JPH01211501A - Method and apparatus for preserving organ - Google Patents

Abstract

PURPOSE:To preserve an organ in an active state, by using a preserving apparatus comprising a cooling device for a liquid cooling medium, a pressure- resistance container immersed in the liquid cooling medium, a solution-supplying device for injecting into the pressure-resistant container a buffer solution for immersing the organ and a device for compressing the buffer solution. CONSTITUTION:An organ is preserved in a good state keeping the activity thereof for a long period by (1) obtaining an organ-preserving apparatus comprising a cooling device 1, a pressure-resistant container 2 for receiving the cooling device 1 and compressing device 3 for raising the pressure of a buffer solution in the container 2, (2) placing an enucleated organ in the pressure-resistant container 2 together with the buffer solution such as Collins' solution or physiological salt solution, (3) providing the buffer solution with a moderate pressure higher than the atmosphere pressure but lower than the critical pressure thereof and subsequently (4) gradually cooling the buffer solution to a temperature near the freezing point thereof under the pressure in a non-frozen state. The above-mentioned method permits to cool the organ to a considerably low temperature without freezing the organ and is useful for the more systematic performance of organ transplantation than the conventional organ transplantation.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a method and an apparatus for preserving various organs extracted from the human body for a long period of time in a good condition while maintaining their activity.

(Prior art) Extracted organs have traditionally been preserved until transplantation, but this preservation method involves collecting Collins fluid at approximately 4°C, which has properties similar to blood, from the organ's artery or portal vein. A so-called perfusion method is known in which the perfused organ is injected and drained through a vein, and the organ after such perfusion treatment is stored at the above-mentioned temperature condition of about 4°C, and blood flow is not allowed to flow into the stored organ at the time of transplantation. I am trying to use it after giving it.

However, when such conventional preservation methods are used, organs can only be preserved for about 12 hours for livers and 96 hours for kidneys, which makes it difficult to coordinate the time between organ donation and demand. , is a major obstacle to organ transplantation.

Here, it is possible to extend the shelf life by lowering the temperature even further than the above 4°C, but if the organ subjected to the above conventional method is further cooled and frozen, cell destruction will occur, and the organ itself This will result in the death of the .

Therefore, in order to solve this problem, the applicant has already
-5E12021 (Patent No. 13119857) proposed the following method.

This method uses not only a buffer solution made by mixing a blood perfusion solution such as Collins solution or physiological saline, which has a coagulation temperature of 0°C, with a blood coagulation inhibitor such as heparin, but also dimethyl sulfoxide (hereinafter referred to as DMSO) as appropriate. ) or use a cryoprotectant such as glycerin.More specifically, first, the above-mentioned buffer solution is used as an environmental solution, the excised organ is placed in it, and the temperature of the environmental solution is gradually lowered. ; By injecting the same environmental fluid from the artery or portal vein of the organ and perfusing it, the internal and external parts of the organ are uniformly cooled to the same temperature. At this time, the freezing temperature of the environmental fluid (0 After cooling the organ to a temperature close to 1 to 2 degrees Celsius (1-2 degrees Celsius), the organ was transferred to the environmental solution containing the above-mentioned cryoprotectant, and perfused with this environmental solution in the same manner as above to reach the freezing temperature of -5 degrees Celsius. The object is to be cooled to a temperature close to -4°C, and the object in this state is to be stored at about -4°C.

When using the above method, the organ in question is kept at a low temperature of -4°C and does not freeze, making it possible to preserve the organ well over a long period of time. Since it is not possible to obtain an even lower cryoprotective agent, the upper limit of the low temperature is around -4℃.For this reason, although organs can be preserved for a longer period of time by lowering the processing temperature, It is considered that no further improvement is possible.

(Problems to be Solved by the Invention) The present invention does not rely on antifreeze agents, but instead places the extracted organ in a normal buffer solution such as Collins' solution, applies pressure to the buffer solution, and increases the pressure. The freezing point of the organ is lowered by 11L, which enables cooling in a non-freezing state to a temperature as low as -19°C, which is much lower than the 14°C of the conventional method. The purpose is to significantly extend the storage period.

(Means for Solving the Problems) In order to solve the above-mentioned object, the present application provides a method for immersing extracted organs in a buffer solution such as Collins solution or physiological saline in a pressure-resistant container. The buffer solution has a pressure higher than atmospheric pressure,
Slow pressurization below the critical pressure is applied, and the buffer solution is kept in a non-frozen state and slowly cooled to a temperature near the freezing point due to the pressurization, and then the organ is kept under substantially the same environmental conditions. The first invention aims to provide a method for preserving organs, which is characterized in that organs are preserved at
A liquid refrigerant contained in an inner tank that can be used to carry out the method,
A cooling device that can freely adjust the temperature to a desired temperature, a pressure-resistant container that is immersed in the liquid refrigerant and formed airtight and can be opened and closed, and a pressure-resistant container that contains the extracted organ and contains Collins solution and physiological saline. It consists of a liquid supply device that can inject and fill a buffer solution such as water, and a pressurization device that can apply a freely adjustable gas pressure to the buffer solution in a pressure-resistant container that is cooled to a desired temperature by the liquid refrigerant. A second invention is an organ preservation device characterized by the following.

