JPH01104272A - Blood treatment apparatus - Google Patents

Abstract

PURPOSE:To independently operate a filter membrane module, by controlling the liquid level detection means of a plasma storage bag and a plasma supply pump so as to operate both of them in connection with each other. CONSTITUTION:A plasma component is stored in the plasma storage bag 4 provided to a plasma supply circuit and air contained in plasma is separated and, when said plasma component is stored in a definite amount or more, the plasma supply pump 5 controlled so as to be operated in connection with a liquid level detection means 10 is operated to take out plasma from the plasma storage bag 4 to send the same to a filter membrane module 6. The purified plasma composed of a low MW substance separated by the filter membrane module 6 is sent to the purified plasma storage bag 8 provided to a purified plasma feedback circuit 22. The separated conc. plasma containing a high MW substance is discharged by the conc. plasma discharge pump 15 provided to a conc. plasma discharge circuit 24 and the flow rate of this pump 15 is controlled in connection with the plasma supply pump 5 so that the flow ratio of the amount of plasma supplied to the filter membrane module 6 and the amount of conc. plasma led out from the module 6 always becomes a predetermined value.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a blood processing device in which a centrifugal separator and a filtration membrane module are connected and integrated.

(Conventional technology and its problems) In recent years, the amount of high molecular weight substances contained in the blood has increased abnormally. It is clear that these high-molecular weight substances are deeply involved in the onset and pathology of various diseases such as cancer, multiple myeloma, metabolic abnormalities such as macroglobulinemia, and various diseases such as hyperviscosity syndrome). Plasma separation methods have become widely used for this purpose. The plasma separation method involves first separating blood into plasma components and blood cell components, removing harmful high molecular weight substances from the separated plasma components, and then injecting the thus treated plasma components and previously separated blood cell components into the body. This is a method of returning the money to the

Conventional methods for separating blood into plasma components and blood cell components include a membrane separation method using a filtration membrane module and a centrifugation method using a centrifugal separator. The plasma separation method using the membrane separation method described above is as follows: (1) After separating blood into plasma components and blood cell components through a membrane, the plasma components containing harmful substances are removed, and new plasma in an amount equivalent to the plasma components is added to the blood cells. A method of mixing with ingredients and returning it to the body.

(2) After separating blood into plasma components and blood cell components through a plasma separation membrane, the plasma components containing harmful substances are brought into contact with an adsorbent to adsorb and remove the harmful substances, and then the plasma components are recombined with blood cell components. How to mix and return to the body.

(8) After separating blood into plasma components and blood cell components via a plasma separation membrane, the plasma components are further separated into low molecular weight substances including albumin and high molecular weight substances using a plasma processing membrane,
A method of returning purified plasma from which high molecular weight substances including harmful substances have been removed into the body by mixing it with blood cell components (Japanese Patent Application Laid-Open No. 56-74
No. 164, No. 56-145860, etc.).

(4) After separating blood into plasma components and blood cell components through a plasma separation membrane, the plasma components are cooled to gel high molecular weight substances including harmful substances, and this gel is removed with a filtration membrane and filtered. A method is known in which only low molecular weight substances that have passed through a membrane are mixed with blood cell components and returned to the body (Japanese Patent Application Laid-open No. 31869/1986).

On the other hand, as a plasma processing membrane using centrifugation method, (1) After separating blood into blood cell components and plasma components using a centrifugal separator,
A method in which plasma components containing harmful substances are removed, and new plasma in an amount equivalent to the blood cell components is mixed with the blood cell components and returned to the body.

(2) After blood is separated into plasma components and blood cell components using a centrifugal separator, the plasma components are separated into high molecular weight substances and low molecular weight substances using a filtration membrane module. A method of returning the ingredients to the body (Japanese Patent Application Laid-open Nos. 57-64058 and 59-8967)
.

It has been known.

