JPH043985B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a plasma filtration device that removes gamma globulin, immune complexes, toxins, etc. from the blood and is used to treat autoimmune diseases and the like.

(Prior art) Plasma exchange has been known as a treatment method for various diseases such as liver failure and autoimmune diseases that are said to be caused by toxins (polymer substances) dissolved in the blood. . In this method, blood is separated into plasma components containing toxins and concentrated blood, and healthy plasma, preserved plasma, plasma substitute, albumin-containing solution, etc. (hereinafter collectively referred to as replacement fluid) are added to the concentrated blood. This is a method in which the patient's body is returned to the patient's body. This method is wasteful in that plasma containing useful components is discarded, requires large amounts of expensive replacement fluids, is difficult to obtain large amounts of plasma from healthy people, and is difficult to prevent serum hepatitis. It has many drawbacks, such as the risk of complications and the use of large quantities of plasma substitutes, which can upset the balance of the patient's blood components.

On the other hand, after separating plasma components and hemolyte-concentrated blood, the plasma is divided into components containing high-molecular substances and components containing low-polymer substances using a plasma filter, and the components containing low high-molecular substances are combined with the hemo-concentrated blood and transferred into the body. A so-called double filtration system has been proposed (Japanese Patent Application Laid-Open Nos. 56-75164, 1982-145859, etc.).

However, in this method, a large amount of useful components such as albumin, which are intended to efficiently block high-molecular substances in the plasma filter, are also blocked in large quantities, and the amount of useful components returned to the body is greatly reduced. If you try to recover a large amount of useful components, a considerable amount of the polymer substances that should be blocked will also pass through (for example, if the immunoglobulin removal rate is 20~20%).
(Currently, only about 30% can be removed), which is insufficient in terms of therapeutic effect.

Furthermore, with this method, plasma components adhere to the membrane and cause clogging, which rapidly reduces the effective membrane area of the plasma filter and increases TMP (transmembrane pressure), resulting in long-term filtration. The disadvantage is that it cannot be done.

(Objective of the Invention) The object of the present invention is to eliminate the above-mentioned drawbacks of double filtration, and to provide a plasma filter that has a high rejection rate for polymeric components in plasma components and is excellent in recovering useful components such as albumin. The goal is to provide equipment.

(Structure of the Invention) The present invention includes a first filter that transmits at least 50% of albumin and globulin among plasma components separated from blood and blocks at least a portion of fibrinogen;
a second filter which substantially blocks polymer components higher than albumin in the liquid drawn out from the first filter; The plasma filtration apparatus is characterized in that it has at least a circuit for introducing the blood into the plasma filtration apparatus.

Although centrifugation can be used as a method for obtaining plasma components to be processed by the device of the present invention, it is possible to use a centrifugation method that does not require a large device. It is preferable to use a membrane type filter that separates blood into plasma components and hemoconcentrated blood because of the advantages of being able to set up a blood purification system.

The first and second filters used in the present invention are preferably of membrane type, and the membrane has a small brimming volume to obtain a wide effective membrane area and to increase the flow rate of the liquid to be filtrated on the membrane surface. It is preferable to use a hollow fiber membrane because it can be removed and reduce the adhesion of proteins, etc. to the membrane surface.

The membrane used in the second filter is permeable to useful components below albumin, and although it differs depending on the disease being treated and the macromolecular components to be removed, it blocks gamma globulin and allows useful components below albumin to pass through. It is also possible to use a material that allows components with a molecular weight of less than that to pass through, blocks immune complexes, and allows components with a lower molecular weight to pass through.

Items that should be removed include protein-bound toxins,
Various antigens such as complement and fetoprotein that mediate inflammatory reactions, Bence-Jone protein anti-DNA antibodies,
Various antibodies such as myelin antibodies can be mentioned. It is preferable to select a membrane depending on the object to be removed.

The degree of inhibition is sufficient as long as it can be inhibited to a degree that is effective in treating the disease, and does not necessarily have to be completely inhibited.

The membrane used in the first filter must be able to block at least a portion of fibrinogen, and a membrane that separates blood into plasma and concentrated blood cannot be used; 2
If the pore size is larger than the membrane used in the filter, fibrinogen tends to adhere to the membrane and can be used.

