fluid purification device can be maintained constant as the flow rate of the unpurified target fluid F11. By making the flow rate of the first fluid F211 higher than that of the first replacement fluid F41, water can be removed from the unpurified target fluid F11 by the amount corresponding to the amount.

[0028] Furthermore, in the present invention, the flow rate of the replacement fluid F41 and the flow rate of the first fluid F211 are approximately the same, and the flow rate of the replacement fluid F41 is less than or approximately the same as the flow rate of F211. At this time, since the diafiltration effluent F21 and the regenerated fluid F22 flow through flow paths of constant volume, when the replacement fluid F41 and the first fluid F211 are the same volume, the flow rates of the unpurified target fluid F11 and the purified target fluid F12 within the target fluid purification device are equal, and when F41 is less than the flow rate of F211, the purified target fluid F12 is less than the unpurified target fluid F11 by a flow rate equal to the difference in flow rate between the replacement fluid F41 and the first fluid F211.

[0029] In this case, by providing a measuring device 35 in the passage through which the diafiltration effluent F21 passes, the concentration of the target substance in the unpurified target fluid F11 can be estimated without providing a measuring device 35 inside the human body or in the untreated target fluid passage 11. Because the composition of the unpurified target fluid can be determined based on the measurement results of the measuring device 35, the target fluid purification system of the present invention adjusts the flow rate, and thereby increases or decreases the flow rate of the replacement fluid, based on the concentration of the target substance. As in the above embodiment, the measuring device 35 is preferably provided in the diafiltration effluent passage through which the diafiltration effluent F21 passes, but this is not limiting and one or more measuring devices may be provided in any of the human body, the unpurified target fluid passage, the separation device, and the diafiltration effluent passage.

[0030] In addition to the target liquid purification device described above, the target liquid purification system of the present invention includes a control device 300 and an alarm device 400, as shown in FIG. 1. The control device 300 includes a storage device (memory such as RAM, ROM, EEPROM, SSD, HDD, etc.) that stores and retains programs (software) and data, a processing device (single-core processor, multi-core processor, CPU, etc.) that reads the necessary programs and / or data from the storage device and executes predetermined arithmetic processing, and an I / O circuit, etc. As described below, the control device 300 controls the flow rates adjusted by the first flow control device 31 and the second flow control device 32, and performs overall control of the target liquid purification device. The control device 300 is also provided with an abnormality detection device 301, which detects abnormalities based on the concentration of the target substance measured by a measurement device, as described below.

[0031] The notification device 400 includes an input interface 401 and an output interface 402. The notification device 400 is a personal computer, a mobile phone (smartphone), or the like, and includes any information terminal device.

[0032] (Configuration of playback circuit) In this embodiment, the reproducing unit 200 may be composed of at least one or more reproducing circuits (reproducing circuit 201, reproducing circuit 202, ... reproducing circuit 20"n" (n is an integer of 3 or more)). When there are two or more reproducing circuits, the reproducing circuits are preferably connected in series with each other, but this is not a limitation and they may be connected in parallel.

[0033] 2 is a schematic diagram showing a regeneration unit 200 configured with two regeneration circuits (regeneration circuit 201 and regeneration circuit 202). In this case, regeneration circuit 201 and regeneration circuit 202 may be configured to remove the same type of target substance, or may be configured to remove different types of target substances. Regeneration circuit 201 includes a first circuit 2011 that brings the upstream second liquid F212 into contact with an adsorbent and then delivers it to the downstream regeneration circuit 202, a second circuit 2012 that delivers the upstream second liquid F212 to the downstream side without bringing it into contact with the adsorbent, and a third flow control device 2013 that adjusts the flow rates of the second liquid F212 delivered to the first circuit 2011 and the second circuit 2012.

[0034] The regeneration circuit 201 also generates a first regenerated liquid F221 and delivers the first regenerated liquid F221 to a regeneration circuit 202 that is connected in series with the regeneration circuit 201 and is provided downstream of the regeneration circuit 201. Similar to the regeneration circuit 201, the regeneration circuit 202 includes a first circuit 2021 that brings the first regenerated liquid F221, which is an upstream liquid, into contact with an adsorbent and then delivers it to the downstream regenerated liquid passage 22, a second circuit 2022 that delivers the first regenerated liquid F221, which is an upstream liquid, to the downstream regenerated liquid passage 22 without bringing it into contact with the adsorbent, and a third flow control device 2023 that adjusts the flow rates of the first regenerated liquid F221 delivered to the first circuit 2021 and the second circuit 2022.

[0035] The third flow control device 2013 of the regeneration circuit 201 is provided with two flow control valves or flow control pumps (third flow control device 2013A and third flow control device 2013B) in each of the first circuit 2011 and the second circuit 2012. The flow control device provided in the first circuit 2011 and the flow control device provided in the second circuit 2012 may be the same or different. Alternatively, a flow control valve or a flow control pump may be provided in either the first circuit 2011 or the second circuit 2021 to adjust the flow rate of the fluid flowing in one circuit, and then the flow rate of the fluid flowing in the other circuit may be adjusted to adjust the flow rates of the second liquid F212 delivered to the first circuit 2011 and the second circuit 2012. Furthermore, By providing a three-way valve at the branch point between the first circuit 2011 and the second circuit 2012, the flow rate of the fluid flowing in one circuit can be adjusted, and then the flow rate of the fluid flowing in the other circuit can be adjusted, thereby adjusting the respective flow rates of the second liquid F212 delivered to the first circuit 2011 and the second circuit 2012.

[0036] In the regeneration circuit 202, the third flow control device 2013 is configured by two flow control valves or flow control pumps (third flow control device 2023A and third flow control device 2023B) in each of the first circuit 2021 and the second circuit 2022, similar to the regeneration circuit 201, but is not limited to this, and the third flow control device 2023 may be configured in a similar manner to the regeneration circuit 201. The configuration of the third flow control device 2013 and the configuration of the third flow control device 2023 may be the same or different.

[0037] In each of the first circuits (first circuit 2011 and first circuit 2021), a check valve (check valve 2014 and check valve 2024) is preferably provided downstream of the third flow control device (third flow control device 2013 and third flow control device 2023) to limit the flow rate from downstream to upstream. Also, in each of the second circuits (second circuit 2012 and second circuit 2022), a check valve (check valve 2015 and check valve 2025) is preferably provided downstream of the third flow control device (third flow control device 2013 and third flow control device 2023) to limit the flow rate from downstream to upstream. By providing a check valve, dialysis can be performed efficiently without circulating fluid in each regeneration circuit. The check valve may be provided only in the first circuit (first circuit 2011 and first circuit 2021), or may be provided in both the first circuit (first circuit 2011 and first circuit 2021) and the second circuit (second circuit 2012 and second circuit 2022), or may be omitted from both the first circuit (first circuit 2011 and first circuit 2021) and the second circuit (second circuit 2012 and second circuit 2022). The configuration of the check valve provided in regeneration circuit 201 and the configuration of the check valve provided in regeneration circuit 202 may be the same as or different from each other.

