JP3239418B2 - Method and apparatus for storing and regenerating living organs - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and apparatus for storing and regenerating living organs.

[0002]

2. Description of the Related Art In cryopreservation / thawing / regeneration of living organs, the key is how to freeze / thaw a whole organ having a large heat capacity uniformly. That is, first, at the time of freezing, it is necessary to control the freezing speed and the freezing temperature so as to avoid intracellular freezing and extracellular freezing, and for that purpose, it is necessary to make the temperature change uniform throughout the organ. On the other hand, at the time of melting, it is an indispensable condition to prevent organ damage by appropriately controlling the melting rate and melting temperature and at the same time making the temperature change throughout the organ uniform.

In a conventional living organ preservation and regeneration system, generally, a excised living organ is preserved by immersing it in liquid nitrogen or a high-temperature solution and freezing or thawing it from the outside.
Also, a method of resuscitation has been adopted (see "Frozen Blood-Its Theory and Practice", written by Yukio Sumida, published on November 15, 1978, Nippon Medical Affairs Shinposha Publishing Bureau, pages 253 to 258).

[0004]

However, in the conventional living organ preservation and regeneration system, the surface side of the organ is rapidly frozen,
Although it is rapidly melted, there is a problem that the rate of temperature decrease and temperature rise inside is very slow, and organ damage is apt to occur. Therefore, for example, apart from preservation of living bodies such as skin, for example, preservation and regeneration of real organs such as kidney, small intestine and heart have hardly been effective.

It is considered that this is because the above-mentioned conventional living organ preserving and reproducing apparatus performs heat exchange for freezing and thawing by cooling and heating from outside the organ.

[0006]

A method for storing and reproducing a living organ according to the present invention according to claim 1 of the present invention and a method for storing and reproducing a living organ according to the present invention according to claim 2 have been made to solve the above problems. And each is configured as follows.

(1) Configuration of the method for storing and regenerating a living organ according to the first aspect of the present invention. The method for storing and regenerating a living organ according to the first aspect of the present invention provides a heat exchange means having a refrigerant liquid storage tank and a cooling and heating function. And a refrigerant liquid supply pump for supplying a refrigerant liquid to a living organ.After the refrigerant liquid in the refrigerant liquid storage tank is cooled or heated by the heat exchange means, the discharge pressure of the refrigerant liquid supply pump is reduced. In the method of storing and regenerating a living organ, the living organ is perfused into blood vessels of the living organ, and the living organ is gradually frozen or thawed from the inside.
The refrigerant liquid storage tank is constituted by a plurality of tanks storing a plurality of types of refrigerant liquid having different evaporation temperatures,
The living organs are frozen or thawed by sequentially opening and closing the plurality of tanks in a stepwise manner in accordance with the temperature change on the living organ side.

(2) Structure of the living organ preserving and reproducing apparatus according to the second aspect of the present invention. The living organ preserving and reproducing apparatus according to the second aspect of the present invention is a heat exchange means having a refrigerant liquid storage tank and a cooling and heating function. And a refrigerant liquid supply pump for supplying a refrigerant liquid to a living organ, wherein the refrigerant liquid in the refrigerant liquid storage tank is cooled or heated by the heat exchange means, and then the discharge pressure of the refrigerant liquid supply pump is increased. In the living organ storage / reproduction device configured to freeze or thaw the living organ from the inside by perfusing the inside of the blood vessel of the living organ by utilizing, the refrigerant liquid storage tank includes a plurality of tanks, each of which has an evaporation temperature. And a plurality of different types of refrigerant liquids are stored and selectively opened / closed in response to a change in temperature of a living organ.

[0009]

The living organ preserving / reproducing method according to the first aspect of the present invention and the living organ preserving / reproducing apparatus according to the second aspect of the present invention are configured as described above. Thus, the following effects are obtained.

(1) Operation of the method for storing and regenerating a living organ according to the first aspect of the invention In the method for storing and regenerating a living organ according to the first aspect of the present invention, a heat exchange means having a refrigerant liquid storage tank and a cooling and heating function. And a refrigerant liquid supply pump for supplying a refrigerant liquid to a living organ, forming a refrigeration system which is a premise for performing the method, and firstly, the refrigerant stored in the refrigerant liquid storage tank. The liquid is taken out, cooled or heated by the heat exchange means to lower or raise the temperature, and then perfused into the blood vessel of the living organ by using the discharge pressure of the refrigerant liquid supply pump, whereby the whole tissue of the same living organ is obtained. Are efficiently frozen or thawed at a gradually uniform temperature from the inside.

