JPS6367857B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a blood test container, and more particularly to a bottomed tubular container used for separating serum from a whole blood sample of a subject by centrifugation. In recent years, coupled with the remarkable progress in inspection technology,
Blood tests such as serum biochemical tests, serum immunological tests, and serum tests have become widely used, and have come to greatly contribute to disease prevention and early diagnosis. Serum tests are the main body of blood tests, and the serum required for tests is usually obtained by coagulating blood collected in a blood test container and then centrifuging it to form blood clots with different specific gravities (fibrin and blood cells). separated from the mixed gel-like mass). Conventional blood test containers are made of glass and synthetic resins such as polystyrene, polymethyl methacrylate, and polyethylene, but these generally have the following drawbacks. One is that it takes a considerable amount of time for blood to coagulate after it is injected into a blood test container, making it impossible to carry out tests quickly, especially when tests need to be carried out urgently. has become a problem. Even glass blood test containers, which are said to have the shortest blood clotting time, require 40 to 60 minutes for blood to coagulate after being injected, and synthetic resin blood test containers... It takes 4 hours or more for the blood to coagulate. Another drawback of conventional blood test containers is that they require a method such as centrifugation to phase-separate coagulated whole blood into serum and blood clots with different specific gravities to collect pure serum for use in tests. , serum separability is generally poor. In other words, 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 makes it difficult to perform serum biochemical tests. There were problems such as causing problems. Even glass blood test containers, which are said to have relatively good serum separation, frequently suffer from the above-mentioned problems when used at low temperatures of 15° C. or lower, especially during winter. In order to eliminate the above-mentioned drawbacks, the present inventors investigated the structure of substances that have the effect of promoting blood coagulation, and in particular, in order to most effectively activate blood coagulation factors, the inventors of the present invention have investigated the formation of the inner wall surface of blood test containers. As a result of intensive research into the structure of substances that should be present in the material, we discovered a catechol derivative that has a remarkable blood coagulation effect, and discovered that this can significantly shorten the time required for blood coagulation and also effectively separate serum components and blood clot components. The invention was completed. The gist of the present invention is as follows: 1. The inner wall forming material has the following formula: [However, R ₁ , R ₂ , and R ₃ are any of the following (a), (b), and (c). (a) One or two of R ₁ , R ₂ , and R ₃ are alkyl groups having 1 to 8 carbon atoms, and the others are hydrogen atoms; (b) R ₁ is an alkyl group having 1 to 8 carbon atoms;

[Formula] is a group in which R ₂ and R ₃ are hydrogen atoms, and (c) R ₁ is

A blood test container characterized by containing a catechol derivative represented by the following formula: wherein R ₂ and R ₃ are hydrogen atoms. Next, the blood test container of the present invention will be explained in more detail. In the present invention, any of thermoplastic resins, thermosetting resins, and modified natural resins can be used as the material for the blood test container, that is, the spittoon. 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-maleic anhydride copolymer. Polymer, styrene-acrylic acid copolymer, styrene-
Methyl methacrylate copolymer, styrene-butadiene copolymer, styrene-isoprene copolymer, ethylene-propylene copolymer, ethylene-
Acrylic acid copolymer, ethylene-acrylic acid ester copolymer, polyvinyl alcohol acetal, polyvinyl alcohol butyral, etc.
Further, as the thermosetting resin, for example, unsaturated polyester resin, epoxy resin, epoxy-acrylate resin, etc. are used. Modified natural resins include cellulose acetate, cellulose propionate,
Cellulose acetate butyrate, ethyl cellulose, ethyl chitin, etc. are used. In the blood test container of the present invention, a catechol derivative having a blood coagulation promoting effect is present in the inner wall forming material. As such a derivative, the formula Those represented by can be used. In the above formula, the types of R ₁ , R ₂ , and R ₃ are classified as follows. (1) 3-alkylcatechol This is the case when R ₁ is an alkyl group having 1 to 8 carbon atoms and R ₂ and R ₃ are hydrogen atoms, such as 3-propylcatechol, 3-normal Butylcatechol, 3-tertiarybutylcatechol, 3-n-hexylcatechol, 3-
2-ethylhexylcatechol and the like. (2) 4-Alkylcatechol This applies when R ₂ is an alkyl group having 1 to 8 carbon atoms, and R ₁ and R ₃ are hydrogen atoms, such as 4-propylcatechol, 4-normal Butylcatechol, 4-tertiarybutylcatechol, 4-n-hexylcatechol, 4-
2-ethylhexylcatechol and the like exist. (3) Para-alkylcatechol This is the case when R ₂ and R ₃ are alkyl groups having 1 to 8 carbon atoms and R ₁ is a hydrogen atom, for example, 1-ethyl-4-tert-butyl Catechol, 1,4-ditertyabutylcatechol, 1,4-dihexylcatechol, 1,4-2
Examples include ethylhexylcatechol. (4) Catechin

[Formula] This is a catechol derivative represented by the formula on the left. Catechins are widely distributed in tree wood, twigs, bark, leaves, etc., and are particularly abundant in gambia and betel nut. It is colorless fine needle-shaped crystals, and those recrystallized from water contain 4 molecules of water of crystallization. Decomposition points are 93-95
℃, and the decomposition point of anhydride is 174-175℃.
The absorption maximum is 280 mμ. (5) Nordihydrogayaretic acid It is a catechol derivative represented by the above formula. Nordihydrogayaretic acid is a substance obtained as the main component of resin from the leaves and stems of Tribulaceae plants, or is a substance obtained by synthesis, and is a white or pale yellow crystal with a melting point of 184-185°C. Slightly soluble in water, insoluble in petroleum ether, easily soluble in ethanol, ether, and acetic acid. Among the above catechol derivatives, those which are particularly excellent as blood coagulation promoters include 3-tertiary butylcatechol, 4-tertiarybutylcatechol, paratertiarybutylcatechol, catex, nordihydrogayaretic acid, etc. be. Presence of the catechol derivative in the inner wall forming material refers to the case where the catechol derivative is present not only on the inner wall surface but also in the inner layer of the wall. The blood test container of the present invention can be manufactured by the following method. In advance, resin is used as a molding material.
The above-mentioned catechol derivatives are uniformly mixed and molded by an appropriate molding method such as injection molding, blow molding, compression molding, transfer molding, vacuum molding, cast molding, or the like. According to this method, the catechol derivative is dispersed throughout the wall of the blood test container, not only on the surface but also in the thickness direction.
After molding, while the container is left standing, the dispersed catechol derivatives gradually migrate to the surface of the blood test container, thereby forming a surface effective for promoting blood coagulation. As a means for more effectively causing the transfer of the catechol derivative to the inner wall surface of the blood test container, it is preferable to mix a bleed-out promoting substance into the resin as the molding material in advance with the catechol derivative. . As the bleed-out accelerator, higher aliphatic alcohols, higher aliphatic carboxylic acids, hydrocarbon waxes, and the like are effective. Although the above-mentioned catechol derivative has a blood coagulation promoting effect even when present in a small amount on the inner wall surface of the container, it is preferable for practical use that the amount present per surface area is 1×10 ^-6 gr/cm. Desirably ² or more. Also, if there is too much,
1×10 ^-3 g as it may interfere with serum tests.
It is desirable that it be less than r/cm ² . According to the blood test container of the present invention, blood coagulation factors in blood are rapidly activated by contact with the catechol derivative, the time required for blood coagulation is significantly shortened, and blood serum and blood clots are separated. is easily separated, the problem of residual fibrin and blood clot components being mixed into the separated and collected serum is resolved, and furthermore, as the clot components are sufficiently contracted, the yield of serum is significantly increased. Effects can be obtained. Therefore, the blood test container of the present invention can be suitably used as blood test blood collection tubes, blood collection syringes that also serve the purpose of blood separation, serum separation containers, and the like. Example 1 A molding material containing 1.0 parts by weight of 4-tertiarybutylcatechol per 100 parts by weight of polystyrene was injection molded, with an outer diameter of 17 m/m, an inner diameter of 15 m/m, and a height.
A 110 m/m blood test container was obtained. After injecting 5 c.c. of fresh human blood into this blood test container, it was left at 20°C, and the time required for the whole blood to stop flowing completely was measured as the blood coagulation time.
Blood coagulability was evaluated. Immediately after blood coagulation, centrifugation was performed at a rotational speed of 3000 rpm for 5 minutes, and 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. As is clear from the results in the Example 1 column of Table 1, the blood test container of the present invention coagulated blood extremely quickly and had good serum separation. Examples 2 to 4 In Example 1, 1.0 part by weight of 4-tertiary butylcatechol was replaced with 1.0 part by weight of paratertiary butylcatechol (Example 2) and 1.0 part by weight of catechin.
A blood test container was obtained in the same manner as in Example 1, except that part by weight (Example 3) and 0.5 part by weight of nordihydrogayaretic acid (Example 4) were used. Next, using this blood test container, blood coagulability, serum separation state, and serum yield were evaluated in the same manner as in Example 1 using the blood test container. The results are shown in the columns of Examples 2 to 4 in Table 1. Comparative Examples 1 to 3 Commercially available polystyrene blood test containers with the same dimensions as in Example 1 (Comparative Example 1), polypropylene blood test containers (Comparative Example 2), and polymethyl methacrylate blood test containers (Comparative Example 3)
was prepared and evaluated for blood coagulation, serum separation state, and serum yield under the same conditions as in Examples 1 and 2, but the blood coagulation time was extremely long and the serum separation state was also poor.

【table】

Claims (1)

[Claims] 1. The inner wall forming material has the formula [However, R ₁ , R ₂ , and R ₃ are any of the following (a), (b), and (c). (a) One or two of R ₁ , R ₂ , and R ₃ is an alkyl group having 1 to 8 carbon atoms, and the others are hydrogen atoms; (b) R ₁ is a group of [formula]; R ₂ and R ₃ are hydrogen atoms; (c) R ₁ is a group of the formula; R ₂ and R ₃ are hydrogen atoms; Blood test container.