[0038] 2 shows a configuration according to one embodiment of the present invention, three or more regeneration circuits may be used in the present invention. In this case, the regeneration circuit 202 may be configured to generate a second regeneration liquid F222 and then deliver the second regeneration liquid F222 to a regeneration circuit 203 provided downstream of the regeneration circuit 202. Furthermore, when there are four or more regeneration circuits, similar configurations may be connected in series.

[0039] 2, the regeneration circuit 201 and the regeneration circuit 202 are each provided with a first circuit (first circuit 2011 and first circuit 2021), a second circuit (second circuit 2012 and second circuit 2022), and a third flow control device (third flow control device 2013 and third flow control device 2023), but these configurations may be omitted in all or part of the regeneration circuits. That is, the configurations of the second circuit and the third flow control device may be omitted in at least one of the regeneration circuits 201 and 202.

[0040] (Target liquid purification method) According to the first embodiment of the target liquid purification device having the above-described configuration, the target liquid purification method is carried out in the following procedure. Each procedure or step can be performed in parallel. An unpurified target liquid F11 is introduced into the first section 110 of the separation device 100 (S1). The unpurified target liquid F11 containing the target substance is passed from the first section 110 through the porous membrane 102 and introduced into the second section 120 of the separation device 100, thereby generating a diafiltration effluent F21 (S2). The target substance contained in the unpurified target liquid F11 is removed by passing through the porous membrane 102, thereby generating a purified target liquid F12 (S3). The purified target liquid F12 is discharged from the first section 110 of the separation device 100 (S4). The diafiltration effluent F21 is discharged from the second section 120 of the separation device 100 (S5). Of the first liquid F211 and the second liquid F212 resulting from separation of the diafiltration effluent F21, the first liquid F211 is discarded as effluent (S6). The second liquid F212 comes into contact with the adsorbent in the regeneration section 200, thereby removing at least a portion of the target substance from the second liquid F212 and generating a regenerated liquid F22 having a reduced concentration of the target substance (S7). The regenerated liquid F22 is introduced into the second section 120 of the separation device 100 (S8). Then, the first replenishment liquid F41 is directly mixed with the liquid to be purified F12 (S9).

[0041] (Method for adjusting flow rate in target liquid purification device) Next, a method for adjusting the flow rate of the replenisher liquid, which is executed in the target liquid purification method in the target liquid purification device of the first embodiment having the above-described configuration, will be described with reference to Fig. 3. First, when the operation of the target liquid treatment device is started in response to an ON operation of the operation switch or the like (Fig. 3 / START), the opening degree OP1 of the first flow rate adjustment device 31 is set to OP 10 The opening OP2 of the second flow control device 32 is controlled to OP 20 , and flag f is initialized (flag f is assigned 0) (FIG. 3 / S310).

[0042] Furthermore, based on the output signal of the measuring device 35, the concentration C of the substance to be removed in the diafiltration effluent F21 in the diafiltration effluent passage 21 is calculated. → is measured, and the first concentration C1, which is the concentration before the predetermined time has elapsed, is → (=(C 11 , C 21 , , C n1 )) the current concentration C of the substance to be removed → (=(C 10 , C 20 , , C n0 )) is inserted (Fig. 3 / S311). At this time, 0 is inserted into the dialysis elapsed time t, and the elapsed time thereafter is measured (Fig. 3 / S311). Here, the concentration of the target substance C is a vector including the concentration of at least one of potassium ions, ammonium ions, calcium ions, magnesium ions, phosphate ions, bicarbonate ions, and organic acid ions, as well as urea, creatinine, uric acid, peptides, proteins, and other pathogenic substances that accumulate in the body due to renal failure, etc. That is, the target substance C → (C 10 , C 20 , , C n0 ) (n is an integer of 1 or more, when n is 1, the target substance C → is a vector with one element (target substance C → =(C 10 ))).

[0043] Next, the first concentration C1 → (=(C 11 , C 21 , , Cn1 )) is the specified concentration C0 → (=(C 100 , C 200 , , C n00 )) or less (Fig. 3 / S312). The "designated concentration" is the value at which the concentration of the target substance is sufficiently normal. If the concentration of the target substance in the target liquid is extremely low, the value of the designated concentration is important from the viewpoint of adverse effects on the human body. The "designated concentration" is the value at which the concentration of the target substance is sufficiently normal. → The concentration of each element (the concentration of each target substance) is determined. → The elements of each of the above are different. For example, the target liquid may contain at least one of potassium ions, ammonium ions, calcium ions, magnesium ions, phosphate ions, bicarbonate ions, and organic acid ions, as well as pathogenic substances that accumulate in the body due to renal failure, such as urea, creatinine, uric acid, peptides, and proteins. However, there is a possibility that the potassium ion concentration may be reduced more than necessary compared to the other target substances. In this case, reducing the potassium ion concentration more than necessary may cause muscle weakness, muscle spasms, twitching, and even paralysis, as well as arrhythmia. For this reason, it is preferable to determine individual specified concentrations for each target substance.

[0044] Specified concentration C0 → may vary depending on the time required for the purification of the target liquid. → is the designated concentration C0 just before the completion of the target liquid purification → In particular, the specified concentration C0 → is preferably set to decrease continuously or discontinuously with time. → Each element of (C 100 , C 200 , , C n00 ) may vary independently depending on the time for purifying the target liquid, or may vary in relation to each other depending on the time for purifying the target liquid.

[0045] Furthermore, even if the concentration of one target substance is below the designated concentration, it is undesirable to continue dialysis from the viewpoint of removing other target substances. Therefore, when the concentration of the target substance is below the designated concentration, it is necessary to terminate dialysis or prevent the concentration of the target substance from decreasing more than necessary, even if the dialysis time is short. For this reason, in the present invention, after dialysis is completed, the configuration of the regeneration unit 200 or the replacement fluid F41 is changed, and then dialysis is restarted, thereby preventing the potassium ion from decreasing more than necessary. Alternatively, as described below, multiple regeneration circuits are used to prevent the concentration of one target substance from decreasing more than necessary.

