JPH0321260A - Medical care method for malignant tumor, composite for cure and external circulating circuit - Google Patents

Abstract

PURPOSE:To cure a person of a malignant tumor by separating blood plasma from blood, treating the blood plasma in contact with a blood plasma treating liquid, mixing the blood plasma with blood corpuscle components and returning the blood in a living body. CONSTITUTION:Blood from an artery 51 of a living body such as a house rabbit 5 or the like is sent to a blood plasma separating means 1 by a reflux means 600 such as a pump 61, a tube 71 and so on to separate a part of blood plasma. The residual blood plasma and blood corpuscle components are sent to a mixing means 3 through a tube 72. On the other hand, the separated blood plasma is passed through a tube 74 and supplied by a pump 62 to a blood plasma treating means 200 to be in contact with a blood plasma treating liquid and be sent to a mixing means 3. The blood plasma and blood corpuscle mixed by the mixing means 3, that is, the blood is adjusted to the environment in the living body by an adjusting means 400 and returned into the living body through a vein 54 by reflux means 600 such as a pump 63, a tube 73 and so on. The artery 51 of the living body and the vein 54 of the living body are suitably connected to an external circulating circuit by an injection needle or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a method for treating malignant tumors, etc., a composition for the treatment, and an extracorporeal circulation circuit used for the treatment. (Prior art) "Double filtration plasma separation method" as a treatment method for intractable diseases such as malignant tumors, autoimmune diseases, liver failure, DIC, hyperlipidemia, etc. (edited by Tetsuzo Agishi; Igaku Shoin, 1984) ) has been proposed. In this method, blood is continuously drawn from the patient, separated into plasma and blood cells using a separation membrane, and the large molecular weight fraction is removed from the obtained plasma using another separation membrane (Albξ The blood is returned to the patient along with the blood cell fraction (plasma protein fractions, etc.) are left behind. The above-mentioned large molecular weight fractions contained in plasma are thought to be various specific and non-specific immunosuppressive substances present in the blood of cancer-bearing patients, for example. Immunosuppressive substances belonging to such a large molecular weight fraction, for example, form a large matrix by binding various substances such as antigens, antibodies, and complement to antibodies produced as specific antigens on the surface of malignant tumor cells. It is thought to be a formal immune complex. In patients with malignant tumors, these immunosuppressive substances cause a decline in immune function, and as a result of a complex interplay of these substances and other factors, tumor cells are unable to escape from the normal immune surveillance mechanism. It is said that it deviates and proliferates and metastasizes. 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 large molecular weight fractions using a separation membrane, there is a risk that a portion of plasma proteins necessary for living organisms may also be removed.

In addition, as an example of improvement of malignant tumors by blood treatment, see this other paper, ``Acute tumor necrosis obtained by intravenous administration of tumor-bearing rabbit serum treated with hypertonic saline'' (Takashi Yamamoto, Clinical Immunology 1986). June issue, pages 544-547). According to this report, serum obtained from tumor-bearing rabbits is mixed with a concentrated sodium chloride aqueous solution, the sodium chloride concentration is lowered by dilution or dialysis, and the treated serum is returned by intravenous injection. . This treatment reduces cancer by 1! It has been certified.

In addition, the treatment method for this malignant tumor was published in Japanese Patent Application Laid-Open No. 63-9133.
It is also disclosed in Publication No. 0. That is, ``(1) contacting plasma or serum obtained from a living body with a malignant tumor with a hypertonic salt solution, and (2) bringing the plasma or serum obtained in step (1) above into contact with said living body. A method for treating malignant tumors, which comprises the step of administering the same or the same species to the same living body. The mechanism of action is believed to be that the immune complex is denatured or dissociated and the activity of the antitumor antibody is restored. Furthermore, this inventor has developed a device for use in this treatment in Japanese Patent Application Laid-Open No. 63-102763.
It is disclosed in the publication No.

? In addition, as a treatment method for such malignant tumors,
3-93730 discloses that as a method for treating plasma, it is effective to treat it not only with hypertonic salts but also with acidic solutions.

