JPH01230372A - Regenerative device for processing body fluid - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a processing device for drawing body fluids such as blood from a human body to the outside of the body, subjecting it to appropriate processing, and then returning it to the body. This relates to a system in which two processors are installed in parallel so that they can be switched, and each processor can be reused by performing regeneration processing on the used processors. This ensures that the switching is done safely and reliably.

[Explanation of terms]

In the present specification, "a body fluid" refers to a liquid component such as blood, lymph, ascites, etc.

In addition, "1 body fluid treatment" refers to removing harmful components, unnecessary components, etc. from the above body fluids, replenishing medicinal components, supplementing old and insufficient components, and replacing specific components.

[Conventional technology]

A body fluid processing method that collects body fluids from the human body, circulates them outside the body, processes them appropriately, and then returns them to the body.
It is applied to the treatment of various diseases.

For example, the above-mentioned body fluid treatment can be used for diseases such as hyperlipidemia, drug addiction, fulminant hepatitis, macroglobulinopathy, multiple osteomyelitis 2, myasthenia gravis, rheumatoid arthritis, liver failure, erythromatosus, and nephritis. The method is valid.

Figure 4 is a schematic diagram of a conventional body fluid treatment device that selectively removes low-density riboprotein (IDL) and very low-density riboprotein (VLDL), which are the main causes of hyperlipidemia, from the blood of patients with hyperlipidemia. The body fluid processing apparatus is comprised of a blood collection area 20, a collected blood processing area 40, and a treated blood return area 60.

In the sampling area 20, there is a blood pressure monitor 21. Blood pressure abnormality detector 22
, blood collection pump 23. Heparin pump 24 for anticoagulation,
Dorisopchanha 25. A plasma separation pressure gauge 26 and the like are provided to enable continuous and safe blood sampling. In addition, near the blood sampling end, there is a supply source 27 of a circulating fluid (physiological saline or Rinkel's solution) for cleaning the device and a fluid cut-off detector 2.
8 are connected.

The processing area 40 is an area where blood is subjected to predetermined processing, and includes a plasma separator 41 that separates plasma components from collected blood.
．． Plasma manometer 42. Blood leakage detector 43. Plasma pump 44. Feeding side drip chamber 45. Delivery blood pressure it46,
Processor 4 for removing LDL and VLDL from plasma
7. Filter to prevent contamination with adsorbents, etc. 48. Return side drip chamber 49. A delivery blood pressure monitor 50 and the like are provided.

In the return area 60, there is a heating hook 61. Dorisobchanhar62. Return blood pressure monitor63. A bubble detector 64 and the like are provided to safely return the treated blood to the human body 70.

Next, the process of executing the process by the -F body fluid processing device will be explained.

First, blood is collected from the patient's body 70 using the blood pump 23 while maintaining an appropriate blood pressure. heparin pump 2
While injecting heparin for anticoagulation from 4, the collected blood is guided to a plasma separator 41. In the plasma separator 41, +
Part or all of the plasma components in the fu/& are separated and sent to the processor 47, and the remaining blood passes through as it is.The processor 47 is filled with an adsorbent, While the collected plasma passes through, LDL and V L I) 1) are adsorbed and removed.The thus treated plasma is combined with the blood that has passed through the blood separator 4I. After being warmed up, blood is returned to the human body.

By the way, the above-mentioned body fluid treatment apparatus had the following practical drawbacks.

1. During body fluid treatment, blood fills the entire device.

This means that a considerable amount of blood is removed from the patient's body. Therefore, it is not possible to unnecessarily increase the size of the device, as this may cause anemia or the like.

ii) Since the amount of extracorporeal blood circulation is large, it is difficult to apply to people with low body weight, anemia, and low blood pressure.

111. As a preparatory step for body fluid treatment, after connecting each component of the device and assembling the device, cleaning the inside of the device by flowing physiological saline or the like is performed in advance. Therefore, before execution of the process, the inside of the apparatus is filled with circulating liquid. Since this circulating fluid is injected into the patient's body as the body fluid treatment is started and progresses, there is a risk that the colloid osmotic pressure of the blood will decrease, causing a +in pressure drop.