[0046] 1st concentration C1 → is the specified concentration C0 → The determination of whether it is equal to or less than the first concentration C1 is made for each element of each vector, and if the result is positive for all elements, → is the specified concentration C0 → If some factors (concentration of the target substance that would have an effect on the human body if the concentration were to decrease more than necessary) are positive, the first concentration C1 → is the specified concentration C1 → It may be determined that the first concentration C1 → The size of the specified concentration C0 → When the magnitude of the first concentration C1 is less than or equal to → is the specified concentration C0 → It may be determined that the first concentration C1 → and specified concentration C0 → When it is determined that the magnitude of the difference in deviation between the first concentration C1 and the second concentration C2 is equal to or less than the reference value, → is the specified concentration C0 → It may be determined that the deviation is equal to or less than the first concentration C1 → and specified concentration C0 → When it is determined that the magnitude of the deviation from the first concentration C1 is equal to or less than the reference value, → is the specified concentration C0 →Here, the magnitude is a concept such as the norm of the vector, and is the Euclidean distance, Chebyshev distance, or Manhattan distance from the origin, or the Euclidean distance, Chebyshev distance, or Manhattan distance between vectors.

[0047] In addition, the judgment is C1 → The determination may be made using any machine learning method based on some or all of the above factors. In this case, any supervised learning method may be used that uses training data that includes the judgments of medical professionals such as doctors in past target liquid purification processes.

[0048] If the determination result is affirmative (FIG. 3 / S312 YES), flag f is incremented by 1 (FIG. 3 / S313). Next, it is determined whether flag f is equal to or greater than threshold value f0 (FIG. 3 / S314). At the start of dialysis, for example, dialysate may remain in the dialysis device, and the first concentration C1 may be lower than the concentration of the target substance in the blood. Therefore, if the first concentration is again lower than the designated concentration C0 after a predetermined time t0 has elapsed, the dialysis termination operation is performed.

[0049] If the determination result is positive (FIG. 3 / S314 YES), the target fluid purification device ends purification of the target fluid (FIG. 3 / END). At this time, the opening OP1 of the first flow control device 31 is set greater than the opening OP2 of the second flow control device 32, thereby removing excess fluid accumulated in the body. In this embodiment, water removal is performed uniformly during the purification of the target fluid, or may be changed depending on the elapsed time during the purification of the target fluid. For example, water removal may be changed depending on the elapsed time using the hematocrit value as a reference. In other words, water removal is preferably performed so as to minimize changes in blood volume as much as possible.

[0050] On the other hand, if the determination result is negative (FIG. 3 / S314··NO), the process from connector X1 onwards is executed. This allows the dialysis operation to be controlled so as to reliably remove the target substance, even though the concentration of the target substance is low in the early stage of dialysis. Then, the process from S315 onwards, which will be described later, is executed. Note that in this embodiment, the processes from S313 to S314 may be omitted.

[0051] On the other hand, if the determination result in S312 is negative (FIG. 3 / S312·NO), the target liquid purification device determines that the purification of the target liquid is insufficient and continues the target liquid purification operation. Next, t is incremented by 1 (FIG. 3 / S316). Note that here, the elapsed time from the stage where t is set to 0 (FIG. 3 / S311) may be automatically measured, and then the process may proceed to S316.

[0052] Thereafter, it is determined whether the dialysis elapsed time t has passed the predetermined elapsed time t0 (FIG. 3 / S316). If the determination result is negative (FIG. 3 / S316: NO), the operations from S315 onwards are executed again.

[0053] If the determination result is positive (FIG. 3 / S316··YES), the second concentration C2 → (=(C 12 , C 22 , , C n2 )) is inserted with the current concentration C of the substance to be removed (Figure 3 / S317).

[0054] Next, the first concentration C1 → and the second concentration C2 → The difference between C1 and → -C2 → (=(C 11 -C 12 , C 21 -C 22 , , C n1 -C n2 )) is the first density difference threshold ΔC1 → (=(ΔC 11 , ΔC 12 , ..., ΔC 12)) or less (FIG. 3 / S318). → is a threshold value for determining whether dialysis is being performed sufficiently after a predetermined elapsed time t0 has elapsed, and the first concentration difference threshold ΔC1, which is the basis for the determination process, is determined by taking into account the predetermined elapsed time t0. → The density difference C1 may be adopted. → -C2 → The magnitude of the first concentration difference threshold ΔC1 indicates the level of the removal performance (or adsorption performance) of the target substance by the target liquid treatment device. → is a vector whose elements are the thresholds of the target substances, and each element is usually a different value. Also, taking into account the predetermined elapsed time t0, the first concentration difference threshold ΔC1 → The first concentration difference threshold ΔC1 may be any of the following: → may vary depending on the time required for the purification of the target liquid. → is the first concentration difference threshold ΔC1 just before the target liquid purification is completed → In particular, the first density difference threshold ΔC1 → is preferably set to decrease continuously or discontinuously with time. → Each element of (ΔC 11 , ΔC 12 , ..., ΔC 12 ) may vary independently depending on the time for purifying the target liquid, or may vary in relation to each other depending on the time for purifying the target liquid.

[0055] C1 → -C2 → is the first density difference threshold ΔC1 → The determination of whether the value is equal to or less than the value in S312 may be performed by a process similar to that in S312 described above. Therefore, the description will be omitted to avoid redundancy. On the other hand, the determination in S318 may be performed by the same processing method as in S311, or may be performed by a different processing method.

[0056] If the determination result is affirmative (FIG. 3 / S318...YES), the flow rate of at least one of the replacement fluid F41, unpurified target fluid F11, and diafiltration effluent F21 is controlled to be reduced (FIG. 3 / S319). This control is performed, for example, by controlling the output of a flow rate regulator (pump) provided in at least one of the unpurified target fluid passage 11, diafiltration effluent passage 21, and replacement fluid passage 41. This control may also be performed by controlling the operation of the first flow rate regulator 31 and the second flow rate regulator 32. This makes it possible to limit the flow rate of the replacement fluid F41. Then, the process from the connector X0 onwards is performed. That is, the first concentration C1 → The process from the measurement process for initializing the dialysis start time t (FIG. 3 / S311) onwards is repeated.

[0057] The degree of decrease in the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration waste fluid F21 is the concentration difference C1 → -C2 → The flow rate of the replacement fluid F41 may be adjusted taking into consideration the magnitude of the replacement fluid F41 or the predetermined elapsed time t0. This allows the amount of the replacement fluid F41 to be optimized. A minimum value may be set for the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21, and in S319, if the flow rate is less than the minimum value, the minimum value may be substituted for the flow rate.

