JPS59141952A - Membrane type serum separator - Google Patents

Abstract

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

Description

BACKGROUND ART Field of the Invention The present invention relates to a membrane type plasma fraction 111 device. More specifically, the present invention relates to a membrane-type plasma separator equipped with a hemolysis prevention device.

BACKGROUND OF THE INVENTION Plasma separation devices are currently used to replace blood plasma in the human body with fresh plasma or to separate abnormal substances from the blood plasma.

Conventionally, such a plasma separation device has a first
A filtrate circuit as shown in the figure is used.

However, the blood that has been removed by the pump 2 through the inlet pipe 1 of the blood circuit connected to the patient's artery or vein (not shown) is once placed in the inlet-side air trap 4 equipped with the blood inlet area 3. After being stored, it is introduced from the blood flow port 5 into the hollow fiber plasma fraction ll1lt device 6. The blood concentrated in the plasma separator 6 flows out from the blood outflow lower and is temporarily stored in the outlet side air trap 9 equipped with the blood inlet area 8, and then led to the outlet pipe 10 and then into the patient's vein (not shown). will be returned to. On the other hand, the plasma filtered by the membrane-type plasma fraction*i device 6 flows out from the plasma outlet 11a or from the plasma outlet 11a, 11b, and is temporarily stored in the plasma side air trap 13 equipped with the plasma pressure gauge 12. After that, the plasma is discharged from the plasma discharge pipe 14 by the action of the pump 15, and normal plasma is introduced from the plasma introduction pipe 16, or a secondary plasma separator (not shown) connected to the plasma discharge pipe 14 is used. The normal plasma separated by the pump 1) is introduced, and these plasmas pass through the outlet air trap 9 and are returned to the patient's vein together with the concentrated blood.

Conventionally, membrane-type plasma separation apparatuses have been used for plasma separation using TMP (diaphragm pressure, transmembrane pressure,
It is said that if the amount of blood (rane pressure) exceeds 50 mm 1-1 g, hemolysis occurs due to destruction of red blood cells.

(where, P is the average TMP1P1 is the arterial M pressure, PO is the venous pressure, and P is the filtrate pressure, where:
Devices have been devised to monitor TMP and prevent hemolysis.

However, the diaphragm pressure (TMP> or P − P
The monitor is only a rough guide.
P. Therefore, various modules have different filtration performance, which may lead to melting and the filtration performance cannot be fully demonstrated. In other words, the critical TMP at which hemolysis occurs varies depending on the shear rate of the blood, and the higher the shear rate, the higher the critical TMP. The blood flow decreases and the shear rate becomes smaller. Therefore, the critical TMP at which hemolysis occurs is lowest at the blood outlet. Also, when the pressure drop P (P − Po) I of the module becomes large, the TMP It is thought that hemolysis occurs near the blood inlet where it is highest, but if PD is small and TMP decreases roughly, hemolysis will occur near the replacement fluid outlet for the reasons mentioned above. You may miss the
Further, there is a problem in that it becomes impossible to increase the filtration flow rate due to excessive caution against hemolysis.

(9) Purpose of the Invention Therefore, the purpose of the present invention is to provide a novel model plasma separation device. Another object of the present invention is to provide a model plasma separation device equipped with a hemolysis prevention device that exhibits sufficient filtration performance, prevents hemolysis, etc., and can be operated safely.

These purposes are achieved by connecting a blood inlet circuit, a blood discharge circuit, and a plasma discharge circuit to a deformed plasma separator having a blood inlet, a concentrated blood outlet, and a plasma outlet. In this model plasma separator, the liquid levels of a blood inlet side air trap, a blood discharge side air trap, and a plasma side air trap connected to each of the circuits are arranged at the same height, and the filtrate is This is achieved by a model plasma separator characterized in that a differential pressure gauge for measuring the difference between the pressure and the blood return side pressure is connected to the blood discharge side air trap and the plasma side air trap.