Among the above plasma processing methods, plasma exchange therapy, in which separated plasma is exchanged with new plasma, has problems in securing plasma from healthy individuals to be transfused to patients, and problems associated with transfusion of plasma from healthy individuals. Because of side effects such as infection with new pathogens and serum sickness, it is considered desirable to purify one's own plasma before transfusion. Among them, after separating blood into blood cell components and plasma components using a centrifugal separator, the separated plasma components are passed through a filtration membrane filter. The method of treating with Neil is an excellent and extremely safe method since there is no concern about a decrease in separation efficiency or hemolysis. However, at present, there are almost no plasma processing methods in which plasma is processed using a combination of a centrifugal separator and a Joule filter membrane. The reason for this is that there are two types of existing centrifugal separators: a batch processing method and a continuous processing method, and it is extremely difficult to connect and integrate the membrane module with the centrifugal separator and the filtration membrane module. Since the capacities are different, it may be difficult to balance the flow rate by controlling only the filtration membrane module independently of the control system of the centrifugal separator. Therefore, the conventional centrifugal separator and filtration membrane module are connected by a dedicated closed circuit, and the control system of the centrifugal separator controls the pump etc. connected to the filtration membrane module. When connecting the filtration membrane module to the centrifuge, it was necessary to modify the control circuit of the centrifugal separator.

In addition, such a device is extremely expensive because it is similar to a device exclusively used for plasma processing.

Therefore, an object of the present invention is to separate the control system of the filtration membrane module from the control system of the centrifugal separator and perform the control separately, and to provide a blood flow system that is continuously connected and integrated with both of the two types of existing centrifugal separators. The object of the present invention is to provide a processing device for the processing.

(Means for Solving the Problems) The present invention continuously connects a centrifugal separator and a filtration membrane module provided in an extracorporeal circulation circuit, and transfers plasma components separated by the centrifugal separator to the filtration membrane module. In a blood processing device that separates high molecular weight substances and low molecular weight substances into high molecular weight substances and returns purified plasma and blood cell components from which high molecular weight substances have been removed to the body, a centrifugal separator and a filtration membrane module in the extracorporeal circulation circuit are connected. A plasma supply circuit is provided with a plasma storage bag and a plasma supply pump capable of adjusting the flow rate so that the liquid level is within a set range by interlocking control with means for detecting the liquid level in the plasma storage bag, and A purified plasma storage bag is provided in the purified plasma return circuit that returns purified plasma from which high molecular weight substances have been removed by the filtration membrane module to the body, and a purified plasma storage bag is provided in the concentrated plasma discharge circuit of the filtration membrane module by interlocking control with the plasma supply pump. This blood processing device is characterized by being provided with a concentrated plasma discharge pump that is set such that the ratio between the amount of plasma introduced into the filtration membrane module and the amount of concentrated plasma discharged is a predetermined value.

In the centrifugal separator connected to the filtration membrane module in the present invention, blood is supplied into the centrifugal bowl on one side, only plasma components are continuously taken out from the bowl on the other hand, and blood cell components are kept in the bowl. When the blood cell detector detects that blood cell components have accumulated and flowed out of the bowl and into the plasma extraction tube, the blood collection is immediately stopped and the blood cell components accumulated in the bowl are removed from the blood supply port. Centrifugal separator (Hae
monetics v-50 type device and PEX type device, etc.), blood is supplied into a centrifugal bowl on one side, and plasma components and blood cell components separated in the centrifugal bowl are continuously taken out on the other side. Continuous centrifugal separator (IBM 2997
molding equipment, etc.).

As the Pii4 membrane module, a module containing a flat membrane or a hollow fiber membrane can be used. In particular, it is preferable to use a module incorporating a hollow fiber membrane from the viewpoint of ease of manufacture and miniaturization. The filtration membrane used in the above filtration membrane module selectively separates plasma components into high molecular weight substances and low molecular weight substances, and the molecular weight cutoff can be set arbitrarily depending on the purpose. For example, in the case of autoimmune disease, which is one of the main target diseases for treatment using the device of the present invention, the molecular weight cutoff can be set at 100,000. This is because the pathogenic substance of autoimmune diseases is γ-, which has a molecular weight of approximately 160,000.
Since it often exists in a form bound to globulin, it is desirable to remove substances with larger molecular weights, and to reflux substances with lower molecular weights such as albumin, which has a molecular weight of 67,000 and is useful for living organisms. Therefore, the molecular weight cutoff is 10
If it is 10,000, the above-mentioned γ-globulin and albumin can be sharply fractionated. The molecular weight cutoff of the filtration membrane should be set depending on the molecular weight of the target pathogenic substance. set between. As such a filtration membrane, any membrane may be used as long as it can fractionate and separate plasma components under pressure, and in this sense, filtration membranes with ultrafiltration properties can be widely used. Therefore, the structure of the membrane is not particularly limited, and a homogeneous microporous membrane or an asymmetric membrane can be used. Materials for such filtration membranes include polyvinyl alcohol (PVA), ethylene-vinyl alcohol:y-#(E
VA) type copolymers, cellulose derivatives such as cellulose acetate, polyolefins, polyamides, polyamides, polyesters, polysulfones, etc. are used. Among these, it is desirable to use PVA type, EVA type, cellulose enzyme conductor, polysulfone, etc., which have excellent biocompatibility.