[0058] On the other hand, if the determination result is negative (FIG. 3 / S318...NO), the first concentration C1 → and the second concentration C2 → The difference between C1 and → -C2 → is the second density difference threshold ΔC2 → (=(ΔC 21 , ΔC 22 , ..., ΔC 22 )) is determined (FIG. 3 / S320). The second concentration difference threshold ΔC2 is a threshold for determining whether dialysis is insufficient after a predetermined elapsed time t0 has elapsed, and some or all of the elements of the second concentration difference threshold ΔC2, which is the basis of the determination process, may be adopted, taking into account the predetermined elapsed time t0. Second concentration difference threshold ΔC2→ may vary depending on the time required for the purification of the target liquid. That is, the second concentration difference threshold ΔC2 → is the second concentration difference threshold ΔC2 just before the target liquid purification is completed → In particular, the second density difference threshold ΔC2 → is preferably set to decrease continuously or discontinuously with time. → Each element of (ΔC 21 , ΔC 22 , ..., ΔC 22 ) may vary independently depending on the time for purifying the target liquid, or may vary in relation to each other depending on the time for purifying the target liquid.

[0059] C1 → -C2 → is the first density difference threshold ΔC2 → The determination of whether the above is true or not may be performed by a process similar to the determination in S312 described above. Therefore, to avoid redundancy, a description thereof will be omitted. On the other hand, the determination in S320 may be performed by the same processing method as either one of S311 and S318, or may be performed by a processing method different from both S311 and S318.

[0060] If the determination result is affirmative (FIG. 3 / S320...YES), the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21 is controlled to increase (FIG. 3 / S321). This control is performed, for example, by controlling the output of a flow control device (pump) provided in at least one of the unpurified target fluid passage 11, the diafiltration effluent passage 21, and the replacement fluid passage 41. This control may also be performed by controlling the operation of the first flow control device 31 and the second flow control device 32. This allows the dialysis operation to be controlled so as to reliably remove the target substance when dialysis is insufficient. Then, the process from connector X0 onward is performed. That is, the process for measuring the first concentration C1 and initializing the dialysis start time t (FIG. 3 / S312) and subsequent processes are repeated. Note that in this embodiment, the processes from S320 to S321 may be omitted.

[0061] On the other hand, if the determination result is negative (FIG. 3 / S320...NO), the operations of the first flow control device 31 and the second flow control device 32 are not controlled, and the processes from connector X0 onwards are executed. That is, the processes from the measurement process for initializing the first concentration C1 and the dialysis start time t (FIG. 3 / S312) onwards are repeated. This allows the dialysis operation to be controlled so that the target substance is not inadvertently removed by dialysis.

[0062] In the above embodiment, the substitution fluid flow rate adjustment method includes: a predetermined elapsed time t0; an increase or decrease in the flow rate of at least one of the substitution fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21; and a first concentration difference threshold ΔC1 → and the second concentration difference threshold ΔC2 → was constant, but the number of times the predetermined elapsed time t0 elapsed or the first concentration C1 → This allows optimizing the amount of F41 in the replenisher, preventing the target substance from being reduced too much, while ensuring that excess target substance is removed.

[0063] S318~S321 C1 → -C2 → is equal to or less than a predetermined value, the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21 is adjusted. However, the present invention is not limited to the above embodiment, and the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21 may be adjusted by adjusting the flow rate of C1 → -C2 → The adjustment may be based on an arbitrary function that uses some or all of the elements of the above as variables. Note that the function may be weighted on some of the variables. That is, steps S318 to S321 may be omitted after step S317, and the rate of increase or decrease in the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21 may each be adjusted based on the first concentration C1 → -C2 → The processing after the connector X0 may be executed by calculating a function with each of the elements of the above as a variable.

[0064] In addition, the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration waste fluid F21 is set to a second concentration C2 → The flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21 may be adjusted based on an arbitrary function having some or all of the elements as variables. Note that the function may be weighted to some of the variables. That is, steps S318 to S321 may be omitted after step S317, and the flow rate of at least one of the replacement fluid F41, the unpurified target fluid F11, and the diafiltration effluent F21 may be adjusted to a value equal to or greater than the second concentration C2 → The processing after the connector X0 may be executed by calculating a function with each of the elements of the above as a variable.

[0065] The flow rate adjustment described above is → -C2 → In this case, any supervised learning may be used, using the judgments of medical professionals such as doctors in past target liquid purification processes as training data.

[0066] Furthermore, in the above embodiment, the first embodiment has been described as an example, but in other cases, for example, when the replenisher liquid is provided through multiple paths, as in the second to sixth embodiments described below, the flow rate adjustment method within the target liquid purification device may be implemented by independently adjusting each replenisher liquid flow path.

[0067] (How to adjust the flow rate in the regeneration circuit) Next, with reference to FIG. 4, a flow rate adjustment method for the third flow rate control device 2013 in the regeneration circuit 201, which is executed in the target liquid purification method in the target liquid purification device of the first embodiment having the above configuration, will be described. Here, the process is denoted by the symbol "S400," which means that it is performed in parallel with "S300" in the process or immediately before or after "S300" (meaning that the same number (10 to 21) is inserted in each "00"). That is, the process in "S410" is performed in parallel with "S310" or immediately before or after "S310." Note that the process in FIG. 4 may be executed with all or part of S310 to S321 in FIG. 3 omitted.

[0068] In this embodiment, the regeneration circuit 201 will be described. Here, the regeneration circuit 201 will be described using an example in which the regeneration circuit 201 includes an adsorbent that adsorbs potassium ions, but it is clear that the regeneration circuit 201 is not limited to this and may be based on any target substance.

[0069] In this process, first, when the operation of the target liquid treatment device is started in response to the ON operation of the operation switch or the like (FIG. 4 / START), the opening degree OP3 of the third flow control device 2013 is set to OP 30 The flag f1 is initialized (flag f1 is set to 0) (FIG. 4 / S410). Here, when OP3 is set to 0, it means that the second liquid is introduced only into the second circuit.

[0070] Furthermore, based on the output signal of the measuring device 35, the concentration C of any substance to be removed (potassium ion) in the diafiltration effluent F21 in the diafiltration effluent passage 21 is calculated. 10 The first concentration of potassium ions, C 11 The first concentration C1 → The first concentration C of potassium ions, which is the concentration before a certain time has elapsed, is 11 The current potassium ion concentration C 10 At this time, 0 is inserted into the dialysis elapsed time t, and the elapsed time thereafter is measured (Fig. 4 / S411).

[0071] Next, the first concentration of potassium ions, C 11 But the specified concentration of potassium ions C 100 It is determined whether the concentration is below the specified concentration (Fig. 4 / S412). The "specified concentration" is the value at which the concentration of the target substance is sufficiently normal. If the concentration of the target substance in the target liquid is extremely low, the value of the specified concentration is important from the viewpoint of adverse effects on the human body. Specified concentration C 100 may vary depending on the time required for the purification of the target liquid. That is, the designated concentration C immediately after the start of the purification of the target liquid 100 is the specified concentration C just before the completion of the target liquid purification 100 In particular, the specified concentration C100 is preferably set to decrease continuously or discontinuously with time.

