JPH09222427A - Blood inspection container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a blood inspection container which comprises a serum (blood plasma) separation material which can be frozen and preserved. SOLUTION: A container is composed of an outer tube 1 as a bottomed tubular container which has an opening part at one end, of an inner tube 2 which is coupled to the inner wall of the outer tube 1 and which forms a noncontact nesting structure with the outer tube 1, of a serum (blood plasma) separation material which is installed inside the inner tube 2 and of an airtight stopper body. Then, the inner tube 2 is the bottomed tubular container which has the opening part at one end and which has a pleat-shaped structure on the peripheral edge of the opening part, and the magnitude of its rigidity is less than the magnitude of the rigidity of the outer tube 1. The serum (blood plasma) separation material is inert to blood, its specific gravity is at 1.03 or higher, and the magnitude of its rigidity is more than the magnitude of the rigidity of the inner tube 2. The blood (serum plasma) separation material is slid on the inner wall surface of the inner tube 2 in a centrifugal separation operation.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a blood test container.

[0002]

2. Description of the Related Art Blood tests such as hematology, blood chemistry, and immunoserologic tests have been remarkably mechanized in recent years, and have greatly contributed to rapid diagnosis of diseases. For example, blood sampling has been changed from a syringe method to a vacuum blood sampling method, standardization of specimens, protection of test workers from specimens with infectiousness and labor saving have been promoted, and the time required for blood collection has been shortened. ing. Furthermore, if an appropriate pretreatment is performed on the collected blood sample, rapid examination is possible, so outpatients should consult a doctor based on the examination result for a short time at the place of visit. You can get it in no time.

The collected blood sample is discarded immediately after being subjected to the test, but it is usually stored by refrigeration or freezing in preparation for remeasurement at a later date. JP-B-63-55670, JP-A-5-107245, JP-A-4-34
No. 0465 discloses a paste-like serum separation material having thixotropic properties, which can be used for refrigerated storage.
Each is disclosed. These serum separation materials have non-fluidity under hydrostatic pressure, but show fluidity when subjected to shearing force during centrifugation, and move due to the difference in specific gravity to separate serum and blood clots. Is.

If these serum separating materials are capable of reliably separating a sample into a serum layer and a blood clot layer, various components in the blood clot do not transfer to the serum layer, and the centrifuged sample remains as it is. It can be stored refrigerated in the state of.

However, the mechanical strength of these serum separation materials is not sufficient. For example, when a sample is frozen and stored after centrifugation, the content ratio of various components in serum and the content ratio of various components in blood clot are different from each other. Since the freezing rate of serum and the freezing rate of blood clots are different, the pressure from the serum layer and the pressure from the blood clot layer accompanying the growth of ice crystals did not act uniformly on the serum separation material, forming a septum layer. There is a problem that the serum separating material is greatly deformed.

US Pat. No. 3,779,383 discloses
As a serum separating material replacing the above-mentioned thixotropic pasty serum separating material, a disc-shaped serum separating material made of an elastomer molded product and a vacuum blood collection tube using this serum separating material are disclosed. This vacuum blood collection tube has a serum separating material provided in the vicinity of the stopper, and at the time of blood collection, a blood collecting needle penetrates the stopper and the serum separating material to introduce blood into the blood collecting tube and centrifuge it. At times, this serum separating material moves toward the bottom of the vacuum blood collection tube while sliding on the inner wall surface of the blood collection tube.

The serum separating material used in the above-mentioned vacuum blood collection tube is internally provided in the vacuum blood collection tube by a force equal to or more than the force applied when penetrating the blood collection needle. Therefore, the sliding frictional force applied to the serum separation material during centrifugation becomes considerably large, and in particular, the movement of the serum separation material under normal centrifugation conditions may stop in the middle of reaching the bottom of the vacuum blood collection tube. In some cases, the movement of serum that accompanies the movement of the serum separating material does not proceed smoothly from the lower part to the upper part of the serum separating material.