Therefore, in Japanese Patent Application No. 60-6341 related to the applicant's earlier application, Ichito Motoyama solved the drawbacks mentioned in -1 by installing multiple processors with a smaller capacity than before in parallel. did. As shown in FIG. 5, the body fluid treatment apparatus described in the above application has a plurality of small treatment units 51 and 52 arranged in parallel in the treatment area, and each of the small treatment units 51 and 52 is provided with a supply source 53 for circulating fluid. ．．
A body fluid delivery mechanism consisting of a liquid delivery pump 54 and a circulating fluid discharge path 55 are connected.

With this configuration, by sequentially using the small processors 51.52, it is possible to reduce the extracorporeal circulation amount of 1f1[liquid], and the flow rate that is initially filled in the small processors 51. By discharging the liquid from the discharge path 55, it is possible to prevent a decrease in the permeability of the colloid. In other words, the body fluid treatment device overcomes the drawbacks 1 to iii above.

[Problem to be solved by the invention]

However, even with the above treatment device, the amount of extracorporeal circulation of blood and the amount of inflow of 1 m of liquid into the body are still reduced, but the total amount of adsorbent used for the - times of treatment is still the same as before. Ru.

Therefore, the more one attempts to reduce the capacity per small processor, the more the number of small processors has to be increased. Moreover, these used small processing units are discarded, resulting in increased costs and increased medical costs.

There remains the problem.

By the way, the present applicant has previously filed the patent application 1986-348.
In No. 8, we presented a method to increase the adsorption capacity of used adsorbents. In this method, ln 1. After adsorbing VLDL and
If you wash it with the electrolyte aqueous solution in 4)! , D1, and V
This is a technique that allows the ability of the adsorbent to be regenerated by filling the adsorbent with melted water.

(11) If we apply biotechnology, we can install multiple small processing units in parallel, process body fluids in one of them, and regenerate the used small processing unit in parallel. Each application allows each small processor to be used repeatedly.
ζ, since the number of small processors can be kept to the necessary minimum, the problem of 1v can be solved.

However, when trying to introduce the above-mentioned regeneration method into the above-mentioned body fluid treatment method using a plurality of treatment devices, the following new problem arises. Of course, the aqueous electrolyte solution for regeneration (regeneration solution) contains electrolytes at a higher concentration than the physiological concentration, and when mixed with body fluids, the salt concentration of the body fluids increases. Furthermore, there is a problem in that the regenerating liquid remaining in the reprocessing device that has been subjected to the regenerating process may be injected into the patient's body, which may cause various disorders.

[Means to solve the problem]

The present invention enables the repeated use of a body fluid treatment device in which a plurality of treatment devices are installed in parallel by performing 4L treatment again, and when reusing the treatment device, there is a To provide a body fluid treatment device that can confirm that no regenerating fluid remains and, if any regenerating fluid remains, immediately start processing the body fluid using the processor.

The body fluid treatment device according to the present invention is characterized by comprising a collection area, a treatment area, and a return area, and the treatment area includes a plurality of treatment devices, a body fluid supply route connected to each treatment device, and a return area. i￥ path, 100ηf liquid (l supply path and discharge path, circulating liquid (Jli supply path and discharge path, means for measuring the salt concentration of the circulating liquid flowing out from each treatment device, and means for measuring the salt concentration of the 1ffl liquid in the flow) The present invention is provided with 1IlF for directing (1IIF), an identification path, means for adjusting the amount of /'Ili of body fluids, regenerating fluids, and circulating fluids, and means for switching each route.

[Operation] The execution status of the processing by the body fluid processing device according to the above configuration will be explained as follows.

First, a predetermined treatment is applied to the collected body fluid in a suitable treatment device selected from a plurality of treatment devices. The processed body fluid is
Send to the return area. When the amount of body fluid processed in the ljI transformation processor reaches a predetermined amount, execution of the process is transferred to the downstream processor. Then, the body fluid treatment is performed in the post-processing device, and the regeneration liquid is supplied to the pre-processing device to perform the regeneration process. When the regeneration process of the pre-processing device is completed, the circulating liquid is continuously supplied to the pre-processing device, and the salt concentration of the flowing liquid flowing out is measured by the salt concentration measuring means. When the amount of body fluid processed in the post-processing device reaches a predetermined amount, processing is transferred to the +iii-stage processing device again while confirming that the salt concentration of the circulating liquid flowing out from the pre-processing device is within a predetermined value range. do.