(Example) In explaining the present application, firstly, the apparatus according to the second invention will be explained using the example shown in FIG.
It is equipped with a pressure-resistant container 2 housed therein, and a pressurizing device 3 for increasing the pressure inside the container 2.

Here, the cooling device 1 has a heat insulating container 1a as is known.
, an outer layer 1b with vacuum insulation on the outside, an intermediate layer 1c filled with low-temperature liquefied gas such as liquid nitrogen as a cold source LM,
Further, an inner layer 1d filled with helium gas He is provided, and a liquid refrigerant if such as Freon is stored in an inner tank 1e opened inside the inner layer 1d, thus serving as a cold source LM of the intermediate layer 1c. The helium gas He functions as a heat exchange medium with the liquid refrigerant H.

That is, for this reason, the sealed pressure of the helium gas He can be adjusted by the pressure regulator 1g, and by adjusting the pressure (density), the heat exchange rate between the cold source LN and the liquid refrigerant If is adjusted. None so that the cooling rate of 1f can be controlled.

Furthermore, the cooling device 1 includes a liquid refrigerant t in the inner tank 1e.
A temperature sensor lh immersed in r and a heater li are connected to an electric controller 1j, and a motor l
A stirrer 1M operated by k is also provided within the liquid refrigerant lf.

Next, the pressure-resistant container 2 is placed on a pedestal 4 installed inside the inner tank 1e and immersed in the liquid refrigerant If. 2b, and inside this closed pressure-resistant container 2, a liquid supply device 2C is attached for supplying a buffer solution such as the aforementioned Collins solution or physiological saline.

In the example shown in FIG. 1, the buffer solution in the buffer tank 2d is supplied by the buffer pump 2e through the supply pipe 2f by opening the buffer main on-off valve 2g. By opening the on-off valve 2b, the buffer liquid is transferred to the liquid refrigerant through the heat exchange section 2i in the pressure-resistant container 2.
It is arranged so that it can also flow from the artery Va or the portal vein Vb of the organ V to be processed immersed in the buffer tank to the vein We at the opening of the buffer tank, and 2j in the figure is immersed in the buffer tank. A pressure sensor is shown and is connected to the electrical controller 1j.

Furthermore, the aforementioned pressurizer! 3, the pressurizer 3a is divided into an air chamber 3C and a liquid chamber 3d by a diaphragm 3b, and an air chamber 3c.
The gas pump 3e is capable of applying gas pressure to the organ V, and in order to ensure that the pressure is increased rapidly and the organ V is gradually pressurized without being damaged, the electrical A pressure regulator 3t controlled by a controller lj is connected.

On the other hand, the liquid chamber 3d is communicated with the inside of the pressure-resistant container 2 through a distribution pipe 3h via an ls liquid distribution on-off valve 3g,
Further, an air bleed pipe 31 is inserted through the diaphragm 3b and opens into the liquid chamber 3d, and an air bleed valve 3j is provided at the end of the pipe drawn out from the air chamber 3C of the intermediate pipe 31.
Therefore, in order to carry out the method according to the first invention of the present application using the above-mentioned device, the removed organ V to be processed, such as the liver or kidney, must be
is housed and sealed in a pressure-resistant container 2 so as to be immersed in the buffer solution, and this pressure-resistant container 2 is placed on a pedestal 4 within a liquid refrigerant If contained in an inner tank 1e of a cooling device 1. .

Next, the buffer main on-off valve 2g of the liquid supply device 2C is opened to operate the buffer pump 2@, but at this time, the buffer solution is distributed between the air bleed valve 3j of the air bleed pipe 31 in the pressurizing device 3 and the flow pipe 3h. The on-off valve 3g is opened, so that the buffer solution in the buffer tank 2d is injected into the pressure vessel 2 from the buffer main on-off valve 2g via the liquid supply pipe 2f.

During the above-mentioned injection, air is vented through the air vent pipe 31 that is attached to the distribution pipe 3h, the liquid chamber 3d, and the diaphragm 3b. The chamber 3d becomes full, and when this state is reached, the air vent pipe 31 is closed.

Next, by operating the gas pump 3e of the pressurizing device 3, air or the like is sent to the air chamber 3c, thereby applying gas pressure to the buffer liquid via the diaphragm 3b. Since there is a risk of damaging the internal organs V within the air chamber 2, it is preferable that the pressure regulator 3f communicated with the air chamber 3c be program-controlled by an electric controller lj.

In this way, the pressure inside the pressure vessel 2 is changed from atmospheric pressure to critical pressure (2200 bar) as shown in FIG.
Thereafter, the pressure is increased until it reaches, for example, 2θ0 Obar, the buffer solution flow on/off valve 3g is closed to stop pressurization, and cooling by the cooling device 1 is started.