In Japanese Utility Model Publication No. 53-5431, a filter is installed on the top surface of the serum separating material so that serum can pass but blood clots cannot pass, so that serum can smoothly move. A vacuum blood collection tube is disclosed.

Japanese Utility Model Laid-Open No. 60-83959 and Japanese Patent Laid-Open No.
JP-A-2-247249 discloses a serum separating material in which a special valve structure is incorporated on the top surface or the bottom surface of the serum separating material so that the movement of serum proceeds smoothly.

These filters and valve structures are excellent in mechanical strength. However, since the serum passage holes of these filters and valve structures are good passages for electrolytes, enzyme proteins, etc. in blood clots, the frozen sample after centrifugation is thawed. , For example, similar to hemolysis of serum after thawing, problems such as migration of various components such as electrolytes and enzymes in blood clots into serum occur, and blood tests using such filters and valve structures The container is not suitable for cryopreservation.

The most desirable preservation of blood specimens is by freezing. However, at present, there is no provision of a serum separating material capable of cryopreservation that does not require transfer of serum.

[0012]

SUMMARY OF THE INVENTION In view of the above, an object of the present invention is to provide a blood test container having a serum (plasma) separating material that can be cryopreserved.

[0013]

The gist of a blood test container according to claim 1 (hereinafter referred to as the present invention 1) is an outer cylinder which is a bottomed tubular container having an opening at one end, and the outer cylinder. An inner cylinder that is locked to the inner wall to form a nested structure that is not in contact with the outer cylinder, and a serum (plasma) separating material provided in the inner cylinder,
A blood test container comprising an airtight stopper,
The inner cylinder is a bottomed tubular container having an opening at one end and having a pleated structure at the periphery of the opening, and the rigidity of the outer cylinder is the same as the rigidity of the outer cylinder. The serum (plasma) separating material is inert to blood, has a specific gravity of 1.03 or more, and has a rigidity of the inner cylinder. Or more, and the serum (plasma) separating material slides on the inner wall surface of the inner cylinder during centrifugation.

The blood test container according to claim 2 (hereinafter, referred to as the present invention 2) is at least of the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, and the internal space formed by the inner cylinder. One is the blood test container according to claim 1, wherein the blood coagulation promoting component and / or the blood component adhesion preventing component or the blood anticoagulant component is independently present.

FIG. 1 is a diagram showing an example of the nested structure. 1 represents an outer cylinder. 2 represents an inner cylinder. Invention 1
The inner cylinder used in (1) is locked to the inner wall of the outer cylinder to form a nested structure that is not in contact with the outer cylinder. The inner cylinder may be in contact with the outer cylinder at the edge of the opening and in contact with the outer cylinder at the bottom as shown in the figure.

The material used for the outer cylinder is not particularly limited, and examples thereof include hard glass, soft glass, borosilicate glass, and plastic. Examples of the plastics include polyethylene terephthalate-based and polyacrylonitrile-based thermoplastic resins, and polyethylene, polypropylene, poly-4-methylpentene-1, disclosed in Japanese Patent Publication No. 1-26504. Thermoplastic resins such as polystyrene and polymethylmethacrylate; thermosetting resins such as unsaturated polyester resins, epoxy resins and epoxy-acrylate resins; modified natural resins such as cellulose acetate, cellulose propionate, cellulose acetate butyrate, ethyl cellulose and ethyl chitin Can be mentioned.

The inner cylinder used in the first aspect of the present invention has a rigidity smaller than that of the outer cylinder.
The rigidity of the inner cylinder may be defined by the Young's modulus of the material used or a mechanical property value corresponding thereto, or may be defined by the deformation rate of the structure.

The material used for the inner cylinder is not particularly limited as long as it is less than the Young's modulus of the material used for the outer cylinder or a mechanical property value according to the Young's modulus. In addition to those used in, crosslinked elastomers, thermoplastic elastomers and the like can be mentioned.