In addition, the present invention enables repeated use of each treatment device by performing regeneration treatment, so it is possible to reduce the capacity of the treatment device required to process the required amount of body fluid. can. Then, by measuring the salt concentration of the flowing liquid flowing out from the treatment device that has completed the regeneration process, we confirm that no regeneration liquid remains in the treatment device before switching the treatment device. There is no risk that it will be injected into the human body.

〔Example〕

The details of the present invention will be explained below based on the drawings showing examples. In Figure 1, plasma is separated from blood and LDL and VIDL are selected from the plasma.1)? This is a first embodiment of the present invention in a body fluid treatment device that removes about 600 ml of body fluid, and the treatment area in the body fluid treatment device is schematically shown.

In this example,! 11 In the processing area, two processors A1. A2 is arranged in parallel, and the processor AI.

A2 is filled with an adsorbent that selectively adsorbs LDL and VLDL. Further, in the processing area, a supply source B of a regenerating liquid that regenerates the processing capacity of the processing device and a supply source C of a flow 1ffl liquid that pushes out the body fluid or the regenerating liquid from the inside of the processing device are provided. The processor AI.

On the inflow side of A2, there is a body fluid supply path, a regeneration liquid supply i ¥1
? fiF and 1m liquid supply path I are connected (however, the regeneration liquid supply path F and the 1m flow liquid supply path II merge in the middle), and on the outflow side, there is a body fluid return path E and a regeneration liquid discharge path. and a discharge path G (+) which also serves as the circulating liquid υI outlet path.
is connected. A confirmation path I (branched from the above-mentioned discharge path G(1) is provided to guide the 1 m liquid flowing out from the treatment units AI and A2 to the salt concentration measuring means 1.Furthermore, a body fluid flow rate A body fluid pump 11 that adjusts the flow rate of the regenerating fluid and the fluid pumps 1 and 2 that adjust the flow rate of the regenerating fluid
is incorporated.

Valve Old to Old 2 are placed at appropriate locations on each path.
Body fluid, 100) 1: Switching of the path through which the fluid or circulating fluid flows is controlled by these.

In addition, in the figure, 1 is a plasma separator that separates plasma components from collected blood, 2 is a blood pressure meter, 3 is a blood leakage detector that monitors the mixing of blood cell components into plasma, and 4 is a feeder that prevents air bubbles from being mixed in. A side drip chamber, 5 is a feeding plasma pressure side, 6 and 7 are liquid cutoff detectors, 8 is a liquid feeding pressure d1, 9 is a regeneration system drip chamber, 10 is for preventing adsorbents from being mixed into plasma. 11 is a return plasma pressure meter, and 12 is a return side drip chamber.

”--the processor A1. The capacity of A2 is less than half of that required for body fluid treatment using a single conventional treatment device.

This is because 1. DL and V L tl L
The ability to remove adsorbent is limited by the total amount of adsorbent used, but because the treatment equipment can now be reused, the total amount used can be increased with a smaller amount of adsorbent than before. be.

The regenerating liquid used in this example is such that the adsorbent is, for example, L D
When a polyanionic compound that adsorbs L and V l rl [, is immobilized on a water-insoluble carrier, a highly concentrated aqueous electrolyte solution is used. To give a specific example, when the adsorbent is cellulose gel on which dextran sulfate is immobilized, the salt concentration of the regenerating liquid is 0.18 to 6.
It is desirable to use a thorium chloride aqueous solution of mol/1 (preferably 0.3 to 1 mol/l).

The circulating fluid is Ringer's solution or physiological saline (salt concentration 0.1
5 mol/1. ) etc. are used. Circulating fluids need to be physiologically harmless because they may come into contact with body fluids or be injected into the human body.

The salt concentration measuring means, I, is for confirming that the salt concentration of the liquid flowing out from the treatment device is a physiological concentration, and includes, but is not limited to, an electrical conductivity meter, etc. .

The plasma separator 1 includes a molded 11-port separator that filters blood with a semipermeable membrane, and a centrifugal plasma separator that uses differences in sedimentation coefficients, but any of the types can also be used. iJ
It is Noh.