The hollow fiber membrane used here is
52123, JP-A-57-42919, JP-A-57-66114, etc., polyolefin porous hollow fibers obtained by spinning, cold stretching, or further hot stretching do not contain impurities and have various pore sizes depending on the purpose. This is preferable because a film of .

The filtration device of the present invention passes plasma components separated from patient blood through a first filtration device to separate them into a component containing a large amount of fibrinogen and a plasma component with no or little fibrinogen (liquid A). The derived liquid A is introduced into a second strainer to remove the polymeric components, and the liquid (liquid B) in the second strainer having a reduced amount of polymeric components or containing no polymeric components is preferably concentrated into blood cells. Toxic components are removed from the patient's blood by combining it with the blood or by adding replacement fluid and returning it to the patient's body.

Conventionally proposed double filtration separates high-molecular substances such as gamma globulin or higher and low-molecular substances such as albumin in one step, but proteins of various molecular weights coexist in solution in plasma. In some cases, the separation of albumin and globulin by the membrane is insufficient, and the effective membrane area rapidly decreases due to the deposition of fibrinogen and other substances on the membrane.
This further reduces the ability to separate albumin and globulin.

Many patients with collagen diseases such as rheumatism patients have high blood viscosity, and in these cases the above-mentioned drawbacks are especially noticeable. There are many cases where this is insufficient.

On the other hand, in the case of the present invention, in which a second strainer that can separate globulin and albumin after removing fibrinogen etc. in the first strainer is used, even if the plasma of a rheumatoid patient is used, the blood of a healthy person is Similarly, it can efficiently separate globulin and albumin.

The present invention will be explained in detail below using the drawings.

FIG. 1 is a block diagram of a blood processing system incorporating the plasma filtration apparatus of the present invention. The patient's blood is introduced by a blood pump 4 through a blood introduction conduit, and sent to a blood transducer 1 via an air trap 6. This strainer 1 houses a membrane that blocks blood cell components and allows only plasma components to pass through, and the blood sent to this strainer 1 is separated into hemoconcentrated blood and plasma components. Plasma may be separated by centrifugation instead of using the blood filter 1. The separated plasma components are sent to the first filter 2 by a roller pump 5 through a plasma outlet line. The first filter vessel 2 houses a membrane that blocks at least a portion of fibrinogen in plasma and allows albumin and globulin to permeate. Filtrate from which at least a portion of fibrinogen has been removed by the first filter 2 (liquid A)
is sent to the second strainer 3 via the liquid outlet line. A replacement fluid may be added to the liquid A between the first filter 2 and the second filter 3.

The second filter 3 houses a membrane that allows albumin to pass therethrough and blocks gamma globulin, for example. The membrane stored in the second diaphragm 3 is for therapeutic purposes,
It is preferable to appropriately select the membrane pore size depending on the substance to be blocked. The liquid (liquid B) drawn out from the second blood strainer 3 is fed by a roller pump, with supplementary fluid added as necessary, and is combined with the concentrated hemocytosis blood separated in the blood strainer 1, and air bubbles are formed in the air trap 7. is removed and then placed back into the patient's body.

In Fig. 1, plasma fluid delivery and fluid delivery of fluid B are carried out by one pump 5, and by the negative pressure in the tube in front of pump 5, it is added to fluid B from the fluid replacement tank 8 via the fluid replacement control valve 9, and is then released from the patient. An equal amount of blood is returned to the patient. Of course, a pump may be inserted between the first supercontainer and the second supercontainer, or two pumps may be used instead of pump 5 to send each liquid, and no replacement fluid is added. Alternatively, it is also possible to add the replacement fluid while adjusting it to a predetermined amount using a pump.

Alternatively, a heat exchanger may be installed in front of the trap 7 to heat it to an appropriate temperature and then return it to the patient's body.

Furthermore, in order to improve the overefficiency and the flow rate of the filtrate on the membrane surface, some of the liquid in the blood filter 1 and/or the first filter 2 and/or the second filter 3 may be recycled. good.

The excess residual liquid drawn out from the first over-container and the second over-container is discarded, but in order to maintain the overpressure in the first over-container and over-container, for example, a constant pressure valve may be provided in the middle of the excess residual liquid discharge pipe. is preferred.

Further, pressure gauges may be attached to locations other than those shown in FIG. 1, and some of the pressure gauges shown in FIG. 1 may be removed.

The present invention will be explained below with reference to Examples.

