JP2010236926A - Reagent storage vessel for clinical inspection - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an inexpensive reagent storage vessel for clinical inspection that can form the vessel easily, perform freeze drying treatment, and store reagents in reagent storage containers used for an automated analyzer for clinical inspection. <P>SOLUTION: The reagent storage container for clinical inspection stores reagents for clinical inspection and is used for the automated analyzer for clinical inspection. The reagent storage container for clinical inspection is obtained by forming a cycloolefin copolymer integrally and can be applied to freeze drying treatment. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a reagent container for clinical testing used in an automatic analyzer for clinical testing.

As an automatic analyzer for clinical tests for analyzing blood collected from a living body, an automatic blood coagulation analyzer, an immune automatic analyzer, a biochemical automatic analyzer, and the like are known. In these automatic analyzers for clinical examinations, by installing a reagent container containing a reagent for a predetermined examination item in the reagent installation section, it is possible to automatically analyze a sample using the reagent. As reagent containers used in such an automatic analyzer, there are various types of reagent containers such as a flat bottom reagent container shown in FIG. 1 of Patent Document 1 and an automatic measurement container shown in FIG. 2 of Patent Document 2. in use. In the case of producing reagent containers of various shapes, resin-made ones are preferable in consideration of cost and ease of molding. Patent Document 2 includes polyethylene, polypropylene, polymethylpentene, polybutene, crystalline polybutadiene, polyphenylene sulfide, chlorinated polyether, cyclic polyolefin, polyethylene terephthalate, and the like as resins for forming such a container. Yes.
The technique described in Patent Document 2 is a technique that aims to provide a container that is excellent in light transmittance and excellent in storage stability of a liquid reagent. In order to solve this technical problem, in the examples, a resin container using polypropylene is described.
However, in the case of a freeze-dried reagent, it is manufactured by putting a target reagent in a reagent container, freezing at a low temperature of −40 ° C. to −50 ° C., drying after evacuation. For this reason, a polypropylene reagent container does not have sufficient strength against temperature changes and pressure changes associated with the freeze-drying process. Under such circumstances, glass reagent containers are generally used as reagent containers for freeze-dried reagents.
On the other hand, the plasma reagent used as a calibrator sample and control sample in the blood coagulation automatic analyzer is a lyophilized reagent. Since the blood coagulation factor is activated by the contact, the plasma reagent cannot be stored in the glass reagent container as it is. For this reason, as a reagent container for a plasma reagent, a glass reagent container in which the inner wall of the container is treated with siliconization is generally used. However, this reagent container has a problem that the cost for performing the siliconization process is high. Further, if the siliconization process is not uniform, a difference between containers is generated and an accurate inspection is hindered. Therefore, it is necessary to perform quality control of the reagent container.

JP 2000-46624 A JP 2004-251638 A

The present invention has been made in view of the circumstances as described above. The purpose of the present invention is to form a container in a reagent container used in an automatic analyzer for clinical testing, and to perform a freeze-drying process. An object of the present invention is to provide an inexpensive reagent storage container for clinical testing that can store a reagent.

  In view of the above problems, the present invention is a clinical test reagent storage container for storing a clinical test reagent and used in an automatic clinical test analyzer, which is obtained by integrally forming a cycloolefin copolymer and freeze-dried. The present invention provides a reagent container for clinical testing, which is applicable to processing.

  According to the clinical test reagent container of the present invention, it is possible to provide a clinical test reagent storage container that can be molded easily, can be freeze-dried, and can store reagents at low cost. .

It is a perspective view which shows the reagent storage container 1 for a clinical test which concerns on one Embodiment of this invention. FIG. 2 is a cross-sectional view including a central axis A-A ′ of the container body 2 of FIG. 1. It is the table | surface which showed the result of having performed the difference test between containers with the container made from COC. It is the table | surface which showed the result of having performed the container difference test of the glass containers which performed the siliconization process. It is a graph which shows the result of having measured prothrombin time as a storage stability test. It is a graph which shows the result of having measured partial thromboplastin time as a storage stability test. It is a graph which shows the result of having measured the fibrin density | concentration as a storage stability test. It is a graph which shows the result of having performed the thrombo test as a storage stability test. It is a graph which shows the result of having performed the hepaplastin test as a storage stability test.

  The reagent storage container for clinical tests used in this embodiment is a reagent that stores reagents for clinical tests used in automatic analyzers for clinical tests such as blood coagulation automatic analyzers, immune automatic analyzers, and biochemical automatic analyzers. Container.

