JPH0534989B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a blood processing device that connects and integrates a centrifugal separator and a membrane module.

(Conventional technology and its problems) In recent years, an abnormal increase in high molecular weight substances in the blood has been associated with autoimmune diseases such as rheumatism, SLE, myasthenia gravis, Guttopastier syndrome, and idiopathic thrombocytopenic purpura. It has become clear that these substances are closely related to the onset and pathology of various diseases such as multiple myeloma, metabolic abnormalities such as macroglobulinemia, and hyperviscosity syndrome. Separation methods became widely used. 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 membrane module and a centrifugation method using a centrifugal separator. The plasma separation method using the membrane separation method described above includes: (1) After separating blood into plasma components and blood cell components through a membrane, plasma components containing harmful substances are removed and new plasma is generated in an amount equivalent to the plasma components. A method of mixing it with blood cell components 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.

(3) After separating blood cells 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, and high molecular weight substances including harmful substances are separated. A method of mixing purified plasma from which molecular weight substances have been removed with blood cell components and returning it to the body (JP-A-56-74164, JP-A-56-74164)
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 containing harmful substances, and this gel is removed with a membrane membrane. A method in which only the low molecular weight substances that have passed through the membrane are mixed with blood cell components and returned to the body (Japanese Patent Laid-Open No. 57-31869).

It has been known.

On the other hand, the plasma processing method using centrifugation is as follows: (1) After separating blood into blood cell components and plasma components using a centrifugal separator, plasma components containing harmful substances are removed, and new plasma is produced in an amount equivalent to the blood cell components. A method of mixing it with blood cell components and returning it to the body.

(2) After separating blood 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 membrane module, and the purified plasma from which only high molecular weight substances have been removed is separated into blood cells. Method for returning ingredients to the body
64058, 59-8967).

It has been known.

Among the above plasma processing methods, plasmapheresis therapy, in which separated plasma is exchanged with new plasma, has problems in securing plasma from healthy individuals to be transfused to patients, and the transfusion of healthy plasma can also lead to the introduction of new pathogens. Because of the side effects such as infection with blood and serum sickness,
It is considered desirable to purify one's own plasma before transfusion. Among them, the method of separating the fluid into blood cell components and plasma components using a centrifugal separator and then processing the separated plasma components using a membrane module is an extremely safe and excellent method because there is no need to worry about a drop in separation efficiency or hemolysis. It's a method. However, at present, there are almost no plasma processing methods in which plasma is processed using a combination of a centrifugal separator and a membrane module. The reason for this is that there are two types of existing centrifugal separators: batch processing and continuous processing.
Since it is extremely difficult to connect and integrate the membrane module and the centrifugal separator and the membrane module have different processing capacities, it is necessary to control only the membrane module independently of the centrifuge control system to balance the flow rate. This may be because it is difficult to do so. Therefore, the conventional centrifugal separator and membrane module are connected through a dedicated closed circuit, and the control system of the centrifugal separator controls the pump, etc. connected to the membrane module. If the membrane module and membrane module were to be connected in series, it was necessary to modify the control circuit of the centrifugal separator. Furthermore, such a device is extremely expensive because it is similar to a device exclusively used for plasma processing.

Therefore, it is an object of the present invention to separate the control system of the membrane module from the control system of the centrifugal separator and perform it separately, and to continuously connect and integrate the control system 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 problem) The present invention continuously connects a centrifugal separator and a membrane module provided in an extracorporeal circulation circuit,
Plasma components separated by a centrifugal separator are separated into high molecular weight substances and low molecular weight substances by a membrane module.
In a blood processing device that returns purified plasma and blood cell components from which high molecular weight substances have been removed into the body, a plasma storage bag is provided in a plasma supply circuit that connects a centrifugal separator and a membrane module in the extracorporeal circulation circuit, and a plasma storage bag is provided. A plasma supply pump is provided that can adjust the flow rate so that the liquid level is within a set range by interlocking control with a means for detecting the liquid level in the bag, and the 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 membrane module is controlled in conjunction with the plasma supply pump to control the amount of plasma introduced into the membrane module and the amount of concentrated plasma discharged. This blood processing apparatus is characterized in that it is provided with a concentrated plasma ejection pump that is set so that the ratio of .