(Function) The blood processing device of the present invention has a plasma storage bag and a purified plasma storage in a plasma supply circuit that connects a centrifugal separator and a filtration membrane module, and a purified plasma return circuit that returns plasma purified by the filtration membrane module to the body. By installing a tank and controlling the liquid level of the plasma storage bag, the air mixed with the plasma supplied from the centrifugal separator is reliably separated in the plasma storage bag, and the filtration membrane is There is no need to match the throughput with that of the centrifugal separator, and the filtration membrane module can be operated independently.

Therefore, the filtration membrane module is connected continuously to both centrifugal separators, and the centrifugal separator and filtration membrane module are each controlled independently, so that the filtration membrane module is controlled by one control system. Blood can be processed continuously.

(Example) Next, one embodiment of the device of the present invention will be described with reference to the drawings.

Figure 1 is a system diagram of a device that combines a continuous centrifugal separator and a transient membrane module.To explain its configuration according to the flow of blood, blood first flows from the patient to the blood introduction section 1 (shunt, injection The blood is transported through a blood introduction circuit 20 from a part (such as a needle that can be connected to an ordinary blood collector or a blood reservoir) to a centrifugal separator 3 by a pump 2 such as a roller pump, if necessary. The blood introduced into the centrifugal separator f&3 is separated into plasma components and blood cell components by centrifugal force, and the separated plasma components are filtered by a roller pump (not shown) built into the centrifuge. The plasma is led out to the plasma supply circuit 21 connected to the membrane module 6, stored in the plasma storage bag 4 provided in the plasma supply circuit, and the air contained in the plasma is separated. On the other hand, the separated blood cell components are led out from the blood cell supply circuit 23 to a mixer 9 such as a Y-shaped connector.

The plasma storage bag 4 is provided with means 10 for detecting the liquid level in the bag. When more than a certain amount of plasma accumulates in the plasma storage bag, a plasma supply pump 5 such as a roller pump, which is controlled in conjunction with the liquid level detection means, is operated to remove plasma from the plasma storage bag and filter it. Send to membrane module 6. A drip chamber (not shown) connected to a pressure gauge is attached to the plasma supply circuit 21, and is used to monitor abnormal pressure caused by clogging of the filtration membrane module 6 or other factors. There is. The plasma sent to the filtration membrane module 6 is separated into high molecular weight substances and low molecular weight substances in this module. The purified plasma consisting of low molecular weight substances separated by the filtration membrane module 6 is sent to the purified plasma storage bag 8 provided in the purified plasma return circuit 22.

The purified plasma drawn out from the purified plasma storage bag 8 is mixed with blood cell components in the mixer 9 provided in the purified plasma return circuit 22, and then delivered to the patient via the purified plasma outlet section 18 (a section that can be connected to a shunt, drip set, etc.). is injected into. On the other hand, the r
The concentrated plasma containing high molecular weight substances separated by the membrane module 6 is discharged by the concentrated plasma discharge pump 15 provided in the concentrated plasma discharge circuit 24. The flow rate of this concentrated plasma discharge pump 15 is controlled in conjunction with the plasma supply pump 5 so that the flow rate ratio between the amount of plasma supplied to the F3fi4 membrane module and the amount of concentrated plasma derived from the module is always a predetermined value. There is. In this case, when the flow rate of the plasma supply pump 5 is set to 30 cc/min, the flow rate of the concentrated plasma discharge pump 15 is 115 to 1/10 or less, that is, 6 cc/min.
/ml n ~3 CC/min or less.