These purposes also include a model in which a blood inlet circuit, a blood discharge circuit, and a plasma discharge circuit are connected to a deformed plasma separator equipped with a blood inlet, a concentrated blood outlet, and a plasma outlet. In the plasma separator, the liquid levels of the blood inlet side air trap, blood discharge side air trap, and plasma side air trap connected to each of the circuits are arranged at the same height, and the filtrate pressure is A differential pressure gauge for measuring the difference between the pressure on the blood return side and the plasma side air trap is connected to the blood discharge side air trap and the plasma side air trap, and the differential pressure gauge and the plasma discharge pump are further connected via a controller. This can also be accomplished with a shaped plasma separator.

Further, the present invention is a deformed plasma separation device in which the shaped plasma separator is a flat membrane plasma separator.

(1) Detailed Description of the Invention Next, one embodiment of the present invention will be described with reference to the drawings. That is, as shown in FIG. 2, the shaped plasma separation device equipped with the hemolysis prevention device according to the present invention first includes a blood introduction tube 21 to be connected to the patient's artery or vein (as shown in the figure), and Pump for introducing blood into the thigh (
For example, it consists of a roller pump) 22 and a blood introduction side air trap 24 connected in the middle, and the other end is connected to a blood inlet 25 of a demolding surface separator 26.

Note that a blood inlet pressure gauge 23 is connected to the blood introduction side air trap 24 . On the other hand, the blood discharge circuit consists of a blood discharge tube 30 connected to a patient's vein (not shown), and a blood discharge side air trap 29 connected in the middle of the tube, and the other end of the blood discharge tube 30 is , connected to the blood outlet 27 of the shaped plasma separator 26. Note that a blood outlet pressure gauge 28 is connected to the blood discharge side air trap 29 .

The plasma discharge circuit consists of a plasma discharge pipe 34 to which a plasma-side air trap 33 is connected and a plasma discharge pump 35 installed in the middle, and one end of which is connected to the shaped plasma separator 2.
The other end is connected to plasma discharge ports 31a and 31b of No. 6, and the other end is used as a discharge port or connected to a secondary plasma separator (not shown). Note that a plasma pressure gauge 32 is connected to the plasma side air trap 33. Further, the blood discharge pipe 30
A plasma inlet pipe 36 is connected between the deformed plasma container 26 and the air trap 29 on the blood J71 outlet side.

Therefore, the liquid levels of the blood introduction side air trap 24, blood discharge side air trap 29, and plasma side air trap 33 are set at the same level. Each air trap 24, 29.
Each pressure of 33 is monitored by a pressure gauge 23゜28.32, and a differential pressure is used to monitor the difference between the blood return side pressure in the blood discharge side air trap 29 and the filtrate pressure in the plasma side air trap 33. An alarm 56 is attached to the differential pressure gauge 55, and a plasma discharge pump controller 57 is attached to the differential pressure gauge 55, which is connected to the plasma discharge pump 35.

As the plasma separator 26 used in the deformed plasma separation device according to the present invention, either a hollow fiber membrane type or a flat membrane type can be used as long as it is deformed, but a flat membrane type plasma separator is preferable. .

Examples of flat membrane plasma separators include those shown in FIGS. 3 and 4. In other words, there is a blood inlet 2 in the center of the bottom.
5 and a circular tubular case main body 42 equipped with a blood outlet 27 on the side wall, plasma outlet ports 31a, 31b, and an O2 on the periphery.
It consists of a case consisting of a lid body 44 to which a ring 43 is attached, and a filtration membrane, a blood flow path regulating plate, and a blood flow path forming plate are housed in this case. That is, a circular plasma flow path forming plate 47 made of a screen mesh having an opening 45 in the center and plasma passage holes 46 near the periphery is sandwiched between two upper and lower circular filtration plates 1!48a and 48b. The periphery of the membrane and the periphery of the center opening are sealed by heat fusion, adhesion, etc., and a sealing material 49 is attached to the outer periphery of the plasma passage hole 46 to form a filtration membrane unit 50.

