JPS61191366A - Serum treatment apparatus - 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 relates to a plasma processing apparatus that can be systematized by connecting a continuous centrifugal separation station and a cleansing system. Such a system can efficiently remove pathogen-related substances and harmful substances such as immune complexes, immunoglobulin aggregates, and nucleic acids contained in the blood.

(Conventional technology and its problems) In recent years, an abnormal increase in high molecular weight substances contained in the blood has been associated with autoimmune diseases such as rheumatism, SLE, myasthenia gravis, Gutbus chair syndrome, and idiopathic thrombocytopenic purpura. It is clear that these high molecular weight substances are deeply involved in the onset and pathology of various diseases such as multiple myeloma, metabolic abnormalities such as macroglobulinemia, and hyperviscosity syndrome. As a result, plasma separation methods have become 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 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 plasma separation membrane, plasma components containing harmful substances are removed and new plasma is produced 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. Method of mixing and returning to the body (3) 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. The purified plasma from which high molecular weight substances including harmful substances have been removed is mixed with blood cell components and returned to the body (Japanese Patent Laid-Open No. 56-7416
(No. 4, 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 containing harmful substances, A method is known in which this gel is removed with a filtration membrane, and only the low molecular weight substances that have passed through the filtration membrane are mixed with blood cell components and returned to the body (Japanese Patent Laid-Open No. 31869/1986). 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. Method of mixing with blood cell components and returning 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 filtration membrane module, A method in which purified plasma from which only high molecular weight substances have been removed is returned to the body along with blood cell components. (Japanese Unexamined Patent Publication Nos. 57-64058 and 59-8967) are known.

Among the plasma processing methods described above, the separated plasma is treated with a new Ith. There are often problems in securing plasma from healthy people to be transfused into elderly patients, and transfusion of plasma from healthy people can have side effects such as infection with new pathogens and infection with serum sickness, so the patient's own plasma must be purified before transfusion. It is considered desirable. Among them, there is a method in which blood is separated into blood cell components and plasma components using a centrifugal separator, and then the separated plasma components are processed using a filtration membrane module.
This is an excellent and extremely safe method as there is no concern about reduction 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 filtration membrane module. The reason for this is that the conventional centrifugal separator and filtration membrane module are connected through a dedicated closed circuit, and the control system of the centrifugal separator controls the pumps etc. connected to the filtration membrane module. This is believed to be because it was difficult to connect the separation device and the filtration membrane module, as it required modifying the control circuit of the centrifugal separator.

(Another Means to Solve the Problems) Therefore, an object of the present invention is to separate the control system of the plasma processing device from the control system of the centrifugal separator and perform it separately, and to connect the control system continuously with the centrifugal separator. The object of the present invention is to provide a plasma processing device that can be used for various purposes.

The present invention is continuously connected to a continuous centrifugal separator provided in an extracorporeal circulation circuit, and plasma components separated by the centrifugal separator are separated into high molecular weight substances and low molecular weight substances including albumin using a filtration membrane module. In a plasma processing device in which purified plasma from which high molecular weight substances have been removed is mixed with blood cell components and returned to the body, a plasma supply circuit is provided that connects a centrifugal separator in the extracorporeal circulation circuit to a filtration membrane module, A plasma storage bag is provided in the circuit and a means for sensing the liquid level in the plasma storage bag is provided, and the liquid level is controlled within a set range by interlocking control with the liquid level sensing means. A plasma supply pump with adjustable flow rate is provided.
Moreover, a circuit is provided for returning purified plasma containing albumin from which high molecular weight substances have been removed by the filtration membrane module to the body, and a purified plasma storage tank is provided in the circuit, and the filtration membrane module is controlled in conjunction with the plasma supply pump. A purified plasma delivery pump is provided, which is set so that the flow rate ratio between the amount of plasma introduced and the amount of purified plasma drawn out is a predetermined value, and the concentrated plasma discharge circuit of the filtration membrane module is set such that the discharge amount of high molecular weight substances is a predetermined value. A concentrated plasma discharge pump is installed, and a fluid replacement circuit is connected to the upstream side of the purified plasma delivery bonder installed in the circuit that returns purified plasma to the body, and the purified plasma is sent to the purified plasma return circuit. This plasma processing apparatus is characterized in that it is provided with a circuit that bypasses pump 1.

The plasma processing device of the present invention is connected continuously to a centrifugal separator to form a system, and the plasma components separated by the centrifugal separator are separated into high molecular weight substances and low molecular weight substances including albumin by a filtration membrane module. The present invention relates to a plasma processing device that returns purified plasma from which high molecular weight substances have been removed to the body.

A continuous centrifugal separator connected to the plasma processing apparatus of the present invention is a continuous centrifugal separator that continuously supplies blood into a centrifugal bowl on one side and continuously extracts blood cell components and plasma components from the bowl on the other side. system equipment (IBM 2997 type equipment, F
C8-3000 type device manufactured by errWIL1, etc.).

