JPH0151941B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a blood test container, and more particularly, a container with a bottom that can be suitably used to separate serum from a whole blood sample of a test subject receiving heparin administration by centrifugation. It relates to a tubular container, the so-called Spitz. In recent years, with the remarkable progress in testing technology, blood tests such as serum biochemical tests, serum immunological tests, and hematology tests have become widespread, and have greatly contributed to disease prevention and early diagnosis. Among these, blood tests are the main body of blood tests, and the serum required for this test is usually obtained by collecting blood into a blood test container, coagulating it, and then centrifuging it to extract blood with different specific gravities. It is obtained by separating it from rice cake (a gel-like mass mixed with fibrin and blood cells). Conventionally, blood test containers such as those mentioned above have been used.
In addition to glass, materials made of synthetic resins such as polystyrene, polymethyl methacrylate, and polyethylene have been used, but these generally have the following drawbacks. First, when using conventional blood test containers,
Generally, after blood is injected into this system, it takes a considerable amount of time for it to coagulate, making it impossible to carry out tests quickly, which is particularly problematic when tests need to be carried out urgently. ing. Even with glass blood test containers, which are said to have the shortest blood coagulation time, it takes 40 to 60 minutes for blood to coagulate after injecting blood from a normal, healthy person.
When it comes to synthetic resin blood test containers, it is necessary to leave them for 4 hours or more before blood coagulates. Second, according to conventional blood test containers, pure serum for use in testing is collected by phase-separating coagulated whole blood into serum and blood clots with different specific gravities by means such as centrifugation. However, in general, the separation of serum is not good. That is, gel-like fibrin or blood clots tend to adhere firmly to the tube wall, which causes the problem of drastically reducing the amount of serum collected.Furthermore, fibrin tends to remain in the serum, which reduces serum production. There are also problems such as causing problems with chemical tests. Even in the case of glass blood test containers, which are said to have good serum separation properties, the above-mentioned problems occur under low temperature conditions of 15° C. or lower, for example in winter. In particular, patients undergoing dialysis or patients with thrombosis are given heparin to prevent blood clots, but these patients have significant concentrations of heparin in their blood. Due to its presence, blood coagulation is difficult to occur during clinical tests.
As a result, there is a problem in that it is difficult to separate and collect serum. The present inventors have discovered that not only normal healthy people but also patients receiving heparin as described above can coagulate blood well and can significantly shorten the time required for blood coagulation. is possible,
Another object of the present invention is to provide a blood test container that can collect serum with good separation. The first blood test container of the present invention has a general formula of (However, in the formula, R ¹ to ^{R 4} are hydrogen atoms, methyl groups or ethyl groups, and X is chlorine or bromine.) and has an average molecular weight of 2000 to 2000.
350,000 in a range of 0.005 mg to 50 mg per 10 c.c. of blood volume.
It is characterized by being present on the inner wall surface of the container. Furthermore, the second blood test container of the present invention includes:
Before blood collection, the polyamine sulfone (a) and ellagic acid (b) are mixed in such a way that the ratio of said (a) and said (b) is 0.0003 to 600.
Part by weight: in the range of 1 part by weight, and (a) in the range of 0.005 mg to 50 mg per 10 c.c. of blood volume,
It is characterized by being present on the inner wall surface of the container. Furthermore, the third blood test container of the present invention includes:
Before blood collection, the polyamine sulfone (a) and a mineral inorganic material selected from the group consisting of silica, glass, kaolin, celite, and bentonite and having a particle size of 50 μm or less and an average particle size of 10 μm or less Powder (b) and powder (b), the ratio of said (a) and said (b) is 0.0005~
10 parts by weight: 1 part by weight, and (a) is present on the inner wall of the container in a range of 0.005 mg to 50 mg per 10 c.c. of blood volume. It is. In the present invention, the blood test container may be made of any one of thermoplastic resin, thermosetting resin, modified natural resin, or glass. Examples of thermoplastic resins include polyethylene, polypropylene, poly-4-methylpentene-1, polystyrene, polymethyl methacrylate, polyvinyl chloride, polyethylene terephthalate, polybutylene terephthalate, styrene-acrylonitrile copolymer, and styrene-butadiene copolymer. coalescence, styrene-isoprene copolymer, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer,
Examples of thermosetting resins include styrene-methyl methacrylate copolymer, ethylene-propylene copolymer, ethylene-acrylic acid copolymer, ethylene-acrylic acid ester copolymer, polyvinyl alcohol acetal, and polyvinyl alcohol butyral. For example, unsaturated polyester resins, epoxy resins, epoxy-acrylate resins, etc. are used, and as modified natural resins, cellulose acetate, cellulose propionate, cellulose acetate butyrate, ethyl cellulose, ethyl chitin, etc. are used. Examples of glass include soda lime glass,
Silicate glasses such as phosphosilicate glass and borosilicate glass, quartz glass, and the like are preferably used. The blood test container of the present invention has a polyamine sulfone represented by the above general formula present as a blood coagulation promoter on the inner wall surface of the container made of the various materials mentioned above. In the polyamine sulfone used as a blood coagulation promoter in the present invention, R ¹ to ^{R 4} are hydrogen atoms, methyl groups, or ethyl groups, and X is chlorine or bromine. The above polyamine sulfones are, for example,
As stated in Special Publication No. 43-28701,
A diallylamine monomer such as diallylamine, dimethallylamine, or its chloride or bromide, etc., and sulfur dioxide are dissolved in an organic solvent such as water, methanol, ethanol, dimethylformamide, dimethyl sulfoxide, etc., and t-butyl hydroperoxide is prepared. , azobisisobutyronitrile,