The method of increasing the deformation rate of the structure of the inner cylinder is not particularly limited. For example, one having a thickness smaller than that of the outer cylinder, one having a shallow cut on the outer surface, etc. Is mentioned. In the present invention 1,
Conversely, a reinforcing rib may be provided on the wall surface of the outer cylinder so that the rigidity of the inner cylinder is less than the rigidity of the outer cylinder.

The serum (plasma) separating material used in the first aspect of the present invention is inert to blood and has a specific gravity of 1.03 or more, and the rigidity is the rigidity of the inner cylinder. Is more than the size of. The serum (plasma) separation material is
It has a function of separating serum and, in some cases, a function of separating plasma.

Since the serum (plasma) separating material moves toward the bottom while sliding on the inner wall surface of the inner cylinder during centrifugal separation, it separates the sample into serum and blood clot, and therefore its specific gravity. Is limited to the above range. Preferably 1.05
That is all.

The magnitude of rigidity of the serum (plasma) separating material may be defined by the Young's modulus of the material used or a mechanical characteristic value corresponding thereto, or by the deformation rate of the structure. The material used for the serum (plasma) separating material is not particularly limited as long as it is equal to or higher than the Young's modulus of the material used for the inner cylinder or a mechanical characteristic value corresponding thereto, and, for example, Examples include those used in cylinders.

FIG. 2 is a diagram showing a perspective view, a lateral view and a top view of an example of the serum (plasma) separating material. FIG. 3 is a diagram showing an example of the pleated structure 3 of the inner cylinder. The shape of the folds and the number of folds forming the fold-like structure are not particularly limited.

The above-mentioned serum (plasma) separating material is internally provided in the above-mentioned inner cylinder, and when the above-mentioned serum (plasma) separating material is internally provided in the pleated structure portion of the above-mentioned inner cylinder, A space is formed between the serum (plasma) separating material and the pleated structure part of the inner cylinder to connect the upper and lower inner cylinder spaces of the serum (plasma) separating material.

When a sample is introduced into the blood test container of the present invention 1, the sample is separated from the serum (plasma) separating material through a gap formed by the serum (plasma) separating material and the pleated structure part of the inner cylinder. Is introduced into the space below.

In the present invention 1, at least one of the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, and the inner space formed by the inner cylinder is independently a blood coagulation promoting component. And / or a blood component-preventing component or a blood anticoagulant component is preferably present, and this preferred form is the second aspect of the present invention.

The blood coagulation promoting component is not particularly limited, and examples thereof include known components such as inorganic powders of glass, silica, kaolin, bentonite, diatomaceous earth and the like; organic powders of ellagic acid and the like.

The component for preventing the adhesion of blood components is not particularly limited, and examples thereof include water-soluble polymer substances such as silicone oil, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol and carboxymethyl cellulose; nonionic surface active substances; polypropylene glycol. Known components can be used.

The blood anticoagulant component is not particularly limited, and examples thereof include ethylenediaminetetraacetate, citrate,
Known substances such as heparin salts and fluoride salts can be used.

The blood coagulation promoting component, the blood component adhesion preventing component, or the blood anticoagulant component is formed on the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, or the inner cylinder. There is no particular limitation on the method of allowing it to exist in the internal space, for example, the blood coagulation promoting component, the blood component anti-adhesion component, or the blood anticoagulant component is dispersed or dissolved in a medium such as water or alcohol. And spray coating, kneading into the molding resin material of the inner cylinder for molding, loading on a carrier that is chemically and physically inert to blood, and then accommodating in the inner cylinder, etc. The method of is mentioned.

A desirable example of the blood test container of the first invention is, for example, a vacuum blood collection tube. In this case, the sample collected in vacuum is treated with a dedicated blood collection needle and a holder to pass serum (plasma) through a gap formed by the pleated structure of the inner cylinder and the serum (plasma) separation material provided in the inner cylinder. ) Introduced into the space below the separating material, after waiting for solidification, it is centrifuged under normal conditions.