Here, the circular plasma flow path forming plate 47 is not limited to the mesh as long as it can secure a flow path for plasma.

Between the plurality of filter membrane units 50, the unit 50
A circular blood flow path regulating plate 5 is provided with a central opening 45 and a plasma passage hole 46 corresponding to the plasma passage hole 46, and a large number of convex portions 54 on both sides (however, the outer periphery of the passage hole 46 is flat).
1 is arranged. Further, above the top and below the bottom of the filter membrane unit 50, the circular blood regulating plate 51 is provided.
Alternatively, the unit 50 is provided with a central opening 45 and a plasma passage hole 46 corresponding to the unit 50, and a large number of convex portions on one side (
However, the outer periphery of the passage hole 46 is flat. ) The circular blood flow path regulating plate 52 is brought into contact with the convex portion thereof.

These filtration membrane unit 50 and blood flow path regulating plate 51
．． 52 are stacked one on top of the other and inserted into the case body 42, and the cover body 44 is placed and pressed to close the case body 4.
2 and sealed fluid-tightly with an O-ring 43, a flat membrane type plasma separator as shown in FIG. 4 is obtained. Moreover, due to such suppression, the filtration membrane unit 50 and the blood flow path regulating plates 51 and 52 are prevented by the sealing material 49.
The passage holes 46 are integrally connected at the outer periphery thereof, and the passage holes 46 are formed in communication with each other.

The i1i membranes 48a and 48b are made of cellulose esters such as organic acid esters such as nitric acid-tZ lullose and cellulose acetate, and synthetic resin membranes (thickness 30 to 200 microns) such as polycarbonate 1 through phase separation method. The film was formed using known methods such as extraction method, stretching method, and charged particle irradiation method.
The average pore diameter is about 0.1 to 1 micron.

The blood flow path regulating plates 51 and 52 are the filter membranes 48a.

48t1, and has a large number of protrusions. Its Young's modulus is 9 or 1, Qx 10~1, Ox 10dyne
/cm2 of material. The reason for this is that when the dispenser is pressed to easily narrow the blood flow path and avoid relaxation, the flow path plastically restores itself and reduces the desired filtration amount by 1q. The materials that control the Young's modulus in this range are:
For example, low density polyethylene, silicone, isoprene rubber, butyl rubber, styrene-butadiene rubber (SBR)
, ethylene-vinyl acetate copolymer resin (EVA), and the like. Further, it is desirable that the surface hardness of the blood flow path regulating plate including the convex portion has a Shore A height of 10 to 100.

The protrusions of the blood circulation section support the filter membranes 48a and 48b to prevent deformation, and ensure a flow of body fluid between the protrusions. This convex part has a height of 50 to 500
A micron diameter is desirable, and a 100 to 250 micron diameter is particularly preferred. The reason for this is that if the diameter is less than 50 microns, it is difficult to adjust the channel pressure, and if it exceeds 500 microns, the deformation is large and errors are likely to occur, and the wall shear rate cannot be increased. Further, the interval between these convex portions is preferably 100 to 2,000 microns, particularly preferably 400 to 800 microns. Further, the ratio of the radius of the bottom of the convex portions, the length of a diagonal line or one side, and the distance between the convex portions is preferably 1:1 to 1:3.

(2) Specific Effects of the Invention Next, a method of using the model plasma separator having the above-mentioned configuration will be explained. That is, as shown in FIGS. 2 to 4, one end of the blood introduction tube 21 constituting the blood introduction circuit is connected to a priming fluid storage tank (for example, an infusion bag), not shown, and then the blood introduction pump 22 is operated to perform menstruation. Priming is performed by flowing a priming solution such as saline or heparinized saline to the deformed plasma separator 26.