It can be obtained by radical copolymerization by heating to about 30° C. in the presence of a suitable polymerization initiator such as ammonium persulfate. In the present invention, polyamine sulfones in which R ¹ and R ² are hydrogen atoms, R ³ and R ⁴ are methyl groups, X is chlorine, and have an average molecular weight in the range of 2,000 to 35,000 are preferably used. It will be done. When such polyamine sulfones come into contact with heparin-containing blood, they adsorb and neutralize heparin, precipitate together with it, and quickly eliminate the action of heparin, thus disrupting the normal blood coagulation function. Since the blood is recovered, the blood in the blood test container is coagulated within a short period of time, and the blood clot and serum are separated by means such as centrifugation, whereby serum can be obtained with good separation. To explain this point in more detail, in normal blood, the activation of factor XII among coagulation factors immediately progresses upon contact between the blood and the inner wall of the blood container.
This serves as a starting point for blood coagulation to proceed in a chain reaction, and finally, thrombin generated by activation of prothrombin acts on fibrinogen to form an insoluble fibrin network and complete coagulation. On the other hand, it is said that in the blood of patients receiving heparin administration, there is usually 1 unit to 10 units of heparin per 10 c.c., and thus, in the case of blood containing heparin, Heparin acts cooperatively with antithrombin present in the blood and significantly inhibits the action of thrombin. In this way, heparin is said to not only inhibit the action of thrombin, but also to inhibit the action of other coagulation factors, including factor XII. Conversion to fibrinogen does not occur, and as a result,
Serum cannot be separated because the blood does not clot. However, according to the blood test container of the present invention, as described above, since heparin is adsorbed to polyamine sulfone and removed from the blood, thrombin and other blood coagulation factors do not function normally. It will recover. In particular, since the polyamine sulfone used in the present invention has sulfonic groups alternating with cationic quaternary nitrogen in the polymer chain, it has excellent adsorption properties for heparin containing sulfonic acid groups, hydroxyl groups, carboxyl groups, etc. Therefore, the blood coagulation-promoting effect is likely to be significantly superior. In the blood test container of the present invention, polyamine sulfone is present on the inner wall surface in a range of 0.005 mg to 50 mg per 10 c.c. of blood volume. If the amount of polyamine sulfone present is less than the above range, the effect of adsorbing and removing heparin will be poor, while if it is present in too large a quantity, abnormalities may occur in clinical test values such as serum biochemical tests. Undesirable. According to the present invention, in addition to the polyamine sulfone described above, the following formula Blood coagulation can be synergistically promoted by allowing ellagic acid represented by the following to exist on the inner wall surface of a blood test container. It is already known that ellagic acid has the effect of activating factor XII, which is one of the blood coagulation factors, but when used in combination with polyamine sulfone, it has the effect of activating factor XII, which is one of the blood coagulation factors. In comparison, blood coagulation is synergistically promoted. It is preferable to use ellagic acid in combination in a range of 0.0003 to 600 parts by weight of polyamine sulfone per 1 part by weight of ellagic acid. Further, according to the present invention, coagulation of blood can be synergistically promoted by using a mineral inorganic powder together with polyamine sulfone and making it present on the inner wall surface of a blood test container. Silica, glass, kaolin, celite, bentonite, etc. are used as the mineral powder. These inorganic powders have the effect of promoting the activation of blood coagulation factors and the coagulation of platelets when they come into contact with blood, and have a synergistic effect with polyamine sulfone to quickly transform blood. Let solidify. More specifically, when such mineral-based inorganic powder is used, factor XII, prekallikrein, and polymer kininogen are adsorbed onto the inorganic powder to form a complex, and
It promotes the activation of factors. In particular, the particle size
Silica having a particle size of 50 μm or less and an average particle size of 10 μm or less is most preferably used. The amount of polyamine sulfone per 1 part by weight of the inorganic powder is preferably 0.0005 to 10 parts by weight. In the present invention, in order to make polyamine sulfone or ellagic acid or the mineral inorganic powder present as a blood coagulation promoter on the inner wall surface of a blood test container, for example, these can be dissolved or dispersed in an appropriate solvent or binder. , apply or spray this on the inner wall surface of the blood test container,
Alternatively, the container may be immersed in a solution or dispersion of the above-mentioned compound, and then dried if necessary to adhere to the inner wall surface of the container. According to the blood test container of the present invention, since the blood coagulation promoter as described above is present on the inner wall surface of the container, it can be used not only for the blood of normal healthy people but also for artificial dialysis patients and blood clots. It also has an excellent blood coagulation effect on the blood of patients receiving heparin administration, such as those of patients suffering from diarrhoea, and the time required for coagulation after blood is collected into a container is significantly shortened, and serum and blood clots can be easily removed. can be separated into
Therefore, the problem of blood clot components being mixed in the separated and collected serum is also solved. Furthermore, the blood test container of the present invention has the advantage that the blood clot components are sufficiently contracted, resulting in a significantly higher serum yield. Therefore, the blood test container of the present invention is suitable for blood test blood collection tubes, blood collection syringes also intended for blood separation, serum separation containers, and the like. The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples in any way. Example 1 In the above formula, R ¹ and R ² are both hydrogen,
A polyamine sulfone having a molecular weight of 2,000 to 5,000, in which both R ³ and R ⁴ are methyl groups and X is a chlorine atom, was added to methanol to prepare a 0.5% by weight dispersion.