That is, by operating the cooling device l, the pressure regulator tg
The cooling rate of the liquid refrigerant 1f is controlled by adjusting the heat exchange rate between the cold source LM and the liquid refrigerant If, and the temperature detected by the temperature sensor ih controls the cooling rate of the intermediate MI.
The He'M pressure of C and the output of the heater 1i are controlled by an electric controller lj.

In this way, the temperature of the liquid refrigerant U is precisely controlled, and the buffer liquid in the pressure-resistant container 2 is thereby adjusted to the desired temperature.
Since there is a risk of causing damage to the buffer solution, the above-mentioned addition is carried out gradually under strict control by a program controller, and based on the relationship between the pressure of the buffer solution and its freezing point as shown in FIG. The temperature is lowered to a temperature near the freezing point based on the pressure value.

Therefore, when < 2000 bar as mentioned above, the temperature is around -19.5°C, which is the freezing point, for example -
It will be cooled to about 19°C.

In carrying out the above method, the organ V is not simply cooled by the buffer solution, but the buffer solution opening/closing valve 2h in the fluid supply device 2C is opened to drain the buffer solution in the buffer solution tank 2d. If it is made to flow from the artery Va or portal vein Vb of the organ V to the vein Ve through the heat exchange part 2i, or if the buffer solution itself in the pressure-resistant container 2 is made to flow back into the organ V,
The organ V is cooled from the inside at the same rate, and cooling is performed more uniformly and the cooling rate can also be increased.

As described above, the organ V can be cooled to a low temperature of, for example, -19°C without freezing the buffer solution.
Instead of first pressurizing the buffer solution to a predetermined pressure value and then cooling it, it is also possible to perform cooling while increasing the pressure. It becomes possible to shorten the time.

However, at this time, of course, it is necessary to continuously detect the increasing pressure value and control the temperature so that it does not always fall below the freezing point at the pressure value. The sensor 2j detects the pressure of the buffer liquid, and the detection signal is input to the electrical controller 1j, thereby performing computer control to calculate the appropriate temperature for the pressure. It is preferable to perform temperature control as shown by the broken line in FIG.

In addition, if a frost damage preventive agent such as DMSO or glycerin is separately mixed into the buffer solution, the above temperature control can be carried out.
This is advantageous because even if a slight cooling condition occurs, freezing will not occur.

Once the cooling process is completed as described above, the apparatus according to the above embodiment is used as is, and the cooling apparatus 1 is switched to constant temperature operation at -18°C in the above embodiment, and the organ V is stored as it is. Alternatively, the pressure-resistant container 2 may be pulled up from the inner tank 1e and housed in another storage constant temperature device (not shown), so that the organ V may be stored substantially at the descending temperature.

(Effect of the invention) The first invention of the present application is an invention of a method carried out as described above. It is possible to cool the organ to a considerably lower temperature than the conventional method, which makes it possible to significantly extend the period of organ preservation in a non-frozen state, which greatly contributes to more systematic implementation of organ transplants.

Moreover, since the storage device used for carrying out the first invention according to the second invention of the present application is also configured as described above, it includes a cooling device, a liquid supply device, a pressure-resistant container, and a gas storage device. By appropriate configuration with pressure pressurization device,
The above method can be carried out smoothly and efficiently.

[Brief explanation of the drawing]

FIG. 1 is a vertical cross-sectional front explanatory view of a preservation device that can be used to carry out the organ preservation method according to the first invention of the present application, and FIG. 2 is a chart showing changes in the freezing point with respect to pressure changes of the buffer solution used in the device. It is. 1...Cooling device 1e...Inner tank 1f...Liquid refrigerant 2...Pressure container 2c...Liquid supply device 3...・・・Pressurization device L・・・Buffer solution ■・・・Organ representative Patent attorney Yoshio Saito

Claims (2)

[Claims] (1) The extracted organ is immersed in a buffer solution such as Collins solution or physiological saline in a pressure-resistant container, and the buffer solution is slowly pressurized to a level higher than atmospheric pressure and below the critical pressure. At the same time, the buffer solution is kept in an unfrozen state and slowly cooled to a temperature near the freezing point at the pressure value caused by the pressurization, and the organ is then stored under substantially the same environmental conditions. A method for preserving organs characterized by: (2) A cooling device that can freely adjust the temperature of the liquid refrigerant stored in the inner tank to a desired temperature, a pressure-resistant container that is immersed in the liquid refrigerant and formed airtight and can be opened and closed, and the extracted internal organs are stored therein. a liquid supply device capable of injecting and filling a buffer solution such as Collins solution or physiological saline into the pressure-resistant container; and a buffer solution in the pressure-resistant container that is cooled to a desired temperature by the liquid refrigerant;
An organ preservation device comprising a pressurizing device capable of applying a freely adjustable gas pressure.