JPS63200769A - Extracorporeal circulation circuit - 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 (Field of Industrial Application) The present invention relates to an extracorporeal circulation circuit used for treatment of malignant tumors and the like.

(Conventional technology) Autoimmune diseases including malignant tumors, liver failure, and DIC.

“Double filtration plasma separation and exchange method” as a treatment method for intractable diseases such as hyperlipidemia (edited by Tetsuzo Agishi; Igaku Shoin, 19
1984) has been proposed. in this way.

Blood is continuously drawn from the patient, separated into plasma and blood cells using a separation membrane, and large molecular weight fractions are removed from the obtained plasma using another separation membrane. The protein is left behind), and the blood is returned to the patient along with the blood cell components. The above-mentioned large molecular weight fractions contained in plasma are believed to be various specific and non-specific immunosuppressive substances present in the blood of cancer-bearing patients, for example. An example of an immunosuppressive substance belonging to such a large molecular weight fraction is 1.

Antibodies produced by the surface of malignant tumor cells as specific antigens,
It is thought to be an immune complex in which various substances such as antigens, antibodies, and complement bind together to form a large matrix.

In patients with malignant tumors, these immunosuppressive substances cause a decline in immune function, and as a result of the complex interplay of these substances and other factors, tumor cells are unable to escape from the normal immune surveillance mechanism. It is said to deviate and proliferate and metastasize. Therefore, malignant tumors can be improved by selectively removing large molecular weight fractions as in the above method. However, such methods of removing immunosuppressive substances do not have the effect of actively attacking malignant tumor cells and causing necrosis. Furthermore, when removing a large molecular weight fraction using a 2-separation membrane, there is a possibility that a portion of plasma proteins necessary for living organisms may also be removed.

Examples of improvement in malignant tumors by treating blood include:
In addition, a report by Takeshi Shiraki titled "Acute tumor necrosis obtained by intravenous administration of tumor-bearing rabbit serum treated with hypertonic saline"
(Clinical Immunology, June 1986 issue, pages 544-547). According to this report, serum obtained from tumor-bearing rabbits is mixed with a concentrated aqueous sodium chloride solution, the sodium chloride concentration is lowered by dilution or dialysis, and the treated serum is returned by intravenous injection. There is. It has been confirmed that cancer shrinks through treatment. However, according to Nakamoto's method, there is a risk that contaminants may be mixed in during each step such as blood collection, separation of serum (or plasma), treatment with aqueous sodium chloride solution, and intravenous injection, and this must be done aseptically. This requires a very complicated operation.

(Problem that the invention attempts to solve) The present invention solves the above-mentioned conventional drawbacks.

The aim is to provide a system that can effectively treat malignant tumors. Another object of the present invention is to provide the above-mentioned system that can easily and safely treat malignant tumors by treating body fluids from living organisms, particularly blood.

(Means for Solving Problems) The extracorporeal circulation circuit of the present invention includes a heating means for heating blood or plasma from a living body to a predetermined temperature, and a heating means for heating blood or plasma from a living body to a predetermined temperature, and a heating means to continuously supply the heated blood or plasma to the living body. Alternatively, the above object can be achieved by having a circulation means that can circulate intermittently.

The circuit of the present invention can be constructed using two circuits, for example as shown in FIG.

It has heating means 200 and circulation means 600. Rabbit 5
Blood or plasma from a living body such as a living body is supplied to the heating means 200 by a circulation means 600 such as a pump 61, where immune complexes present in the blood or plasma are dissociated. It is returned to the living body by means 600.

The heating means 200 includes a heater 21 and a processing tank 22, for example. The heater 21 is not particularly limited as long as it is a device that can heat the blood or plasma in the processing tank 22 to 37 to 50° C. and maintain it in the above temperature range for a predetermined period of time. The shape of the processing tank 22 is also not particularly limited. In addition to the usual box-type reaction tank and round-bottom reaction tank, the heat energy from the heater 22 is sufficiently transferred to the blood or plasma.

For example, spiral reactor, loop reactor.

Coiled reactors may also be utilized.

The circuit of the present invention preferably includes a temperature adjustment means 300 for lowering the blood or plasma treated by the heating means 200 to the level of the body's body temperature.

It is arranged downstream of the heating means 200. The temperature adjusting means 300 has a constant temperature bath 32 that is controlled to a predetermined temperature by a temperature controller 31, for example.

When dissociating immune complexes in plasma using this circuit, as shown in FIG. A mixer 4 is arranged to mix the plasma and blood cell components.

(Example) The invention will be explained below with reference to examples.

As shown in FIG. 1, the blood of rabbits 5 and others is supplied to the plasma separator 1 by a pump 61 together with heparin (blood coagulation inhibitor) from a heparin supply device 52.

It is separated into blood cell components and plasma. The separated plasma is supplied to the processing tank 22 of the heating means 200 and heated to 37 to 50°C by the heater 21. This heat treatment causes the immune complexes contained in the plasma to dissociate.

Malignant tumor-specific antibodies are released. The heating time is not particularly limited, but a range of 30 minutes to 3 hours is appropriate in order to sufficiently dissociate the immune complex. If the treatment time is extremely short, sufficient effects may not be obtained, and if the treatment time is extremely long, proteins in the blood may be denatured.

Next, this plasma is supplied by the pump 63 via the filter 30 to the constant temperature bath 32 of the temperature adjustment means 300.

This plasma is then sent by pump 64 to mixer 4 where it is mixed with blood cells from plasma separator 1 (transported by pump 62). Protamine is added to this mixture from a protamine supplier 53 to neutralize the heparin contained therein.

This mixture 9 is then returned to the vein of the rabbit 5. The blood (plasma) circulation rate in this circuit can be adjusted, for example, by each of the pumps 61 to 64 and the cock 23, and can be processed continuously or intermittently.