As a filtration membrane module for separating plasma in a plasma processing apparatus, 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 from the viewpoint of ease of production and miniaturization. The filtration membrane used in the filtration membrane module selectively separates plasma components into high molecular weight substances and low molecular weight substances,
Depending on the purpose, the molecular weight cutoff can be set arbitrarily.

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 substances of autoimmune diseases often exist in a form bound to r-globulin, which has a molecular weight of about 160,000, so substances with larger molecular weights are removed, and it is difficult to detect low-molecular-weight children. Albumin, which has a molecular weight of 67,000 and is useful for living organisms, has a value of 67,000 (desired → 1).
stomach. Therefore, if the molecular weight cutoff is 100,000, the above.

R-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. It is set between 10,000 rooms. As such a filtration membrane, any filtration membrane may be used as long as it can fractionate and separate plasma components under pressure, and in this sense, filtration membranes having 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. The material for such a filtration membrane is polyvinyl alcohol (PVA).
i, ethylene-vinyl alcohol (EVA) thread copolymer, cellulose derivatives such as cellulose acetate, polyolefin, polyacrylonitrile, polyamide, polyester, polysulfone, etc. are used. Among these, it is desirable to use PVA type, EVA type, cellulose derivatives, polysulfone, etc., which have excellent biocompatibility.

FIG. 1 is a system diagram in which the plasma processing device 6o of the present invention is connected continuously to a continuous centrifugal separator 50 to form a system.
To explain its configuration according to the flow of blood, blood first flows from the blood introduction section 1 (a part that can be connected to a normal blood collection device such as a shunt or a syringe needle or a blood storage device) to the blood introduction circuit 1.
0, the blood is transported to the POU/I/3 of a centrifugal separator 50 by a pump 2, such as a roller pump, if necessary, and separated into blood cell components and plasma components. The plasma components separated by the centrifugal separator 50 are transferred to the plasma processing device 60 of the present invention.
is continuously supplied. In other words, the plasma components separated by the centrifugal separator are transferred to the roller bonder 1 built into the centrifuge.
4, the plasma is led out from the plasma inlet 80 to the plasma supply circuit 16,
The plasma is stored in a plasma storage bag 4 provided in the circuit. The plasma storage bag 4 is provided with means 21 for sensing 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 sensing means, is operated to take out the plasma from the bag and remove it from the filtration membrane module 6. send to The plasma supply circuit 16 is provided with a drip chamber 22 connected to a pressure gauge 23, which monitors abnormal pressure due to clogging of the filtration membrane module/I/6 or other factors. When the plasma processing device 60 of the present invention is connected to a continuous centrifugal separator to form a system, the flow rate of the plasma supply pump 5 is set to be higher than the flow rate of the roller pump 14 that discharges plasma from the centrifugal separator. By doing so, the plasma accumulated in the plasma storage bag can be quickly disposed of, and the amount of extracorporeal blood circulation can be minimized. The plasma sent to the filtration membrane module 6 is separated therein into high molecular weight substances and low molecular weight substances including albumin. The purified plasma consisting of low molecular weight substances separated by the filtration membrane module 6 is sent to the purified plasma storage tank 8 provided with the purified plasma return circuit 171c by the purified plasma delivery pump 7 which is controlled in conjunction with the plasma supply pump 5. The purified plasma drawn out from the purified plasma storage tank 8 is sent from the purified plasma outlet 81 to the mixing device 9 by the roller pump 19 built in the centrifugal separator, and there, the purified plasma is sent to the mixing device 9 by the roller pump 19 built in the centrifugal separator.
5, the blood cell components are mixed with the blood cell components derived in step 1. The purified blood mixed with purified plasma and blood cell components is drawn out from a purified blood outlet section 18 (a section that can be connected to a shunt, an intravenous drip set, etc.) provided in the purified blood return circuit 20. When using the roller pump 19, the mixing device may be used as a purified plasma reservoir. On the other hand, the concentrated plasma containing high molecular weight substances separated by the filtration membrane module 6 is discharged to the drain tank 28 by the concentrated plasma discharge pump 26 provided in the concentrated plasma discharge circuit 27. The flow rate of this pump 26 is normally set to less than % of the flow rate of the plasma supply pump 5. Further, the pump 26 may be controlled in conjunction with the plasma supply pump 5 so that the flow rate ratio between the amount of plasma supplied to the filtration 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 is plasma supply pump 5
When the flow rate of is set to 30cc/min, its Vts
-”Ao or less, i.e. 6 cc/min ~ 3 c
c/min or less. Further, the purification surface adjusts the flow rate ratio between the amount of plasma fed to the filtration membrane module 6 and the amount of purified plasma sent out from the filtration membrane module to a predetermined value. For example, if the flow rate of the plasma supply pump 5 is set to 30 cc/min, the purified plasma delivery pump will be controlled at 24 to 3 QCC/min. When the entire amount of plasma is filtered by the membrane module, the flow rates of the plasma supply pump and the purified plasma delivery pump are set to be equal. Then, the concentrated plasma discharge bond is stopped.

