Target liquid purification apparatus

Abstract

The objective of the present invention is to provide a target liquid purification apparatus that can ensure performance of dialysis and removal of a substance to be discarded during the dialysis without excess or deficiency, while reducing the total amount of a dialysate used in the dialysis. A target liquid purification apparatus according to the present invention comprises: a separation device 100; an unpurified target liquid passage 11; a purification target liquid passage 12; a regeneration unit 200; a filtration dialysis drainage passage 21; a regenerated liquid passage 22; a drainage passage 24; a first replenishment liquid passage 412; a first flow rate adjustment device 31; a second flow rate adjustment device 32; a measurement device 35 that measures the concentration of a target substance; a control device 300; and a notification device 400.

Description

Target liquid purification equipment

[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.

[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 substance removed and / or its concentration in the blood after dialysis varies depending on the blood flow rate and / or dialysis time, but these are treatment conditions that are primarily determined by other factors. Therefore, the concentration of the target substance in the dialysis fluid is generally changed to ensure that the amount of target substance removed and / or its concentration in the blood after dialysis are appropriate. 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 / or the risk of hospitalization or death (see Non-Patent Document 1). Therefore, adjusting the concentration of the target substance to minimize the difference between the patient's serum and dialysate concentrations is beneficial for the patient. To minimize 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 1.5 mEq / L lower than that in the patient's serum at the start of treatment and then exponentially lowered during treatment (see Non-Patent Document 2). However, because there is no device that measures blood concentrations 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).

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

[0007] 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: 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

[0008] By utilizing the dialysis method and apparatus disclosed in Patent Document 1, it is possible to remove unwanted ions such as potassium from a target liquid such as a dialysis effluent while maintaining the fluidity of the dialysis effluent, thereby enabling the target substance to be removed efficiently and with an appropriate controlled concentration difference. On the other hand, when the dialysis method and apparatus disclosed in Patent Document 1 are used with a conventional dialysis apparatus (e.g., Patent Document 2), a substitution fluid is supplied during dialysis, which poses the problem that the total amount of dialysis is still large and also requires a large amount of substitution fluid, making it impossible to reduce 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). To determine whether dialysis has been performed sufficiently, simply removing a single target substance (a substance that can be adsorbed by a single adsorbent) in the proper amount is insufficient. It is necessary to determine whether dialysis has been performed sufficiently after removing multiple target substances in the proper amount. However, Patent Document 1 does not disclose a method for performing the proper removal of multiple target substances, which poses a problem that each of the multiple target substances is not removed in the proper 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.

[0011] In order to achieve the above object, the liquid purification device has the following invention-specific features.

[0012] a target liquid purification device for removing at least one target substance from an unpurified target liquid, the target liquid purification 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, the separation device generating a diafiltration effluent by passing the unpurified target liquid containing the target substance from the first portion through the porous membrane and introducing it into the second portion, and generating a purified target liquid by removing the target substance contained in the unpurified target liquid by this passage; an unpurified target liquid passage for introducing the unpurified target liquid into the first portion of the separation device; a purified target liquid passage for leading the purified target liquid from the first portion of the separation device; a diafiltration effluent passage for leading the diafiltration effluent from the second portion of the separation device; and a drainage passage branching from the diafiltration effluent passage for discarding the first liquid as effluent, of a first liquid and a second liquid resulting from separation of the diafiltration effluent. The separation device is characterized by comprising: a regeneration unit having 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, and which includes two or more regeneration circuits each connected in series; a regenerated liquid passage for introducing the regenerated liquid from the regeneration unit into the second part of the separation device; a first replenishment liquid passage for directly introducing a replenisher liquid into at least one of the unpurified target liquid passage and the purified target liquid passage; and at least one measuring device provided in any of the unpurified target liquid passage, the separation device, and the dialysis filtration discharge passage, which measures the concentration of the target substance.

[0013] In the target liquid purification device having the above-described configuration, 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 side without bringing it into contact with the adsorbent, and a flow rate control device that adjusts the flow rate of the upstream liquid introduced into the first circuit and the second circuit, and 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 filtration dialysis effluent measured by the measuring device.

[0014] In any of the target liquid purification devices having the configuration described above, it is preferable to further include an abnormality detection device that detects abnormalities based on time-series fluctuations in the concentration of the target substance, and an alarm device that notifies of abnormalities detected by the abnormality detection device.