As an extracorporeal circulation circuit for this treatment, JP-A-63-
No. 200768 is disclosed. These treatments (
As shown in Fig. 6, the processing device (Japanese Patent Application Laid-Open No. 63-102763) or the extracorporeal circulation circuit (Japanese Patent Application Laid-Open No. 63-200768) is a plasma separation means for separating plasma from blood collected from a living body. , a plasma processing means for treating the separated plasma by contacting it with a processing agent such as a hypertonic salt solution, and an adjustment means for adjusting the treated plasma to an in-vivo environment;
It is equipped with a mixing means for mixing the adjusted plasma and the blood cell components separated by the plasma separation means, and a reflux means capable of refluxing the mixed substance into the living body, and the upstream side of the mixing means An adjustment means is arranged in the.

Although such treatment methods and devices (circuits) are highly effective in treating malignant tumors, they have not always reached a level where complete cure can be expected. Therefore,
There is a need for something even more effective.

(Problems to be Solved by the Invention) The present invention solves the above-mentioned conventional drawbacks, and its purpose is to provide a more effective treatment method for malignant tumors, etc., a therapeutic composition for the treatment, and an effective biological treatment method. An extracorporeal circulation circuit that can effectively treat malignant tumors without removing components, and the above that can treat malignant tumors in a simple, safe, and continuous manner by efficiently processing blood collected from living bodies. The purpose is to provide an extracorporeal circulation circuit.

(Means for Solving the Problems) The method for treating malignant tumors, etc. of the present invention includes a plasma separation step of separating plasma from blood collected from a living body, and a step of separating the separated plasma into an inorganic salt solution and an organic salt solution. and a plasma processing step of treating the plasma by contacting it with at least one selected from the group of plasma processing solutions consisting of acidic solutions; and a mixing step of mixing the treated plasma with the blood cell components separated in the plasma separation step. The composition for treating malignant tumors, etc. of the present invention includes a conditioning step of adjusting the mixed blood to the in-vivo environment, and a reflux step of circulating the adjusted blood into the in-vivo. is plasma separated from blood collected from a living body and subjected to contact treatment with at least one kind selected from the group of plasma treatment solutions consisting of inorganic salt solutions, organic salt solutions, and acidic solutions, and blood cells of the blood. The blood mixed with the components is adjusted to the environment within the living body, thereby achieving the above purpose.

The extracorporeal circulation circuit of the present invention includes: 1. Plasma separation means for separating plasma from blood collected from a living body, and contacting the separated plasma with at least one plasma processing solution selected from the group of plasma processing solutions consisting of inorganic salt solutions, organic salt solutions, and acidic solutions. a mixing means for mixing the treated plasma and blood cell components separated by the plasma separation means; and an adjustment means for adjusting the mixed blood to the in-vivo environment. ,
2. An extracorporeal circulation circuit comprising a circuit equipped with a reflux means capable of continuously or intermittently refluxing the adjusted blood into the living body, and in which the adjusting means is disposed downstream of the mixing means; 2. The extracorporeal circulation circuit according to the above item 1, further comprising a backflow prevention means between the plasma processing means and the mixing means. This circuit achieves the above objectives.

The treatment method of the present invention is carried out, for example, using an extracorporeal circulation circuit.

The circuit of the present invention includes, for example, as shown in FIG.
Mixing means 3 for treated plasma and blood cell components, adjustment means 400, bombs 61, 62, 63-1, etc., and tubes 71, 72
．． Reflux means 600 consisting of 73, 74, 75, etc.
has.

Blood from an artery 51 of a living body such as a domestic rabbit 5 is sent to the plasma separation means 1 by a reflux means 600 such as a bomb 61 and a tube 71, and a part of the plasma is separated. The remaining plasma and blood cell components are sent to the mixing means 3 through the tube 72. On the other hand, the separated plasma passes through the tube 74 and is supplied to the plasma processing means 200 by the bomb 62, where it is brought into contact with a plasma processing solution and sent to the mixing means 3. The blood plasma and blood cells mixed by the mixing means 3 are then adjusted to the in-vivo environment by the adjusting means 400, and then returned to the living body through the vein 54 by the reflux means 600 such as the pump 63 and tube 73.

Connections between the living body's arteries 51 and the living body's veins 54 and the extracorporeal circulation circuit of the present invention are made as appropriate using injection needles and the like.