At the time of centrifugation, the serum (plasma) separating material is
After sliding along the inner wall surface of the inner cylinder and moving toward the bottom and passing through the pleated structure site, the sample sealed in the space below the serum (plasma) separating material is compressed. The specimen whose water pressure has increased due to the compressive force temporarily blocks the movement of the serum (plasma) separating material toward the bottom.

The rigidity of the inner cylinder used in the present invention 1 is less than the rigidity of the outer cylinder, and the rigidity of the serum (plasma) separating material is the rigidity of the inner cylinder. Because of the above, at this time, the inner cylinder expands and deforms due to the increased water pressure of the sample to form a gap with the serum (plasma) separating material.
Through this gap, the serum component of the sample moves to the space above the serum (plasma) separating material. With the movement of the serum component, the water pressure of the sample sealed in the space below the serum (plasma) separation material decreases, and the serum (plasma) separation material starts moving toward the bottom again. Through such repetition, the serum (plasma) separating material finally reaches the upper end of the clot and stops to seal the clot.

Since the blood test container of the present invention 1 is sealed by the airtight stopper, after the serum (plasma) separating material reaches the upper end of the blood clot and the serum and the blood clot are separated from each other. Does not mix due to vibration, inclination, falling, etc., and serum is stably stored. When cryopreservation is performed, the serum (plasma) separating material used in the present invention 1 is not destroyed, so that a good preservation state can be maintained.

When the specimen is refrigerated at 4 ° C., it is impossible to completely prevent the inactivation of the enzyme activity in the serum, but the blood test container of the present invention 1 can be frozen and preserved at −80 ° C. Therefore, it is possible to completely prevent the inactivation of the enzyme activity in serum.

In the blood test container of the first aspect of the present invention, the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, or the inner space formed by the inner cylinder contains a blood coagulation promoting component. In addition, since the time required for blood coagulation after blood collection can be significantly shortened, the time required for centrifugation can be shortened, and the examination work can be speeded up.

In the blood test container of the present invention 1, the inner surface of the inner cylinder, the surface of the blood serum (plasma) separating material, or the inner space formed by the inner cylinder is provided with a component for preventing adhesion of blood components. In some cases, it is possible to prevent strong adherence of blood components, especially blood clots, to the inner wall of the container, which often occurs when blood coagulation is performed rapidly. It is possible to prevent hemolysis caused by being peeled off in advance.

In the case of the blood test container of the present invention 1, the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, or the inner space formed by the inner cylinder contains blood anticoagulant components. The obtained samples are tested for coagulation function tests, emergency tests,
It can be used for various test purposes such as a blood glucose test.

A blood test container according to a third aspect of the present invention (hereinafter referred to as the present invention 3) is a bottomed tubular container having an opening at one end, and has a tapered shape whose diameter decreases from the opening end toward the bottom. An outer cylinder having an outer cylinder, an inner cylinder that is locked to the inner wall of the outer cylinder to form a nested structure that is not in contact with the outer cylinder, a serum (plasma) separating material provided in the inner cylinder, and an airtightness A blood test container comprising a stopper having an inner cylinder having openings at both ends thereof, and a cylindrical body having a pleated structure at the periphery of the opening on the opening side of the outer cylinder. A structure, which is locked to the inner wall of the outer cylinder at the edges of the both openings, and has a rigidity magnitude less than that of the outer cylinder. The plasma) separating material is inert to blood, has a specific gravity of 1.03 or more, and has a high rigidity. Is intended at least the size of the stiffness of the inner cylinder, the serum (plasma) separation material, during centrifugation resides at is to slide the inner wall surface of the inner cylinder.

The gist of the blood test container according to claim 4 (hereinafter referred to as the present invention 4) is at least the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, and the internal space formed by the inner cylinder. One is the blood test container according to claim 4, wherein a blood coagulation promoting component and / or a blood component anti-adhesion component or a blood anticoagulant component is independently present.

The present invention 3 will be described below.