Example 1 Using the system shown in Figure 1, a polyethylene hollow fiber membrane EHF270T (manufactured by Mitsubishi Rayon Co., Ltd.; gas flux 27×10 ⁴ /m ² was used as the blood filter 1)
A module with a membrane area of ^0.5m2 containing hr0.5atm) is used as the first filter and a polyethylene hollow fiber membrane is used as the first filter.
EHF370C (manufactured by Mitsubishi Rayon Co., Ltd.; Gas flux 14
×10 ⁴ /m ² hr0.5atm) with a membrane area of 0.5m ² was used as the second filter, and a polypropylene hollow fiber membrane KPF190M (manufactured by Mitsubishi Rayon Co., Ltd.; gas flux 7 × 10 ⁴ /m ² hr0. Two modules with a membrane area of 0.5 m ² containing 5 atm) were connected in parallel, and both membranes were made hydrophilic and sterilized to treat the blood of rheumatism patients.

The plasma before treatment has a total protein of 5.8 g/dl and an albumin/globulin ratio (hereinafter referred to as A/G ratio) of 1.1.
However, after 3 hours of treatment at a blood processing rate of 100c.c./min and a plasma flow rate of 12c.c./min, the total protein was 5.0g/min.
dl and A/G ratio were improved to 2.15. At the beginning of the treatment, the transmembrane pressure was approximately 30 mmHg in both the first and second tubes, and even after 3 hours, it was approximately 100 mmHg in the first tube and 100 mmHg in the second tube.
The transmembrane pressure difference was approximately 150 mmHg in the filter chamber.

Example 2 The same system and hollow fiber module as used in Example 1 were used, and the same treatment as in Example 1 was carried out except that the blood processing amount was 100 c.c./min and the plasma filtration amount was 20 c.c./min. I did it. Plasma before processing has a total protein of 5.6
The g/dl and A/G ratio were 1.0, but after 2.5 hours of treatment, the total protein was improved to 5.0 g/dl and the A/G ratio was 2.1. At the beginning of the treatment, the transmembrane pressure difference was about 33 mmHg in both the first and second filters, and even after 2.5 hours, the transmembrane pressure difference was about 110 mmHg in the first filter and about 150 mmHg in the second filter.

Comparative Example Plasma drawn from the blood transducer is directly transferred to the second transducer via the pump 5 without using the first transducer shown in FIG.
Blood from a rheumatism patient was treated under the same conditions as in the example except that it was introduced into a blood vessel. After 60 minutes, the membrane of the second strainer became clogged and the transmembrane pressure rose to 500 mmHg, so the treatment was stopped. Next, the blood flow rate was fixed at 100 c.c./min to reduce the rise in transmembrane pressure, and the overdose was initially started at 5 c.c./min.
When the treatment was performed while changing the excess dose, 10 c.c./min after 20 minutes and 12 c.c./min after 50 minutes, the plasma before treatment had a total protein of 5.4 g/dl and an A/G ratio of 0.9. On the other hand, the total protein of the liquid in the second filter was 2.1 g/dl, and the A/G ratio
The A/G ratio of 0.95 was not much different from before treatment, and only the total protein was reduced, that is, albumin and globulin were removed without distinction, and no favorable results were obtained.

[Brief explanation of drawings]

FIG. 1 is an example of a blood purification system using the plasma filtration apparatus of the present invention. 1: blood vessel, 2: first blood vessel, 3: second blood vessel
4: blood pump, 5: plasma pump,
6, 7: Air bubble trap, 8: Replacement fluid tank, 9: Throttle valve, 10 to 14: Pressure gauge, 15, 16: Constant pressure valve.

Claims (1)

[Scope of Claims] 1. A first component that transmits at least 50% of albumin and globulin among plasma components separated from blood and blocks at least a portion of fibrinogen.
a second filter which allows at least 50% or more of albumin to pass therethrough and substantially blocks high molecular weight components higher than albumin in the liquid discharged from the first filter.
1. A plasma filtration device comprising at least a filtration device, and a circuit for introducing a liquid drawn from the first filtration device into a second filtration device. 2. The plasma filtration device according to claim 1, wherein the plasma component is separated from blood by a blood filtration device. 3. The plasma filtration device according to claim 2, further comprising a circuit for combining the liquid drawn out from the second filtration device with the remaining components after plasma components have been separated from the blood.