The cycloolefin copolymer is an amorphous cyclic olefin resin that is a copolymer of a cyclic olefin and an olefin such as ethylene. Cyclic olefins include polycyclic cyclic olefins and monocyclic cyclic olefins. Examples of polycyclic cyclic olefins include norbornene, methylnorbornene, dimethylnorbornene, ethylnorbornene, ethylidenenorbornene, butylnorbornene, and dicyclohexane. Examples include pentadiene, dihydrodicyclopentadiene, methyldicyclopentadiene, dimethyldicyclopentadiene, tetracyclododecene, methyltetracyclododecene, dimethylcyclotetradodecene, tricyclopentadiene, tetracyclopentadiene, and the like. Examples of the cyclic olefin include cyclobutene, cyclopentene, cyclooctene, cyclooctadiene, cyclooctatriene, cyclododecatriene and the like.
The cycloolefin copolymer in the present embodiment is not particularly limited as long as it is a cyclic olefin resin having sufficient strength against temperature change and pressure change accompanying freeze-drying treatment. A resin made of a copolymer of ethylene and norbornene or a copolymer of ethylene and tetracyclododecene is preferable. The copolymer of ethylene and norbornene is “TOPAS (registered trademark): manufactured by Polyplastics”, and the copolymer of ethylene and tetracyclododecene is “APEL (registered trademark): manufactured by Mitsui Chemicals, Inc.” Commercially available.

In the automatic analyzer, the shape of the reagent container used in the present embodiment can be formed in accordance with the shape of the reagent installing portion where the reagent container is installed and the amount of reagent used.
For example, the reagent container shown in FIG.1 and FIG.2 is mentioned. FIG. 1 is a perspective view of a clinical test reagent storage container 1 according to an embodiment of the present invention, and FIG. 2 is a cross-sectional view including a central axis AA ′ of the container body 2 of FIG. The clinical test reagent storage container 1 includes a container body 2 and a lid 3. The container body 2 has a cylindrical appearance having an opening 4 on the upper end side and a bottom 5 on the lower end side. The lid 3 is screwed into the opening 4 to close the opening 4 of the container body 2. The inner surface of the bottom 5 has a flat bottom inner bottom surface 5a.

  As a method for integrally molding the container body 2, injection blow molding, which can be molded into various shapes, is preferable.

  The reagent for clinical examination in the present embodiment is not particularly limited as long as it is a reagent used in an automatic analyzer for clinical examination. For example, a predetermined reagent used in an automatic blood coagulation analyzer, an immune automatic analyzer, and a biochemical automatic analyzer. The inspection reagent of the inspection item is mentioned.

The predetermined test item indicates an item that is analyzed by the clinical analyzer automatic analyzer and serves as a diagnostic index. Specifically, in blood coagulation tests, from basic items such as PT (prothrombin time), APTT (activated partial thromboplastin time), fibrinogen, etc., complex factors such as TTO, HPT, synthetic substrate method, ATIII, PLC, immune ratio There are various inspection items such as FDP and Ddimer by the turbidity method.
When measuring these predetermined inspection items, a reagent corresponding to the inspection item is used. For example, in the case of a blood coagulation test reagent, thrombocheck PT plus (manufactured by Sysmex) for PT measurement, thrombocheck APTT-SLA (manufactured by Sysmex) for APTT measurement, thrombocheck Fib (manufactured by Sysmex) for fibrin concentration measurement, In the complex factor measurement, a complex factor T “Kokusai” (manufactured by Sysmex Corporation) or the like is used.

Further, the reagent for clinical examination includes a calibrator sample and a control sample.
The calibrator sample is a sample used for calibration of an automatic analyzer for clinical examination. For example, in a blood coagulation automatic analyzer, human plasma is used as a calibrator sample, and specifically, Coagtrol N (manufactured by Sysmex Corporation) and the like can be mentioned. The human plasma is easily stored by being freeze-dried, and is dissolved in purified water before use.

  The control sample is a sample used as a standard when measuring an inspection item. For example, in an automatic blood coagulation analyzer, human plasma is used as a control sample, specifically, Coagtrol IX / IIX (manufactured by Sysmex Corporation). This human plasma has been lyophilized in the same manner as the calibrator plasma.

The reagent to be freeze-dried is manufactured by placing the target reagent in a container, freezing at a low temperature of −40 ° C. to −50 ° C., drying after evacuation. For this reason, the reagent storage container for clinical examinations needs to have sufficient strength against the temperature change and pressure change accompanying the freeze-drying process. Therefore, a glass reagent container is generally used. However, the plasma reagent containing a blood coagulation factor such as human plasma activates the blood coagulation factor when the blood coagulation factor comes into contact with a solid phase having a negative charge such as glass. For this reason, when using a glass container, it is necessary to siliconize the inner surface of the container. The reagent container used in the present embodiment is particularly suitable as a container for storing a reagent containing such a blood coagulation factor because the blood coagulation factor is not activated even if the plasma reagent is stored as it is.
Hereinafter, in one embodiment of the reagent container for clinical examination of the present invention, an example is shown in which a stability test and a difference test between containers are performed on a plasma reagent containing a blood coagulation factor when lyophilization is performed.

  In the following examples, results of a container-to-container difference test and a stability test of a reagent container molded with a cycloolefin copolymer (hereinafter referred to as COC) using human plasma will be described.

Example 1 : Difference test between containers molded with COC A container made of COC was prepared by injection blow molding using a copolymer of ethylene and norbornene (TOPAS (registered trademark): manufactured by Polyplastics Co., Ltd.). . 1 mL of human plasma was placed in this COC container, and the opening of the COC container was half-capped.
Next, the lyophilization of the plasma stored in the COC container was performed. Freeze-drying was frozen at about -70 ° C to -10 ° C, and then dried under high vacuum. The temperature during drying was about -40 ° C to 4 ° C. After the freeze-drying process, the opening of the COC container was closed.
In the COC container after the freeze-drying treatment, cracks and deformation due to strength reduction, and white turbidity due to transparency reduction were not observed.

