JPH05305123A - Preservation of blood for transfusion or blood preparation - Google Patents

Abstract

PURPOSE:To enable the preservation of blood for transfusion or blood preparation with the removal of disorders as caused by oxygen by preserving them in an atmosphere of nitrogen, a dinitrogen monoxide gas or a mixed gas of the both. CONSTITUTION:In the preservation of blood for transfusion or erythrocite preparation (hereinafter called 'blood'), to reduce disorders caused by oxygen of the blood being preserved, air is replaced with nitrogen or a dinitrogen monoxide gas or a mixed gas of the both to lessen active oxygen in the blood and the blood is preserved with a decrease in the concentration of oxygen in the blood. The nitrogen or dinitrogen monoxide or a mixed gas of the both is supplied into a blood preservation container or an atmosphere of the blood preservation container quickly in large quantities at the time of blood sampling or immediately after the sampling of the blood to purge air in the container or in the atmosphere thereof. Then, a processing is performed to prevent the oxygen in the atmospheric air from permeate diffusively into the blood preservation container by adding the nitrogen or dinitrogen monoxide or a mixed gas of the both continually.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for preserving blood or red blood cell preparations for transfusion (hereinafter simply referred to as blood).

[0002]

2. Description of the Related Art Conventionally, blood for transfusion is collected in a sterilized hermetically sealed container containing a preservative solution (eg, CPD solution) containing a blood anticoagulant, glucose, etc., and stored in a refrigerator at 4 to 6 ° C. in the atmosphere. Stored at the temperature of. In Japan, the expiration date for blood stored in this state is set to be 3 weeks after blood collection. At present, various measures have been made to extend the expiration date. One of them is a preservation method in which a drug such as adenine is added in addition to the conventional preservation solution licensed and used in the United States. In Japan, the preservation of red blood cell concentrate with MAP solution was recently approved at 4 to 6 ° C for up to 6 weeks. However, these methods prevent hemolysis that occurs due to long-term storage, that is, increase in free hemoglobin concentration in plasma that is caused by hemoglobin in red blood cells leaking from red blood cells due to destruction of red blood cells or changes in red blood cell membrane. I can't. Also,
This method has a point to be improved because an excess amount of an additive such as adenine or its metabolite hypoxanthine may cause a side effect after injecting blood into a living body.

The freezing temperature of blood is about -2 ° C,
There is a method of storing the blood by lowering the storage temperature of the blood before freezing the blood. Although this method has few side effects at the time of injecting into a living body and enables extension of the storage period, an increase in free hemoglobin in plasma (hemolysis) due to injury due to low temperature is observed. In this regard, the present inventors have previously added glycerin and manitol, which are currently clinically frequently used in the form of infusion drip, in small amounts, respectively, and added hemolyzing disorders due to this low temperature and sodium inside and outside erythrocytes. We have developed a method to prevent and correct abnormal distribution of electrolytes such as potassium and potassium.
, 62534), the blood is vulnerable to low temperature injury, which is rarely expected to have the expected effect, and the cause thereof has been pursued and improved.

[0004]

DISCLOSURE OF THE INVENTION The inventors of the present invention have found that the main cause of the above-mentioned low temperature disorder in plasma increases with decreasing temperature,
We have found that it is a disorder caused by dissolved oxygen in blood, especially active oxygen. That is, the blood circulating in the living body is exposed to active oxygen by increasing the oxygen concentration in the lungs, but the blood has a physiological defense function against the active oxygen held by itself, and the oxygen concentration in the tissue. Owing to the deterioration of itself, oxygen damage is less likely to occur under normal conditions. However, the phenomenon that the solubility of gas increases at low temperature is no exception for stored blood, and the oxygen concentration in blood increases as the temperature becomes lower. However, tissues such as red blood cells that are exposed to oxygen always have SOD.
It contains a large amount of active oxygen scavenging enzymes such as (superoxide dismutase) and catalase.
Since the preserved blood also obtains these functions, the damage caused by oxygen was almost ignored.

However, the present inventors have studied storage in a pre-freezing region (0 ± 2 ° C.) in which the storage temperature is lower than before,
Specifically, in the process of conducting the experiment in the range of 0 ± 1 ° C, the preserved blood that does not need to contain oxygen unlike the in-vivo blood is always kept in an abnormally high amount of oxygen during the preservation period. However, since the function of enzymes such as SOD also decreases as the temperature decreases, it was thought that conventional storage methods would not be able to prevent the damage caused by oxygen. Therefore,
The present inventors have found that when the concentration of oxygen during storage, which is the causative substance, is positively reduced by using another gas as a means for preventing the damage due to this oxygen, it withstands long-term storage, and the present invention The object of the present invention, which has been completed, is to provide a long-term liquid storage method for blood or red blood cell preparations for transfusion.

[0006]

The gist of the present invention is to store blood or blood products for transfusion under the atmosphere of nitrogen or nitrous oxide gas, or a mixed gas of both, or A method for storing a blood product, in which case blood for transfusion or a blood product is housed in a container having good gas permeability, and preferably stored under an atmosphere of nitrogen or nitrous oxide gas or a mixed gas of both. Further, after blood collection, it is preferable to purge the atmosphere (environment) with nitrogen or nitrous oxide gas or a mixed gas in order to reduce oxygen contained in blood for transfusion or blood products at an early stage.