[0015] FIG. 1 is a diagram illustrating the configuration of a target liquid purification device according to a first embodiment; FIG. 2 is a diagram illustrating the configuration of a regeneration section in the target liquid purification device according to the first embodiment; FIG. 3 is a flowchart illustrating a method for adjusting the flow rate of replenishment liquid in the target liquid purification device according to the first embodiment; FIG. 4 is a flowchart illustrating a method for adjusting the flow rate in a regeneration circuit in the target liquid purification device according to the first embodiment; FIG. 5 is a diagram illustrating the configuration of a target liquid purification device according to a sixth embodiment; FIG. 6 is a diagram illustrating the concentration of urea nitrogen in the unpurified target liquid and the concentration of the first liquid for each flow rate of replenishment liquid F41 in the target liquid purification device according to the example; Ｄ (replenishment fluid flow rate) and C ＤＯ1 is a diagram showing the relationship between the urea nitrogen concentration and the position of the separation device as seen from the unpurified target liquid passage when the flow rate of the replenisher liquid is 500 mL / min in the target liquid purification device of the embodiment. FIG. 2 is a diagram showing the relationship between the urea nitrogen concentration and the position of the separation device as seen from the unpurified target liquid passage when the flow rate of the replenisher liquid is 230 mL / min in the target liquid purification device of the embodiment. FIG. 3 is a diagram showing the relationship between the urea nitrogen concentration and the position of the separation device as seen from the unpurified target liquid passage when the flow rate of the replenisher liquid is 150 mL / min in the target liquid purification device of the embodiment.

[0016] 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 target substances contained in the unpurified target fluid F11 (e.g., blood, plasma, dialysis effluent, hemofiltrate) to pass through. The "target substances" include, 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 during illness, such as urea, creatinine, uric acid, peptides, and proteins. The separation device 100 generates a diafiltration effluent F21 (filtrate and / or dialysis effluent) by passing the unpurified target fluid F11 from the first portion 110 through the porous membrane 102 and introducing it into the second portion 120. The separation device 100 is configured to generate a purified target fluid F12 by removing the target substances contained in the unpurified target fluid F11 through the porous membrane 102.

[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, etc.) (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, etc.) (not shown) to adjust the flow rate of the purification target liquid F12. The separation device 100 is configured, for example, by a dialyzer. The first section 110 is the internal space of hollow fibers formed by dialysis membranes. The second section 120 is 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 liquid F11 in the first portion 110 and the flow direction of the regenerated liquid F22 in the second portion 120 are opposite or opposite to each other. On the other hand, in other embodiments, the separation device 100 may be configured as a "parallel current separation device" in which the flow direction of the unpurified liquid F11 in the first portion 110 and the flow direction of the regenerated liquid F22 in the second portion 120 are parallel or in the same direction.

[0020] The regeneration unit 200 has an adsorbent that adsorbs the target substance. Examples of the adsorbent include activated carbon and / or activated carbon-based adsorbents, porous adsorbents, adsorbents made of cation exchange resins, anion exchange resins, zirconia-based ceramics, zeolites, and mixtures thereof. The regeneration unit 200 removes at least a portion of the target substance by contacting a portion of the diafiltration effluent (second liquid F212) with the adsorbent. The regeneration unit 200 is configured to generate 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 portion 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 replacement 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 portion 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 portion 120 of the separation device 100.

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

[0023] The first flow rate control device 31 is, for example, a pump, a flow rate control valve, or a mass flow controller, and is provided in the drain passage 24. The first flow rate control 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 dialysate 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 dewatering 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 calculation 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 kg of body weight per hour.

[0027] Since it is usually difficult to achieve 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, 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, the flow rate of the replenishment fluid F41 and the flow rate of the first fluid F211 are approximately the same, and the flow rate of the replenishment 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 replenishment 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. Furthermore, when the flow rate of the replenishment fluid F41 is less than the flow rate of the first fluid 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 replenishment 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 unpurified target fluid passage 11. Since 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 adjusts the flow rate according to the concentration of the target substance, thereby increasing or decreasing the flow rate of the replacement fluid. 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 a limitation, and one or more measuring devices can be provided in any of the human body, the unpurified target fluid passage, the separation device, and the diafiltration effluent passage.

