JPS6315862B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION (Field of the Invention) The present invention relates to an extracorporeal circulation blood circuit device with a heat exchanger suitable for use in whole body hyperthermia therapy (hyberthermia) for cancer. (Prior Art) Recently, thermotherapy, which takes advantage of the fact that cancer is sensitive to high temperatures, has been attracting attention as a new cancer treatment method. This method includes local therapy and systemic therapy, and the former involves heating locally from the outside using microwaves, radio waves, ultrasound, etc. On the other hand, the extracorporeal circulation method, in which blood is circulated outside the body and heated with a heat exchanger, is of course used for local therapy, but is also suitable for systemic therapy. Although there are still few reports of whole body hyperthermia in Japan, it generally has a synergistic effect when used in combination with radiation and anticancer drugs (bleomycin, adriamycin, etc.). The basics of cancer treatment are early diagnosis and early surgery, but unfortunately there are many cases where diagnosis is delayed and metastasis or recurrence occurs, and local treatment is insufficient, especially for advanced cancers. Systemic therapy, which treats the entire body, is appropriate. However, the extracorporeal circulation method is currently performed using a heat exchanger used in a heart-lung machine, and was not developed for thermotherapy. Hyperthermia therapy requires precise temperature control as will be described in detail later, but heat exchangers for heart-lung machines do not yet have sufficient precision and reliability in temperature control. Furthermore, cancer patients generally have decreased immune function and are exposed to high temperatures, so the most important consideration with this therapy is to prevent infection. Regarding this point, no one with sufficient reliability has been developed so far. Purpose of the Invention Therefore, the purpose of the present invention is to provide an extracorporeal circulation blood circuit device with a heat exchanger that has no chance of contamination when assembled and used in a medical field, and can therefore prevent infection to cancer patients. This is what I am trying to do. Another object of the present invention is to provide a sterilized, self-contained, extracorporeal circulation blood circuit device with a heat exchanger that does not require any additional operations such as briming operation when used in a medical field. Another object of the present invention is based on the above object,
The object of the present invention is to provide an extracorporeal circulation blood circuit device with a heat exchanger that can maintain precision in temperature control over a long period of time. (Structure of the Invention) The present invention is an extracorporeal circulation blood circuit device with a heat exchanger that constitutes a blood circulation circuit by an elastic tube and a heat exchanger provided in the middle of the tube, The tube has at least one pump portion having a length necessary for blood delivery by a roller pump, and both ends of the tube are connectable to shunts formed in the patient in advance, A connector that ensures sufficient blood flow is attached, the tubes in the pump part have the same inner diameter and the same wall thickness, at least one opening is provided in the middle of the tube, and caps are attached to both connectors in a fluid-tight manner. The present invention also provides a blood circuit device for extracorporeal circulation with a heat exchanger, characterized in that the inner space of the tube with the heat exchanger and connector is filled with a desired liquid and sterilized. It is preferable that the pump section is formed in each tube connected to the upstream side and the downstream side of the heat exchanger, so that they can be used interchangeably. In order to form a laminar flow that reduces damage to the blood, the heat exchanger should preferably have a multitubular structure consisting of many rigid tubes, with a thin film of material inert to blood inside each tube. For example, silicone resin,
It is preferable to coat with a urethane-based coating material or the like. Tubes used in blood circuits have a degree of polymerization of 2000 to 3100 and a total amount of plasticizer so that properties such as filling volume and elasticity do not change during long-term operation at high temperatures.
Preferably, it is composed of 60 to 100 parts of soft vinyl chloride. The assembly of the present invention does not require any brimming operation during use and can be connected to the patient's shunt immediately.
It is filled with a physiologically acceptable liquid that is harmless to the human body, such as Ringer's solution, and the entire assembly is sterilized by a desired method such as gamma rays or autoclaving. Because it is the blood that undergoes heat exchange, it cannot be heated to extremely high temperatures. Due to this relationship, the perfusate should be kept at 49°C.
The device of the present invention has heat exchange characteristics such that the liquid maintains the body temperature within the temperature range of 41.5 to 42.0°C, which is said to have a remarkable thermal effect for a long time. Demonstrate. DETAILED DESCRIPTION OF THE INVENTION Next, a preferred embodiment of the extracorporeal circulation blood circuit device with a heat exchanger according to the present invention will be described in detail with reference to the accompanying drawings. First, whole body thermotherapy using extracorporeal circulation will be briefly explained using the diagram in FIG. A blood circuit 2 is connected to a shunt previously formed in the patient 1, and this circuit includes a heat exchanger 3 and a blood pump 4, such as a roller pump.
is inserted, and blood is circulated extracorporeally while being heated through a temperature control device 5 (for example, a constant temperature bath) while the patient is under general anesthesia. Heat exchanger and patient (bladder) at this time
Figure 2 shows the temperature change. The patient's temperature measurement area is the deep temperature part of the bladder, rectum, esophagus, forehead, etc., and the temperature is set to 41.5℃ or higher and 42.0℃ or lower, where the thermal effect is significant and does not adversely affect normal cells. It is said to be maintained for 4 to 6 hours at all times. This is repeated several times to make one course. Maximum care must be taken as the thermal effect will be reduced if the temperature is not maintained within this range for this amount of time. Additionally, the temperature of the perfusion fluid in the heat exchanger must be 49°C or lower. This is because heating the blood at a temperature higher than this poses a risk of causing degeneration of the blood. In the present invention, the heat exchanger and the tube are integrated in terms of structure and characteristics so that the above-mentioned whole body thermotherapy can be applied with simple operation and without infection to the patient. An example of the configuration of an extracorporeal circulation blood circuit device assembly 10 with a heat exchanger according to the present invention is shown in FIG. In the assembly 10 of the present invention, a heat exchanger 11 is provided in the middle of an elastic tube, that is, a blood inlet on the upstream side A and a blood outlet on the downstream side B of the heat exchanger 11. A tube 12 having a length that allows insertion of the blood pump 4 shown in FIG. 1 is connected to each of the tubes. A portion of the tube 12 into which the blood pump 4 is inserted is referred to as a pump section 19, and in this pump section 19, the tube 12 is squeezed by, for example, a roller pump, and blood is sent. Therefore, the tubes 12, especially the tubes 12 on the side having the pump portion 19, are made to have the same inner diameter and the same wall thickness so that blood can be sent uniformly and stably by the blood pump. Each end of tube 12 has a shunt (not shown) pre-formed in the patient.
A connector 13 connectable to is attached. Further, the connector 13 has a cross-sectional area that allows blood to flow sufficiently through the flow path. The connector 13 can be equipped with a cap 14 that can provide a liquid-tight seal and a caulking member 15 that can make the connection firm. heat exchanger 11,
The connecting portions of tube 12 and connector 13 are firmly connected by caulking member 15 so that they will never come off. Since it is more convenient to apply the blood pump 4 to both tubes 12 (blood circuits) on the upstream side A and downstream side B in the medical field, as shown in FIG. Although it is preferable to provide a pump portion 19 for each, it is not necessarily necessary to provide a pump portion for both, and only one may be provided as a pump portion 19 and extended by a necessary length. Of course, the upstream side A and the downstream side B of the blood circuit shown in FIG. 3 can be made interchangeable. The tube 12 is provided with a spout such as a mixed injection spout or a temperature measuring spout depending on the desired purpose. For example, it is convenient to provide at least one mixed injection port 16 for a therapeutically necessary drug such as heparin in the tube 12 on the upstream side A and/or the downstream side B. Mixed spout 16
can also be used for blood sampling. Further, it is preferable to provide a temperature measurement port 17 in the tube 12 to measure the temperature of blood. In this case, in order to avoid contamination, it is necessary to configure the temperature measurement device so that it is not directly immersed in blood through the temperature measurement port. . The heat exchanger 11 is a multi-tubular type consisting of a large number of rigid tubes, as shown in a partial cross section in FIG. This is preferable because it has a large contact area with blood. Further, the rigid tube can also be composed of at least one spiral tube. In order to increase the heat exchange efficiency, it is preferable to form a smooth thin film of a substance inert to blood, such as a silicone resin or urethane coating material, on the inner wall of each tube. Reference numeral 18 denotes a heating medium inlet/outlet from the temperature control device 5, and the heating medium may be used in either parallel flow or countercurrent flow with the blood. Priming and bubble removal from the inside of the rigid tube can be done in medical settings, such as by filling the tube with CO ₂ gas, but this increases the chance of contamination, which is not preferable. In the present invention, the internal space of the assembly 10 of the heat exchanger 11 and the blood circuit tube 12 is filled with a physiologically acceptable liquid that does not have an adverse effect on the human body, such as distilled water, physiological saline, glucose solution, Ringer's solution, etc. The entire assembly is completely sterilized by a desired method such as gamma rays or autoclaving. As a result, when in use, it can be directly applied without performing the difficult and time-consuming briming operation, which is conventionally performed in medical settings to remove air bubbles, and there is almost no chance of contamination. Since the tube 12 is used as a blood pump, it must have characteristics compatible with this. A typical applicable material is soft vinyl chloride. The total amount of plasticizer in this resin is preferably 60 to 100 parts, and the type of plasticizer is
Examples include DOP, DOA, DOS, and epoxidized soybean oil. This is because if the amount of plasticizer is less than the above, the properties such as strength and elasticity will be poor when used as a pump part, and if the amount is too much than the above, problems such as elution into the blood will occur. In addition, the degree of polymerization of vinyl chloride resin (polyvinyl chloride, Asakura Shoten, P619 ~
620) and tube the blood (bovine blood) using a roller pump to examine the flow characteristics and changes over time.
The results of the test at Ht=40, 45°C are shown in Table 1 below.