Many blood vessels in a living organ run in the living organ with a substantially uniform pressure loss distributed over the details. Therefore, when cooling or heating is performed by perfusing a refrigerant liquid into the blood vessel, unlike the case of cooling or heating from the outside, it is possible to achieve extremely efficient and uniform temperature lowering or heating, and a rapid operation that does not cause organ damage. Freezing and rapid thawing effects are realized. Moreover, in that case, in particular, the refrigerant liquid storage tank includes a plurality of tanks, and a plurality of types of refrigerant liquids having different evaporation temperatures are stored in the plurality of tanks. Since the opening and closing control is selectively performed correspondingly, the type of the refrigerant liquid can be appropriately selected and used in response to a decrease in the heat exchange temperature due to the progress of the freezing action, and it is always possible to use it. Since a stable liquid state can be ensured, a reliable freezing operation can be realized without inducing blood vessel damage or the like due to evaporation and expansion of the refrigerant liquid.

(2) Operation of the living organ preserving and regenerating apparatus according to the first aspect of the invention In the living organ preserving and regenerating apparatus according to the first aspect, a refrigerant exchange tank and a heat exchange unit having a cooling and heating function And, comprising a refrigerant liquid supply pump that supplies a refrigerant liquid to the living organs, forming a cooling system that is a premise for freezing or thawing of the living organs, first stored in the refrigerant liquid storage tank The cooling liquid is taken out and cooled or heated by the heat exchange means to lower or raise the temperature, and then, the discharge pressure of the cooling liquid supply pump is used to perfuse the blood vessel of the living organ to thereby permeate the living organ. The whole tissue is efficiently frozen or thawed at a more uniform temperature than the inside.

A large number of blood vessels in a living organ run in the living organ with a substantially uniform pressure loss and distributed in detail. Therefore, when cooling or heating is performed by perfusing a refrigerant liquid into the blood vessel, unlike the case of cooling or heating from the outside, it is possible to achieve extremely efficient and uniform temperature lowering or heating, and a rapid operation that does not cause organ damage. Freezing and rapid thawing effects are realized. Moreover, in that case, in particular, the refrigerant liquid storage tank includes a plurality of tanks, and a plurality of types of refrigerant liquids having different evaporation temperatures are stored in the plurality of tanks. Since the opening and closing control is selectively performed in response, the type of the refrigerant liquid can be appropriately selected in response to a decrease in the heat exchange temperature due to the progress of the freezing action, and the liquid state of the refrigerant liquid can be always secured. A highly reliable freezing operation can be realized without causing blood vessel damage or the like due to evaporation and expansion.

[0014]

Therefore, according to the method and apparatus for preserving and regenerating a living organ of the present invention, it is possible to rapidly freeze and thaw a real living organ having a large heat capacity without causing organ damage, and to promote the progress of organ transplantation. Be able to contribute.

[0015]

FIG. 1 shows a configuration of a living organ preservation / reproduction method according to an embodiment of the present invention and a living organ preservation / reproduction apparatus for executing the method.

In the drawing, reference numeral 1 is a heat exchanger, 2 is a refrigerant liquid supply pump, 3 is a real living organ having a large heat capacity, such as a kidney, and 6a to 6e are a plurality of samples having different evaporation temperatures shown in FIG. a plurality of coolant storage tank that stores the liquid refrigerant R ₁ to R ₅ seeds, 4 a to 4 e, 5 a to 5 e is provided respectively each on the upstream side and downstream side of the plurality of coolant liquid storage tank 6a~6e These are the first and second solenoid on-off valve groups.

The components are connected to each other through a coolant perfusion passage 7 formed by, for example, a flexible tube made of synthetic resin as shown in the figure.

The heat exchanger 1 has both cooling (refrigeration) and heating functions for the refrigerant liquid passing through the inside thereof, and either one of the cooling and heating is controlled by an external control operation (storage / regeneration command operation). Function can be selected.

The refrigerant liquid supply pump 2 is, for example, a pump having the same structure as that already used as a pump for an extracorporeal circulation device in the medical field, and converts the refrigerant liquid heat-exchanged in the heat exchanger 1 into a living body. Cooling or heating is performed by supplying and perfusing into each blood vessel of the organ 3.

Further, the living organ 3 is interposed between the refrigerant perfusion passages 7 via a predetermined connector in a state where both ends of a large number of blood vessels are gathered. Cooling or heating is efficiently performed from the inside.