As the plasma separation means 1, for example, a hollow fiber type plasma separator or a centrifugal type plasma separator can be used, but preferably a hollow fiber type plasma separator is used.

Further, the plasma processing means 200 includes a plasma processing liquid storage tank 21, a bomb 22, a tube 23, a plasma processing reaction tank 24, and a cock 25 if necessary. The processing liquid storage tank 21 stores a plasma processing liquid. The shape of the reaction tank 24 is not particularly limited. In addition to box-shaped reaction vessels, syringe-shaped reaction vessels, and bag-shaped reaction vessels, spiral-shaped reactors, coil-shaped reactors, and loop-shaped reactors are also used to effectively bring plasma into contact with the plasma processing solution. obtain.

However, for the former two, the cock 25 is attached to the plasma processing means 200.
It is desirable to add . Additionally, in order to improve contact between the plasma and the treatment solution, it is recommended to set the reaction tank in an inverted rocker platform type mixer, or to install a stirrer inside the container. As the plasma processing solution, at least one of an inorganic salt solution, an organic salt solution, and an acidic solution is used. Inorganic salts used include sodium chloride, potassium chloride, magnesium chloride, magnesium sulfate, sodium phosphate, potassium phosphate, ammonium phosphate, ammonium sulfate, sodium borate, potassium borate, and the like. Organic salts include, for example, sodium citrate, potassium citrate, sodium acetate, potassium acetate, sodium pyrophosphate, potassium pyrophosphate, sodium phthalate, potassium phthalate, sodium fumarate, potassium fumarate, sodium tartrate, potassium tartrate. , sodium succinate, potassium succinate, sodium formate, potassium formate, sodium lactate, and potassium lactate. Furthermore, r
PIFES- is known as a component of Good's buffer solution.
Sodium, PIFES-potassium, MOPS-sodium, MOPS-potassium, HEPES-sodium,
HEPES-potassium, Tris monohydrochloride, glycine-hydrochloride, Tricine hydrochloride, TAPS-sodium, TAPS monopotassium, CAPS-sodium, CAP
Examples include S-potassium, TBS-sodium, TBS-potassium, and Bicine hydrochloride. The above-mentioned inorganic salts and organic salts have a pH buffering effect in the range of 6.0 to 8.0 by using a pairing acid or base, or a combination thereof, or by using an appropriate buffer solution to a pH of 6.0 to 8.0. 0-8
．． It is preferable to set it to 0. These inorganic salts or organic salts should be used in an aqueous solution (hypertonic salt) of 0.5 M or more, preferably about 1 to 4 M, and should be used at a concentration of 0.5 M or more per 1 IR of plasma. 1-100
m, preferably used at a ratio of 0.5 to 30 m. As the acidic solution, a common aqueous inorganic or organic acid solution such as hydrochloric acid, phosphoric acid, acetic acid, or citric acid can be used, and various acidic buffers are preferably used. Examples of acidic buffers include glycine-hydrochloric acid buffer, citrate buffer, acetate buffer, phosphate buffer, borate buffer, and potassium phthalate-hydrochloric acid buffer. The pH of the acidic aqueous solution when mixed with plasma is 5.0 or less, preferably 3.5 or less (
(usually 10-3 mol or more). The mixing means 3 may be of any type as long as it can mix the treated plasma and blood cell components. It is not essential to provide a special stirring means, and a simple container may be sufficient. Preferred examples include air chambers used in normal blood circuits. In addition, the mixing conditions must be determined in advance to avoid hemolysis or damage to blood cells, and the mixing must be performed within that range. The adjusting means 400 is, for example, a desalting device or a diluting device, and has a function of adapting the blood, which has a high salt concentration or a low pH as a result of processing in the plasma processing means 200, to the original in-vivo environment. have

As the desalting device, a dialysis device, an ion exchanger, a gel filtration device, etc. are used. For example, a hollow fiber type dialyzer is suitable for the dialysis device.

Furthermore, in order to remove NaCl using an ion exchange resin, a cation exchange resin column for removing Na'' and an anion exchange resin column for removing Ct are sequentially arranged. A liquid feeding path (not shown) is provided to remove salts that are eluted late from the circuit.These desalting devices are equipped with a device that has a function of dehydrating as well as desalting, and water is removed at the same time. is preferred.

