JPH0517885B2 - - Google Patents

Description

Detailed Description of the Invention Background of the Invention [Technical Field] The present invention relates to a red blood cell preservation agent and a red blood cell preservation bag.More specifically, the present invention relates to a red blood cell preservation agent and a red blood cell preservation bag. The present invention relates to a red blood cell preservation agent added to the blood component and a red blood cell preservation bag containing the same. Blood transfusion is a special medical practice in which blood is collected from a donor, so to speak, and sacrifices are made, and due to its special nature, those involved in blood transfusion have a social mission to use blood as effectively as possible. is in charge of Furthermore, since blood contains many components, some of which may cause undesirable side effects, it is desirable to infuse only the components necessary for the patient. Due to this need, component transfusion, in which collected blood is fractionated into each component, stored, and transfused, is widely practiced. In this case, blood from many donors is collected into multiple blood bags;
The red blood cells are fractionated into each component by centrifugation and concentrated to obtain concentrated red blood cells (CRC). [Prior art and its problems] When CRC is separated from whole blood, most of the plasma is removed.
citratedextrose) liquid and CPD liquid (citrate
Anticoagulant/preservation solutions such as phosphate dextrose (phosphate dextrose) are also removed, which tends to cause a shortage of components that serve as metabolic substrates during storage, such as glucose, contained in anticoagulation/preservation solutions. Additionally, the concentrated red blood cells present problems with higher concentrations of metabolic waste products and increased viscosity of the CRC, which impedes rapid transfusion.
In order to solve these problems, in recent years, physiological saline containing glucose, adenine, and a colloidal osmotic pressure regulator (mannit) has been used for CRC after fractionation.
A method of preserving it by adding it to In the above storage solution, the colloid osmotic pressure regulator plays an important role in preventing hemolysis during storage. When red blood cells are suspended in a solution made isotonic with only membrane-permeable substances, the red blood cells contain membrane-impermeable substances, causing an imbalance in colloidal osmotic pressure, stressing the red blood cells, and causing hemolysis. Cause. It is known that such a phenomenon can be avoided by adding membrane-impermeable substances, ie colloidal osmotic pressure regulators, to the red blood cell suspension. (Nakao: Blood biochemistry P.103
Asakura Shoten (1974)) Adding the above preservation solution to storage reduces the viscosity of CRC, making it easier to infuse, and the adenine-glucose contained in the preservation solution increases the adenosine-5′ of red blood cells. - The concentration of triphosphate (ATP) is kept high, resulting in an excellent effect of increasing the survival rate of red blood cells after transfusion. On the other hand, however, in the conventional method of preservation by adding a prescription preservation solution, the concentration of 2,3-diphosphoglycerate (2,3-DPG), which plays an important role in the oxygen carrying ability of red blood cells, is There is a problem in that the oxygen carrying capacity is lower than when stored without adding liquid, and the oxygen carrying capacity is lowered. Furthermore, it has been reported in Transfusion (1982), pp. 723-731, that fructose 1,6-diphosphate is effective in preserving red blood cells. This report states that the addition of fructose 1,6-diphosphate prevents the concentration of 2,3-DPG and ATP from decreasing during storage of red blood cells. However, it is technically difficult to introduce two phosphoric acids into a sugar such as fructose, and the production cost is high. OBJECTS OF THE INVENTION An object of the present invention is to provide a red blood cell preservation agent that can prevent the concentration of ATP and 2,3-DPG from decreasing during red blood cell storage. A further object of the present invention is to provide a red blood cell preservation agent that also serves as a colloid osmotic pressure regulator during the preservation of red blood cells. Another object of the present invention is to provide a red blood cell bag containing the above-mentioned red blood cell preservation agent. The above objects of the present invention are achieved by a red blood cell preservation agent having the following structure. (1) A red blood cell preservation agent characterized by containing a monophosphorylated derivative of a monosaccharide. (2) Monosaccharides are red blood cell preservatives in item 1, which are hexoses. (3) Monophosphorylated derivatives of monosaccharides are glucose-
1-phosphate, glucose-6-phosphate, fructose-1-phosphate or fructose-6-phosphate
The red blood cell preservative of item 2 which is phosphoric acid. (4) The red blood cell preservation agent according to item 1, which contains 5 to 500 mmol/liter of a monophosphorylated monosaccharide derivative. (5) A red blood cell storage bag containing a red blood cell preservation agent containing a monophosphorylated monosaccharide derivative. DETAILED DESCRIPTION OF THE INVENTION The present invention consists of a red blood cell preservative containing a monophosphorylated derivative of a monosaccharide. The monosaccharide monophosphorylated derivative used in the present invention is a monophosphorylated product of pentose or hexose,
1- or 6-monophosphoric oxides of hexoses are preferred. Particularly preferred examples include glucose-1-phosphate, glucose-6-phosphate, and fructose-1-phosphate.
Mention may be made of 1-phosphate and fuctose-6-phosphate. These compounds are known substances and can be easily produced by phosphorylating monosaccharides by methods known per se. Furthermore, since the above-mentioned compounds are substances commonly found in living organisms, they can be used safely without worrying about toxicity. The preservative of the present invention is prepared by adding the above monophosphorylated monosaccharide derivative to an anticoagulant/preservative solution known per se, such as an ACD solution or a CPD solution. The concentration of phosphorylated monosaccharide derivatives in the preservative is preferably from 5 to 500 mmol/liter. The preservative of the present invention is used by adding it to a concentrated red blood cell solution according to a conventional method and storing it in liquid form at a low temperature. The preservative of the present invention can also be added to whole blood if it is desired to preserve the blood in the form of whole blood. As will be shown later, the phosphorylated derivatives of the present invention are virtually impermeable to red blood cell membranes, and thus also serve as colloidal osmotic pressure regulators in preservation solutions. The red blood cell storage bag of the present invention is prepared by filling an appropriate amount of the above-mentioned preservative into a known soft vinyl chloride resin bag. Next, the present invention will be explained in more detail with reference to Examples and Reference Examples. Example CPD-added human whole blood CRC (hematocrit 70%) was prepared, and 4 ml each was dispensed into two stoppered plastic test tubes. 2 ml of storage solution A having the composition shown in Table 1 was added to one test tube, and 2 ml of storage solution B was added to the other test tube, and the test tubes were stored at 4°C. Immediately after preparation and 1, 2, and 3 weeks later, the amounts of ATP and 2,3-DPG in red blood cells were measured. The results are shown in Tables 2 and 3.