[0030] In this embodiment, the target liquid purification system includes, in addition to the target liquid purification device described above, a control device 300 and an alarm device 400, as shown in FIG. 1 . The control device 300 includes a storage device (such as RAM, ROM, EEPROM, SSD, HDD, etc.) that stores and retains programs (software) and data, a processing device (such as a single-core processor, multi-core processor, or CPU) that reads necessary programs and / or data from the storage device and executes predetermined arithmetic processing, and I / O circuits. 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 provided with an abnormality detection device 301, which detects an abnormality 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 the Reproducing Circuit) In this embodiment, the reproducing unit 200 may be configured with 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, the regeneration circuits 201 and 202 may be configured to remove the same type of target substance, or may be configured to remove different types of target substances. The 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 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, each of the first circuit 2011 and the second circuit 2021 may be configured to adjust the flow rate of the fluid flowing in one circuit by providing a flow control valve or a flow control pump in either the first circuit 2011 or the second circuit 2021, and then adjust the flow rate of the fluid flowing in the other circuit, thereby adjusting the respective flow rates of the second liquid F212 delivered to the first circuit 2011 and the second circuit 2012. By providing a three-way valve at the branch point between the first circuit 2011 and the second circuit 2012, each of the first circuit 2011 or the second circuit 2021 may be configured to adjust the flow rate of the fluid flowing in one circuit, and then adjust the flow rate of the fluid flowing in the other circuit, thereby adjusting the respective flow rates of the second liquid F212 discharged to the first circuit 2011 and the second circuit 2012.

[0036] In the regeneration circuit 202, similar to the regeneration circuit 201, 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, 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) may be 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) may be 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). Note that 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 of one embodiment, but is not limited to this, and three or more regeneration circuits may be used. In this case, the regeneration circuit 202 may be configured to generate the second regeneration liquid F222 and then deliver the second regeneration liquid F222 to the 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 circuits 201 and 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 target liquid purification device of the first embodiment configured as described above, 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 a 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 the 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 with 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 of adjusting flow rate in target liquid purification device) Next, a method of adjusting the flow rate of the replenisher liquid, which is performed in the target liquid purification method in the target liquid purification device of the first embodiment having the above-mentioned configuration, will be described with reference to Figure 3. 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 (Figure 3 / START), the opening degree OP of the first flow rate adjustment device 31 is adjusted. １ The opening theme １０ The opening degree OP of the second flow control device 32 is controlled to ２ The opening theme ２０ The flag f is initialized (0 is assigned to the flag f) (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 dialysis filtration effluent F21 in the dialysis filtration effluent passage 21 is calculated. → is measured, and the first concentration C １ → (=(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 ion, ammonium ion, calcium ion, magnesium ion, phosphate ion, bicarbonate ion, and organic acid ion, and the concentration of at least one of pathogenic substances that accumulate in the body due to renal failure, etc., such as urea, creatinine, uric acid, peptides, and proteins. That is, the concentration C of the target substance → (C １０ , C ２０ , ..., C ｎ０ ) (n is an integer of 1 or more, when n is 1, the concentration of the target substance C → is a vector with one element (target substance C → = (C １０ ))) is a vector.

[0043] Next, the first concentration C １→ (=(C １１ , C ２１ , ..., C ｎ１ )) is the specified concentration C ０ → (=(C １００ , C ２００ , ..., C ｎ００ )) or less (FIG. 3 / S312). The "designated concentration" is a concentration that indicates a value where 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 target substance C → The concentration is determined for each element (the concentration of each target substance). ０ → The elements of each of the above are different. For example, the target solution 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, potassium ions may be reduced more than necessary compared to 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 designated concentrations for each target substance.

[0044] Specified concentration C ０ → may vary depending on the time required for the purification of the target liquid. ０ → is the designated concentration C just before the completion of the target liquid purification ０ → In particular, the designated concentration C ０ → is preferably set to decrease continuously or discontinuously with time. ０ → Each element (C １００ , C ２００ , ..., C ｎ００) may vary independently depending on the target liquid purification time, or may vary in relation to each other depending on the target liquid purification time.

[0045] Furthermore, it is not desirable to continue dialysis when the concentration of a target substance is below a designated concentration. Therefore, when the concentration of the target substance is below the designated concentration, even if the dialysis time is short, it is necessary to terminate dialysis or prevent the concentration of the target substance from decreasing more than necessary. Therefore, after dialysis is completed, the configuration of the regeneration unit 200 or the replacement fluid F41 is changed, and dialysis is restarted to prevent the concentration of the target substance from decreasing more than necessary. Alternatively, as described below, multiple regeneration circuits are used to prevent the concentration of the target substance from decreasing more than necessary.