In addition, pressure detectors 81, 82, 83 are installed at appropriate locations in the circuit.
An example of these is a pillow-type pressure sensor.

By the way, in this circuit, the part of the circuit from the pump 61 through the tube 71, the plasma separating means 11 tube 72, and the mixing means 3 to the adjusting means 400 (the part surrounded by a solid line in FIG. 1) is not shown. It tends to be stressful. When a positive pressure condition is established, a mixture of plasma and blood cells treated with a treatment solution such as concentrated sodium chloride flows back through the tube 75 to the plasma processing reaction tank 24 side, and is treated with a treatment solution such as concentrated sodium chloride. By contacting the processing liquid,
There is a risk of damage to blood cell components. In order to avoid this, it is preferable to provide backflow prevention means 9 between the plasma processing means 200 and the mixing means 3, as shown in FIG. As the backflow prevention means 9, various commercially available backflow prevention valves can be used, and there is no particular limitation. For example, a duck beak-shaped one as shown in Figure 3 is good. In FIG. 3, 91 is a housing, 92 is a valve body, 93 is a connecting tube, and the valve body 9 is installed in the housing 91.
2, as shown in FIG. 4, a valve portion 95 with a pointed tip extends from the distal end of a cylindrical portion 94, and a flange 98 is provided at the proximal end of the cylindrical portion 94. The valve portion 95 has a pair of opposing inclined pieces 96.96, both inclined pieces 96.96.
A cut 97 is provided at the tip of 96 to allow separation between both inclined pieces 96 and 96. The valve body 92 is made of an elastic material such as rubber or flexible plastic, and when a liquid with a pressure higher than a predetermined pressure acts on the inner surfaces of the pair of inclined pieces 96.96, both inclined pieces 96.96 When the tip of the tube is pushed by the pressure of the liquid and deforms outward, a cut 97 is opened, and the liquid can pass through the cut 97. Further, when the pressure of the liquid acting on the inner surfaces of the pair of inclined pieces 96.96 is less than a predetermined pressure, both inclined pieces 96.9
The distal end of valve 6 is not deformed and the cut 97 is closed, so that liquid cannot pass through this valve body 92. Examples of this type of backflow prevention valve include a backflow prevention valve (trade name: Ni-Otsuka Infusion Set PC-A) manufactured by Otsuka Pharmaceutical Co., Ltd. and Nihon Iiko Co., Ltd., sold by Otsuka Pharmaceutical Co., Ltd. and manufactured by Nihon Iiko Co., Ltd.

Other types of check valves, such as ball valves and disc valves used as artificial valves, can also be used.

(Function) In this circuit, since the adjustment means is arranged downstream of the mixing means, the mixture of processed plasma and blood cell components is still exposed to the highly concentrated treatment liquid until it reaches the adjustment means. Therefore, not only the liquid component of blood but also the blood cell component is treated. Treatment using this circuit allows for more effective treatment than when the regulating means is placed upstream of the mixing means. Although the mechanism of action behind this higher effect than the conventional circuit is unknown, it is likely that non-specific immunostimulatory effects are promoted by stimulating blood cell components, resulting in anti-tumor activity. It's probably more sexual.

(Example) Below, experimental examples and examples of the present invention will be given and further explained.

Using the circuit shown in Figure 5, blood cell concentration and high concentration NaC
Hemolysis of blood cells and blood cell images upon contact with the L solution were observed.

In FIG. 5, a blood bag 50 contained 200 ae of fresh heparin-added blood collected from a domestic rabbit, and a plasma processing liquid storage tank 21 contained a 3M NaCl aqueous solution. Activate Bomb 61 and plasma separator (Asahi Medical: AM-03)
1 He1 0 ml! Blood was drawn and plasma separated at a rate of /min. Both plasma and plasma processing solution are pumped 2. by pumps 62 and 22, respectively. 5WI1/m
The plasma processing reaction tank 24 (blood bag:
Terumo Separation Bag Telflex 150rd was introduced into Terumo Corporation. The cock 25 was kept closed at this time.

Further, the concentrated blood cell components that passed through the plasma separator 1 were pooled in the chamber 31.

