JPS5846962A - Blood treating 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 The present invention relates to an apparatus for separating KIF-decomposed substances (solutes) in blood. More specifically, pretreatment is performed to efficiently remove soluble macromolecular solutes such as immunoglobulins, immunoglobulin aggregates, complements, immune complexes, cold aggregates, and nucleic acids contained in blood. The present invention relates to a blood processing device.

In recent years, it has become clear that high molecular weight solutes such as immunoglobulins, immunoglobulin aggregates, complement, immune complexes, cold aggregates, and nucleic acids are deeply involved in the occurrence and pathology of intractable diseases such as autoimmune diseases. Plasma exchange therapy has come to be used for the purpose of removing these high molecular weight solutes. Plasma exchange therapy is also being applied to hepatitis, cancer, etc. However, in plasma exchange, there are problems in securing plasma from healthy people to be transfused to patients;
Plasma transfusion can cause problems such as new infections and serum sickness, so it is desirable to purify and re-infuse the patient's own plasma. As a workaround, there are methods such as treating the plasma with an adsorbent, using a porous membrane with a small pore size, and cooling to aggregate the cold aggregates and then treating the plasma with a porous membrane with a small pore size. is being attempted. However, when treating with adsorbents, the currently developed activated carbon is effective against drug poisoning, but has little effect on autoimmune diseases, and with porous membranes, it is difficult to treat autoimmune diseases. Although this method is somewhat effective, it has problems such as the amount of high molecular weight solutes that can be removed is small and the amount of albumin that needs to be recovered and returned to the patient is also significantly reduced.

The inventors of the present invention have arrived at the present invention, which comprises a pre-treatment, in order to be able to solve the above-mentioned problems associated with the prior art regarding blood purification treatment.

The present invention provides a blood circulation system including a plasma separation device and a blood-plasma mixing section between a blood introduction section and a purified blood output section;
a plasma reflux system path connected to the thread path for causing the plasma separated by the plasma separation device to flow into the blood-plasma mixing section through a desalting dialysis device, a plasma filtration device, and a conditioning dialysis device; and the plasma separation device is composed of a porous membrane that allows substantially all soluble components in the plasma to pass through while not allowing blood cell components with an average pore diameter of 12 to 2.0 μm to pass through; is composed of a porous membrane with an average pore size of [1LO5 to 5.0μ], and the desalting dialysis device and the conditioning dialysis device are ordinary dialysis devices for artificial kidneys, and the blood entering from the blood inlet is converted into plasma. The separated plasma is separated into concentrated blood and plasma using a separator, and the separated plasma is desalted using a desalting dialysis device, and the high molecular weight solutes that aggregate as a result are removed by a subsequent plasma filtration device.
Blood processing in which the salt concentration, water content, glucose concentration, etc. of filtered plasma are adjusted using the following adjustment dialyzer, mixed with concentrated blood in a blood-plasma mixing section, and then discharged from a purified blood output section. The gist of this paper is the equipment used for this purpose.

In the present invention, the blood introduction section usually refers to a device for introducing blood into the blood processing device using a shunt, a blood collector using a syringe needle, other conduits and cocks, and a pump if necessary, and a purified blood outlet section. refers to a device that directs blood purified by the blood processing device from the blood processing device using a conduit and a cock, and if necessary, a blood pressure control valve, a shunt, an intravenous drip, etc. In addition, the blood-plasma mixing section is for mixing purified plasma and concentrated blood, and a Y-shaped connector, T-shaped blood circuit, or other device for merging the two fluids is sufficient. can achieve that purpose. The blood processing device of the present invention includes a blood distribution system mainly consisting of a plasma separation device and a blood-plasma mixing section, and a plasma separated by the plasma separation device in this blood distribution system, which is desalted and has a high molecular weight. A desalting dialysis device for coagulating and precipitating solutes, a plasma filtration device for removing aggregated high molecular weight solutes from plasma, and a plasma filtration device for returning the salt concentration, water content, glucose concentration, etc. of filtered plasma to normal values. The main feature is that the plasma reflux system is connected to the conditioning dialysis machine, but valves, pumps, and filters may be used as necessary between each component device, the blood circulation system, and the plasma reflux system. and are connected by a conduit and configured to allow blood and/or plasma to flow in a circulatory manner.