[0046] First concentration C １ → is the specified concentration C ０ → The determination of whether or not the first concentration C is less than or equal to the first concentration C is made for each element of each vector. １ → is the specified concentration C ０ → 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 determination may be made as to whether the first concentration C １ → is the specified concentration C １ → The determination may be made by determining whether the concentration is equal to or less than the first concentration C １ → The size of the specified concentration C ０ → When the first concentration C １ → is the specified concentration C ０ → It may be determined that the first concentration C １ → and specified concentration C ０ → When it is determined that the magnitude of the difference in deviation between the first concentration C １ → is the specified concentration C ０ →Alternatively, the deviation of some elements may be weighted and the first concentration C １ → and specified concentration C ０ → When it is determined that the magnitude of the deviation from the first concentration C １ → is the specified concentration C ０ → Here, the magnitude is a concept such as the norm of the vector, and may be 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 １ → The determination may be made using any machine learning method based on some or all of the above factors. The machine learning may be any supervised learning method using 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 (YES in S312 of FIG. 3), the flag f is incremented by 1 (S313 of FIG. 3). ０ At the start of dialysis, for example, there may be cases where dialysate remains in the dialysis device, and the first concentration C １ may be lower than the concentration of the target substance in the blood. ０ After a certain time has elapsed, the first concentration again becomes the designated concentration C. ０ If the value is less than the predetermined value, the dialysis termination operation is performed.

[0049] If the determination result is affirmative (FIG. 3 / S314...YES), the target liquid purifier ends the purification of the target liquid (FIG. 3 / END). At this time, the opening degree OP of the first flow control device 31 １ is the opening degree OP of the second flow control device 32 ２By making the value larger than , excess water accumulated in the body is removed by dehydration. In this embodiment, dehydration may be performed uniformly during the purification of the target liquid, or may be varied depending on the elapsed time during the purification of the target liquid. For example, dehydration may be varied depending on the elapsed time using the hematocrit value as a reference. In other words, dehydration is preferably performed so as to minimize changes in blood volume.

[0050] On the other hand, if the determination result is negative (FIG. 3 / S314...NO), the connector X １ The following processes are executed. As a result, in the early stage of dialysis, the dialysis operation can be controlled so as to reliably remove the target substance, even though the concentration of the target substance is low. Then, the processes from S315 onwards, which will be described later, are 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 the target liquid purification operation continues. Next, t is incremented by 1 (FIG. 3 / S316). Note that here, the elapsed time from the stage where t was set to 0 (FIG. 3 / S311) may be automatically measured, and then the process may proceed to S316.

[0052] After that, the dialysis elapsed time t reaches a predetermined elapsed time t ０ It is determined whether the time has elapsed (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 C ２ → (=(C １２ , C ２２ , ..., C ｎ２ )) is inserted with the current concentration C of the substance to be removed (FIG. 3 / S317).

[0054] Next, the first concentration C １ → and the second concentration C ２ → The difference between１ → -C ２ → (=(C １１ -C １２ , C ２１ -C ２２ , ..., C ｎ１ -C ｎ２ )) is the first density difference threshold ΔC １ → (=(ΔC １１ , ΔC １２ , ..., ΔC １２ )) or less (FIG. 3 / S318). １ → is a predetermined elapsed time t ０ is a threshold value for determining whether dialysis is being performed sufficiently after a predetermined elapsed time t ０ is taken into consideration, the first density difference threshold value ΔC １ → The density difference C may be used. １ → -C ２ → 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 threshold values ​​of the target substances, and each element is usually a different value. ０ Taking into consideration the first density difference threshold value ΔC1 that is the basis of the determination process, → Some or all of the elements of the first density difference threshold ΔC1 may be adopted. → may vary depending on the time required for the purification of the target liquid. → is the first concentration difference threshold ΔC1 immediately before the completion of the target liquid purification → In particular, the first density difference threshold ΔC → is preferably set to decrease continuously or discontinuously with time. → Each element (ΔC １１ , ΔC １２ , ..., ΔC １２) may vary independently depending on the target liquid purification time, or may vary in relation to each other depending on the target liquid purification time.

[0055] C １ → -C ２ → is the first density difference threshold ΔC １ → The determination of whether the value is equal to or less than the value in step S312 may be performed by a process similar to that in step S312 described above. Therefore, a description thereof will be omitted to avoid redundancy. On the other hand, the determination in step S318 may be performed by the same process as in step S311, or may be performed by a different process.

