JPS61113463A - Circuit and method for serum operation system - 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 (Explanation of Terms) In this specification, plasma refers to a liquid component in blood, and blood cells refer to red blood cells and white blood cells from which all or part of plasma has been removed. , formed components such as platelets, or a portion of blood containing formed components. In addition, plasma processing refers not only to the removal of harmful substances and unnecessary components, the addition of medicinal substances, and the replenishment of deficient components to plasma, but also the treatment of plasma with fluid replacement or replacement with other plasma. It shall also include carrying out.

B3 Purpose of the invention (industrial application field) Some diseases can be alleviated or cured by plasma treatment. For example,
drug addiction, fulminant hepatitis, macroglobulinosis, hyperlipidemia,
Six diseases, including multiple myelopathy and myasthenia gravis, are eligible for treatment through plasma processing as covered by health insurance. In addition to the above-mentioned diseases, common and effective cases have been reported for rheumatoid arthritis, liver failure, lupus erythematosus, and nephritis.

The purpose of the present invention is to treat various diseases including these diseases, and the present invention separates blood collected from a patient into plasma and blood cells, performs plasma processing, mixes the plasma with blood cells again, and then administers the blood to the patient. Plasma manipulation system circuit and blood gI for performing plasma manipulation consisting of a series of steps of returning blood.
t operation method.

(Prior art) Treatment of patients with the above-mentioned diseases using plasma treatment!
A circuit for the conventional ``l operation ``yl-r'' which is used for ``2'' and 6'' is shown in No. 91m (a).

A conventional circuit for a plasma manipulation system includes a blood sampling unit 1 that collects blood from a human body, a blood pump 2 that maintains an appropriate blood sampling pressure, a blood sampling normality/abnormality detector 3, and a blood sampling unit that prevents blood from coagulating during perfusion of the circuit. An anticoagulant injection mechanism 4, an abdominal plasma separator 50 that has the function of separating collected blood into plasma and blood cells, a separated plasma processing function area 6, and a plasma that adjusts the flow rate of the plasma. A plasma processing circuit 9 that includes a pump 7 and a blood leakage detection device 8 for preventing blood cells from getting mixed into the plasma, and is connected to the abdominal plasma separator 5, a heater 10 that adjusts the blood temperature to an appropriate temperature, and a A drip chamber 11 for deaerating air bubbles in the blood or plasma provided therein, a bubble detection device 12 for preventing air bubbles from being mixed into the blood, a pressure gauge 13 for measuring blood pressure or plasma pressure in the flow path, Mixing section 30 for the treated plasma and blood cells flowing out from the protective plasma separator 5
, a blood return unit 14 that returns the mixed blood to the human body, and the like.

Blood collected from a patient is sent to an abdominal plasma separator 50 through a degassing device such as a drip chamber 11, where it is separated into plasma and blood cells.
After being led to the plasma processing circuit 9 and subjected to necessary processing, it is mixed with blood cells flowing out from the abdominal plasma separator 50 in the mixing section 30, and returned to the human body through the blood return section 14.

(Problems to be Solved by the Invention) By the way, in such a circuit configuration, clogging is likely to occur when the plasma separation pressure becomes excessive. No. 9 in No. 145590
We proposed a circuit configuration as shown in Figure (b).

Blood manipulation using the circuit configuration according to Japanese Patent Application No. 58-145590 includes the above-mentioned separation step and mixing step, in addition to the function of separating blood into plasma and blood cells, the function of mixing separated plasma and blood cells. Membrane plasma separation device 5
The main point is to do it in

The configuration of the membrane plasma separation device 5 used in the circuit will be explained based on FIG. and an outer cylindrical body 17 provided with an outflow port 15b, a discharge port 16a for separated plasma, and a return port 16b on the side wall, and both ends fixed to the inside of the outer cylinder 17 with a resin layer 18 such as a polyurethane resin. The resin layer 18 allows the inside of the membrane plasma separation device 5 to form a blood inflow section 20.
It is divided into an outflow section a, an outflow section 20b, and a plasma separation section 21. The hollow fibers 19 are formed by molding a semipermeable membrane impermeable to blood cells into a hollow fiber shape, and preferably have a pore diameter of 0.01 to 5 μm.

Blood enters from the inlet 15a of the membrane plasma separation device 5 and flows inside each hollow fiber 19. While blood passes through the inside of the hollow fiber 19, plasma is separated and leached from the membrane wall of the hollow fiber 19, which is a semipermeable membrane. The plasma is guided from the outlet 16a to the plasma processing circuit, and after being subjected to a predetermined plasma processing, returns to the membrane plasma separation device 5. The processed plasma is transferred to the return port 1.
6b, it flows into the plasma separation section 21, penetrates into the interior of the hollow fiber 19 from the outer surface, and is mixed with blood cells.