20 minutes after the start of plasma separation, bombs 61, 62, 22
stopped.

After another 10 minutes, open the cock 25 and release the concentrated blood cell components and N.
aC1-treated plasma at pumps 63 and 64, respectively.
．． 5a! i! /ffiin and 5#+j! The mixture was mixed by flowing into the chamber 32 at a speed of /win.

10.20.30 minutes after the start of mixing, chamber 32
Samples were taken from the sample, and the chloride ion concentration was measured, blood cell images were observed using a microscope, centrifuged (IOOOG) L, the supernatant was observed, and OD415 nm was measured. The chloride ion concentration was measured using an ion chromatograph (DEIONEX). As a result, the chloride ion concentration was 24.
．． 85g/Il (sodium chloride concentration: 0.7M), and the blood cell image, supernatant observation, and OD415nm are shown in Table 1.
The results shown are obtained. This shows that hemolysis does not occur up to 20 minutes after mixing, and that it is possible to mix blood cells and treated plasma using this method.

(Margins below) Table 1 Transplantable cancer VX2 was implanted subcutaneously on the backs of 20 domestic rabbits.
On the 15th day, a tumor of approximately 2CI+1X2CI was found by palpation. On the 16th day, an administration experiment was conducted on 5 domestic rabbits using the extracorporeal circulation circuit shown in Figure 1. In Figure 1, Pharmacia Pelister pumps were used for pumps 61, 62 and 22, 63. Sterilized vinyl chloride tubes were used for the tubes 71, 72, 73, 74, 75, and 23. As the plasma separation means 1, a plasma separator MicrofloTipe H-2 (Asahi Medical Co., Ltd.) was used. A steam sterilized 3M NaCl aqueous solution was placed in the plasma processing liquid storage tank 21. The reaction tank 24 is equipped with a blood bag (Terumo separation bag Telflex 150-
, Terumo Co., Ltd.) was used. As the mixing means 3, a normal air chamber was used as a mixer.

The adjustment means 400 includes the aforementioned Microflo Ti'
A dialysis machine using a PE H-2 housing filled with the hollow fiber portion of Plasma Flow AP-03H (Asahi Medical Co., Ltd.) was used. At this time, the system containing the external dialysis fluid was kept under negative pressure so that water could be removed at the same time. Before performing extracorporeal circulation, for tube 23, use 3M
Plying was performed with an aqueous NaCl solution, and all circuits except the plasma treatment liquid storage tank 21, tube 23, and reaction tank 24 were plyed with heparin-containing physiological saline. From rabbit auricular artery 51, 5trdl/ at Bonp 61
IIin led blood into the circuit. Heparin supply device 52 to hepa? (blood clotting inhibitor) 0. 3 #11! /
Added in win. The plasma bomb 62 and the plasma treatment liquid bomb 22 were operated at lm/+sin, and each was introduced into the reaction tank 24. The cock 25 was closed in advance, and 30 minutes after the start of plasma separation, the cock 25 was opened, and the reacted plasma and blood cell fraction were combined with the blood cell fraction in the mixer 3. In addition, when the cock 25 was opened, blood cells were seen to flow back from the mixer 3 to the reaction tank 24 side. To neutralize heparin after performing dialysis and water removal (IId/IIlin) using physiological saline as an external dialysis fluid at 100 rtrl/tain in the dialyzer 400 in a whole blood state. Protane was added from the protane supply device 53, and the blood was returned to the auricular vein 54 on the opposite side.

The time from the meeting to the return of blood was approximately 12 minutes■. After the administration experiment was completed, the rabbits were continued to be observed and the average number of days of survival after tumor implantation was determined.The results shown in Table 2 were obtained.

1. Of the 20 rabbits transplanted with VX2 of Example 1-1,
Except that for the five birds that were not used in the administration experiment of Example 1-1, the extracorporeal circulation circuit shown in Fig. 2, which was equipped with a backflow prevention means, was used instead of the extracorporeal circulation circuit shown in Fig. 1. An administration experiment was conducted in the same manner as in Example 1-1, and the average survival days were determined. As the backflow prevention means 9,
The check valve shown in FIG. 3 was used.

The results of this experiment are also shown in Table 2.