[Table] From the above table, it was confirmed that if it is less than 2000, the change in flow rate over time is too large, which is not desirable for keeping blood temperature constant, and it is difficult to have elasticity and strength that can be used as a blood pump part. . Furthermore, when the value is larger than 3100, it is difficult to process the tube using non-toxic vinyl chloride compounded with a so-called zinc-calcium stabilizer. Therefore, it has been found that vinyl chloride with a value between 2000 and 3100 is suitable for use in the present invention. did. Next, a method of using the extracorporeal circulation blood circuit device with a heat exchanger according to the present invention will be explained along with examples. First, the heat exchanger 11 is connected to the temperature control device 5, and the tube 12 is attached to the blood pump section. After removing the caps 14 at both ends and connecting the upstream side A connector 13 to the patient's femoral artery shunt, and pushing out the filling fluid in the tube and exchanger using arterial pressure, connect the downstream side B connector 13 to the patient's femoral artery shunt. Connect to the venous shunt and begin treatment. In this way, the product of the present invention does not require any brimming operation, which is troublesome and has many chances of contamination, in medical practice. As a tube, it is 2700, and the total amount of plasticizer is 75
A tube of PVC resin with an inner diameter of 6.5 mmφ and an outer diameter of 10.2 mm was used (hardness Shore A).
65). The heat exchanger used 160 stainless steel pipes (inner diameter 1.40 mmφ, inner thickness 0.5 mm) conforming to ASTM-A632, and the effective surface area was 0.16 m ² . The heat exchanger performance is as follows: Blood used: bovine blood Ht = 40, blood flow rate 1/mm, blood feeding temperature 37°C, perfusate temperature 49°C, perfusate flow rate 10/mm,
The heat exchange efficiency coefficient was 0.80. A roller pump is used as the blood pump, and due to the above-mentioned perfusion fluid characteristics,
The patient's blood at 36.5℃ was treated with a blood flow rate of 1.1/mm, and the temperature of the perfusate gradually decreased from 49℃ and was maintained at 43℃ for treatment.
The temperature was maintained at ℃. Specific Effects of the Present Invention According to the present invention, the blood circuit includes a tube and a heat exchanger provided in the middle thereof, and the internal space thereof is filled with a desired liquid in a liquid-tight manner. Since it is completely sterilized, there is no need to re-do the cumbersome and difficult briming procedure in the medical field, making it extremely easy to prepare and minimizing the chance of contamination, making it ideal for cancer patients with weakened immune systems. infection can be prevented.