The present invention will be explained in more detail below with reference to the accompanying drawings.

FIG. 1 is an explanatory diagram showing an example of the basic configuration of the blood processing apparatus of the present invention. The device of the present invention will be explained according to the flow of blood. The patient's blood to be purified is introduced from a blood inlet 1 and is sent to a plasma separation device 3 by a pump 2, such as a roller pump, if necessary. A shaft (not shown) is typically used for direct blood introduction. The plasma separated by the plasma separator 6 is sent to the desalination dialysis device 5 by a pump 4 such as a roller pump as needed, and dialyzed using water instead of the dialysate of the artificial kidney device to remove sodium ions in the plasma. , potassium ions, magnesium ions, chloride ions, and other inorganic salt ions are removed. The normal conditions for this desalination treatment are a plasma flow rate of 10 to 50 ml/min, and a water flow rate of 100 ml/min.
~1000 me/min, typical examples are plasma flow rate 3 Q me/min, water flow rate 500 m
e/min.

It is possible to remove more than 80 inorganic salt ions.

Although it depends on the patient's medical condition and blood composition, desalinated plasma becomes cloudy due to aggregation and precipitation of immunoglobulins (particularly Ig-M), immunoglobulin aggregates, complement, immune complexes, and the like. Plasma that has been desalted in the desalting dialyzer 5 and in which high molecular weight solutes have been aggregated is sent to a plasma filtration device 6, where high molecular weight harmful substances present in the plasma are removed as a filtration residual liquid. The purified hyperplasma is dialyzed using the same method as the adjustment dialysis device, and the salt concentration, water content, pH, glucose concentration, etc. in the plasma are adjusted to near normal values. The usual conditions for this conditioning process are plasma flow rate of 10-8 Q ml/min;
The flow rate of the dialysate is 100 to 10,100 O/min, and the water that flows into the desalting dialyzer based on the osmotic pressure is removed by the adjusting dialyzer. The purified plasma adjusted by the conditioning dialyzer 7 is sent to a blood-plasma mixing section 8, where it is mixed with concentrated blood drawn out from the plasma separator, and then drawn out to a blood drawing section 9.

As shown in FIG. 2, in the plasma filtration device 6, plasma containing a filtration residual liquid containing high molecular weight solutes or a portion thereof is transferred to a plasma mixing unit 11VC by a pump 10 such as a roller pump.
A circulating reflux method in which the plasma is sent, mixed with plasma from the desalination dialyzer 5, and high molecular weight solutes are separated and removed in the plasma filtration device 6 is also a preferred method and is included in the present invention.

Further, in the plasma filtration device 6, it is also preferable to prevent the plugging of the plasma filtration device by continuously discharging a portion of the filtration residual liquid or filter containing high molecular weight solutes out of the system, and the present invention included in Depending on the patient's condition, that is, the type of high molecular weight solutes to be removed, the desalted plasma from the desalted dialysis device 5 may be cooled to promote aggregation of cold aggregates, immune complexes, etc., thereby increasing their removal efficiency. It is also a preferable method to increase the In that case, plasma li
The conduit to the filtration device 6 or the plasma 1 filtration device and the circulation circuit for the filtration residue containing high molecular weight solutes shown in FIG.
This is achieved by cooling with a cooling plate or the like.