[0056] If the determination result is affirmative (FIG. 3 / S318...YES), the target fluid purification device is controlled to reduce the flow rate of at least one of the replacement fluid F41, unpurified target fluid F11, and diafiltration effluent F21 (FIG. 3 / S319). 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, diafiltration effluent passage 21, and 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 makes it possible to limit the flow rate of the replacement fluid F41. Then, the connector X ０ The following process is executed. That is, the first concentration C １ → 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 determined by the concentration difference C １ → -C ２ → or the magnitude of a predetermined elapsed time t ０The flow rate of the replacement fluid F41 may be adjusted taking into consideration the magnitude of the flow rate of the replacement fluid F41. 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 C １ → and the second concentration C ２ → The difference between １ → -C ２ → is the second density difference threshold ΔC ２ → (=(ΔC ２１ , ΔC ２２ , ..., ΔC ２２ )) or more (FIG. 3 / S320). ２ is a predetermined elapsed time t ０ is a threshold value for determining whether dialysis is insufficient after a predetermined elapsed time t ０ is taken into consideration, the second density difference threshold value ΔC ２ A part or all of the elements of the second density difference threshold ΔC may be adopted. ２ → may vary depending on the time required for the purification of the target liquid. ２ → is the second concentration difference threshold ΔC just before the target liquid purification is completed ２ → In particular, the second density difference threshold ΔC ２ → is preferably set to decrease continuously or discontinuously with time. ２ → Each element (ΔC ２１ , ΔC ２２ , ..., ΔC ２２ ) may vary independently depending on the target liquid purification time, or may vary in relation to each other depending on the target liquid purification time.

[0059] C １ → -C ２ → is the first density difference threshold ΔC ２ → The determination of whether the number of the inputs is equal to or greater than the number of the inputs may be performed by a process similar to the determination in S312 described above. The description of this determination process will be omitted to avoid redundancy. Meanwhile, the determination in S320 may be performed by the same processing method as either one of S311 or 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 target fluid purification device is controlled to increase the flow rate of at least one of the replacement fluid F41, unpurified target fluid F11, and diafiltration effluent F21 (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, diafiltration effluent passage 21, and 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 connector X ０ The following process is executed. That is, the first concentration C １ The process of measuring the initial value of 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 connector X ０ The following process is executed. That is, the first concentration C １ The process of measuring the initial value of the dialysis start time t (FIG. 3 / S312) and subsequent processes are repeated. This controls the dialysis operation so that the target substance is not inadvertently removed by dialysis.

[0062] In the above embodiment, in the method for adjusting the flow rate of the replenishment liquid, the predetermined elapsed time t ０ , the degree 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 wastewater F21, and the first concentration difference threshold ΔC １ → and the second density difference threshold ΔC ２ → was constant, but after a predetermined elapsed time t ０ The number of times elapsed or the first concentration C １ → This allows optimizing the amount of F41 in the replenisher, preventing the target substance from being reduced too much, and ensuring that the excess target substance is removed.

[0063] S318 to S321 C １ → -C ２ → 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, this 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 １ → -C ２ → The adjustment may be based on an arbitrary function that uses some or all of the elements of the formula (1) as variables. Note that the function may be weighted to some of the variables. That is, S318 to S321 after S317 may be omitted, and the degree 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 be adjusted based on the first concentration C １ → -C ２ → A function with each element of is calculated as a variable, and the connective X ０ The following processing may be performed.

[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 value equal to or greater than the second concentration C ２ →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 of the second concentration C 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 based on the second concentration C ２ → A function with each element of is calculated as a variable, and the connective X ０ The following processing may be performed.

[0065] The flow rate adjustment described above is １ → -C ２ → The adjustment may be based on any machine learning based on some or all of the above factors. The machine learning may be any supervised learning 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, as in the second to sixth embodiments described below, where the replenishment liquid is provided through multiple paths, the flow rate adjustment method within the target liquid purification device may be implemented by independently adjusting each replenishment liquid flow path.