In addition, forceps, pinch cocks, etc. are used for valves old to old 2, but solenoid type pinch cocks are easy to control and have a simple structure. In this case, if the solenoid type pinch switch is opened when 3 m is energized and closed when energized, it is possible to prevent accidents in emergencies such as power outages. Furthermore, if a suitable detection stage is installed to detect the operation of the pinch cock, accidents caused by erroneous operations can be avoided.

Next, the operation of the processing device described above is illustrated in FIG. 2 (al to (j)).
Explain using. In addition, in the drawing, valve old ~ M1
The open state of 2 is indicated by O, and the closed state is indicated by . Further, a path in which liquid such as body fluid is flowing is shown by a solid line (-), and a path in which it is not flowing is shown by a broken line (-). The order of use of the J0 processor is that A1 is the first stage and A2 is the second stage.

■ [See Figure 2 (a)] First, blood collected from the human body is sent to the plasma separator 1, plasma components are separated from the blood, and the blood is transferred to the body fluid delivery path I].
Supplied to pre-processor AI.

As mentioned earlier, by the washing a1 step before processing,
Since the insides of each of the processing units Al and A2 are filled in advance with a circulating fluid such as physiological saline, the inflow of plasma forces out the flow 1ffl liquid from the pre-processing unit A1. However, according to the present invention, the capacity of the processor is much smaller than that of the conventional one. Therefore, even if the circulating liquid of the individual culm of the processor is injected into the body, it will not cause any trouble. Therefore, only at the start of execution of the process, the circulating fluid is led to the body fluid return path 1shi and merged with the useful blood immediately after plasma separation. Rather, it is preferable that the circulating liquid flowing out from the pre-processing device A1 be sent to the human body first, since there is a risk of problems if the a-thick blood is returned to the human body as it is. However, if necessary, it is also possible to guide the circulating fluid pushed out by the blood 9 to the discharge path G (1) and discharge it outside the apparatus.

(See Figure 2 (bll) After filling the pre-processing device A1 with plasma, the plasma is subsequently fed to the pre-processing device AI to perform the pre-processing step.

The treated body fluid passes through the body fluid return path E, where it is combined with the blood that has passed through the plasma separator 1, and then is returned to the human body through the return area.

[See Figure 2 [C1]] When the amount of body fluid processed in the pre-processor A1 reaches a predetermined amount, the plasma supply is switched to the post-processing step 2, and the outflow side of the post-processor A2 is connected to the discharge path G. Connect to (1). Then, the circulating liquid is supplied to the pre-processing device Δ1.

As a result of this operation, the plasma in the pre-processing device A1 is pushed out by the circulating fluid to the body fluid return path E and returned to the human body, and the circulating fluid in the post-processing device A2 is discharged out of the circuit by the plasma. Note that in order to keep the blood sampling rate and the blood return rate constant, it is desirable to equalize the plasma feeding rate and the circulating fluid feeding rate.

■ [See Figure 2+d+] After pushing out the plasma from the pre-processor AI, the outflow side is switched to the discharge path G(1). At the same time, after discharging the circulating fluid from the post-processing device Δ2, the outflow side of the post-processing device A2 is switched to the body fluid return path E, and the post-processing process is executed.

(See figure 2, tel) In parallel with the post-processing process, a predetermined amount of regenerating liquid is supplied to the pre-processing device Δ1. When the adsorbent is cellulose gel on which dextran sulfate is immobilized and the regenerating liquid is a 0.7 mol/l saline solution, the optimum amount of regenerating liquid to restore the processing capacity is approximately 70% of the processing capacity. It is about %. The circulating liquid pushed out by the regenerating liquid is discharged from the discharge path G (+) to the circuit (E). With these two culms, L D L
, vl, and DL elute from the adsorbent, and the throughput of the adsorbent becomes the same fu.

■ [See Fig. 2 (see fll) After a predetermined amount of swarm liquid has been supplied, the inlet side of the 1111-stage processor 81 is switched to /M, +ffl liquid supply iX path H, and the regenerated liquid is The pre-processor A1
and expel it from the device.

(See FIG. 2(g)) After discharging the rlf4t-liquid from the pre-processing device A1, the circulating liquid is continuously supplied to clean the inside of the pre-processing device AI, and the salt concentration is returned to the physiological concentration. When the regenerating liquid is the above-mentioned 0.7 mol/p saline and the circulating liquid is physiological saline, after supplying the regenerating liquid, the circulating liquid is increased to /N1Jllll in an amount of 1.5 to 2 times the capacity of the processor. This is desirable.