〔Test method〕
A container-to-container difference test was performed using lyophilized human plasma.
The inter-container difference test was performed by measuring the test items of prothrombin time, activated partial thromboplastin time, fibrin concentration time, thrombotest and hepaplastin test. Blood coagulation measuring device Coaglex (manufactured by Sysmex Corporation) is used as a measuring device, and thrombocheck PT, thrombocheck APTT, thrombocheck Fib, complex factor T “Kokusai”, complex factor H “Kokusai” (Sysmex) as a measuring reagent 20 samples were measured for each test item according to the instruction manual of the measuring apparatus.
An average value (AVG.) Standard deviation (SD) coefficient of variation (CV) was calculated from the results of measuring 20 samples in each test item.

Comparative Example 1
The COC container of Example 1 was measured using the same method as in Example 1 except that a glass container subjected to siliconization treatment was used.

Results The results obtained in Example 1 and Comparative Example 1 are shown in FIGS. Comparing the results obtained in Example 1 and Comparative Example 1, the CV value (%) of the COC container was smaller than that of the glass container in each inspection item. For this reason, it can be seen that the COC container has less difference between the containers than the glass container. Therefore, it was shown that the COC container can be used at least as much as the glass container.

Example 2 : Stability test at 2-8 ° C. of human plasma contained in a container molded with COC.
A COC container was prepared by injection blow molding using a copolymer of ethylene and norbornene (TOPAS (registered trademark): manufactured by Polyplastics Co., Ltd.). 1 mL of human plasma was placed in this COC container, and the opening of the COC container was half-capped.
Next, the lyophilization of the plasma stored in the COC container was performed. Freeze-drying was frozen at about -70 ° C to -10 ° C, and then dried under high vacuum. The temperature during drying was about -40 ° C to 4 ° C. After the freeze-drying process, the opening of the COC container was closed.
In the COC container after the freeze-drying treatment, cracks and deformation due to strength reduction, and white turbidity due to transparency reduction were not observed.

〔Test method〕
Lyophilized human plasma was stored at 2-8 ° C. for 0, 30, 60, 90, 120, 180 days, and stability tests were performed using human plasma after storage for each period.
For the stability test, prothrombin time measurement, activated partial thromboplastin time measurement, fibrin concentration time measurement, thrombotest and hepaplastin test were performed. A blood coagulation measuring device Coaglex (manufactured by Sysmex) is used as a measuring device for performing each test, and thrombocheck PT, thrombocheck APTT, thrombocheck Fib, complex factor T “Kokusai”, complex factor Using H “Kokusai” (manufactured by Sysmex Corporation), the above-mentioned inspection items were measured according to the instruction manual of the above-described measuring apparatus.

Comparative Example 2
The measurement was carried out using the same method as in the above example, except that a glass container subjected to siliconization treatment was used instead of the COC container of Example 2.

Results The results obtained in Example 2 and Comparative Example 2 are shown in FIGS. 5 to 9 are graphs showing the measurement results of plasma stored for each day for each test item when the measurement result of plasma stored on day 0 is taken as 100%.
When Example 2 and Comparative Example 2 were compared, in FIGS. 5 to 9, in storage stability, there was almost no difference in long-term stability between the glass container subjected to the siliconization treatment and the COC container. . From this, it was shown that the COC container can be used in the same manner as a conventionally used glass container.

Claims (9)

A clinical test reagent storage container for storing clinical test reagents and used in an automatic analyzer for clinical tests,
Obtained by integrally molding a cycloolefin copolymer,
A reagent storage container for clinical testing, which is applicable to freeze-drying processing. The reagent storage container for a clinical test according to claim 1, wherein the cycloolefin copolymer is a copolymer of ethylene and norbornene or tetracyclododecene. The reagent container for clinical examination according to claim 1 or 2, wherein the reagent for clinical examination is a calibrator sample or a control sample of an automatic analyzer for clinical examination. The reagent container for clinical examination according to claim 1 or 2, wherein the reagent for clinical examination is an examination reagent for a predetermined examination item. The clinical test reagent storage container according to claim 1 or 2, wherein the clinical test automatic analyzer is a blood coagulation test automatic analyzer, and the clinical test reagent is a blood coagulation test reagent. The said container is a reagent storage container for clinical tests in any one of Claims 1-5 shape | molded by the injection blow system. A container for storing a blood coagulation test reagent,
A reagent container for blood coagulation test, which is integrally formed of a cycloolefin copolymer. The reagent container for blood coagulation test according to claim 7, wherein the reagent for blood coagulation test is calibrator plasma or control plasma of an automatic analyzer for blood coagulation test. The reagent storage container for blood coagulation test according to claim 8, wherein the reagent for blood coagulation test is any one of a prothrombin time measurement reagent, an activated partial thromboplastin time measurement reagent, a fibrin concentration measurement reagent or a complex factor measurement reagent.

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