By heat-treating blood or plasma using the circuit of the present invention, immune complexes present in body fluids of patients with malignant tumors are dissociated. Immune complexes.

As mentioned in the prior art section, there are various types of antigens, including antibodies generated when the surface of a malignant tumor serves as an antigen.

It is said to be a complex formed by binding of antibodies, complement, etc. When this is dissociated using the circuit of the present invention, malignant tumor-specific antibodies are thought to be released.

Malignant tumor-specific antibodies act specifically on malignant tumor cells.

The malignant tumor cells are necrotized or reduced in size.

An example of an immunological method for treating malignant tumors using antibodies capable of recognizing cancer cells is a method of administering monoclonal antibodies. but.

Monoclonal antibodies that are effective in treatment have only been obtained against specific types of malignant tumor cells.

Its preparation also requires complex steps. In contrast, the circuit of the present invention can be applied to the treatment of all types of malignant tumors in which malignant tumor-specific antibodies can be obtained by dissociation of immune complexes. The structure of this circuit and its method of use are simple, and the treatment can be performed safely and inexpensively without contaminating blood or plasma during treatment. Using this circuit 9
for example.

Patients for whom surgery is difficult or patients with malignant tumors for whom anticancer drug administration is inappropriate can be effectively treated.

(Experiment example) The invention will be explained below with reference to experimental examples.

Tumor cells Vx2 were transplanted subcutaneously on the back of a rabbit with a 1-maw, and a 4X4CO1φ tumor was obtained one month later. The circuit of the present invention was connected to this rabbit as shown in FIG. Blood 80- was introduced into the system from the femoral artery 51 of rabbit 5 through a blood collection tube. After heparin was supplied from the heparin supply device 52, it was separated into blood cell components and plasma by the plasma separator 1 and supplied to the processing tank 22. The plasma was heated to 43° C. for 1 hour by heater 21. The cock 23 is opened, the plasma is sent to the filter 30 by the pump 63, and then the temperature controller 31 is sent to the filter 30.
It was supplied to a constant temperature bath 32 whose temperature was controlled by . After the temperature of the plasma was set to 37° C., it was supplied to the mixer 4 using a pump 64. Here, the blood was mixed with blood cell components sent from the plasma separator 1 by the pump 62, and after adding protamine from the protamine supply device 53, the blood was returned to the femoral vein 54 of the rabbit 5.

Three days after extracorporeal blood circulation using the circuit of the present invention, the tumor diameter was reduced to 3×3aaφ. A rabbit that did not undergo extracorporeal circulation (control).

However, the patient died 44 days after the tumor cell transplantation.

Rabbits that underwent extracorporeal circulation survived for 82 days.

A clear life-prolonging effect was observed.

1.1 When tumor cells Vx2 were subcutaneously transplanted into the back of a rabbit, a 4×4QIIφ tumor was obtained one month later. The circuit of the present invention was connected to this rabbit as shown in FIG. Blood was continuously introduced into the system from the femoral artery 51 of the rabbit 5 through a blood collection tube using a pump 61. After heparin was supplied from the heparin supply device 52, it was separated into blood cell components and plasma by the plasma separator 1. The plasma was introduced into the spiral processing device 24 and heated to 43° C. by the heater 21. The plasma after the heat treatment was supplied to a coiled tube 32 whose temperature was controlled by a temperature controller 31 . After the temperature of the plasma was set to 37°C, it was supplied to the mixer 4. Here, from the plasma separator 1 to the pump 62
The mixed blood was mixed with the blood cell components sent by the femoral vein 54 of the rabbit 5, and the blood was returned to the femoral vein 54 of the rabbit 5. The flow rate of the extracorporeal circulation is 2M in the pump 61.
1/min and in the spiral processor 24 1-7
Extracorporeal circulation was performed continuously for 30 minutes.

Three days after extracorporeal blood circulation using the circuit of the present invention, the tumor diameter was reduced to 2.5 x 3 cmφ. A rabbit that did not undergo extracorporeal circulation (control).

However, the patient died 38 days after the tumor cell transplantation.

Rabbits that underwent extracorporeal circulation survived for 72 days.

A clear life-prolonging effect was observed.

(Effects of the Invention) As described above, malignant tumors and the like can be effectively treated using the circuit of the present invention. The basic operation method is to process the patient's blood and return it, so it does not put a burden on the patient's body like a surgical operation.

There is almost no loss of plasma proteins during processing.

Furthermore, since the circuit is isolated from the outside environment, it is safe and free from contamination by germs. Using this circuit.

For example, patients for whom it is difficult to undergo single surgery or patients with malignant tumors for whom anticancer drug administration is inappropriate can be effectively treated.

4. A large amount of ゛H Figures 1 and 2 show the circuit of the present invention applied to a domestic rabbit,
It is an explanatory diagram in which a malignant tumor is treated by processing the blood.

1...Plasma separator, 4...Mixer, 5...Rabbit,
21... Heater, 22... Processing tank, 24... Spiral shaped processing device.

32... Constant temperature chamber, 200... Heating means, 300...
- Temperature adjustment means, 600... circulation means.

Figure 1

Claims (1)

[Scope of Claims] 1. A heating means that heats blood or plasma from a living body to a predetermined temperature, and a circulation means that can continuously or intermittently circulate the heat-treated blood or plasma into the living body. Extracorporeal circulation circuit with. 2. The extracorporeal circulation circuit according to claim 1, further comprising temperature adjustment means for lowering the treated blood or plasma to substantially the body temperature of the living body. 3. The extracorporeal circulation circuit according to claim 1, wherein a plasma separator is disposed downstream of the living body and between the living body and the heating means.