In the centrifugal separator connected to the membrane module of the present invention, blood is supplied into the centrifuge bowl from one side, only plasma components are continuously taken out from the bowl from the other side, blood cell components are accumulated in the bowl, and blood cells are collected. A batch-type centrifugal separator (manufactured by Haemonetics) that immediately stops blood collection and extracts the blood cell components accumulated in the bowl from the blood supply port when the blood cell detector detects that components have overflowed the bowl and flowed into the plasma extraction tube. V-50 type device, PEX type device, etc.), and a continuous type centrifugal separator (IBM 2997 type device manufactured by the company).

As the membrane module, a module having a built-in flat membrane or hollow fiber membrane can be used. In particular, it is preferable to use a module containing a hollow fiber membrane because it is easy to manufacture and can be miniaturized. The membrane used in the 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 causative substances of autoimmune diseases often exist in a form bound to γ-globulin, which has a molecular weight of about 160,000, so substances with a larger molecular weight are removed, and substances with a lower molecular weight and less harmful to the body are removed. It is desirable to reflux especially useful albumin, which has a molecular weight of 67,000. Therefore, if the molecular weight cutoff is 100,000, the above-mentioned γ-globulin and albumin can be sharply fractionated. The molecular weight cutoff of the membrane is
It should be set depending on the molecular weight of the target pathogenic substance, and in addition to the above-mentioned examples, when the cause is an immune complex, the molecular weight cutoff is set between 100,000 and 200,000. As such a membrane, any membrane can be used as long as it can fractionate and separate plasma components under pressure, and in this sense, membranes with ultra-permeability 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. Examples of the membrane material include polyvinyl alcohol (PVA), ethylene-vinyl alcohol (EVA) copolymers, cellulose derivatives such as cellulose acetate, polyolefin, polyacrylonitrile, polyamide, polyester, polysulfone, and the like. Among these, it is desirable to use PVA type, EVA type, cellulose derivatives, 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 circuit in a plasma supply circuit that connects a centrifugal separator and a membrane module, and a purified plasma return circuit that returns plasma purified by the membrane module to the body. By installing a tank and controlling the liquid level of the plasma storage bag, the air contained in the plasma supplied from the centrifugal separator is reliably separated in the plasma storage bag, and the amount processed by the membrane module is reduced by centrifugation. The membrane modules can be operated independently without the need to match the throughput of the separation device. Therefore, the membrane module is connected continuously to either of the two types of centrifugal separators, and the centrifugal separator and the membrane module are each controlled independently, allowing the blood to be continuously processed as if it were controlled by a single control system. can be processed.

(Example) Next, an example of the apparatus 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 membrane module. To explain its configuration according to the flow of blood, blood first flows from the patient into the blood introduction section 1 (shunt, injection The blood is transported from a part (such as a needle that can be connected to an ordinary blood collector or a blood reservoir) through a blood introduction circuit 20 to a centrifugal separator 3 by a pump 2 such as a roller pump, if necessary. Blood introduced into the centrifugal separator 3 is separated into plasma components and blood cell components by centrifugal force, and the separated plasma components are connected to the membrane module 6 by a roller pump (not shown) built into the centrifuge. plasma supply circuit 21
The plasma is drawn out and stored in a 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 a certain amount of plasma is accumulated 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 activated to take out the plasma from the plasma storage bag and transfer it to the membrane module. 6
send. A drip chamber (not shown) to which a pressure gauge is connected is attached to the plasma supply circuit 21, and monitors abnormal pressure caused by clogging of the membrane module 6 or other factors. . The plasma sent to the 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 membrane module 6 is sent to the purified plasma return circuit 22.
The purified plasma is sent to a purified plasma storage bag 8 provided at
The purified plasma drawn out from the purified plasma storage bag 8 is mixed with blood cell components in a mixer 9 provided in the purified plasma return circuit 22, and then delivered to the patient via the purified plasma output section 18 (a section that can be connected to a shunt, drip set, etc.). is injected into. On the other hand, the concentrated plasma containing high molecular weight substances separated by the membrane module 6 is transferred to the concentrated plasma discharge pump 1 provided in the concentrated plasma discharge circuit 24.
It is discharged by 5. This concentrated plasma evacuation pump 1
The flow rate 5 is controlled in conjunction with the plasma supply pump 5 so that the flow rate ratio between the amount of plasma supplied to the membrane module and the amount of concentrated plasma derived from the module is always a predetermined value. In this case, the flow rate of the concentrated plasma discharge pump 15 is 30% higher than the flow rate of the plasma supply pump 5.
When set to cc/min, less than 1/5 to 1/10 of that,
That is, it is automatically adjusted to 6c.c./min to 3c.c./min or less.

