JPS606865A - Vessel for inspecting blood - Google Patents

Abstract

PURPOSE:To obtain a vessel (spitze) for inspecting blood which clots satisfactorily the blood of a patient receiving heparin dose, can reduce considerably the time for clotting and permits sampling of the serum with good separability by allowing polyamine sulfone to exist on the inside wall surface of said vessel. CONSTITUTION:This vessel for inspecting blood is constituted by allowing the polyamine sulfone expressed by the general formula shown in the figure to exist as an accelerator for blood clotting on the inside wall of a vessel consisting of various materials such as a thermoplastic resin, thermosetting resin, modified natural resin, glass, etc. The polyamine sulfone when brought into contact with the blood contg. heparin adsorbs and neutralizes the heparin and settles together with the heparin to deprive the hetarin of its effect and to restore the normal clotting function of the blood according to the above-mentioned vessel for inspection and therefore the serum is obtd. with good separability by clotting the blood in the vessel in short time and separating the blood-clot and the serum by a means such as centrifugal sepn.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a blood test container, and more specifically, it can be suitably used to separate serum from a blood sample of a test subject receiving administration of valine by centrifugation. It relates to a bottomed tubular container, the so-called spitz.

In recent years, along with the remarkable progress in testing technology, blood tests such as serum biochemical tests, serum immunological tests, and blood cell tests have become widespread, and have greatly contributed to disease prevention and early diagnosis1vi. Among these, serum tests are the main body of blood tests, and the blood required for this test is energized, collected into a blood test container, coagulated, and then centrifuged. It is obtained by separating blood clots (gel-like lumps containing fibrin and blood cells) with different specific gravity using Hi11.

Conventionally, containers for blood tests such as those mentioned above have been made of glass, polystyrene, polymethyl methacrylate [...]
Containers made of synthetic resin, such as Boriedine, have been used, but these have the following drawbacks: First, when using conventional blood test containers, Generally, after injecting 1 full liquid, 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. Even with a glass liquid test container, which is 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. For blood test containers, +f
n lt1 Requires 4 hours or more to solidify.

Second, according to conventional blood test containers, it is difficult to phase-separate coagulated whole blood into serum and blood clots with different specific gravities by means such as centrifugation to collect pure serum for use in tests. However, in general, the separation of blood lrt is not good. Immediately, there is a problem that gel-like fibrin or blood clots tend to adhere firmly to the tube wall, which drastically reduces the amount of serum collected.Furthermore, fibrin tends to remain in the serum, which causes There are also problems such as interference with biochemical tests.

Even in the case of glass blood test containers, which are said to have good serum separation properties, there are two problems 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 clotting occurs during clinical tests! 1ltt <, as a result, 1f1
[It is difficult to separate and collect the supernatant.] There is a problem of 11.

The present inventors have successfully coagulated blood, not only in normal healthy people, but also in patients receiving heparin administration as described above, and significantly shortened the time required for blood coagulation. It is an object of the present invention to provide a blood test container which is capable of collecting blood serum with good separability.

The blood test container of the present invention has a polyamine sulfone consisting of a repeating unit represented by the general formula (1) (wherein R1 to R4 represent a hydrogen atom or a hydrocarbon group) present on the inner wall surface of the container. It is characterized by a story.

In the present invention, the blood test container is made of thermal ijJ plastic resin,
It may be formed from any of thermosetting resin, modified natural resin, or glass. 411J plasticity (as 61 fat,
For example, polyethylene, polypropylene, poly-4-methylbentene-1, polystyrene, polymethyl methacrylate, polyvinyl chloride, polyethylene terephthalate, polybutylene prephthalate, styrene-acryloni I/lyl copolymer, styrene-butadiene copolymer Coalescence, styrene-isoprene copolymer, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer, styrene-methyl meccrylate copolymer, ethylene-propylene copolymer, ethylene-acrylic acid copolymer , ethylene-acrylic acid ester copolymer, polyvinyl alcohol acetal, polyvinyl alcohol acetal, etc., and as the thermosetting resin, for example, unsaturated polyester 4^.1 resin, epoxy resin, epoxy-acrylate resin, etc. In addition, modified natural resins include cellulose acetate, cellulose propionate, cellulose acetate butyrate,
Ethyl cellulose, ethyl chitin, etc. are used.

As the glass, for example, silicate glasses such as soda lime glass, phosphosilicate glass, and borosilicate glass, quartz glass, and the like are preferably used.