[0072] If the determination result is affirmative (FIG. 4 / S412 YES), the flag f1 is incremented by 1 (FIG. 4 / S413). 10 At the start of dialysis, for example, dialysate may remain in the dialysis device, and the first concentration C of potassium ions may be higher than the first concentration C of potassium ions. 11 may be lower than the concentration of the target substance in the blood. 10 After the time has passed, the first concentration of potassium ions C 11 is the specified concentration of potassium ions, C 10 If the value is less than 0.05% for several consecutive times, control is performed so that potassium ions are not removed more than necessary.

[0073] If the determination result is positive (FIG. 4 / S414 YES), 0 is inserted into the opening OP3 of the third flow control device 2013. Note that when OP3 is 0, this means that the second liquid F212 is introduced only into the second circuit 2012. Therefore, the target liquid purification process can be performed so as to reduce other target substances without inadvertently reducing potassium ions.

[0074] On the other hand, if the determination result is negative (FIG. 3 / S414··NO), the process from connector X1 onwards is executed. This allows the dialysis operation to be controlled so as to reliably remove the target substance in the early stage of dialysis, even though the potassium ion concentration is low due to dilution with a priming solution or the like. Then, the process from S415 onwards, which will be described later, is executed. Note that in this embodiment, the processes from S413 to S414 and S412 may be omitted.

[0075] On the other hand, if the determination result in S412 is negative (FIG. 4 / S412·NO), the target liquid purification device determines that the purification of potassium ions in the target liquid is insufficient, and continues the target liquid purification operation. Next, t is incremented by 1 (FIG. 4 / S416). Note that the elapsed time from the point where t is set to 0 (FIG. 4 / S411) may be automatically measured, and then the process may proceed to S416.

[0076] After that, the dialysis elapsed time t is equal to the predetermined elapsed time t 10 It is determined whether the time has elapsed (FIG. 4 / S416). If the determination result is negative (FIG. 4 / S416·NO), the operations from S415 onwards are executed again. 10 and t0 may be the same or may be different.

[0077] If the determination result is positive (FIG. 4 / S416··YES), the second concentration C of potassium ions, which is the concentration after a predetermined time has elapsed, is 21 The current potassium ion concentration C 10 is inserted (Fig. 4 / S417).

[0078] Next, the first concentration of potassium ions, C 11 and the second concentration C 21 The difference between C 11 -C 21 is the first concentration difference threshold ΔC of potassium ions 11 It is determined whether the first concentration difference threshold ΔC of potassium ions is less than or equal to the first concentration difference threshold ΔC (FIG. 4 / S418). 11 is the predetermined elapsed time t 10 is a threshold value for determining whether dialysis is being performed sufficiently after a predetermined elapsed time t 10 is taken into consideration, the first concentration difference threshold value ΔC 11 may be adopted. 11 -C 21 The magnitude of the first concentration difference threshold ΔC indicates the level of potassium ion removal performance (or adsorption performance) of the target liquid treatment device. 11 may vary depending on the time required for the purification of the target liquid. 11is the first concentration difference threshold ΔC just before the target liquid purification is completed 11 In particular, the first density difference threshold ΔC 11 is preferably set to decrease continuously or discontinuously with time.

[0079] If the determination result is affirmative (FIG. 4 / S418 ･･･ YES), the opening OP3 of the third flow control device 2013 is set to ΔOP 31 The third flow control device 2013 is controlled so that the first concentration C is decreased by 0 (FIG. 4 / S419). Here, the minimum value of the opening OP3 is 0, and in S319, if the opening OP3 becomes negative, 0 is substituted for the opening OP3. This makes it possible to prevent potassium ions from being reduced more than necessary from the body fluid. That is, 11 The processes from the measurement process for initializing the dialysis start time t (FIG. 4 / S411) onwards are repeated.

[0080] The third flow rate control device 2013 is 11 -C 21 or the magnitude of a given elapsed time t 10 This can reduce an unnecessarily rapid decrease in the potassium ion concentration.

[0081] On the other hand, if the determination result is negative (FIG. 4 / S418 ‥ NO), the first concentration C 11 and the second concentration C 21 The difference between C 11 -C 21 is the second concentration difference threshold ΔC 21 It is determined whether the second concentration difference threshold ΔC of potassium ions is greater than or equal to the second concentration difference threshold ΔC (FIG. 4 / S420). 21 is the predetermined elapsed time t 10 is a threshold value for determining whether dialysis is insufficient after a predetermined elapsed time t 10 Taking this into consideration, the second concentration difference threshold ΔC 21 The second density difference threshold ΔC may be used. 21 may vary depending on the time required for the purification of the target liquid.21 is the second concentration difference threshold ΔC just before the target liquid purification is completed 21 In particular, the second density difference threshold ΔC 21 is preferably set to decrease continuously or discontinuously with time.

[0082] If the determination result is affirmative (FIG. 4 / S420 ･･･ YES), the opening OP3 of the third flow control device 2013 is set to ΔOP 32 The operation of the third flow rate control device 2013 is controlled so that the concentration of potassium ions is increased by the amount of the first concentration C (FIG. 4 / S421). This allows the dialysis operation to be controlled so that potassium ions are reliably removed even if the adsorption of potassium ions is insufficient. Then, the process from the connector X0 onwards is executed. That is, 11 The processes from the measurement process for initializing the dialysis start time t (FIG. 4 / S412) onwards are repeated. Note that in this embodiment, the processes from S420 to S421 may be omitted.

[0083] On the other hand, if the determination result is negative (FIG. 4 / S420...NO), the operation of the third flow control device 2013 is not controlled, and the processes from the connector X0 onwards are executed. 11 The processes after the measurement process for initializing the dialysis start time t (FIG. 4 / S412) are repeated. This makes it possible to control the dialysis operation so that the target substance is not inadvertently removed by dialysis.

[0084] In the above embodiment, in the method for adjusting the flow rate in the regeneration circuit, a predetermined elapsed time t 10 , opening fluctuation ΔOP 31 , opening fluctuation ΔOP 32 , first concentration difference threshold ΔC 11 and the second concentration difference threshold ΔC 21 was constant, but after a certain elapsed time t 10 Number of times elapsed or first concentration C 11 This allows potassium ions to be removed individually from the body fluid, while preventing the potassium ion concentration from decreasing more than necessary.

[0085] 2, control similar to the flow rate adjustment in the regeneration circuit 201 is also performed in the regeneration circuit 202 provided downstream of the regeneration circuit 201, and therefore a description thereof will be omitted. The adsorbent provided in the regeneration circuit 202 is an adsorbent that adsorbs a target substance different from the adsorbent provided in the regeneration circuit 201, for example, an adsorbent that adsorbs urea nitrogen. Here, the control in the regeneration circuit 201 and the control in the regeneration circuit 202 are controlled independently of each other. Furthermore, three or more regeneration circuits may be provided, and in this case, each is also controlled independently of each other. As a result, even if, for example, potassium ions are reduced more than necessary but urea nitrogen still remains, the urea nitrogen can be efficiently removed while suppressing the removal of potassium ions.