A fluid replacement circuit 25 that replenishes purified plasma with replacement fluids such as albumin and hydroxyethyl starch (HES) from a fluid replacement bag to supplement the concentrated plasma removed by the membrane module 6 is connected to the purified plasma return circuit 22.
is connected to the inlet side of the purified plasma storage bag via a fluid replacement 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. As the liquid level detection means, a method using a pressure sensor that detects the liquid level using pressure, a method that detects the liquid level using weight, a method that directly detects the liquid level using ultrasonic waves, etc. can be used.

The amount of plasma stored in the plasma storage bag 4 is detected by this liquid level detection means 10, and the rotation speed of the plasma supply pump 5 is automatically changed or the switch is automatically turned on by interlocking control with this detection means. - By turning it 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 temporarily stopped. In particular, automatically turn on the plasma supply pump.
In the OFF method, if the flow rate of the plasma supply pump is set higher than the flow rate of plasma derived from the centrifugal separator, the plasma can be processed quickly without a large amount of plasma accumulating in the plasma storage bag 4.

The means for controlling the flow rate of each of the pumps 5, 7, and 15 may be a method of electrically controlling the rotational speed of the pumps. Alternatively, a double or triple roller pump may be used. In this case, the flow rate of liquid flowing through each circuit can be adjusted by changing the diameter of each tube. As the plasma storage bag 4, a flexible bag of 50 to 300 c.c., for example, a plasma bag can be used. Furthermore, a flexible bag with a capacity of 200 to 3000 c.c. is normally used as the purified plasma storage bag 8, but when purified plasma is returned to the body by the purified plasma delivery pump 7, a container with a capacity of 10 to 50 c.c. may be used. can. As this container, a drip chamber used in dialysis or the like may be used. The above device may further be provided with a plasma warmer for warming the plasma cooled during extracorporeal circulation and a prefilter for removing formed components in the plasma on the upstream side of the membrane module.

FIG. 2 is a system diagram of an apparatus that combines a batch type centrifugal separator and a 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 sterile air causes the blood cell components accumulated in the bowl to flow into the bowl. It's starting to get kicked out. In addition, in the batch-type centrifugal separator, blood is collected and returned (or returned plasma) 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. A part that can be connected to a blood reservoir or the like) is transported through a blood introduction circuit 20 into a bowl of a centrifugal separator 3 by a pump 2, such as a roller pump, if necessary. 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 membrane module 6 separated by centrifuge during blood collection
will be processed. 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 a plasma storage bag 4 provided in the circuit. Plasma components stored in the plasma storage bag 4 are separated into high-molecular weight substances and low-molecular weight substances by the membrane module 6 in the same manner as shown in FIG. and sent to the purified plasma storage tank 8. The purified plasma drawn from the purified plasma storage bag 8 is infused into the patient from the purified plasma return circuit 22 through the purified plasma delivery section 18 (a section that can be connected to a shunt, 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 taken out, the inside of the bowl becomes negative pressure, 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 20, 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 membrane module, and the purified plasma return circuit that connects the membrane module and the plasma outlet, respectively. 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 There is no need to match the plasma throughput in the membrane module with the plasma flow rate separated by the centrifuge, and the membrane module 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 allows for efficient and safe removal of harmful substances from the blood without damage or loss of red blood cells or platelets or loss of serum proteins.

[Brief explanation of drawings]

The drawings show an 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 centrifugal separator and a membrane module, and FIG. 2 shows a batch-type centrifugal separator. FIG. 2 is a system diagram of a device that combines a device and a membrane module. 1...Blood introduction port, 3...Centrifugal separator, 4...
...Plasma storage bag, 5...Plasma supply pump, 6...
...Permembrane module, 7...Replenishment pump, 8...
Purified plasma storage bag, 15... Concentrated plasma discharge pump, 18... Blood outlet.

Claims (1)

[Claims] 1 A centrifugal separator and a 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 membrane module. In a blood processing device for returning purified plasma from which molecular weight substances have been removed and blood cell components to the body, a plasma storage bag is provided in a plasma supply circuit connecting a centrifugal separator and a membrane module in the extracorporeal circulation circuit, and a plasma storage bag is provided. A plasma supply pump is provided that can adjust the flow rate so that the liquid level is within a set range by interlocking control with a means for detecting the liquid level in the bag, and the 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 membrane module is controlled in conjunction with the plasma supply pump to control the amount of plasma introduced into the 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