In order to supplement the concentrated plasma removed by the filtration membrane module 6, a fluid replacement circuit 25 replenishes the purified plasma with replacement fluids such as Aldazun and hydroxyethyl starch (HES) from the fluid replacement bag 11, and a purified plasma storage circuit 22 is connected to the fluid replacement circuit 25. It is connected to the inlet side of the bag via a replacement fluid pump 7. In this case, the concentrated plasma discharge pump 15 and the replacement fluid pump 7 are controlled in conjunction with each other so that a replacement fluid equal to the amount of concentrated plasma discharged is added to the purified plasma.

Preferably, the means 10 for detecting the liquid level in the plasma storage bag 4 constantly monitors the liquid level because the setting of the liquid level can be easily changed. Examples of liquid level detection means include a method using a pressure sensor that detects the liquid level using pressure, a method that uses weight to detect the liquid level, and a method that directly detects the liquid direction level using ultrasonic waves. can be used.

This liquid level detection means 10 detects the amount of plasma stored in the plasma storage bag 4, and the number of revolutions of the plasma supply pump 50 is automatically changed or the switch is automatically turned on by interlocking control with this detection means. By turning it ON-OFF, the liquid level in the plasma storage bag can be controlled to be within the set range. For example, if the liquid level falls below a set level, the rotation speed of the plasma supply pump 5 may be slowed down or stopped temporarily. In particular, in a system where the plasma supply pump is automatically turned OFF, if the flow rate of the plasma supply pump is set higher than the plasma flow rate derived from the centrifugal separator, a large amount of plasma will accumulate in the plasma storage bag 4. Plasma can be processed quickly without any problems.

The means for controlling the flow rate of each of the pumps 5, 71, 15 may be a method of electrically controlling the rotational speed of the pumps. Alternatively, a two-barrel type or two-barrel type mouth-rabon pump may be used. In this case, the flow rate of liquid flowing through each circuit can be adjusted by changing the diameter of the pot tube. The plasma storage bag 4 may be a flexible bag of 50 to 3000 cc, such as a blood bag. Further, as the purified plasma storage bag 8, a flexible bag with a capacity of 200 to 3000 cc is normally used, but when the purified plasma is returned to the body by the purified plasma delivery pump 7, a container with a capacity of 10 to 50 cc can also be used. This container may also be a drip chamber used in dialysis or the like. The above device may further be provided with a plasma warmer for warming the plasma cooled during extracorporeal circulation and a pre-filter for removing formed components in the plasma on the upstream side of the filtration membrane module.

FIG. 2 is a system diagram of an apparatus that combines a batch-type centrifugal separator and a filtration membrane module. In a batch-type centrifugal separator, sterile air flows into or out of the centrifuge bowl during the blood collection and blood return steps. In other words, the sterile air initially filled in the centrifuge bowl is expelled by the blood introduced into the bowl during blood collection, but when blood is returned, the blood cell components accumulated in the bowl flow into the bowl. It is designed to be expelled with sterile air. In addition, in a batch-type centrifugal separator, blood collection and blood return (or return plasma) are carried out using separate needles in a two-arm method, in which purified plasma and blood cell components are mixed in a centrifuge bowl and the blood is returned from the blood inlet. There is an arm method. Figure 2 shows an example of a device using the two-arm method, and its configuration will be explained according to the blood flow. If necessary, the blood is transported from the blood introduction circuit 20 to the bowl of the centrifugal separator 3 by a pump 2 such as a roller pump, for example.

Then, the sterile air filled in the centrifugal bowl is expelled by the blood supplied by the pump 2, and first the sterile air and then the separated plasma components are transported to the plasma storage bag 4 via the plasma supply circuit 21. On the other hand, the separated blood cell components are accumulated as they are in the centrifuge bowl. When a blood cell detector (not shown) detects that the blood cell components accumulated in the centrifugal bowl overflow from the centrifugal bowl and flow into the plasma supply circuit, the drive of the centrifugal separator is stopped and the blood collection process is completed. , move on to the blood return process. Plasma separated by a centrifugal separator during blood collection is processed by a filtration membrane module 6. That is, the plasma components separated by the centrifugal separator are delivered to the plasma supply circuit 21 by a roller pump (not shown) built into the centrifugal separator, and stored in the plasma storage bag 4 provided in the circuit. The plasma components stored in the plasma storage bag 4 are separated into high molecular weight substances and low molecular weight substances by the filtration membrane module 6 in the same way as shown in FIG. and sent to the purified plasma storage tank 8.