[Brief explanation of the drawing]

Figure 1 is an explanatory diagram of extracorporeal circulation whole body thermotherapy;
FIG. 2 is a graph showing temperature changes during whole-body thermotherapy, and FIG. 3 is a partially sectional side view of an example of the configuration of an extracorporeal circulation blood circuit device with a heat exchanger according to the present invention. Explanation of symbols 1...Patient, 2...Tube, 3...Heat exchanger, 4...Blood pump, 5...Temperature control device, 1
0... Extracorporeal circulation blood circuit device with heat exchanger of the present invention, 11... Heat exchanger, 12... Tube, 13... Connector, 14... Cap, 15... Caulking member, 1
6... Mixed injection port, 17... Temperature measurement port, 18... Irrigation liquid port, 1
9...Pump section.

Claims (1)

[Scope of Claims] 1. A blood circuit device for extracorporeal circulation with a heat exchanger comprising a blood circulation circuit comprising an elastic tube and a heat exchanger provided in the middle of the tube, comprising: The tube has at least one pump section having a length necessary for blood delivery by a roller pump, and each of the ends of the tube has a sufficient length that can be connected to a shunt previously formed on the patient. A connector is attached to ensure blood flow, the tubes in the pump part have the same inner diameter and the same wall thickness, at least one opening is provided in the middle of the tube, and caps are attached to both the connectors in a fluid-tight manner, A blood circuit device for extracorporeal circulation with a heat exchanger, characterized in that the inner space of the tube with the heat exchanger and the connector is filled with a desired liquid and sterilized. 2. The extracorporeal circulation blood circuit device with a heat exchanger according to claim 1, wherein the pump section is formed in each tube connected to the upstream side and downstream side of the heat exchanger. 3. The heat exchanger is of a tubular type consisting of at least one rigid hollow tube, and each tube is coated with a smooth thin film of a substance inert to blood. The extracorporeal circulation blood circuit device with a heat exchanger according to item 1 or 2. 4. The extracorporeal circulation with a heat exchanger according to any one of claims 1 to 3, wherein the tube is made of soft vinyl chloride with a degree of polymerization of 2000 to 3100 and a total amount of plasticizer of 60 to 100 parts. Blood circuit device for use. 5. The blood circuit device for extracorporeal circulation with a heat exchanger according to any one of claims 1 to 4, wherein the internal space of the heat exchanger and the tube with a connector is filled with a physiologically acceptable liquid. 6. The extracorporeal circulation blood circuit device with a heat exchanger according to any one of claims 1 to 5, wherein the sterilization is performed by gamma rays or an autoclave method.