By the way, during execution of plasma manipulation using the circuit configuration according to the above-mentioned Japanese Patent Application No. 58-145590, the membrane wall of each hollow fiber 19 in the abdominal plasma separation device 5 separates the area where plasma from blood is separated from the plasma. It is divided into a region where it mixes with blood cells and a region where it mixes with blood cells. In the area where plasma is separated from blood, the flow is always from the inside of the hollow fiber to the outside.
As shown in Figure 9(a), clogging is more likely to occur than in the conventional circuit configuration. There was a concern that the efficiency of separation and mixing would be permanently reduced and at the same time an imbalance would occur between plasma separation and mixing.

Structure of the Invention (Means for Solving the Problems and Their Effects) A blood storage mechanism for accumulating plasma separated by a membrane plasma separation device in the plasma processing circuit of the plasma processing system circuit. ,
A flow path control means for controlling the flow of plasma in one direction between the membrane plasma separation device and the plasma processing circuit is provided, and the process of separating plasma from blood and the process of mixing plasma with blood cells are alternately performed. I decided to do this repeatedly. Therefore, the state in which plasma flows out from the membrane plasma separation device to the plasma processing circuit and the state in which plasma returns from the plasma processing circuit to the membrane plasma separation device are alternated repeatedly.

(Example) The circuit for a plasma manipulation system and the plasma manipulation method according to the present invention were applied to low-density lipoproteins and extremely low-density lipoproteins in plasma, which are considered to be the cause of hyperlipidemia, hypercholesterolemia, arteriosclerosis, etc. A case where the present invention is applied to the removal of lipoproteins (hereinafter abbreviated as LDL) will be explained.

FIG. 1 schematically shows the main parts of a circuit for a plasma manipulation system according to the present invention.

The plasma processing circuit 31 connected to the membrane plasma separation device 5 includes:
It is equipped with an LDL removal device 32 provided in the processing function area, a blood storage mechanism 33 for accumulating plasma, and a flow path control means 34 provided at an appropriate location in the flow path, and also includes an LDL removal device 32 provided in the processing function area, and a flow path control means 34 provided at an appropriate location in the flow path. A blood leakage detection device 8 to prevent blood leakage, a plasma pump 7 to adjust the flow rate of plasma in the plasma processing circuit, a drip chamber 11 to degas bubbles in the plasma, and a blood pressure or plasma pressure in the flow path to be measured. A pressure gauge 13 and the like are appropriately arranged.

The membrane-type plasma separation device 5 used in the circuit for the plasma manipulation system according to the present invention has a plasma outlet and a return port respectively provided on the side wall, but these can also be used as two openings.

The LDL removal device 32 used in this example is a device for removing L in plasma.
A column packed with an adsorbent that selectively adsorbs DL, L
This refers to DL filter membranes, normal plasma replacement equipment, etc.

The blood storage mechanism 33 for sequentially accumulating plasma may be a closed container with a variable capacity that has no communication with the outside air, and can discharge the accumulated plasma without leaving it behind. For example, the syringe 35 shown in FIG.
6(A), a mechanism in which a bellows-shaped outer shell 36 covers the
A bag body having an outflow port and an inflow port shown in (B), or a bag body having a stretchable outflow port and an inflow port shown in FIG. A mechanism including a bag body 38 having an inlet port 37a and an outlet port 37b shown in b), and means for pumping out the plasma accumulated in the bag body 3B, such as a pressure roller 39 and a pressure-receiving wall 40, etc. There is.

The flow path control means 34 used in this embodiment is an appropriate flow path opening/closing means such as forceps, pinch pulp, gate valve, cock, etc.

The plasma manipulation method according to the present invention will be described below.

Blood collected from a patient is sent to the membrane plasma separation device 5 through a degassing device such as a drip chamber.

The membrane plasma separation device 5 can be operated by closing the flow path through which plasma returns from the plasma processing circuit 31 to the membrane plasma separation device 5 and opening the flow path through which plasma flows out from the membrane plasma separation device 5 to the plasma processing circuit 31. Separated plasma components, which perform only plasma separation, are delivered by the plasma pump 7 from the delivery port 16a on the side wall of the membrane plasma separator to the blood storage mechanism 33 provided in the plasma processing circuit 31, where they are sequentially accumulated. Blood plasma storage mechanism 33
The discharge port of the blood storage mechanism 33 is closed while a predetermined amount of blood is accumulated.

When a predetermined amount of plasma has been accumulated, the inlet of the blood storage mechanism 33 and the flow path through which plasma flows out from the membrane plasma separation device 5 to the plasma processing circuit 31 are closed, and the plasma flows from the plasma processing circuit 31 to the membrane plasma separation device. The flow path returning to 25 is opened and the plasma pump 7
The plasma is transferred to the LDL removal device 32 at a predetermined flow rate. After being processed in the LDL removal device 32, the plasma is returned to the membrane plasma separation device 5. Plasma penetrates from the outer surface into the interior of the hollow fiber, mixes with blood cells, and eventually returns to the human body.

The blood storage 5i machine +R33 may be installed downstream of the LDL removal device 32 as shown in FIG. 2. In this case, the plasma separated by the membrane plasma separation device 5 is first After being processed by the LDL removal device 32, it is stored in the blood storage mechanism 33.