A circuit 13 for replenishing the purified plasma with replacement fluids such as albumin and hydroxyethyl starch (HES) from the fluid replacement bag 12 to supplement the concentrated plasma removed by the filtration membrane module/L/6 is connected to a circuit 13 for supplying purified plasma to the purified plasma return circuit 17. It may be connected to the upstream side of the bond. In this case, the flow rate of the purified plasma delivery pump 7 is adjusted so that the amount of plasma supplied to the filtration membrane module/L'6 is equal to the amount of purified plasma that is the amount of purified plasma to which replacement fluid is added to the purified plasma sent out from the filtration membrane module. If set so that the amount of concentrated plasma discharged by the concentrated plasma discharge pump 26 is equal to the amount of concentrated plasma discharged by the concentrated plasma discharge pump 26
Book QW Sohi 1 I fig Door L Ir becomes. When a fluid replacement circuit is provided, it is preferable to provide a bypass circuit 24 that bypasses the purified plasma delivery pump. Due to clogging of the filtration membrane module 6, this bypass circuit
When a problem such as replacing a membrane module occurs and all Ω pumps in the plasma processing equipment are stopped, the pulp 25
is opened to bypass and transport the replacement fluid to the purified plasma storage tank 8. When the trouble is resolved, the valve 25 can be closed and normal operation can be resumed. Therefore, even when the device is stopped, continuous infusion can be carried out to the patient without interruption, resulting in a high level of safety.

It is preferable that the means 21 for detecting the liquid level in the plasma storage bag 4 constantly monitor the liquid level because the setting of the liquid level can be easily changed. As this liquid level detection means, a method using a pressure sensor that detects the liquid level by pressure, a method of sensing the liquid level by weight, a method of directly detecting the liquid level by ultrasonic waves, etc. can be used. .

FIG. 2 shows an example in which a pressure sensor is used as the liquid level sensing means 21, and a tube 31 with an inner diameter of 1 mm or less, usually 0.8 III, is connected to the pressure detection hole 30 provided at the bottom of the plasma storage bag 4. , a pressure sensor 21 is attached to the end thereof. A diaphragm type pressure transducer is usually used as this pressure sensor. When plasma is supplied into the plasma storage bag and the liquid level changes, head pressure is applied to the air sealed in the thin tube, and this air pressure causes the diaphragm to move AK. This minute displacement of the diaphragm is detected by a metal wire strain gauge, a semiconductor strain gauge, or the like, and the detection signal is transmitted to a control device 32 that controls the drive of each pump. The signal sent from the pressure sensor is sent to the amplification circuit 3.
The signal is amplified by 3 and sent to the comparison circuit 34. The comparator circuit compares the liquid level with the liquid level set by the setting circuit 35, and the signal is sent to the drive circuit 36 to control the rotation of the pump 5.7.26. This liquid level detection means 21) senses the amount of plasma stored in the plasma storage bag 4, and automatically changes the rotation speed of the plasma supply bong 5 or automatically switches it on by interlocking control with this detection means. ON-
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. This liquid level detection means 21 may be provided in the purified plasma storage tank 8. In this case, the pulp 25 provided in the circuit 24 that bypasses the purified plasma delivery pump is controlled in conjunction with the liquid level detection means. That is, when the liquid level in the purified plasma reservoir drops to a predetermined level, the valve is opened to send replacement fluid to the reservoir 9, and when the level returns, the valve is closed. Through interlocking control between the liquid level detection means and the valve, purified plasma is always stored in a predetermined area in the purified plasma storage tank. Therefore, accidents such as air being mixed into the purified plasma returned to the human body due to liquid shortage can be completely prevented.

The means for controlling the flow rate of each of the pumps 5, 7.26 described above may be a method of electrically controlling the rotational speed of the pumps. Also double-barreled or dual-barrel roller pumps! l1
It is possible to adjust the flow rate of the liquid flowing through each circuit by changing the diameter of the cooperative pipe with the li1-I&R layer. The plasma storage bag 4 is flexible and has a thickness of 50 to 3000 c.
c bags, such as blood bags, can be used.

Further, as the purified plasma storage tank 8, a flexible bag of 200 to 3000 cc is normally used, but when purified plasma is returned to the body by the purified plasma delivery pump 7, a container of 10 to 53 cc can be used. As this container, a drip chamber used in dialysis or the like may be used.