This was applied by spraying onto the inner wall of a commercially available 10 ml glass spittoon and air-dried. Add 1 ml of heparin to this blood test container.
5 ml of fresh human blood containing 1.5 units was injected, stirred gently, and left at 23°C. The time required until the whole blood stopped flowing completely was evaluated as the blood coagulation time. In addition, in the above, the amount of polyamine sulfone present on the inner wall of the container is per ml of blood.
It was 0.1 mg. Immediately after this blood coagulation, the mixture was centrifuged at a rotational speed of 3000 rpm for 5 minutes, the state of serum separation was observed, and the supernatant serum was collected with a pipette, and the amount was taken as the serum yield. The state of serum separation was evaluated by the presence or absence of residual blood clot adhesion on the vessel wall in the serum layer and the presence or absence of fibrin network precipitation. Note that the precipitation of fibrin network was observed again 24 hours later. The results are shown in the table. Example 2 Blood coagulation time and serum yield were evaluated in the same manner as in Example 1 except that polyamine sulfone having a molecular weight of 170,000 to 230,000 was used. The results are shown in the table. Example 3 The same polyamine sulfone and ellagic acid as in Example 1 were dispersed in methanol at a concentration of 0.5% by weight and 1.0% by weight, respectively. Add this to 10ml of commercially available
It was applied by spraying onto the inner wall of a polyethylene spittoon, dried, and evaluated for blood coagulation time and serum yield in the same manner as in Example 1. The results are shown in the table. Example 4 Same polyamine sulfone as Example 1 and particle size 5 μm
Hereinafter, finely powdered silica having an average particle size of 1 μm was dispersed in methanol at a concentration of 0.5% by weight and 1.0% by weight, respectively. This was applied by spraying onto the inner wall of a commercially available 10 ml polyethylene spittoon, dried, and evaluated for blood coagulation time and serum yield in the same manner as in Example 1. The results are shown in the table. Comparative Example After injecting 5 ml of the same human fresh blood as in Example 1 into a commercially available 10 ml glass spittoon without any treatment on its inner wall surface, blood coagulation time and serum yield were measured in the same manner as in Example 1. was evaluated. The results are shown in the table. 【table】

Claims (1)

[Claims] 1. Before blood collection, the general formula (However, in the formula, R ¹ to ^{R 4} are hydrogen atoms, methyl groups or ethyl groups, and X is chlorine or bromine.) and has an average molecular weight of 2000 to 2000.
350,000 in a range of 0.005 mg to 50 mg per 10 c.c. of blood volume.
A blood test container characterized by being present on the inner wall surface of the container. 2. Before blood collection, general formula (However, in the formula, R ¹ to ^{R 4} are hydrogen atoms, methyl groups or ethyl groups, and X is chlorine or bromine.) and has an average molecular weight of 2000 to 2000.
Polyamine sulfone (a) having a molecular weight of 350,000 and ellagic acid (b) in a ratio of (b) to 0.0003.
600 parts by weight: within the range of 1 part by weight, and the (a),
1. A blood test container, characterized in that a blood amount of 0.005 mg to 50 mg per 10 c.c. of blood is present on the inner wall of the container. 3. Before blood collection, general formula (However, in the formula, R ¹ to ^{R 4} are hydrogen atoms, methyl groups or ethyl groups, and X is chlorine or bromine.) and has an average molecular weight of 2000 to 2000.
350,000 range, and a mineral inorganic material selected from the group consisting of silica, glass, kaolin, celite, and bentonite and having a particle size of 50 μm or less and an average particle size of 10 μm or less. Powder (b) and the ratio of said (a) and said (b) is 0.0005
~10 parts by weight: in the range of 1 part by weight, and the (a),
1. A blood test container, characterized in that a blood amount of 0.005 mg to 50 mg per 10 c.c. of blood is present on the inner wall of the container.