Of the 20 rabbits transplanted with VX2 from Example 1-1,
For the five birds that were not used in the administration experiment in Example 1-1.1-2, we continued to observe them without conducting an administration experiment using a circuit, and calculated the average survival days after tumor implantation. Ta. The results are also shown in Table 2.

Among the rabbits transplanted with VX2 of Example 1-1, Example 1
-1.1-2 and Comparative Example 1-1, five birds not used in Comparative Example 1-1 were administered on day 16 using a conventional extracorporeal circuit as shown in FIG. That is, this is a method in which treated plasma is adjusted (dialyzed) and then mixed with blood cell components.

In FIG. 6, pumps 61, 62, 63, 22, tubes 71, 72, 73, 74, 75, 23, plasma separation means 1, plasma processing reaction tank 24, mixing means 3, and adjustment means 400 are shown in FIG. The same one as in 1-1 was used. A steam sterilized 3M NaCl aqueous solution was placed in the plasma processing liquid storage tank 21 in the same manner as in Example 1-1.

Before performing extracorporeal circulation, for tube 23, use 3M
Priming was performed with an aqueous NaCl solution, and the entire circuit except for the plasma processing liquid storage tank 21, tube 23, and reaction tank 24 was transferred to. Priming was performed with parin-containing physiological saline. From rabbit auricular artery 51, pump 61 with 5 mI. /
Win led the blood into the circuit. Heparin was added from a heparin supply device 52 at a rate of 0.3rd/win. The plasma pump 62 and the plasma processing liquid pump 22 are 1 aml/win.
and introduced each into the reaction tank 24. The cock 25 was closed in advance and opened 30 minutes after the start of plasma separation.

Next, in the dialyzer 400, 1 portion of physiological saline was added as the external dialysis fluid.
Dialysis and water removal using 0 0 affi/sin (
1 m/min). After dialysis, transfer plasma to mixer 3
After mixing with blood cells, protamine was added from the brotamine supply device 53, and the blood was returned to the auricular vein 54 on the opposite side.

After the administration experiment was completed, the rabbits were continued to be observed, and the average number of days they survived after tumor implantation was determined. The results are also shown in Table 2.

Table 2 As a result, Examples 1-1 and 1-2 were adjusted to the in-vivo environment after mixing the treated plasma components and blood cell components.
It was found that the average survival time was increased. In Example 1-2 in which a check valve was used, the average survival period was particularly prolonged.

In Example 1-1, 3M N
aC! The experiment was conducted in the same manner as in Example 1-1, except that a 3M sodium citrate aqueous solution was used instead of the aqueous solution, and the average survival days were determined. The results are shown in Table 3.

Fusashi Group 121 In Example 1-2, 3M N
The experiment was conducted in the same manner as in Example 1-2, except that a 3M sodium citrate aqueous solution was used instead of the aCl aqueous solution, and the average survival days were determined. The results are shown in Table 3.

Among the 20 rabbits transplanted with VX2 in Example 2-1,
For the five birds that were not used in the administration experiment in Example 2-1.2-2, observation was continued without conducting an administration experiment using a circuit, and the average survival days after transplanting Il1wj were determined. Ta. The results are also shown in Table 3.

Comparison amount 121 Among the rabbits transplanted with VX2 of Example 2-1, Example 2
-1.2-2 and the five birds not used in Comparative Example 2-1, the experiment was carried out in the same manner as Comparative Example 1-2, except that 3M sodium citrate aqueous solution was used instead of 3M NaCl aqueous solution. Then, the average number of days of survival after tumor transplantation was determined. The results are also shown in Table 3. (Margin below) Table 3 As a result, it was found that the average survival days were prolonged in Examples 2-1 and 2-2. In Example 2-2, which used an anti-reflux valve, the average survival period was particularly prolonged. Direct Dankan Uni 1 In Example 1-1, 3M NaC was used as the plasma treatment solution.
] Instead of an aqueous solution, O. 15M NaCl containing 0. 1
The experiment was conducted in the same manner as in Example 1-1, except that M acetic acid aqueous solution was used, and the average survival days were determined. The results are shown in Table 4.