The porous membrane for plasma separation used in this device is a membrane that allows substantially all of the soluble components in plasma to pass through while not allowing blood cell components to pass through, and has an average pore diameter of 012 to 2.0μ,
More preferably a 0.6-0.8μ membrane is used. Any form of membrane can be used, such as hollow fiber, keel, or coil, but since the plasma separation rate is greatly affected by the shear rate of blood on the membrane surface (5hear rate), hollow fiber forms are preferred. It is advantageous and preferable to use a membrane made of
It is approximately 1.5 m.

The porous membrane for the plasma filtration device used in this device depends on the type of high molecular weight solute to be removed, but is generally 0.05
Membranes with an average pore size of ~5.0μ, usually 0.08-0.8μ are used.

As the desalination dialysis device used in this device, the device normally used in artificial kidney dialysis devices can be used, and water, preferably sterile deionized water, is used instead of the dialysate in the case of artificial kidneys. be done.

Any membrane can be used as long as it has a high dialysis efficiency for urea, creatinine, etc. to the extent that it can be used in artificial kidneys. - In this device, water moves to the plasma side, so there is some dilution of the plasma, but the water content will be adjusted in the next adjustment dialysis device.

As the adjusting dialysis device used in this device, a device used in a normal artificial kidney dialysis device can be used as well as a desalting dialysis device. As for the membrane/seal, a membrane with high water removal performance, which is used in hemofiltration therapy in an artificial kidney, from which water can be easily removed, is preferably used.

In carrying out the present invention, it is also possible to further provide a buffer tank in the circuit shown in FIGS. 1 and 2, or to insert other blood purification means such as an activated carbon adsorbent.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Hollow fiber type HFAK "Filtlizer B2-20" which is commercially available as a desalination dialysis device for artificial kidneys
0" (Toshi Co., Ltd., material: polymethyl methacrylate, membrane area 1.5 m2), human serum heated to 37°C was flowed at 50 ml/min on the blood side, and 25°C on the dialysate side. 500 mg/'mi of deionized water
I ran it with n. Desalinated serum obtained from the blood side outlet of HFAK was obtained at a rate of 51 serum/min and was cloudy. 102-0 obtained between 10 and 12 minutes after the start of the experiment and the serum before desalting treatment were analyzed and the results shown in Table 1 were obtained.

This value has been corrected to compare the dilution with water (21 ml/min), which has increased due to the treatment, with that after treatment.

Further, the amount of precipitated aggregates after centrifuging the desalted serum at 200 rpm was 0.29 g.

Analysis of the post-treatment serum was performed using the supernatant from which the aggregates were removed.

That is, by desalting, a hollow fiber plasma separator (average pore diameter: approx. 0.5 μ, membrane area o, s m2>, HFAK “Filtlizer 82-200” as a desalting dialysis device,
The plasma filtration device is the same as the plasma separation device, and the adjustment dialysis device is HFAK ``Filtlyzer B1'' (Toshi Co., Ltd., material: polymethyl methacrylate, membrane area 1
．． 15rn2) and 3000 yd of fresh bovine blood added with 6000 units of heparin, 1 nvit at 57°C.
r.

We conducted an experiment.

When the blood flow rate to the plasma separator is constant at 100-/min, the speed of the plasma pump (double type) is 50 ml.
Plasma was stably obtained at a rate of /min, and the plasma was supplied to the desalination dialyzer at a constant rate.

The dialysate side of the desalting dialysis machine (outside the hollow fibers) was supplied with ion-exchanged water at a rate of 500 d/min, and the dialysate side of the conditioning and dialysis machine was supplied with dialysis fluid for artificial kidneys "AK-Solid" (Shimizu Pharmaceutical Co., Ltd.). Co., Ltd.) 55 times diluted solution / 500ml /
One of the dual plasma pumps was placed between the adjusting dialyzer and the blood-plasma mixing section, and the plasma flow rate of the adjusting dialyzer was kept constant at 5 Qme/m + n.

Blood obtained from the purified blood outlet section 20 to 22 minutes after the start of the experiment was analyzed as processed blood.