[0067] (Method for Adjusting Flow Rate in Regeneration Circuit) Next, with reference to FIG. 4, a method for adjusting the flow rate of the third flow 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 "S4OO," which means that "S4OO" is performed in parallel with "S3OO" in the process or immediately before or after "S3OO" (meaning that the same number (10 to 21) is inserted in each "OO"). 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 method for adjusting the flow rate in the regeneration circuit will be described using the regeneration circuit 201 as an example. Here, the regeneration circuit 201 is a regeneration circuit that includes an adsorbent that adsorbs potassium ions, but it is clear that the regeneration circuit 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 OP of the third flow control device 2013 is ３ The opening theme ３０ and the flag f １ is initialized (flag f １ (FIG. 4 / S410). Here, OP ３ A state of 0 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 C of potassium ions is measured. １１ means the first concentration C １ → The first concentration C of potassium ions, which is the concentration before the predetermined time has elapsed, is one of the elements. 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 C of potassium ions １１ But the specified concentration of potassium ions C １００ It is determined whether the concentration is equal to or less than the reference concentration (FIG. 4 / S412). The "designated concentration" is a 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. Designated concentration C １００ may vary depending on the time required for the purification of the target liquid. １００ is the designated concentration C just before the completion of the target liquid purification １００ In particular, the designated 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 f １ Next, the flag f １ is the threshold value f １０ At the start of dialysis, for example, dialysate may remain in the dialysis device, and the first potassium ion concentration C １１ may be lower than the concentration of the target substance in the blood. １０ After the time has elapsed, the first concentration C of potassium ions is again 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 affirmative (FIG. 4 / S414...YES), the opening degree OP of the third flow control device 2013 is ３ 0 is inserted in OP ３ The state where is 0 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. As a result, in the early stage of dialysis, the dialysis operation is controlled to reliably remove the target substance, given that 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 (NO in S412 in FIG. 4), the target liquid purification device determines that the purification of potassium ions in the target liquid is insufficient, and the target liquid purification operation continues. Next, t is incremented by 1 (S416 in FIG. 4). Note that the elapsed time from the point where t was set to 0 (S411 in FIG. 4) may be automatically measured, and then the process may proceed to S416.

[0076] After that, the dialysis elapsed time t reaches a 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 ０ may be the same or different.

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

[0078] Next, the first concentration C of potassium ions １１ and the second concentration C ２１ The difference between 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 equal to or less than the first concentration difference threshold ΔC (FIG. 4 / S418). １１ is a 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 density difference threshold value ΔC １１ The density difference C may be used. １１ -C ２１ The magnitude of the first concentration difference threshold ΔC indicates the level of the 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. １１ is the first concentration difference threshold ΔC just before the target liquid purification is completed１１ 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 degree OP of the third flow control device 2013 is ３ is ΔOP ３１ The third flow control device 2013 is controlled so that the opening degree OP is reduced by the opening degree OP (FIG. 4 / S419). ３ The minimum value of is 0, and in S319, the opening OP ３ When it becomes negative, the opening OP ３ This makes it possible to prevent potassium ions from being reduced more than necessary from the body fluid. １１ The process from the measurement process for initializing the dialysis start time t (FIG. 4 / S411) onwards is repeated.

[0080] The third flow rate control device 2013 is configured to adjust the concentration difference C １１ -C ２１ or the magnitude of a predetermined 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 １１ -C ２１ is the second concentration difference threshold ΔC of potassium ions ２１ It is determined whether the second concentration difference threshold ΔC of potassium ions is equal to or greater than the first concentration difference threshold ΔC (FIG. 4 / S420). ２１ is a predetermined elapsed time t １０ is a threshold value for determining whether dialysis is insufficient after a predetermined elapsed time t １０ is taken into consideration, the second density difference threshold value ΔC ２１ The second density difference threshold value ΔC may be adopted. ２１ may vary depending on the time required for the purification of the target liquid. ２１is 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 degree OP of the third flow control device 2013 is ３ is ΔOP ３２ The operation of the third flow control device 2013 is controlled so that the flow rate is increased by the amount of the third flow control device 2013 (FIG. 4 / S421). As a result, even if the adsorption of potassium ions is insufficient, the dialysis operation is controlled so that the potassium ions are reliably removed. ０ The following process is executed. That is, the first concentration C １１ The process of measuring the initial value of the dialysis start time t (FIG. 4 / S412) and subsequent processes 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 connector X ０ The following process is executed. That is, the first concentration C １１ The process of measuring the initial value of the dialysis start time t (FIG. 4 / S412) and subsequent processes are repeated. This controls 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 density difference threshold ΔC ２１ was constant, but after a predetermined elapsed time t １０ The number of times elapsed or the 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] In Figure 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. The control in the regeneration circuit 201 and the control in the regeneration circuit 202 are controlled independently of each other. Three or more regeneration circuits may be provided, and even in this case, each is 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 removal of potassium ions is suppressed and the urea nitrogen is efficiently removed.

[0086] S418 to S421 C １１ -C ２１ Based on the concentration of only ３ However, this is not limited to the above embodiment, and the opening OP ３ is C １１ -C ２１ In other words, S418 to S421 may be omitted after S417, and the opening degree OP ３ The opening theme ３ =OP ３ (C １１ -C ２１ ) and the connector X ０ The following processing may be performed.