That is, in the present invention, in order to reduce the oxygen damage of blood during storage, the air is replaced with nitrogen or nitrous oxide gas or a mixed gas of both to reduce active oxygen in the blood. Blood is stored by reducing the oxygen concentration, and a large amount of nitrogen, nitrous oxide, or a mixed gas of both is rapidly supplied to the blood storage container or the atmosphere of the blood storage container during or immediately after blood collection. Then, purge the air in the container or its atmosphere, and then continuously add nitrogen or nitrous oxide or a mixed gas of both to diffuse and permeate oxygen in the atmosphere into the stored blood container. It provides a way to prevent it.

Next, the present invention will be described in detail. In the present invention, blood transfusion refers not only to the supply of blood from another person, but also to the supply from the storage of autologous blood before surgery, and the nitrous oxide used in the present invention is also called laughing gas. When using the laughing gas, it is expected that the anesthetic action stabilizes the cell membrane, and that the affinity with water molecules prevents the damage due to ice crystal formation at low temperatures. Good for cryopreservation of blood. Further, as the container for storing blood in the present invention, a container having good gas permeability is preferable, and a container containing blood in the container and filled with nitrogen or nitrous oxide or a mixed gas of both is used. Installed in, diffuses and permeates nitrogen or nitrous oxide from the outside of the container that contains blood, suppresses the increase of blood oxygen concentration during storage at low temperature and oxygen that permeates into blood from the atmosphere. be able to.

In the present invention, a container having good gas permeability suitable for storing blood means a plastic film or sheet of polyvinyl chloride, polyolefin, polysilicon or the like having a film thickness of about 0.02 to 0.4 mm. It is composed of the following, for example, Japanese Patent Publication No. 63-44374.
Containers described in JP-B No. 1-42214 and JP-B No. 1-24214 are suitable. And the gas permeability of these containers is about 6
It is around 500 ml / m ² · 24 hr · atm. The storage temperature of stored blood is in the range of -2 ° C to + 6 ° C,
The preferred range is 0 ° C ± 1 ° C. In addition, by adjusting and controlling the carbon dioxide concentration of blood in the storage environment, the blood pH index during storage can be maintained in a preferable state for blood metabolism. Normally, the carbon dioxide concentration of blood during storage is 85 mmHg after 1 week of storage.
The blood pH index during storage is 6.8 to
It is preferably in the range of 7.5.

Next, the present invention will be described more specifically with reference to Examples.

[Examples] The target blood was CPD from 6 healthy adult males.
A film thickness of 380 μm containing glycerol and mannitol (final concentrations are 0.5 and 0.125 W / V%, respectively) in the solution.
200 ml per person in a PVC standard medical container and a medical PVC thin film container with a film thickness of 130 μm in total 4
00 ml of blood was collected. The blood collection order of the normal container and the thin film container was changed alternately (crossover design). After the inspection on the day of blood collection, the thin-film container blood was placed in a metal container having a total volume of 9 l, and the air in the metal container was immediately replaced with laughing gas. For thin-film container blood, use this metal container for 4-6
While ventilating with laughing gas at a flow rate of ml / min, the blood was stored for 5 weeks in the same refrigerator kept at 1 ± 1 ° C. together with a normal container blood (control group) for comparison. The laughing gas used for ventilation is directly discharged to the outside of the refrigerator so that it does not affect the control group. Table 1 shows a part of the measurement results. In addition, about the measurement, Student's pa
An ired t-test statistical test was used. The risk rate was p <0.05.

[0011]

[Table 1]

In Table 1, the values in parentheses are units, the numerical values are mean values and standard errors (mean ± SD). Stud
As a result of a statistical test using ent's paired t-test, the value at the 5th week was 5% or less (p <0.05) with a significant difference from the control group for any of the items. Admitted. That is, the storage method according to the present invention suppresses an abnormality in hemolysis and permeability of red blood cell membranes by suppressing an increase in oxygen concentration as compared with the control group, and changes such as a decrease in glucose level and an increase in lactate level are not observed. It shows that metabolism was performed more actively, and the blood pH was kept much higher than the current average pH of 6.6 for blood stored for 3 weeks, even though the blood pH should be lowered corresponding to the metabolic amount. Further, it shows that the electrolyte balance was preserved in a more preferable state, which shows the superiority of the present invention.

[0013]

As described above, according to the present invention, it is possible to suppress an increase in free hemoglobin due to hemolysis during storage, and it is possible to store blood at a lower temperature than before. The quality of stored blood can be improved over a long period of time as compared with the storage method. Therefore, the blood preservation according to the present invention reduces the waste of valuable preserved blood. In addition, by prolonging the preoperative blood storage period of autologous blood, it is possible to easily store high-quality autologous blood and use it for reducing side effects and complications of blood transfusion associated with using blood from other people.

Claims (3)

[Claims] 1. A method for preserving blood or a blood product for transfusion, which comprises storing the blood or blood product for transfusion under an atmosphere of nitrogen or nitrous oxide gas, or a mixed gas of both. 2. A blood for blood transfusion, characterized in that the blood for blood transfusion or a blood product is housed in a container having good gas permeability and stored under an atmosphere of nitrogen or nitrous oxide gas, or a mixed gas of both. Or how to store blood products. 3. Blood transfusion, characterized in that, after blood collection, the atmosphere gas of the blood or blood product for transfusion is purged with nitrogen or nitrous oxide gas or a mixed gas of air or oxygen at an early stage. How to store blood products.