On the other hand, in each of the first to fifth refrigerant liquid storage tanks 6a to 6e, the first to fifth refrigerant liquids R _{1 to} R ₅ having different evaporation temperatures are sequentially provided as described above. When the first and second electromagnetic on / off valves 4a to 4e and 5a to 5e on the upper and lower ends of each of the tanks are selectively opened, the refrigerant corresponding to the opened electromagnetic on / off valves is stored. The refrigerant liquid (one of R _{1 to} R ₅ ) in the liquid storage tank is supplied into the blood vessel of the living organ 3 via the above-described heat exchanger 1 and the refrigerant liquid supply pump 2, and further opened second. It is returned to the corresponding refrigerant liquid storage tank via the electromagnetic on-off valve. This perfusion state is repeated until the living organ 3 reaches a predetermined set freezing or thawing temperature.

That is, the first to fifth plural kinds of refrigerant liquids R _{1 to} R ₅ are employed in such a manner that the evaporating temperature is gradually reduced by a predetermined width, and the refrigerant liquid is changed from a normal temperature state to a low temperature state to a final state. Cooling temperature for each stage until the frozen state is reached (for example, “normal temperature” → “4 ° C.” → “−100 ° C.” → “−170 ° C.” → “−196”)
° C), the refrigerant is sequentially switched and selected so as to always maintain the liquid state without evaporating and expanding the refrigerant. Therefore, freezing can be safely achieved without causing damage to the blood vessels of the living organ 3. The selection of the refrigerant liquids R _{1 to} R ₅ is based on the first and second solenoid on-off valves 4 a to 4 e and ₅ a to ₅ e based on the temperature change of the refrigerant liquid detected at the outlet side of the heat exchanger 1. This is performed by sequentially controlling the opening and closing by a microcomputer within a predetermined temperature range. It should be noted that each of the refrigerant liquids R ₁ to R ₁
To R ₅ is, for example glycerol, ethylene glycol, cryoprotectant such as dimethyl sulfoxide are mixed.

On the other hand, when the living organ 3 frozen as described above is thawed, the heat exchanger 1 is first switched to a heating function to select any one of the optimal refrigerant liquids and to sequentially heat the liquid refrigerant. While flowing through the blood vessel of the living organ 3 by the coolant liquid supply pump 2, the refrigerant is effectively melted from the inside. As a result, rapid melting is possible.

Therefore, according to the above configuration, the living organ 3
The entire organ can be rapidly frozen or thawed simply by connecting a refrigerant liquid perfusion tube to the blood vessel and perfusing the liquid refrigerant for cooling / heating. As a result, occurrence of organ damage can be suppressed as much as possible.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing a configuration of a storage / reproduction device for performing a method of storing / reproducing a living organ according to an embodiment of the present invention.

FIG. 2 is a graph showing a specific example of a plurality of refrigerant liquids used in the same device.

[Explanation of symbols]

1 is a heat exchanger, 2 is a refrigerant liquid supply pump, 3 is a living organ,
4a to 4e are first solenoid on-off valves, respectively, and 5a to 5e are second solenoid valves.
Electromagnetic on-off valve.

Claims (2)

(57) [Claims] 1. A refrigerant liquid storage tank comprising: a refrigerant liquid storage tank; heat exchange means having cooling and heating functions; and a refrigerant liquid supply pump for supplying a refrigerant liquid to a living organ. After cooling or heating by the heat exchange means, perfused into the blood vessel of the living organ using the discharge pressure of the refrigerant liquid supply pump, so as to gradually freeze or thaw the living organ from the inside A method for storing and regenerating living organs, wherein the refrigerant liquid storage tank is constituted by a plurality of tanks storing a plurality of types of refrigerant liquids having different evaporation temperatures, and the plurality of tanks are adapted to temperature changes on the living organ side. A method for storing and regenerating a living organ, wherein the living organ is frozen or thawed by controlling the opening and closing of the living organ in a stepwise manner. 2. A refrigerant liquid storage tank comprising: a refrigerant liquid storage tank; heat exchange means having cooling and heating functions; and a refrigerant liquid supply pump for supplying a refrigerant liquid to a living organ. Is cooled or heated by the heat exchange means, and then the living organ is frozen or thawed from the inside by perfusing the inside of the blood vessel of the living organ using the discharge pressure of the refrigerant liquid supply pump. An organ preserving / regenerating apparatus, wherein the refrigerant liquid storage tank comprises a plurality of tanks, each of which stores a plurality of types of refrigerant liquid having a different evaporation temperature, and selectively controls opening and closing according to a temperature change of a living organ. A living organ preserving and reproducing apparatus characterized in that it is adapted to be stored.