[0086] S418~S421 C 11 -C 21 The opening degree OP3 is adjusted based on the concentration of only C. 11 -C 21 In other words, S418 to S421 may be omitted after S417, and the opening OP3 may be adjusted based on an arbitrary function with a variable of OP3=OP3(C 11 -C 21 ) and the processing from connector X0 onwards may be executed.

[0087] Also, the opening OP3 is C 21 In other words, S418 to S421 may be omitted after S417, and the opening OP3 may be adjusted based on an arbitrary function with a variable of OP3=OP3(C 11 -C 21 ) and the processing from connector X0 onwards may be executed.

[0088] In this embodiment, the processes (S310 to S321) described in Fig. 3 and the processes (S410 to S422) described in Fig. 4 are performed in parallel with "S300" or immediately before or after "S300", as indicated by the reference numeral "S400", but this is not limiting. In this embodiment, in the processes (S310 to S321) described in Fig. 3, S410 to S422 may be omitted and S310 to S321 may be processed, or in the processes (S410 to S422) described in Fig. 4, S310 to S321 may be omitted and S410 to S422 may be processed. If S310 to S321 are omitted, the processes (S410 to S422) described in Fig. 4 may be terminated when a predetermined time has elapsed.

[0089] (Second embodiment) The target liquid purification device according to a second embodiment of the present invention shown in Fig. 5 has a configuration in which a second replenishment liquid passage 422 is added to the target liquid purification device according to the first embodiment (see Fig. 1). The second replenishment liquid passage 422 is configured to directly introduce the second replenishment liquid F42 into the regenerant liquid passage 22. The supply sources of the second replenishment liquid F42 and the first replenishment liquid F41 may be a common supply source or separate supply sources.

[0090] At this time, it is preferable that the total flow rate of the second replenisher liquid F42 and the first replenisher liquid F41 is approximately the same as the flow rate of the first liquid F211, and in the replenisher liquid flow rate adjustment method, the total flow rate of the second replenisher liquid F42 and the first replenisher liquid F41 is controlled so that the flow rate is approximately the same as the flow rate of the first liquid F211.

[0091] The flow rates of the second replenisher liquid F42 and the first replenisher liquid F41 may be the same or different. For example, any flow rate can be used as long as the ion concentration detected by the measuring device 35 is the same as that of the unpurified target liquid F11. The ratio can be adjusted depending on factors such as the likelihood of membrane clogging and the removal characteristics of substances from the unpurified target liquid F11 in the separation device 100.

[0092] The other configurations of the target liquid purification device and replenishment liquid flow rate adjustment method of the second embodiment are almost the same as the configurations of the target liquid purification device and replenishment liquid flow rate adjustment method of the first embodiment, so similar configurations are given the same symbols and descriptions are omitted.

[0093] (Third embodiment) The target liquid purifying device according to the third embodiment of the present invention shown in Fig. 6 has a configuration in which a regenerated liquid branch passage 221 is added to the target liquid purifying device according to the first embodiment (see Fig. 1). The regenerated liquid branch passage 221 is configured to directly introduce a portion of the regenerated liquid F22 into the unpurified target liquid passage 11.

[0094] The other configurations of the target liquid purification device and replenishment liquid flow rate adjustment method of the third embodiment are almost the same as the configurations of the target liquid purification device and replenishment liquid flow rate adjustment method of the first embodiment, so similar configurations are given the same symbols and descriptions are omitted.

[0095] (Fourth embodiment) The target liquid purification device according to the fourth embodiment of the present invention shown in Fig. 7 includes a first replenishment liquid passage 411 instead of the first replenishment liquid passage 412 in the target liquid purification device according to the first embodiment (see Fig. 1). The first replenishment liquid passage 411 is configured to introduce the first replenishment liquid F41 directly into the unpurified target liquid passage 11, rather than into the purification target liquid passage 12.

[0096] The other configurations of the target liquid purification device and replenishment liquid flow rate adjustment method of the fourth embodiment are almost the same as the configurations of the target liquid purification device and replenishment liquid flow rate adjustment method of the first embodiment, so similar configurations are given the same symbols and descriptions are omitted.

[0097] (Target liquid purification method) According to the fourth embodiment of the target liquid purification device having the above-described configuration, the target liquid purification method is carried out in the following procedure. Each procedure or step can be performed in parallel. An unpurified target liquid F11 is introduced into the first section 110 of the separation device 100 (S1). The unpurified target liquid F11 containing the target substance is passed from the first section 110 through the porous membrane 102 and introduced into the second section 120 of the separation device 100, thereby generating a diafiltration effluent F21 (S2). The target substance contained in the unpurified target liquid F11 is removed by passing through the porous membrane 102, thereby generating a purified target liquid F12 (S3). The purified target liquid F12 is discharged from the first section 110 of the separation device 100 (S4). The diafiltration effluent F21 is discharged from the second section 120 of the separation device 100 (S5). Of the first liquid F211 and the second liquid F212 resulting from separation of the diafiltration effluent F21, the first liquid F211 is discarded as effluent (S6). The second liquid F212 comes into contact with the adsorbent in the regeneration section 200, thereby removing at least a portion of the target substance from the second liquid F212 and generating a regenerated liquid F22 having a reduced concentration of the target substance (S7). The regenerated liquid F22 is introduced into the second section 120 of the separation device 100 (S8). Then, the first replenishment liquid F41 is directly mixed with the unpurified target liquid F11 (S9').

[0098] (Fifth embodiment) A target liquid purification device according to a fifth embodiment of the present invention, shown in Fig. 8, has a configuration in which a second replenishment liquid passage 422 is added to the target liquid purification device according to the fourth embodiment (see Fig. 7). The second replenishment liquid passage 422 is configured to directly introduce the second replenishment liquid F42 into the regenerant liquid passage 22. The supply sources of the second replenishment liquid F42 and the first replenishment liquid F41 may be a common supply source or separate supply sources.

[0099] Other configurations of the target liquid purifying device of the fifth embodiment are almost the same as those of the target liquid purifying device of the fourth embodiment, so the same components are given the same reference numerals and descriptions thereof will be omitted.

[0100] The other configurations of the replenishment liquid flow rate adjustment method of the fifth embodiment are almost the same as the configurations of the target liquid purification method of the second embodiment or the target liquid purification method of the fourth embodiment, so similar configurations are given the same symbols and descriptions are omitted.