The purified plasma drawn out from the purified plasma storage bag 8 is infused into the patient through the purified plasma return circuit 22 through the purified plasma delivery section 18 (a section that can be connected to a tube, an infusion set, etc.).

In the blood return process, the roller pump 2 that introduces blood into the centrifugal bowl is rotated in the opposite direction. Then, the blood cell components accumulated in the bowl are sucked into the blood introduction circuit 20 and returned to the body from the blood introduction section 1 through the circuit. This blood return operation is performed using a centrifugal separator. When the blood cell components in the bowl are removed, a negative pressure is created in the bowl, so that the sterilized air accumulated in the upper part of the plasma storage bag 4 is sucked into the bowl from the plasma supply circuit 21. When the blood cell components in the bowl are completely replaced with sterile air and this sterile air is further sucked by the roller pump 2 and flows out into the blood introduction circuit 2o, an air bubble detector (not shown) provided in the blood introduction circuit is activated. The pump 2 is then stopped, and the blood return process is thus completed. The above two steps of blood collection and blood return are considered as one cycle, and this is repeated as many times as necessary.

Note that in FIG. 2, the same parts as in FIG. 1 are given the same numbers and their explanations will be omitted.

(Effects of the Invention) As described above, the device of the present invention has a plasma storage bag and purified plasma storage in the plasma supply circuit that connects the centrifugal separator and the filtration membrane module, and the purified plasma return circuit that connects the filtration membrane module and the plasma outlet. By providing a bag and controlling the liquid level detection means of the plasma storage bag in conjunction with the plasma supply pump, the air contained in the plasma drawn out from the centrifugal separator can be reliably separated by the plasma storage bag, and the air can be filtered. There is no need to match the plasma throughput in the membrane module with the plasma flow rate separated by the centrifugal separator, and the filtration membrane modules can be operated independently. Therefore, it is possible to provide a blood processing device that is continuously connected to various existing centrifugation devices. This system eliminates damage and loss of red blood cells and platelets, as well as loss of serum proteins.
It is possible to efficiently and safely remove paralytic substances from the blood.

[Brief explanation of the drawing]

The drawings show one embodiment of the blood processing device of the present invention. FIG. 1 is a system diagram of a blood processing device that combines a continuous type centrifugal separator and a filtration membrane module, and FIG. 2 shows a batch type blood processing device. FIG. 2 is a system diagram of a device that combines a centrifugal separator and a filtration membrane module. 1...Blood inlet meter...Centrifugal separator 4...Plasma storage bag 5...Plasma supply Pump 6... Filtration membrane module 7...
... Fluid replacement pump 8 ... Purified plasma storage bag 15 ...
...Concentrated plasma evacuation pump 18...
Blood outlet patent applicant RiRa Shi Co., Ltd.

Claims (1)

[Claims] The centrifugal separator and filtration membrane module installed in the extracorporeal circulation circuit are connected continuously, and the plasma components separated by the centrifugal separator are separated into high molecular weight substances and low molecular weight substances by the filtration membrane module. In a blood processing device for returning purified plasma from which substances have been removed and blood cell components to the body, a plasma storage bag is provided in a plasma supply circuit that connects a centrifugal separator and a filtration membrane module in the extracorporeal circulation circuit, and the plasma storage bag. A plasma supply pump is provided that can adjust the flow rate so that the liquid level is within a set range by slow-acting control with a means for detecting the liquid level in the membrane, and the purification membrane module removes high molecular weight substances. A purified plasma storage bag is provided in the purified plasma return circuit that returns plasma to the body, and the concentrated plasma discharge circuit of the filtration membrane module is controlled in conjunction with the plasma supply pump to control the amount of plasma introduced into the filtration membrane module and the amount of concentrated plasma discharged. 1. A blood processing device comprising: a concentrated plasma discharge pump set such that the ratio of