Furthermore, blood storage WkII! The number of A structures 33 is not limited to one, but it is also possible to provide a plurality of A structures. That is, as shown in FIG. 3, two membrane-type plasma separation devices 5 and two blood storage mechanisms 33 are provided in the circuit for the blood 51 operation system, and - LDL removal devices 32 are used in common. A plasma processing circuit equipped with a mechanism 33 is a combination of two membrane-type blood cells.
5 are connected to each other. When one plasma processing circuit is used for plasma separation and accumulation, the other plasma processing circuit is used to release and mix the accumulated plasma, and this process is repeated alternately. By employing this method, the LDL removal device will be in constant operation, and the time required to remove a predetermined amount of LDL from plasma can be shortened.

In addition, both when storing plasma and when releasing it from the blood storage mechanism, by passing it through the LDL removal device,
It is possible to increase the removal efficiency of LDL. That is, as shown in FIG. 4, in the plasma processing circuit 31, the LD
A circuit for a plasma manipulation system is provided with a flow path connecting the downstream side of the L removal device 32 and the inlet of the blood storage mechanism 33 and a flow path connecting the outlet of the blood storage mechanism 33 and the inlet of the LDL removal device 32. By using this, plasma separated by the membrane plasma separation device 5 first passes through the LDL removal device 32 and is temporarily accumulated in the plasma storage mechanism 33. When a predetermined amount is accumulated, the elevated plasma is passed through the LDL removal device 32 and returned to the membrane plasma separation device 5, where it is mixed with blood cells. According to this method,
Since the separated plasma passes through the LDL removal device 32 twice, the LDL removal efficiency is improved.

C1 Effects of the invention
豐By using the circuit for a plasma manipulation system and the plasma manipulation method according to the present invention, the step of separating plasma from blood and the step of mixing separated plasma with blood cells are performed alternately, so that the process of separating plasma from blood and mixing the separated plasma with blood cells are performed alternately. The direction of the flow of plasma across the membrane wall of the hollow fibers changes during the separation process and during the mixing process. Therefore, the micropores in the hollow fiber membrane wall are less likely to be clogged, and even if clogging occurs, the flow direction of the plasma is changed, thereby eliminating the clogging.

Therefore, the hollow fiber membrane wall maintains a good flow of plasma, so that the efficiency of separating and mixing plasma becomes very high, and the time required for plasma manipulation is shortened.

Furthermore, since the entire hollow fiber is used for separation during the separation process, plasma can be easily separated with low transmembrane pressure, eliminating the risk of hemolysis.

[Brief explanation of the drawing]

FIGS. 1 to 4 schematically show embodiments of a circuit for a plasma manipulation system according to the present invention, and respectively show
The first to fourth embodiments show the process of sequentially accumulating plasma separated from blood. 5 to 8 respectively show embodiments of the blood storage mechanism according to the present invention. FIG. 5 is a partial sectional view of the blood storage mechanism having a bellows-shaped outer shell, and FIG. A) and (B) are front and side views of a bag body having an inlet and an outlet; FIG. 7 is a stretchable bag body having an inlet and an outlet;
Figures (a) and (b) are a front view and a side view of a blood storage mechanism consisting of a bag body having an inlet and an outlet, and means for pumping out the accumulated plasma, which is made up of a compression roller and a pressurized surface. It is a diagram. FIG. 9(a) is a schematic diagram showing a conventional circuit for a plasma manipulation system, and FIG. 9(b) is a schematic diagram showing a circuit for a plasma manipulation system according to the invention described in Japanese Patent Application No. 145590/1983. 10 are partial cross-sectional views of the membrane plasma separation device. 5-Membrane plasma separation device 31-・Plasma processing circuit 32-・
LDL removal device 33.--Blood storage and mechanism 34.--Flow path control means Patent applicant Kanebuchi Chemical Industry Co., Ltd. Application agent Patent attorney 1) Toshihiko (B) Figure 8 (A)

Claims (1)

[Scope of Claims] 1. A membrane-type plasma separation device that has not only the function of separating blood into plasma and blood cells but also the function of mixing the separated plasma and blood cells, and a functional area for processing the separated plasma. and a plasma processing circuit including a plasma storage mechanism and connected to the membrane plasma separation device, and a flow path control means for controlling the flow of plasma in one direction between the membrane plasma separation device and the plasma processing circuit. and circuits for plasma manipulation systems. 2. During the plasma manipulation process, the flow path where plasma returns from the plasma processing circuit to the membrane plasma separator is closed, and the flow path from the membrane plasma separator to the plasma processing circuit is opened and the membrane plasma separator is closed. The step of separating plasma from blood by sequentially accumulating the separated plasma in a plasma storage mechanism provided in the plasma processing circuit, and closing the flow path through which plasma flows from the membrane plasma separation device to the plasma processing circuit. It is characterized by alternately performing the step of mixing plasma with blood cells by opening the flow path returning from the plasma processing circuit to the membrane plasma separation device and gradually releasing the plasma accumulated in the plasma storage mechanism. , plasma manipulation methods.