[0101] (Sixth embodiment) The target liquid purification device according to the sixth embodiment of the present invention shown in Fig. 9 has a configuration in which a regenerated liquid branch passage 222 is added to the target liquid purification device according to the fourth embodiment (see Fig. 7). The regenerated liquid branch passage 222 is configured to directly introduce a portion of the regenerated liquid F22 into the purification target liquid passage 12.

[0102] Other configurations of the target liquid purifying device of the sixth embodiment are almost the same as those of the target liquid purifying device of the fourth embodiment, so the same components are given the same reference numerals and descriptions thereof will be omitted.

[0103] The other configurations of the replenishment liquid flow rate adjustment method of the sixth embodiment are almost the same as the configurations of the target liquid purification method of the second embodiment or the target liquid purification method of the fourth embodiment, so similar configurations are given the same symbols and descriptions are omitted.

[0104] (effect) According to the subject fluid purification device and subject fluid purification method of the present invention, a replacement fluid is supplied to an appropriate location in the regeneration circuit in order to reduce the total amount of dialysate used in the dialysis method. By reducing the amount of dialysate transported, the device can be made more compact, making it suitable for use in home environments and environmentally friendly.

[0105] (Another embodiment of the present invention) The first replenishing liquid passage 411 in the target liquid purification device of the fourth to sixth embodiments of the present invention (see FIGS. 7 to 9) may be added to the target liquid purification device of the first to third embodiments of the present invention (see FIGS. 1, 5 and 6). In this case, the first replenishing liquid is supplied or introduced directly from each of the pair of first replenishing liquid passages 411 and 412 to the unpurified target liquid passage 11 and the purification target liquid passage 12, respectively. The pair of first replenishing liquid passages 411 and 412 may communicate with a common replenishing liquid supply source or with separate replenishing liquid supply sources.

[0106] The regenerated liquid branch passage 222 of the sixth embodiment of the present invention (see FIG. 9) may be added to the target liquid purifiers of the first to fifth embodiments of the present invention (see FIGS. 1, 5 to 7). The regenerated liquid branch passage 221 of the third embodiment of the present invention (see FIG. 6) may be added to the target liquid purifiers of the second and fourth to sixth embodiments of the present invention (see FIGS. 5 and 7 to 9).

[0107] (Anomaly detection method) In addition to the configuration of the above embodiment, the target liquid purification device of the present invention is equipped with an abnormality detection device 301 that detects abnormalities based on time-series fluctuations in the concentration of the target substance, and an alarm device 400 that alarms the abnormality detected by the abnormality detection device 301.

[0108] The anomaly detection device 301 constitutes a part of the control device 300, and is a device that detects anomalies based on the time series of the concentration of the target substance. Here, the time series fluctuation of the concentration of the target substance is, for example, the first concentration C1 → This is information that shows the value of each time series. At this time, the first concentration C1 → The values ​​of a plurality of target substances may be used as the value of . Based on the time series information of the concentrations of the plurality of target substances, an abnormal value is calculated statistically or using a machine learning method. For example, → If the value of does not change, it can be determined that dialysis is not being performed sufficiently. Also, if a certain substance is present in a larger amount than other substances, it can be determined that the composition of the replacement fluid is insufficient.

[0109] Notification device 400 is connected to the target liquid purification device via wireless communication such as a network or wired communication such as a cable (see FIG. 1). Notification device 400 is, for example, software installed on a personal computer, smartphone, etc. Notification device 400 is carried by, for example, a patient using the target liquid purification device, their family, or a medical professional in charge.

[0110] If an abnormality is detected by the abnormality detection device 301, the output interface 402 of the alarm device 400 will report this. This allows the user to recognize deterioration of the target liquid purification device, and based on this recognition, can reliably carry out purification of the target liquid. Furthermore, since medical personnel can recognize in advance the presence or absence of disease or the risk of disease, this can be beneficial in maintaining the health of patients using the target liquid purification device. [Example]

[0111] Example 1 is a target fluid purification device having the configuration of the first embodiment of the present invention. Figure 10 is a graph showing the concentration of urea nitrogen, as a target substance, in the unpurified target fluid F11 and the first fluid F211 when the flow rate of the replenishment fluid F41 in the target fluid purification device of Example 1 was set to 100, 200, 300, and 450 mL / min. Note that the unpurified target fluid F11 (blood flow rate) was 250 mL / min. Referring to Figure 10, when the flow rate of the replenishment fluid F41 was higher than the flow rate of the unpurified target fluid F11 (replenishment fluid F41 flow rate: 100, 200 mL / min), the urea nitrogen concentration in the unpurified target fluid F11 and the urea nitrogen concentration in the first fluid F211 were approximately the same. On the other hand, when the flow rate of the replenisher fluid F41 was higher than that of the unpurified target fluid F11 (flow rate of the replenisher fluid F41: 300, 450 mL / min), the urea nitrogen concentration of the first fluid F211 was lower than that of the unpurified target fluid F11.

[0112] Here, the removal performance when passing through the target liquid purification device once is expressed as an index called clearance CL. Clearance CL is the urea nitrogen concentration C in the unpurified target liquid F11. BI, urea nitrogen concentration C in the purification target liquid F12 BO , flow rate Q of unpurified target liquid F11 B Using this, it is expressed by the following relational expression (1).

[0113] CL =((C BI -C BO ) / C BI )*Q B (1)

[0114] Here, Q B When the flow rate is 250 mL / min, a CL of 230 to 250 mL / min means that approximately 100% of the urea nitrogen is removed in one pass through the target liquid purification device. Furthermore, the concentration of urea nitrogen in the first liquid F211 at this time can be calculated from the mass balance by dividing the concentration of urea nitrogen in the replenisher F41, the concentration of urea nitrogen in the first liquid F211, and the flow rate of the replenisher F41 by C. DI , C DO , Q D and is expressed by the following relational expression (2).

[0115] Q B *(C BI -C BO )=Q D *(C DO -C DI ) (2)

[0116] Furthermore, when the overall mass transfer area coefficient KoA is used, the following relational expression (3) is obtained.

[0117] (C BI -C BO ) / (C BI -C DI )= (1-exp(KoA(1 / Q BI -1 / Q BO ))) / (Q BI / Q DI -exp(KoA(1 / Q BI -1 / Q BO ))) ··(3)

[0118] Based on the above equations (1) to (3), CDO At this time, the operating conditions can be calculated as follows: B = 200 mL / min, C BI = 100 mg / dL, in the case of urea nitrogen, KoA can be considered to be about 3000, so the length of the separation device (dialyzer) is 25 cm and the membrane area is 1.5 m 2 Then, Q D When C is changed DO Calculating this, we obtain Figure 11 below.