Next, the priming liquid reservoir is removed, and the blood introduction tube 21 is connected to the patient's artery or vein (not shown). Further, when the blood introduction pump 22 is operated, the removed blood is temporarily stored in the blood introduction side air trap 2'4, and then flows into the demolding surface separator 26 from the blood inlet 25. This blood is transferred from the central opening 45 to the blood flow path regulating plate 51.
．． 52 and 12- The filter membrane 48a of the filter membrane unit 50 flows through the gap between the protrusions formed between the filter membrane unit 50.
, 48b. The filtered plasma passes through the gap between the plasma flow path forming plates 47 in the filtration membrane unit 50, reaches the plasma passage hole 46, and is then discharged from the plasma outlet ports 31a and 31b provided in the lid 44. .

On the other hand, the filtered residual liquid (pure blood) in which white blood cells are concentrated flows through the gap between the blood flow path regulating plate 51, 52 and the filtration membrane unit 50, and is discharged from the blood outlet 27 to the blood discharge circuit. Ru.

The plasma discharged from the plasma outflow ports 31a and 31b is discharged from the plasma discharge pipe 34 constituting the plasma discharge circuit by the action of the plasma discharge pump 35, and is temporarily stored in the plasma side air trap 33 before being discharged from the system. whether it is discharged into
Alternatively, plasma is further separated again by a secondary plasma separator (not shown). On the other hand, replacement fluid or purified plasma for diluting the blood concentrated by plasma separation is introduced from the plasma introduction pipe 36, and is introduced into the blood discharge pipe 30.
Detyped plasma fraction 1 Slt device 26 and blood discharge side air trap 2
It merges with 9 in the middle. This concentrated blood mixed with plasma is returned from the blood discharge side air trap 29 to the patient's vein (not shown) via the blood discharge pipe 30.

Therefore, during the operation described in -J1, the liquid levels of blood introduction side air 1 to lap 2/4, blood discharge side air 1 to lap 29, and plasma side air 1 to lap 33 are kept at the same level. put. Each pressure of each air trap 24, 29.33 is measured by a pressure gauge 23.
28.32, the difference between the blood return side pressure in the blood discharge side air trap 29 and the filtrate pressure in the plasma side air trap 33 is remonitored by the differential pressure gauge 155, and the differential pressure is constant (for example - 2On+m1-1g), the alarm 56 sounds, the plasma discharge pump controller 57 operates, and the plasma discharge pump 35 stops.

■1 Effect of the invention As mentioned above, the deformed plasma separation device according to the present invention has the following effects:
A deformed plasma separator comprising a model plasma separator having a blood inlet, a concentrate outlet, and a plasma outlet connected to a blood inlet circuit, a blood outlet circuit, and a plasma outlet circuit, respectively. The liquid levels of the blood inlet side air trap, blood discharge side air trap, and plasma side air trap connected to the circuit are arranged at the same level, and the difference between the filtrate pressure and the blood return side pressure is Since the measurement differential pressure gauge is connected to the blood 1/1 outlet side air trap and the plasma side air trap, the average diaphragm pressure can be adjusted by arranging each liquid level at the same height. (, difference between filtrate pressure and venous pressure pp-n (
=pF-po> can be measured, and by measuring this pressure difference, a decrease in filtration performance can be immediately detected for the following reason, and necessary measures can be taken.

(1) The critical diaphragm pressure at which hemolysis occurs varies depending on the shear rate of blood; the greater the shear rate, the higher the critical diaphragm pressure. On the other hand, since plasma is filtered in the plasma #i device, the blood flow rate is smaller at the blood outlet than at the blood inlet, and the shear rate is smaller. Therefore, the critical diaphragm pressure at which hemolysis occurs is lowest at the blood outlet.

15- <2) Also, the pressure loss of the module Fj) (-P■-P
If o) becomes large, it is thought that a dissolution surface will occur near the blood inlet where the average diaphragm pressure is highest, but if PD is small and the filtrate pressure PF roughly decreases, the blood outlet Nearby hemolysis occurs. therefore,
If you only monitor the average diaphragm pressure, you may miss the latter hemolysis, and if you are more careful about hemolysis than necessary, you will not be able to increase the filtration flow rate.