The blood test container of the present invention is one in which polyamine sulpon represented by the above general formula is present as a blood coagulation promoter on the inner wall surface of the container made of various materials as described in 1.

In the polyamine sulpon used as a blood coagulation promoter in the present invention, R1 to R4 are hydrogen atoms or hydrocarbon groups having 1 to 18 carbon atoms, and this hydrocarbon group has, for example, an acid group or a hydroxyl group. Good too. Furthermore, in the above formula, X is a halogen atom or an acid group, and the halogen atom is preferably chlorine, bromine, or iodine, and the acid group is, for example, preferably a sulfate group, a sulfite group, a formic acid group, an acetate group, etc. It is.

The above-mentioned polyamine sulpons are, for example,
As described in Japanese Patent No. 3-28701, diallylamine monomers such as diallylamine, halides thereof, sulfates, sulfites, formates, acetic acid 14. T, etc. and sulfur dioxide are dissolved in a nitrogen-containing agent such as water, methanol, ethanol, dimethylbormamide, dimethylsulfoxyl, etc. to produce t-butyl hydroperoxide, abbisisobutyronitrile,
3 in the presence of a suitable polymerization initiator such as ammonium persulfate.
It can be obtained by heating to about 0°C to carry out radical copolymerization.

In the present invention, R1 to R''J < hydrogen atom, methyl group, alkyl group such as ethyl, aryl group such as phenyl group,
Aryl alkyl groups such as Hensyl group and phenethyl group, β
-Hydroxyethyl group, β-carboxylethyl group, β
- A polyamine sulpon which is an alkyl group having an acid group or a hydroxyl group at the terminal such as a sulboethyl group or a carboxylmethyl group is preferably used, but in particular, R and R are hydrogen atoms, R3 and R4 are methyl groups, X is a halogen atom, especially chlorine, and the average molecular weight is 2000 to 35
Polyamine sulpones in the range of 0,000 are preferably used.

When such polyamine sulpon comes into contact with blood containing heparin, it adsorbs and neutralizes heparin, precipitates together with it, and quickly eliminates the action of heparin, thus improving the coagulation function of compacted blood. The blood in the blood test container is coagulated within a short period of time, and the centrifugation fraction is
By separating blood clots and serum by means such as I, serum can be separated to a degree of separation.

To explain this point in more detail, in normal blood, when the blood comes into contact with the inner wall surface of the blood container, activation of factor Blood coagulation progresses and eventually BL11
・Thrombin generated by activation of thrombin acts on fibrinogen, forms an insoluble fibrin network, and completes coagulation.

On the other hand, it is said that the blood of patients receiving heparin administration usually contains 1 to 10 units of valine per 10 cc, and as shown above, in the case of blood containing heparin, Heparin acts cooperatively with anti-I-thrombin present in the blood to significantly inhibit the action of thrombin. In this way, it is said that heparin not only inhibits the action of 1-thrombin, but also inhibits the action of other coagulation factors, including factor ll containing
In 1t t(l, conversion of fibrinogen to fibrin does not occur, and as a result, blood does not coagulate7, so blood/+'f cannot be separated.

However, according to the blood test container of the present invention, as described above, heparin is adsorbed to polyamine sulfone and removed from the blood, so that other blood coagulation factors are not normal. It restores blood coagulation. In particular, the polyamine sulfone used in the present invention has sulfone groups alternating with cationic quaternary nitrogen in the polymer chain, so the adsorption of heparin, which has sulfonic acid groups, hydroxyl groups, carboxyl groups etc. Therefore, it probably has a much better blood coagulation promoting effect.

In the blood test container of the present invention, polyamine sulfone is present on the inner wall surface in an amount ranging from 0.005 to 50 cm per Etl'Occ of blood. When the amount of polyamine sulfone present is less than the above range, it has poor adsorption and removal effect on heparin, while when it is present in too large a quantity, there is a risk that clinical test values such as serum biochemical tests will be affected. I don't like it because there is.

According to the present invention, blood coagulation can be synergistically promoted by providing ellagic acid represented by the following formula on the inner wall surface of a blood test container together with the polyamine sulfone described in 1. It is already known that ellagic acid has the effect of activating factor X, which is one of the liquid coagulation factors. Blood coagulation is synergistically promoted compared to when

It is preferable to use ellagic acid in an amount of 0.0 (103 to 600 parts by weight) per 1 part by weight of polyamine sulfone.