[0087] Also, opening OP ３ is C ２１ In other words, S418 to S421 may be omitted after S417, and the opening degree OP ３ The opening theme ３ =OP ３ (C １１ -C ２１ ) and the connector X ０ The following processing may be performed.

[0088] In this embodiment, the processing (S310 to S321) described in FIG. 3 and the processing (S410 to S422) described in FIG. 4 are performed in parallel with "S3OO" or immediately before or after "S3OO" in the reference numeral "S4OO," but this is not limited to this. In this embodiment, in the processing (S310 to S321) described in FIG. 3, S410 to S422 may be omitted and S310 to S321 may be processed, or in the processing (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 processing (S410 to S422) described in FIG. 4 may be terminated when a predetermined time has elapsed.

[0089] Second Embodiment The target liquid purification device of the second embodiment shown in Fig. 5 has a configuration in which a second replenishment liquid passage 422 is added to the target liquid purification device of 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 replenishment liquid F42 and the first replenishment liquid F41 is approximately the same as the flow rate of the first liquid F211, and in the replenishment liquid flow rate adjustment method, the total flow rate of the second replenishment liquid F42 and the first replenishment 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, if the ion concentration detected by the measuring device 35 is the same as that of the unpurified target liquid F11, the flow rates of the second replenisher liquid F42 and the first replenisher liquid F41 can be adjusted depending on the likelihood of membrane clogging, the removal characteristics of substances from the unpurified target liquid F11 in the separation device 100, etc.

[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] 6 is a third embodiment of the target liquid purification device, which is similar to the first embodiment of the target liquid purification device (see FIG. 1) except that a regenerated liquid branch passage 221 is added to the target liquid purification device of the first embodiment. 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] 7, the target liquid purification device of the fourth embodiment is provided with a first replenishing liquid passage 411 instead of the first replenishing liquid passage 412 in the target liquid purification device of the first embodiment (see FIG. 1). The first replenishing liquid passage 411 is configured to introduce the first replenishing 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 target liquid purification device of the fourth embodiment 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 the 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 producing a regenerated liquid F22 with 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). The first replenishment liquid F41 is then directly mixed with the unpurified target liquid F11 (S9').

[0098] Fifth Embodiment The target liquid purification device of the fifth embodiment shown in Fig. 8 has a configuration in which a second replenishment liquid passage 422 is added to the target liquid purification device of 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] The 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 the same symbols are used for similar configurations and descriptions are omitted.

[0101] 9 is a configuration in which a regenerated liquid branch passage 222 is added to the target liquid purification device of 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] The 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 the same symbols are used for similar configurations and descriptions are omitted.

[0104] (Effects) According to the target fluid purification device and target fluid purification method of the above-described embodiment, the 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, and it can be configured to be suitable for use in home environments and be environmentally friendly.

[0105] Other Embodiments The first replenishing liquid passage 411 of the target liquid purification device of the fourth to sixth embodiments (see FIGS. 7 to 9) may be added to the target liquid purification device of the first to third embodiments (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 (see FIG. 9) may be added to the target liquid purification devices of the first to fifth embodiments (see FIGS. 1 and 5 to 7). The regenerated liquid branch passage 221 of the third embodiment (see FIG. 6) may be added to the target liquid purification devices of the second and fourth to sixth embodiments (see FIGS. 5 and 7 to 9).

[0107] (Abnormality detection method) In addition to the configuration of the above embodiment, the target liquid purification device 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 C １ → At this time, the first concentration C １ → The values ​​of a plurality of target substances may be used as the value of the first concentration C. 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, １ → 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] The 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 ). The notification device 400 is, for example, software installed on a personal computer, smartphone, etc. The 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 the abnormality detection device 301 detects an abnormality, 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 perform target liquid purification. Furthermore, since medical professionals can recognize in advance the presence or absence of disease or the risk of disease, they can beneficially perform target liquid purification to maintain the health of patients using the target liquid purification device.

[0111] Example 1 is a target fluid purification device having the configuration of the first embodiment. Figure 10 is a graph showing the concentration of urea nitrogen, a target substance, in the unpurified target fluid F11 and the first fluid F211 when the flow rate of the replenishment fluid F41 was 100, 200, 300, and 450 mL / min in the target fluid purification device of Example 1. 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 greater 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 liquid F41 was greater than the flow rate of the unpurified target liquid F11 (flow rate of the replenisher liquid F41: 300, 450 mL / min), the urea nitrogen concentration of the first liquid F211 was lower than the urea nitrogen concentration in the unpurified target liquid F11.