FIG. 4 is a diagram showing an example of the nested structure. Reference numeral 4 represents an outer cylinder. 5 represents an inner cylinder. Invention 3
The shape of the outer cylinder used in 1. is the same as the shape of the outer cylinder of the present invention 1, except that the outer cylinder is limited to a taper shape whose diameter decreases from the opening end toward the bottom. The material used for the outer cylinder is not particularly limited, and examples thereof include those mentioned in the description of the first invention.

The inner cylinder used in the third aspect of the present invention forms a nested structure that is locked to the inner wall of the outer cylinder and is not in contact with the outer cylinder. The inner cylinder has an opening at both ends, and is a tubular structure having a pleated structure at the edge of the opening on the opening side of the outer cylinder, and as shown in the figure, the outer cylinder is Abutting the outer cylinder on the opening side on the opening side and contacting the inner wall of the outer tube on the side of the opening on the bottom side of the outer cylinder, It is locked to the inner wall of the outer cylinder.

FIG. 5 is a diagram showing an example of the pleated structure 6 of the inner cylinder. The shape of the folds and the number of folds forming the fold-like structure are not particularly limited.

The rigidity of the inner cylinder is less than the rigidity of the outer cylinder. The rigidity of the inner cylinder may be defined by the Young's modulus of the material used or a mechanical property value corresponding thereto, or may be defined by the deformation rate of the structure.

The material used for the inner cylinder is not particularly limited as long as it is less than the Young's modulus of the material used for the outer cylinder or a mechanical property value equivalent thereto, and for example, the outer cylinder is used. In addition to those used in, crosslinked elastomers, thermoplastic elastomers and the like can be mentioned.

The method of increasing the deformation rate of the structure of the inner cylinder is not particularly limited. For example, one having a thickness smaller than that of the outer cylinder, one having a shallow cut on the outer surface, etc. Is mentioned. In the present invention 3,
Conversely, a reinforcing rib may be provided on the wall surface of the outer cylinder so that the rigidity of the inner cylinder is less than the rigidity of the outer cylinder.

The length of the inner cylinder in the direction of the central axis is not particularly limited, but normally the hematocrit of a blood sample is about 50.
%, It is preferably 1/2 or more of the length of the outer cylinder in the central axis direction.

The serum (plasma) separating material used in the present invention 3 is inert to blood and has a specific gravity of 1.03 or more, and the rigidity is determined by the rigidity of the inner cylinder. Is more than the size of. The serum (plasma) separation material is
It has a function of separating serum and, in some cases, a function of separating plasma.

The serum (plasma) separating material moves toward the bottom while sliding on the inner wall surface of the inner cylinder during centrifugation to separate the sample into serum and blood clot, and therefore its specific gravity Is limited to the above range. Preferably 1.05
That is all.

The rigidity of the serum (plasma) separating material may be defined by the Young's modulus of the material used or a mechanical characteristic value corresponding thereto, or by the deformation rate of the structure. The material used for the serum (plasma) separating material is not particularly limited as long as it is equal to or higher than the Young's modulus of the material used for the inner cylinder or a mechanical characteristic value corresponding thereto, and, for example, Examples include those used in cylinders.

An example of the shape of the serum (plasma) separating material is the same as in the first embodiment.

The above-mentioned serum (plasma) separating material is provided inside the above-mentioned inner cylinder, and when the above-mentioned serum (plasma) separating material is provided inside the pleated structure part of the above-mentioned inner cylinder, A space is formed between the serum (plasma) separating material and the pleated structure part of the inner cylinder to connect the upper and lower inner cylinder spaces of the serum (plasma) separating material.

When the sample is introduced into the blood test container of the third aspect of the present invention, the sample is separated from the serum (plasma) separating material through a gap formed by the serum (plasma) separating material and the pleated structure part of the inner cylinder. Is introduced into the space below.

In the present invention 3, at least one of the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, and the inner space formed by the inner cylinder is independently a blood coagulation promoting component. And / or a blood component-preventing component or a blood anticoagulant component is preferably present, and this preferred form is the present invention 4.

The above-mentioned blood coagulation promoting component, blood component anti-adhesion component and blood anticoagulant component are not particularly limited, and examples thereof include those mentioned in the description of the present invention 1.