■ [Figure 2 (see HL]) If the supply amount of the circulating liquid exceeds the specified amount -), while continuing to supply the circulating liquid, move the outflow side of the iiiI stage treatment I to the confirmation route l〈 Switch. Then, the circulating liquid flowing out from the pre-processing device A1 is guided to the salt concentration measuring means J. The regenerating liquid flowing out of the processing device and the circulating liquid immediately after the regenerating liquid is discharged contain protein components such as LDL, vl, and DL eluted from the adsorbent. If this is introduced into a salt concentration measuring means J such as electrical conductivity 11, a portion of the sensor will be contaminated and the reliability of measurement accuracy will be lost. Therefore, the salt concentration measuring means, J
In this case, a stream 1Jii liquid containing almost no protein components after the above-mentioned washing bottom stopper is introduced is assumed to be -.

■ [See Figure 2 [i1]] When the amount of body fluid processed in the post-processing process reaches a predetermined value, confirm that the salt concentration of the fluid flowing out from the pre-processing process 1 is at a physiological concentration, and The pre-processor AI
At the same time, the supply of the circulating liquid is switched to the post-processing device A2. The salt concentration in the pre-processing device Al gradually decreases through the washing process, and returns to the physiological concentration at the end of the washing. However, in the unlikely event that the salt concentration has not decreased to the physiological concentration, either stop switching the plasma feeding route and continue cleaning the pre-processor A1 for another 1 hour, or restart the body fluid treatment. Cancel continuation.By the switching operation B described in 1-, the plasma in the post-processing device A2 is pushed out into the circulating fluid and returned to the human body.The circulating fluid in the pre-processing step 1 is pushed out into the plasma and released from the device. is discharged.

By the way, blood! It is desirable to keep the feeding speed of No. 1 equal to the feeding speed of the circulating liquid.

[Phase] [See Figure 2 (j)] When the circulating fluid is discharged from the pre-processing device A1 and filled with 1III plasma, the outflow side is switched to the body fluid return path E and the pre-processing step is performed again.). At the same time, the body fluid is sent from 2 to the post-processing device to fill it with circulating fluid, and then the outflow side is switched to the discharge path G(1).

■ [Illustrations omitted] When the pre-processing device A1 and the post-processing device A2 are repeatedly used alternately, the post-processing device A2 is regenerated in parallel with the pre-processing step described in 1. Prepare for post-processing steps.

As described above-1-, according to the present invention, the treatment device can be reused, and the regenerating liquid is not injected into the body, and the regenerating liquid and body fluids do not come into contact with each other. It is possible to switch routes safely.

By alternately and repeatedly using the pre-processor AI and the post-processor A2, it is possible to significantly reduce the amount of adsorbent used, and at the same time reduce the capacity of the processor to reduce the amount of extracorporeal blood circulation. can be extremely reduced.

By the way, although in the embodiment described in (1)--21111 processors were installed in parallel, it is of course possible to install three or more processors in parallel in the processing area. - As an example, FIG. 3 shows three processors, namely 3. Middle stage processor Δ4. An embodiment in which post-processing units 85 are arranged in parallel is shown. In this embodiment, processor introduction, A4. A5 is used repeatedly in the order of the front stage, middle stage, and rear stage, but in this case, the following 41 steps may be added.

B. After the amount of body fluid processed by the front-stage processor Δ3 reaches a predetermined amount, the supply of body fluid is switched to the middle-stage processor A4. and,
In parallel with the execution of body fluid processing in the middle stage processor A4, the regeneration process of the front stage processing clan is performed.

After the amount of body fluid processed by the middle stage processor A4 reaches a predetermined amount, the supply of body fluid is switched to the second stage processor A5. and,
[Execution of body fluid processing to be sent to the post-processing device A5] In parallel with the second step, re-processing of the middle-stage processing device A4 is performed.

Note that the regeneration treatment of the pre-processing clan and the washing aI treatment of the regenerated liquid may be completed by the time the body fluid treatment sent to the post-processing device 5 is completed.

The invention is not limited to the embodiments described above. For example, LDI in plasma separated from blood, and V
Needless to say, the present invention can be applied to body fluid treatment other than treatment for removing LDL. As you can see, the present invention can be modified in various ways depending on the embodiment.