Further, according to the present invention, coagulation of blood can be synergistically promoted by using mineral +231 powder together with polyamine sulfone and making it present on the inner wall surface of the +m liquid test container. can. Preferred examples of the above-mentioned mineral powder include silica, glass, kaolin, celite, and hentonite. When this R-free powder comes into contact with blood, it has the effect of promoting the activation of blood coagulation factors and the coagulation of platelets, and has the effect of synergistically with polyamine sulfone to quickly transform blood. Let solidify. More specifically, when such a mineral inorganic powder is used, factor It promotes it. In particular, 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 present polyamine sulpon or ellagic acid or the above-mentioned mineral inorganic powder as a blood coagulation promoter on the inner wall surface of a blood test container, for example, they can be mixed with an appropriate solvent or binder. After dissolving or dispersing it in a blood test container and applying or blowing it on the inner wall surface of a blood test container, or immersing the container in a solution or dispersion of the above compound, dry it as necessary. , 41 pieces may be placed on 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. The blood of patients receiving heparin administration, such as those with thrombosis, has an excellent blood coagulation effect, and the time required for coagulation after blood is collected into a container is significantly shortened, and serum and blood clots are separated. Even easily in minutes! Therefore, the problem of blood clot components being mixed in the 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, 1111 river syringe 1 serum container, etc., which are also used for blood separation.

The present invention will be described below with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 In nif notation, F2' and R2 are both hydrogen, R3 and R4 are both methyl groups, and X is a chlorine atom. A polyamine sulfone having a molecule i of 2000 to 5000 is added to methanol, and 0. A 5% dispersion was prepared.

This was applied by spraying onto the inner wall of a commercially available 10 m glass spittoon and air-dried.

Inject 5 ml of fresh blood containing 1.5 units of heparin per ml into this blood test container, stir gently, and leave at 23°C until the whole blood stops flowing completely. The time taken was evaluated as the blood coagulation time. In the above, the amount of polyamine sulfone present on the inner wall of the container was 081 mg per ml of blood.

Immediately after this blood coagulation, centrifuge for 5 minutes at a rotation speed of 3000 revolutions/rotation, observe the +111 lFi fraction 1, and collect the supernatant + In supernatant with a pipette.
That boat was designated as Serum Layer ♀. +f++ Kiyoshi’s portion! 1111
The spread was determined by checking the presence or absence of residual blood clot adhesion on the wall of the container that adhered to the serum layer and by self-illumination of the Jli'' appearance of the fibrino network. The precipitation of the fibrin network was observed again 24 hours later.

The results are shown in the table.

Example 2 In Example 1, the molecular weight is 170,000 to 23,000.
Blood coagulation time and 1111 serum yield were evaluated in the same manner except that polyamine sulpone with 0.0% polyamine was used. The results are shown in the table.

Example 3 Same as Example 1, polyamine sulfone and ellagic acid were dispersed in methanol at a concentration of 0.5% by weight and 1.0% by weight, respectively. Spray this onto the inner wall of a commercially available 10m1 polyethylene spittoon and let it dry.
, Blood coagulation time and serum yield were evaluated in the same manner as in Example 1. The results are shown in the table.

Example 4 The same polyamine sulfone as in Example 1 and finely powdered silica particles (5 μm or less, average particle size 1 μm) were each mixed at 0.5 μm.
It was dispersed in methanol to give a concentration of 5% by weight and 1.0% by weight. 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 A commercially available 10m1 glass spittoon was coated with the same large slanted blood 5 as in Example 1 without any treatment being applied to its inner wall surface.
After injecting ml, blood coagulation time and serum yield were measured in the same manner as in Example 1. The results are shown in the table.

Claims (1)

[Scope of Claims] (11) A polyamine sulfone consisting of a repeating unit represented by the general formula (in which R1 to R4 represent a hydrogen atom or a hydrocarbon group) is present on the inner wall surface of the container. A blood test container characterized by: (2) A polyamine sulpon consisting of a repeating unit represented by the general formula (wherein R1 to R4 represent a hydrogen atom or a hydrocarbon group) and ellagic acid are placed on the inner wall of the container. (3) A polyamine sulfone consisting of a repeating unit represented by the general formula (wherein R1 to R4 represent a hydrogen atom or a hydrocarbon group) A blood test container characterized in that a mineral inorganic powder is present on the inner wall surface of the container.