Naohonkan 121 In Example 1-2, 3M Na
0.1M containing 0.15M NaCl instead of C1 aqueous solution
The experiment was conducted in the same manner as in Example 1-1, except that an acetic acid aqueous solution was used, and the average survival days were determined. Table 4 shows the results.
It was shown to. Of the 20 rabbits transplanted with VX2 in Example 3-1,
For the five birds that were not used in the administration experiment in Example 3-1.3-2, we continued to observe them without conducting an administration experiment using a circuit, and calculated the average survival days after tumor implantation. Ta. The results are also shown in Table 4. Calibration amount i21 Among the rabbits transplanted with VX2 of Example 3-1, Example 3
-1.3-2 and Comparative Example 3-1 ゜5
For the wings, instead of 3M NaCl aqueous solution, 0.
The experiment was conducted in the same manner as in Comparative Example 1-2, except that a 0.1M acetic acid aqueous solution containing 15M NaCl was used, and the average survival days after tumor transplantation were determined. This result is also shown in Table 4.
It was shown to. Table 4 As a result, it was found that Examples 3-1 and 3-2 had longer average survival days. Example 3 using a check valve
2, the average survival time was particularly prolonged. (Effect of the invention) In this way, since the adjusting means is arranged downstream of the mixing means, not only plasma components but also blood cell components are stimulated.
Malignant tumors can be treated more efficiently. Furthermore, by providing a backflow prevention means between the plasma processing means and the mixing means, hemolysis or damage to blood cell components is prevented, and malignant tumors can be treated more efficiently.

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, and there is almost no loss of plasma proteins during the process. Since the circuit is isolated from the outside environment, it is safe and free from contamination by germs.

Using this circuit, patients who are difficult to undergo surgery or patients with malignant tumors for whom anticancer drug administration is inappropriate can be continuously and effectively treated.

Figure 1 is an explanatory diagram showing one example of the circuit of the present invention, Figure 2 is an explanatory diagram showing another example of the circuit of the present invention, and Figure 3 is an explanatory diagram showing an example of the circuit of the present invention. Front view showing one example, Fig. 4(a)(b)(C)
5 is a partially cutaway front view, bottom view, and side view of the valve body of the check valve; FIG. 5 is an explanatory view showing an experimental device of the present invention; and FIG. 6 is an example of a conventional circuit. It is an explanatory diagram.

1 - Plasma separation means, 3 - Mixing means, 5 - Rabbit, 9 - Backflow prevention means, 21 - Plasma processing liquid storage tank, 24 - Plasma processing reaction tank, 25 - Cook, 22, 61,62
．． 63・-Bonpu, 23, 71, 72.73, 74.7
5...-Tube, 200--Plasma processing means, 400-
1. Adjustment means, 600--Recirculation means.

Claims (1)

[Claims] 1. A plasma separation step of separating plasma from blood collected from a living body, and separating the separated plasma from a plasma processing solution selected from the group of inorganic salt solutions, organic salt solutions, and acidic solutions. a plasma processing step in which the plasma is treated by contacting with at least one species; a mixing step in which the treated plasma is mixed with the blood cell components separated in the plasma separation step; and the mixed blood is adjusted to the in-vivo environment. 1. A method for treating malignant tumors, etc., comprising: a conditioning step of refluxing the conditioned blood into the living body. 2. Plasma separated from blood collected from a living body is subjected to contact treatment with at least one kind selected from the group of plasma treatment solutions consisting of inorganic salt solutions, organic salt solutions, and acidic solutions; and blood cells of the blood. A composition for treating malignant tumors, etc., comprising blood mixed with components adjusted to the in-vivo environment. 3. A plasma separation means for separating plasma from blood collected from a living body, and treating the separated plasma with at least one plasma processing solution selected from the group consisting of an inorganic salt solution, an organic salt solution, and an acidic solution. Plasma processing means for processing by contact; mixing means for mixing the treated plasma and blood cell components separated by the plasma separation means; and adjustment for adjusting the mixed blood to the in-vivo environment. and a reflux means capable of continuously or intermittently refluxing the adjusted blood into the living body, the adjusting means being disposed downstream of the mixing means. Extracorporeal circulation circuit. 4. The extracorporeal circulation circuit according to claim 3, further comprising a backflow prevention means between the plasma processing means and the mixing means.