The mixing device is for mixing purified plasma and blood cell components, and may be a flammable bag, a drip chamber, or the like. The above device may further be provided with a plasma warmer for warming the plasma cooled during extracorporeal circulation and a P-V filter for removing formed components in the plasma on the upstream side of the filtration membrane module.

FIG. 3 is a perspective view of a part of the monitor constituting the plasma processing apparatus of the present invention. The supply circuit 16 and purified plasma diagram #&17 are attached. Further, a pipe 31 that leads the head pressure of the plasma storage bag 4 to a pressure sensor is connected to the connector 61, and a pipe that leads the pressure inside the drip chamber 22 provided in the plasma supply circuit to a pressure gauge is connected to the connector 62. 63 is a digital liquid level gauge that displays the liquid level of the plasma storage bag, and displays the head pressure (liquid level) in a per graph. Reference numeral 76 is a switch for setting the plasma level, and the plasma level can be set arbitrarily by this switch. 64 is a pressure gauge that displays the pressure on the inlet side of the filtration membrane module.

This is a knob for setting the flow rate of the 71Fi plasma supply pump 5. The instantaneous flow rate of this pump is digitally displayed on a flow meter 67. The total amount of plasma supplied to the membrane module by the pump is displayed on the totalizer 70.

72 is a main switch. 73 is a changeover switch between automatic operation and manual operation. During automatic operation, when the plasma level in the plasma storage bag is above the set value, the lamp 74 lights up and the pump rotates.

When the plasma level falls below the set value, the above lamp will turn off.
The pump will stop. 75 is an integration reset button.

The monitor is provided with a rung that indicates an abnormality when an abnormality occurs. 65 is a pressure alarm lamp that lights up when the pressure on the inlet side of the filtration membrane module exceeds the upper and lower limit alarm settings, 66 is a lamp that lights up when the cover of pump 68 is opened, and 67 is a lamp that lights up when the cover of the pump 68 is opened. This lamp lights up when plasma has accumulated beyond its capacity.

The control system of the plasma processing apparatus of the present invention is all housed in a part of the monitor. Therefore, when the apparatus of the present invention and the centrifugal separator are connected in series to form a system, the control of the centrifugal separator and the apparatus of the present invention can be performed completely separately.

(Effects) As described above, the device of the present invention includes a plasma storage bag and a purified plasma storage tank, and also controls the liquid level detection means of the plasma storage bag, the plasma supply pump, and the purified plasma delivery bond in an interlocked manner. A blood processing system can be provided that is serially connected to an existing continuous centrifuge device. This system can efficiently and safely remove harmful substances from the blood without damaging or losing red blood cells or platelets or losing serum proteins.

[Brief explanation of the drawing]

The drawings show an embodiment of the plasma processing device of the present invention, and FIG. 1 is a system diagram of a system that combines a continuous centrifugal separator and the plasma processing device of the present invention, and FIG. Referring to the electric circuit diagram of the surface detection means, FIG. 3 is a perspective view of the plasma processing apparatus of the present invention.

Claims (1)

[Claims] 1. Continuously connected to a continuous centrifugal separator provided in the extracorporeal circulation circuit, plasma components separated by the centrifugal separator are filtered through a filtration membrane module into low-containing substances containing high molecular weight substances and albumin. In a plasma processing device that separates into molecular weight substances and removes high molecular weight substances, purified plasma is mixed with blood cell components and returned to the body, and a plasma supply unit that connects a centrifugal separator and a filtration membrane module in the extracorporeal circulation circuit. A circuit is provided, a plasma storage bag is provided in the circuit, and a means for sensing the liquid level in the bag is provided, and the liquid level is controlled within a set range by interlocking control with the liquid level sensing means. In addition, a circuit for returning purified plasma containing albumin from which high molecular weight substances have been removed by the filtration membrane module to the body is provided, and a purified plasma storage tank is provided in the circuit. A purified plasma delivery pump is provided, which is set so that the flow rate ratio between the amount of plasma introduced into the filtration membrane module and the amount of purified plasma taken out is a predetermined value by interlocking control with the plasma supply pump, and a concentrated plasma discharge circuit from the filtration membrane module. A concentrated plasma discharge pump is provided in which the discharge amount of high molecular weight substances is set to a predetermined value, and a fluid replacement circuit is connected to the upstream side of the purified plasma discharge pump installed in the circuit for returning purified plasma to the body. Moreover, the plasma processing apparatus is characterized in that the purified plasma return circuit is provided with a circuit that bypasses the purified plasma delivery pump. 2. The purified plasma storage tank is equipped with a means for sensing the liquid level in the tank, and a switching valve that opens and closes in conjunction with the liquid level sensing means is provided in the circuit that bypasses the purified plasma delivery pump. A plasma processing apparatus according to claim 1, characterized in that: