JPS6367859B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a blood test container, and more particularly to a so-called spitz, 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 hematology 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 substance structure that should be present in the material, we discovered phosphite as a substance with a remarkable blood coagulation effect, and found that this significantly shortened the time required for blood coagulation and improved the concentration of serum and clot components. We found that it was possible to separate this from 2, 2', 4,
The present inventors have discovered that a synergistic effect can be obtained by using 4'-tetrahydroxybenzophenone, a catechol derivative, and p,p'-isopropylidene diphenol in combination, and have completed the present invention. The gist of the present invention is as follows: 1. Inner wall surface forming material, formula: (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , and R ₃ is a phenyl group, or an alkyl phenyl group in which 1 to 3 hydrogen atoms of the phenyl group are substituted with a nonyl group or an octyl group, and others is a decyl group.) A container for blood testing, characterized in that a phosphite ester represented by the following formula is present: (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , and R ₃ is a phenyl group, or an alkyl phenyl group in which 1 to 3 hydrogen atoms of the phenyl group are substituted with a nonyl group or an octyl group, and others is a decyl group.) 1 part by weight of a phosphite ester represented by
2',4,4'-tetrahydroxybenzophenone 0.1
3. A container for blood testing, characterized in that the inner wall surface forming material is present with the formula: (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , R ₃ is a phenyl group,
Alternatively, the phenyl group is an alkylphenyl group in which 1 to 3 hydrogen atoms are substituted with a nonyl group or an octyl group, and the others are decyl groups. ) 1 part by weight of a phosphite ester represented by
A blood test characterized by the presence of 0.1 to 5.0 parts by weight of a catechol derivative selected from tertiary butylcatechol, 4-tertiarybutylcatechol, paratertiarybutylcatechol, catechin, and nordihydrogayaretic acid. 4. For the inner wall surface forming material, the formula (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , R ₃ is a phenyl group,
Alternatively, the phenyl group is an alkylphenyl group in which 1 to 3 hydrogen atoms are substituted with a nonyl group or an octyl group, and the others are decyl groups. ) and 1 part by weight of phosphite ester represented by P, P'-
The present invention provides a blood test container characterized by containing 0.1 to 5.0 parts by weight of isopropylidene diphenol. 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-butadiene copolymer. , styrene-isoprene copolymer, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer, styrene-methyl methacrylate copolymer,
Ethylene-propylene copolymer, styrene-acrylic acid copolymer, ethylene-acrylic acid ester copolymer, polyvinyl alcohol acetal, polyvinyl alcohol butyral, etc., and thermosetting resins include, for example, unsaturated polyester resin, Epoxy resin, epoxy-acrylate resin, etc. are used. As the modified natural resin, cellulose acetate, cellulose propionate, cellulose acetate butyrate, ethyl cellulose, ethyl chitin, etc. are used. In the blood test container of the present invention, a phosphite having a blood coagulation promoting effect is present on the inner wall surface. As such a phosphite ester, the formula (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , and R ₃ is a phenyl group, or an alkyl phenyl group in which 1 to 3 hydrogen atoms of the phenyl group are substituted with a nonyl group or an octyl group, and others is a decyl group.) is used. In the above formula, phosphorous esters suitable for use in the present invention are classified as follows depending on the types of R ₁ , R ₂ , and R ₃ . (1) When R ₁ , R ₂ , and R ₃ are all phenyl or alkylphenyl groups: For example, trisphenyl phosphite, tris (monononylphenyl) phosphite, tris (dinonylphenyl) phosphite, tris (torino) These include nilphenyl) phosphite, tris(monoctylphenyl) phosphite, tris(dioctyl phenyl) phosphite, tris(trioctylphenyl) phosphite, and the like. (2) When R ₁ and R ₂ are phenyl or alkylphenyl groups, and R ₃ is an alkyl group: For example, diphenyldecyl phosphite, di(monononylphenyl)decyl phosphite,
di(dinonylphenyl)decyl phosphite,
Examples include di(trinonylphenyl)decyl phosphite, di(monooctyl phenyl) decyl phosphite, di(dioctyl phenyl) decyl phosphite, and di(toluoctylphenyl) decyl phosphite. (3) When R ₁ is a phenyl group or an alkylphenyl group and R ₂ and R ₃ are alkyl groups: For example, phenyltridecyl phosphite, nonylphenyl didecyl phosphite, dinonylphenyl didecyl Examples include phosphite, trinonylphenyl didecyl phosphite, monooctylphenyl didecyl phosphite, dioctyl phenyl didecyl phosphite, trioctyl phenyl didecyl phosphite, and the like. Among the above-mentioned phosphorous esters having a blood coagulation effect, those which are particularly preferably used include tris(mononylphenyl) phosphite, tris(dinonylphenyl) phosphite,
These include tris(trinonylphenyl) phosphite, didecyl phenyl phosphite, diphenyl decyl phosphite, and the like. Presence of the above-mentioned phosphite in the inner wall forming material refers to the case where the phosphite 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 phosphite esters 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 phosphorous ester 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 phosphite gradually migrates to the surface of the blood test container, thereby forming a surface effective for promoting blood coagulation. As a means to more effectively cause the transfer of the phosphite ester to the inner wall surface of the blood test container, a bleed-out promoting substance is mixed in advance with the phosphite ester into the resin serving as the molding material. is preferable. As the bleed-out accelerator, higher aliphatic alcohols, higher aliphatic carboxylic acids, hydrocarbon waxes, and the like are effective. Although the above-mentioned phosphite 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. / ^cm2 or more is desirable. 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 . In the above case, when the phosphite ester is present alone, a significant blood coagulation promoting effect is observed. However, the above phosphite ester and 2,
2',4,4'-tetrahydroxybenzophenone,
By using a catechol derivative or p,p'-isopropylidene diphenol in combination, the effect of promoting blood coagulation can be further improved. One of the substances that exhibits a synergistic blood coagulation promoting effect when used in combination with the above-mentioned phosphite is 2,2',4,4'-tetrahydroxybenzophenone. 2,2',4,4'-tetrahydroxybenzophenone has the following chemical structure. 2,2',4,4'-tetrahydroxybenzophenone has a melting point of 195℃ and a solubility in solvents of 30℃.
0.1% by weight for water, 50% by weight for methanol, 40% by weight for ethanol, and 10% by weight for a 1:1 water-ethanol solution. Further, the maximum absorption wavelength position is 345 mμ, and the color value (Gardner) is No. 8 in a 1% by weight methanol solution. The weight ratio of 2,2',4,4'-tetrahydroxybenzophenone to 1 part of phosphite is preferably 0.1 to 3.0. Other substances that synergistically exhibit a blood coagulation promoting effect when used in combination with the phosphite are catechol derivatives. As the catechol derivative, one represented by the following formula is used. In the case of the above formula, the catechol derivative is R ₁ ,
Depending on the type of R ₂ and R _3, 3-alkylcatechol,
It is divided into 4-alkylcatechol, para-alkylcatechol, catechin, nordihydrogayaretic acid, ellagic acid, etc. Among these, those which show particularly remarkable synergistic effects are 3-tert-butylcatechol, 4-tert-butylcatechol, para-tert-butylcatechol, catechin, and nordihydrogayaretic acid. The weight specific gravity of the catechol derivative used is preferably 0.1 to 5.0 based on 1 part of the phosphorous acid ester. Another substance that synergistically exhibits a blood coagulation promoting effect when used in combination with the phosphite is p,p'-isopropylidene diphenol.
This is a substance commercialized as bisphenol A, and has been used as a raw material for producing epoxy resins, but it was not known to have a blood coagulation promoting effect. The weight ratio of p,p'-isopropylidene diphenol to 1 part of the phosphite is preferably 0.1 to 5.0. According to the blood test container of the present invention, blood coagulation factors are activated rapidly, the time required for blood coagulation is significantly shortened, and serum and blood clots can be easily separated, and blood coagulation factors can be rapidly activated. The problem of contamination with residual fibrin and blood clot components has also been resolved.
Furthermore, as a result of sufficient contraction of the blood clot components, the yield of serum can be significantly increased. Therefore, the blood test container of the present invention can be suitably used for 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 1.5 parts by weight of tris(monononylphenyl) phosphite per 100 parts by weight of polypropylene was injection molded, and the outer diameter was 17 m/m and the inner diameter was 15 m.
A blood test container with a height of 110 m/m and a height of 110 m/m 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 3 A molding material having a composition in which 2.0 parts by weight of tris(dinonylphenyl) phosphite was used instead of 1.5 parts by weight of tris(monononylphenyl) phosphite in Example 1 (Example 2), tris(monononylphenyl) ) Blood test containers were obtained in the same manner as in Example 1 from the molding material (Example 3) using 2.0 parts by weight of diphenyldecyl phosphite instead of 1.5 parts by weight of phosphite. Next, using this blood test container, Example 1
Blood coagulability, serum separation status, and serum yield were evaluated in the same manner as above. The results are shown in the columns of Examples 2 and 3 in Table 1. Examples 4 to 6 Per 100 parts by weight of styrene-butadiene copolymer,
Molding material containing 1.5 parts by weight of tris(dinonylphenyl) phosphite and 0.7 parts by weight of 2,2',4,4'-tetrahydrokidibenzophenone (Example 4), styrene-butadiene copolymer 100
Molding material containing 1.5 parts by weight of tris(dinonylphenyl) phosphite and 0.7 parts by weight of 4-tert-butylcatechol (Example 5), per 100 parts by weight of styrene-butadiene copolymer, tris(dinonylphenyl) Blood test containers were obtained in the same manner as in Example 1 using a molding material (Example 6) having a composition containing 1.5 parts by weight of phosphite and 0.7 parts by weight of p,p'-isopropylidene diphenol. Next, using this blood test container, Example 1
Blood coagulability, serum separation status, and serum yield were evaluated in the same manner as above. The results are shown in the columns of Examples 4 to 6 in Table 1, and a remarkable synergistic effect in promoting blood coagulation was observed, as well as an extremely good serum separation condition. 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 Example 1, but the blood coagulation time was extremely long and the serum separation state was also poor. 【table】

Claims (1)

[Claims] 1. The inner wall surface forming material has the following formula: (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , R ₃ is a phenyl group,
Alternatively, the phenyl group is an alkylphenyl group in which 1 to 3 hydrogen atoms are substituted with a nonyl group or an octyl group, and the others are decyl groups. ) A blood test container characterized by containing a phosphite ester represented by: 2 For the inner wall surface forming material, the formula (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , R ₃ is a phenyl group,
Alternatively, the phenyl group is an alkylphenyl group in which 1 to 3 hydrogen atoms are substituted with a nonyl group or an octyl group, and the others are decyl groups. ) 1 part by weight of a phosphite ester represented by
A container for blood testing, characterized in that 2',4,4'-tetrahydroxybenzophenone (0.1 to 3.0 parts by weight) is present. 3 Inner wall surface forming material: Formula (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , R ₃ is a phenyl group,
Alternatively, the phenyl group is an alkylphenyl group in which 1 to 3 hydrogen atoms are substituted with a nonyl group or an octyl group, and the others are decyl groups. ) 1 part by weight of a phosphite ester represented by
A blood test characterized by the presence of 0.1 to 5.0 parts by weight of a catechol derivative selected from tertiary butylcatechol, 4-tertiarybutylcatechol, paratertiarybutylcatechol, catechin, and nordihydrogayaretic acid. container. 4 For the inner wall surface forming material, the formula (In the above formula, R ₁ , R ₂ , and R ₃ are all phenyl groups, or alkylphenyl groups in which 1 to 3 hydrogen atoms of the phenyl group are substituted with nonyl groups or octyl groups. , one or two of R ₁ , R ₂ , and R ₃ is a phenyl group, or an alkyl phenyl group in which 1 to 3 hydrogen atoms of the phenyl group are substituted with a nonyl group or an octyl group, and others is a decyl group) and 1 part by weight of a phosphite represented by p,
A container for blood testing, characterized in that 0.1 to 5.0 parts by weight of p'-isopropylidene diphenol is present.