【table】

【table】

[Table] Both storage solutions A and B shown here are after adjustment.
It is added to CRC as a preservation solution. The difference between solutions A and B is that solution A uses mannitol as a colloid osmotic pressure regulator, while solution B uses glucose-1-phosphate, a phosphorylated derivative of monosaccharides. be. Looking at the changes in the amount of ATP in Table 2, there is no difference in the effectiveness of solutions A and B in maintaining the ATP level, and solutions A and B are considered to be equivalent. On the other hand, looking at the changes in 2,3-DPG shown in Table 3, after the second week of storage, the 2,3-DPG level in solution B was clearly higher, and the 2,3-DPG level was superior to solution A. It shows the preservation effect. In the above example, similar results can be obtained when red blood cells are stored in a CRC in a red blood cell storage bag made of a conventionally known soft vinyl chloride resin blood bag containing a red blood cell preservation agent instead of a plastic test tube. Ta. Reference Example The following experiment was conducted to demonstrate that the red blood cell preservation agent of the present invention is impermeable to red blood cell membranes. Each drug shown in Table 4 was added to CPD-added human whole blood at a concentration of 300 mmol/liter and incubated at 37°C for 1 hour. ) was measured. The results are shown in Table 4. Monosaccharides such as glucose, xylose, and mannose enter the blood cells because they are permeable to the red blood cell membrane, and as a result, water flows into the blood cells and the MCV becomes larger than the control. In contrast, disaccharides such as maltose and sucarose, mannitol, a sugar alcohol, and glucose, a phosphorylated derivative of monosaccharides,
Since 1-phosphate is membrane impermeable, it cannot enter the red blood cells; on the other hand, water exits from the red blood cells, causing MCV.
was slightly smaller than the control. This data indicates that glucose-1-phosphate is virtually impermeable to red blood cell membranes.

【table】

[Table] Specific Effects of the Invention As detailed above, the red blood cell preservation agent according to the present invention can maintain a higher level of 2,3-DPG during preservation, and does not adversely affect the ATP level. Furthermore, since the phosphorylated monosaccharide derivative of this invention is virtually impermeable to red blood cell membranes,
It also plays a role as a colloid osmotic pressure regulator and has the effect of preventing hemolysis during storage. Furthermore, since some phosphorylated derivatives of monosaccharides are extremely common in living organisms, it is advantageous from the point of view of safety if such substances are employed as components of red blood cell preservation agents.

Claims (1)

[Scope of Claims] 1. A red blood cell preservation agent characterized by containing a monophosphorylated derivative of a monosaccharide. 2. Claim 1 that the monosaccharide is a hexacarbon sugar
Red blood cell preservative. 3 Monophosphorylated derivatives of monosaccharides are glucose-
The red blood cell preservation agent according to claim 2, which is 1-phosphate, glucose-6-phosphate, fructose-1-phosphate or fructose-6-phosphate. 4 Claim 1 containing 5 to 500 mmol/liter of a monophosphorylated monosaccharide derivative
Red blood cell preservative. 5. A red blood cell storage bag containing a red blood cell preservation agent containing a monophosphorylated monosaccharide derivative.