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

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

[0114] Here, Q ＢWhen 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. In addition, 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 relations (1) to (3), C ＤＯ At this time, the operating conditions are Ｂ =200mL / 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 changing C ＤＯ is calculated, and FIG. 11 is obtained.

[0119] 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 becomes 100 mg / dL, which is approximately the same as the unpurified target liquid F11. This is because the urea nitrogen moves very quickly from the unpurified target liquid F11 to 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 FIG.

[0120] In Figure 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 filtered body fluid F12 is 25), 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 Figure 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 Figure 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. Meanwhile, as the flow rate of the replacement fluid F41 decreases, the urea nitrogen concentration of the first fluid F211 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 measuring the urea nitrogen concentration of the first fluid F211 or the diafiltration effluent F21, without the need to provide a measuring device 35 in the unpurified target fluid F11 (blood). As a result, the above-mentioned process is carried out, so that the total amount of replenisher fluid F41 in the target fluid purification device can be reduced and purification can be carried out reliably.

[0121] Although the results were shown using the values ​​of urea nitrogen in the examples, 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, such a target liquid purification device can accurately measure the concentrations of multiple target substances, enabling overall control of the target liquid purification device based on the concentrations.

[0122] As described above, the target fluid purification device 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.

[0124] 11. Passage for unpurified liquid to be purified 12. Passage for liquid to be purified 21. Diafiltration drainage passage 22. Regenerated liquid passage 24. Drainage passage 31. First flow rate adjustment device 32. Second flow rate adjustment device 35. Measuring device 100. Separation device 102. Porous membrane 110. First part 120. Second part 200. Regeneration section 201. Regeneration circuit 202. Regeneration circuit 221. Regenerated liquid branch passage 222. Regenerated liquid branch passage 300. Control device 301. Abnormality detection device 400. Notification device 401. Input interface 402. Output interface 411. First replenishing liquid passage 412. First replenishing liquid passage 422. Second replenishing liquid passage 2011. First circuit (regeneration circuit 201) 2012. Second circuit (regeneration circuit 201) 2013: Third flow control device (regeneration circuit 201) 2021: First circuit (regeneration circuit 202) 2022: Second circuit (regeneration circuit 202) 2023: Third flow control device (regeneration circuit 202) F11: Unpurified target liquid F12: Target liquid for purification F21: Filtration dialysis effluent F211: First liquid (effluent) F212: Second liquid F22: Regenerated liquid F41: First replacement liquid F42: Second replacement liquid.

Claims

1. A target liquid purification device for removing at least one target substance from an unpurified target liquid, 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 from the first portion through the porous membrane and introduced into the second portion to produce a diafiltration effluent, and the target substance contained in the unpurified target liquid is removed by this passage, thereby producing a purified target liquid; an unpurified target liquid passage for introducing the unpurified target liquid into the first portion of the separation device; a purified target liquid passage for leading the purified target liquid from the first portion of the separation device; a diafiltration effluent passage for leading the diafiltration effluent from the second portion of the separation device; and a drainage passage branching from the diafiltration effluent passage, for discarding the first liquid as effluent, of the first and second liquids resulting from separation of the diafiltration effluent. 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 regenerated liquid passage for introducing the regenerated liquid from the regeneration unit into the second part of the separation device; a first replenishment liquid passage for directly introducing a replenisher liquid into at least one of the unpurified target liquid passage and the purified target liquid passage; and at least one measuring device provided in any of the unpurified target liquid passage, the separation device, and the dialysis filtration discharge passage, which measures the concentration of the target substance.

2. A target liquid purification device as described in claim 1, wherein one of the regeneration circuits comprises a first circuit that brings upstream liquid into contact with the adsorbent and then discharges it downstream, a second circuit that introduces upstream liquid into the downstream side without bringing it into contact with the adsorbent, and a flow rate adjustment device that adjusts the flow rate of the upstream liquid introduced into the first circuit and the second circuit, respectively, wherein the flow rate adjustment device adjusts the flow rate introduced into the first circuit and the flow rate introduced into the second circuit in accordance with the concentration of the target substance in the filtration dialysis effluent measured by the measuring device.

3. A target liquid purification device according to claim 1 or 2, characterized in that it comprises an abnormality detection device that detects abnormalities based on time-series fluctuations in the concentration of the target substance, and an alarm device that notifies of abnormalities detected by the abnormality detection device.

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