[0119] Referring to Figure 11, when the flow rate of the replenisher F41 is less than 200 mL / min, which is approximately the same as the flow rate of the unpurified target liquid F11, the first liquid F211 has a concentration of 100 mg / dL, which is approximately the same as the unpurified target liquid F11. This is because the urea nitrogen in the unpurified target liquid F11 moves very quickly through the separation device in the target liquid purification device. In this case, the concentration distribution of urea nitrogen on the unpurified target liquid F11 side and the replenisher F41 side in the target liquid purification device can be calculated as shown in Figure 12 below.

[0120] In FIG. 12, the horizontal axis represents the longitudinal position of the separation device 100 (the inflow portion of the unpurified target fluid F11 into the separation device is 0, and the outflow portion of the filtrate fluid F12 is 25 on the horizontal axis), and the vertical axis represents the urea nitrogen concentration. Here, the solid line represents the urea nitrogen concentration on the first portion 110 side, and the dotted line represents the urea nitrogen concentration on the second portion 120 side. Referring to FIG. 12A, when the flow rate of the replenisher fluid F41 is 500 mL / min, it can be considered that the urea nitrogen in the unpurified target fluid F11 is substantially 100% removed (the urea nitrogen value at 25 cm is substantially 0). Referring to FIG. 12B, when the flow rate of the replenisher fluid F41 is 230 mL / min, the urea nitrogen is also substantially 100% removed. In this case, the value of the y-intercept, which represents the urea nitrogen concentration of the first fluid F211, is 40 mg / dL when the flow rate of the replacement fluid F41 is 500 mL / min, which is lower than the urea nitrogen concentration of the unpurified target fluid F11. However, as the flow rate of the replacement fluid F41 decreases, the urea nitrogen concentration increases. Referring to FIG. 12C, in the graph where the flow rate of the replacement fluid F41 is 150 mL / min, the urea nitrogen concentrations of the unpurified target fluid F11 and the first fluid F211 are approximately 100 mg / dL and can be considered equivalent. This allows the urea nitrogen concentration of the unpurified target fluid F11 to be determined by examining the urea nitrogen concentration of the first fluid F211 or the diafiltration effluent F21, without the need to install a measuring device 35 in the unpurified target fluid F11 (blood). This execution of the above-described process reduces the total amount of replacement fluid F41 in the target fluid purification device and ensures purification.

[0121] Although the results were shown using the value of urea nitrogen, similar results were observed for substances other than urea nitrogen that had high permeability to the separation membrane. Although not specifically shown, similar results were also observed in an example using potassium ions. Therefore, according to the present invention, the concentrations of multiple target substances can be accurately measured, enabling the overall control of the target liquid purification device based on the concentrations.

[0122] As described above, the target fluid purification device of the present invention can reduce the amount of dialysis fluid and perform control to reliably remove target substances from the target fluid. Therefore, it can be used for home dialysis, etc. Furthermore, if an abnormality occurs during home dialysis, the abnormality can be communicated to a remote medical professional, etc., thereby providing reliable dialysis treatment.

[0123] It should be noted that the present invention is not limited to the above-described embodiments or examples, and it is clear that the scope of the present invention can be modified or altered within a range that is obvious to those skilled in the art. It is also clear that the scope of the present invention is not limited to the above-described embodiments or examples, but also includes modifications and alterations thereof. [Explanation of symbols]

[0124] 11. Unpurified liquid passage 12. Purification target liquid passage 21. Diafiltration drainage passage 22‥Regeneration liquid passage 24. Drainage passage 31‥1st flow rate adjustment device 32‥Second flow rate adjustment device 35. Measuring equipment 100‥Separation equipment 102‥Porous membrane 110‥1st part 120‥Second part 200‥Reproduction section 201‥Regeneration circuit 202‥Regeneration circuit 221...Regenerated liquid branch passage 222...Regenerated liquid branch passage 300...Control device 301. Anomaly detection device 400. Alarm device 401...input interface 402: Output interface 411‥1st replenisher passage 412‥1st replenisher passage 422‥2nd replenisher passage 2011...First circuit (regenerative circuit 201) 2012...Second circuit (regenerative circuit 201) 2013‥Third flow rate adjustment device (regeneration circuit 201) 2021...First circuit (regeneration circuit 202) 2022: Second circuit (regeneration circuit 202) 2023‥Third flow rate adjustment device (regeneration circuit 202) F11...Unpurified liquid F12...Liquid to be purified F21: Diafiltration effluent F211...First liquid (drainage) F212...Second liquid F22‥Regeneration liquid F41‥1st replenisher F42‥Second replenisher.

Claims

1. 1. A target liquid purification device for removing at least one target substance from an unpurified target liquid, comprising: a separation device comprising a porous membrane having a pore size that allows the target substance contained in the unpurified target liquid to pass through, and a first portion and a second portion separated by the porous membrane, wherein the unpurified target liquid containing the target substance is passed through the porous membrane from the first portion and introduced into the second portion to produce a diafiltration effluent, and the target substance contained in the unpurified target liquid is removed by the passage, thereby producing a purified target liquid; an unpurified liquid passage for introducing the unpurified liquid into the first portion of the separation device; a liquid to be purified passage for leading the liquid to be purified from the first portion of the separation device; a diafiltration drain passageway for conducting the diafiltration drain from the second portion of the separation device; a drainage passage branching from the dialysis filtration drainage passage, for discarding the first liquid as a drainage liquid, of a first liquid and a second liquid resulting from separation of the dialysis filtration drainage; a regeneration unit including two or more regeneration circuits connected in series, each of which has an adsorbent that adsorbs the target substance, and which removes at least one of the target substances from the second liquid by bringing the second liquid introduced from the dialysis filtration discharge passage into contact with the adsorbent, thereby producing a regenerated liquid having a reduced concentration of the target substance; a regenerant passage for introducing the regenerant from the regeneration section to the second portion of the separation device; a first replenishment liquid passage for directly introducing replenishment liquid into at least one of the unpurified liquid passage and the purification liquid passage; and a measuring device provided in at least one of the unpurified target liquid passage, the separation device, and the filtration dialysis discharge passage, for measuring the concentration of the target substance.

2. The target liquid purification device according to claim 1, one of the regeneration circuits comprises a first circuit that brings the upstream liquid into contact with the adsorbent and then discharges it downstream, a second circuit that introduces the upstream liquid into the downstream without bringing it into contact with the adsorbent, and a flow rate control device that adjusts the flow rates of the upstream liquid introduced into the first circuit and the second circuit, The target liquid purification device is characterized in that the flow rate control device adjusts the flow rate introduced into the first circuit and the flow rate introduced into the second circuit depending on the concentration of the target substance in the filtration dialysis effluent measured by the measuring device.

3. The target liquid purification device according to claim 1 or 2, an anomaly detection device that detects an anomaly based on a time-series variation in the concentration of the target substance; a notification device that notifies of an abnormality detected by the abnormality detection device.

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