Additionally, no problems such as hemolysis or leakage of red blood cells from the plasma separator were observed during the experiment. The analysis results are shown in Table 2.

Table 2 below shows that it was possible to remove the globulin fraction using the apparatus of the present invention. Further, a system in which a pump interlocked with the plasma pump 4 is installed on the outlet side of the regulating dialyzer 7 is a preferable method for adjusting the water flowing into the desalting dialyzer.

[Brief explanation of the drawing]

FIG. 1 is an explanatory diagram illustrating the configuration of the apparatus of the present invention. FIG. 2 is an explanatory diagram illustrating another configuration of the device of the present invention. 1...Blood introduction port, 2...Pump (blood pump),
6...Plasma separator, 4...Pump (plasma pump)
, 5... Desalting dialysis device, 6... Plasma filtration device, 7
... Adjustment dialysis device, 8 ... Blood-plasma mixing section, 9
...Blood outlet, 10...Pump (plasma circulation pump), 11...Plasma mixing part. Patent Applicant Toshi Co., Ltd. Sai 21 Procedures Amendment Book Showa -,9,:4Ua Commissioner of the Patent Office Shima 1) Haruki Tono 2 Name of the Invention Blood Processing Device S Voluntary person making the amendment 5 Amending The number of inventions will increase.None.The entire specification subject to the S amendment.Contents of the amendment (no negative history)Procedure , Case indication 2, Name of the invention Blood processing device
5 Number of inventions increased by amendment None 6 Target of amendment Amendment submitted on September 2, 1981 (Type-written specification) l Contents of amendment j Eve-written specification 1, Claims attached as attachment Correct as shown. 2. tL Sada 1st) line - I7th line ``And the above...
・・・・・−・・・・・−11111 dialysis equipment," is deleted. 3. In the 20th 1st ζ line to the 9th line, "average pore diameter is 0.2 to 2.0 μ" is corrected to 1, "normal average pore diameter is about 0.2 to 2.0 μ". L (Attachment) Claims [A blood circulation system path that includes a plasma separation device and a blood-plasma mixing section, and is connected to the thread path between the blood introduction section and the purified blood output section. a plasma reflux system path for causing plasma separated by a plasma separator to flow into the blood-plasma mixing section via a desalination dialyzer, a plasma υi filtration device, and an adjustment dialyzer; Incoming blood is separated into concentrated blood and plasma using a plasma separator, and the separated plasma is desalted using a desalting dialysis device. The salt concentration, glucose concentration, etc. of the F-treated plasma are adjusted using the next adjustment dialyzer, mixed with concentrated blood in a blood-plasma mixing section, and then discharged from a purified blood outlet section. A blood processing device characterized by: ”

Claims (1)

[Claims] Between the blood inlet part and the purified blood outlet part, there is a blood distribution system path including a plasma separator and a blood-plasma mixing part, and a blood circulation system path connected to the thread path to remove the plasma separated by the plasma separator. comprising a reflux system path for plasma to flow into the blood-plasma mixing section via a salt dialysis device, a plasma filtration device, and a conditioning dialysis device;
and the plasma separator has an average pore diameter of 0.2 to 2.0.
The plasma filtration device is made of a porous membrane that allows substantially all of the soluble components in plasma to pass through while not allowing blood cell components of μ to pass through. The desalting dialysis device and the conditioning dialysis device are comprised of ordinary dialysis devices for artificial kidneys, and the blood entering the blood inlet is separated into concentrated blood and plasma by a plasma separator. Plasma is desalted using a desalting dialysis device, and the high molecular weight solutes that aggregate as a result are removed by a subsequent plasma filtration device, and the salt concentration, glucose concentration, etc. of the filtrated plasma are adjusted as follows. A blood processing device characterized in that the blood is adjusted with a dialysis machine, mixed with concentrated blood in a blood-plasma mixing section, and then discharged from a purified blood discharging section.