〔Effect of the invention〕

According to the present invention, the effects listed below can be obtained.

1. Since it is now possible to reuse a used treatment device, the capacity of the treatment device can be made smaller than before, and the amount of extracorporeal circulation of body fluids can be further reduced. Therefore, it is now possible to treat patients with small body weight and low blood pressure, who were thought to be inapplicable until now.

■The amount of adsorbent is smaller than before, but it is the same as before (J
Beyond that, the ability to handle body fluids is reduced.

Therefore, the treatment cost can be reduced.

(2) When reusing a recycled treatment device, switch the route after confirming that the regeneration liquid has been completely drained and the salt concentration in the treatment device has returned to the physiological concentration. Therefore, the regenerating fluid will not be injected into the body, nor will the salt concentration of the body fluid increase due to contact with the regenerating fluid. That is, a safe route switching system is guaranteed.

(2) It becomes an extremely reliable safety confirmation method when switching routes is automatically controlled using a computer or the like. When computer control is employed, path switching is usually automatically performed depending on the fluid flow rate or flow time. By using the present invention, safety can be further improved by measuring the salt concentration of the fluid at the time of switching and determining whether or not the switching is appropriate (11).

In short, the present invention provides an extremely practical body fluid treatment device that is low in cost, safe, and reliable.

[Brief explanation of the drawing]

1 to 3 show an embodiment of the present invention, and FIG. 1 does not schematically show the treatment area of the body fluid treatment device.
Figures 2 (al to (Jl are -1-) are schematic diagrams showing the operation of the body fluid treatment device, and Figure 3 is a schematic diagram showing an embodiment of another aspect. Figures 4 and 5 are conventional diagrams. As an example, FIG. 4 is a schematic diagram showing the entire body fluid treatment device, and FIG.
1 is a schematic diagram showing a treatment area of the body fluid treatment device described in No. 1. FIG. A1 to A 5-Processor B-Regeneration liquid supply source C Circulating liquid supply source D Integrated liquid supply path E Body fluid return path F Regeneration liquid supply path G-Regeneration liquid discharge path H Circulating liquid supply path I Circulating liquid discharge path J - One confirmation route for salt concentration measuring means Ll Plasma pump L2 - Liquid feeding pump M1 to M12 - Pulp 20 -
Collection area 40-Processing area 60-Return area Patent applicant
Kanebuchi Chemical Industry Co., Ltd. Yokogawa Electric Corporation Representative Patent Attorney Toshihiko Uchida J Figure 2 Figure 2 (C) (d) Figure 2 Figure 2 (h)

Claims (1)

[Scope of Claims] 1. A body fluid processing device comprising a collection area for collecting body fluids from a human body, a processing area for subjecting the collected body fluids to predetermined processing, and a return area for returning the processed body fluids to the human body, the device comprising: A regenerative body fluid treatment device characterized in that the area consists of the following components A to M. A: A plurality of processors installed in parallel B: A source of regenerating fluid that regenerates the processing capacity of the processors: C: A source of circulating fluid that pushes body fluids or regenerating fluids from inside the processor to the outside of the processor D: Inflow side of each processor A body fluid delivery path E connected to the outlet side of each treatment device to send the collected body fluid to the treatment device A body fluid return path F connected to the outflow side of each treatment device to send the processed body fluid to the return area A regeneration liquid supply path G connected to the outlet side of each treatment device to supply the regeneration liquid to the processing device.A regeneration liquid discharge path H connected to the outflow side of each treatment device and used to discharge the regeneration liquid flowing out from the treatment device to the outside of the device. Circulating liquid supply path I connected to the inflow side and for supplying the circulating liquid to the processing device. Circulating liquid discharge path J connected to the outflow side of each processing device for discharging the circulating liquid flowing out from the processing device to the outside of the circuit. Means K for measuring the salt concentration of the circulating liquid flowing out from the vessel K. A confirmation path L that is connected to the outflow side of each treatment device or is provided branching off from the circulating liquid discharge path and guides the circulating liquid to the salt concentration measuring means. Flow rate adjustment means M for adjusting the respective flow rates of body fluid, regenerating fluid, and circulating fluid flowing through each route M switching means for each route