(3) Furthermore, if the plasma separation ability decreases due to clogging with proteins, platelets, etc., the filtrate pressure will decrease, and this can be confirmed by comparing the value of the difference P between the filtrate pressure and the venous pressure with -0. . Therefore, in the above formula I, PF-0 and Po
When we introduce , we get the following formula ■.

P””X P P p-0(Ir)TM
The pressure drop PD of the D module varies depending on changes in the hematocrit value, clogging of the arterial chamber, and differences in the module, and the decrease in filtration ability is represented by -0 in P.

Therefore, if you monitor the direct part -〇, the filtration 16
− Excessive flow rate can also be easily determined.

Therefore, hemolysis in the 5 liter device for deformed plasma can be prevented.

In addition, by connecting the differential pressure gauge and the plasma discharge pump via a controller, the difference between the filtrate pressure and the venous pressure can be measured, and the pressure difference can be used to immediately prevent the filtration performance from decreasing below a predetermined level. Since the operation of the plasma discharge pump 35 can be stopped, there is no need to worry about hemolysis. Furthermore, by using a flat membrane type as the demolding surface separator, commercial losses are reduced.

[Brief explanation of the drawing]

FIG. 1 is a circuit diagram showing an example of a conventional deformed plasma separation device,
FIG. 2 is a circuit diagram showing an example of the detached plasma separator according to the present invention, FIG. 3 is an exploded perspective view showing an example of a flat membrane plasma separator used in the present invention, and FIG. The figure is the third
FIG. 3 is a cross-sectional view showing the assembled state of the separator shown in the figure. 21...Blood introduction tube, 22.35...Pump, 2
4.29.33...Air trap, 23.28°3
2.39...Pressure gauge, 25...Blood inlet, 26
... Detyped plasma separator, 27... Blood outflow port, 30
...Blood discharge pipe, 31831b...Plasma discharge port,
34...Plasma discharge tube, 36...Plasma introduction tube, 55
...Differential pressure gauge, 56...Alarm, 57...Pump controller for plasma discharge. Patent applicant Terumo Co., Ltd.
Company 19 - Figure 3 44 1a 3 6 48a - 550 48b ~ 5
I54;. 〈 0 0Z%”6”” 7 Figure 4

Claims (4)

[Claims] (1) In a deformed plasma separator in which a model plasma separator equipped with a blood inlet, a concentrated blood outlet, and a plasma outlet is connected to a blood inlet circuit, a blood outlet circuit, and a plasma outlet circuit, respectively. , a blood introduction side air trap and a blood discharge side air trap connected to each of the circuits, respectively;
Each liquid level is arranged at the same height as the plasma side air trap, and a differential pressure gauge for measuring the difference between the filtrate pressure and the blood return side pressure is connected to the blood discharge side air trap and the plasma side air trap. Characteristics of the deformed plasma separation device. (2) The detyped plasma separator according to claim 1, wherein the # type plasma separator is a flat membrane type plasma separator. (3) In a deformed plasma separator in which a blood introduction circuit, a blood discharge circuit, and a plasma discharge circuit are connected to a model plasma separator equipped with a blood introduction port, a concentrated blood discharge port, and a plasma discharge port, respectively. , a blood introduction side air trap and a blood discharge side air trap connected to each of the circuits, respectively;
The liquid levels of the ri + plasma side air trap are arranged at the same height, and a differential pressure gauge for measuring the difference between the filtrate pressure and the blood return side pressure is connected to the blood discharge side air trap and the plasma side air trap, Furthermore, the membrane-type plasma fraction 11t[
i. (4) The demolded plasma separator according to claim 3, wherein the model plasma separator is a flat membrane plasma separator.