The blood coagulation promoting component, the blood component adhesion preventing component, or the blood anticoagulant component is formed on the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, or the inner cylinder. The method of making the internal space exist is not particularly limited, and is, for example, the same as the method described in the description of the present invention 1.

A desirable example of the blood test container of the third aspect of the present invention is, for example, a vacuum blood collection tube. In this case, the sample collected in vacuum is treated with a dedicated blood collection needle and a holder to pass serum (plasma) through a gap formed by the pleated structure of the inner cylinder and the serum (plasma) separation material provided in the inner cylinder. ) Introduced into the space below the separating material, after waiting for solidification, it is centrifuged under normal conditions.

During centrifugation, the serum (plasma) separating material is
After sliding along the inner wall surface of the inner cylinder and moving toward the bottom and passing through the pleated structure site, the sample sealed in the space below the serum (plasma) separating material is compressed. The specimen whose water pressure has increased due to the compressive force temporarily blocks the movement of the serum (plasma) separating material toward the bottom.

The rigidity of the inner cylinder used in the present invention 3 is less than the rigidity of the outer cylinder, and the rigidity of the serum (plasma) separating material is the rigidity of the inner cylinder. Because of the above, at this time, the inner cylinder expands and deforms due to the increased water pressure of the sample to form a gap with the serum (plasma) separating material.
Through this gap, the serum component of the sample moves to the space above the serum (plasma) separating material. With the movement of the serum component, the water pressure of the sample sealed in the space below the serum (plasma) separation material decreases, and the serum (plasma) separation material starts moving toward the bottom again. Through such repetition, the serum (plasma) separating material finally reaches the upper end of the clot and stops to seal the clot.

Since the blood test container of the present invention 3 is sealed by the airtight stopper, after the serum (plasma) separating material reaches the upper end of the blood clot and the serum and the blood clot are separated from each other. Does not mix due to vibration, inclination, falling, etc., and serum is stably stored. Further, when cryopreservation is carried out, the serum (plasma) separating material used in the present invention 3 is not destroyed, so that a good preservation state can be maintained.

When the sample is refrigerated and stored at 4 ° C., inactivation of enzyme activity in serum cannot be completely prevented, but the blood test container of the present invention 3 can be frozen and stored at −80 ° C. Therefore, it is possible to completely prevent the inactivation of the enzyme activity in serum.

In the blood test container of the third aspect of the present invention, the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, or the inner space formed by the inner cylinder is a blood coagulation promoting component, a blood component adhesion preventing component, or The effects in the case where the blood anticoagulant component is present are the same as the effects described in the explanation of the present invention 1, respectively.

[0064]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 Preparation of Outer Cylinder, Inner Cylinder, and Serum (Plasma) Separation Material An outer cylinder shown in FIG. 6 was injection-molded using polymethylmethacrylate (Young's modulus 300 kg / mm ² , specific gravity 1.2). Created by. The inner cylinder shown in FIG. 7 was formed by blow molding using low density polyethylene (Young's modulus 20 kg / mm ² , specific gravity 0.92). The serum (plasma) separation material shown in FIG. 8 was prepared by injection molding using polystyrene (Young's modulus 350 kg / mm ² ) having a specific gravity of 1.04.

Assembly of blood test container The inner cylinder was press-fitted and fixed to the outer cylinder, and the serum (plasma) separating material was inserted and installed inside the pleated portion near the open end of the inner cylinder so that the blood collection volume was 6 ml. The inside was depressurized and sealed with a stopper made of isoprene-isobutylene rubber. Three such blood test containers were prepared.

Evaluation Human fresh blood was vacuum-collected in three blood test containers. About 2
After allowing to stand at room temperature of 3 ° C for 1 hour to coagulate blood,
Centrifugation was performed at 4000 rpm for 10 minutes. After visually observing the serum separability by the serum (plasma) separating material, immediately after that, half of the serum was dispensed into a clean hard glass test tube, and frozen and stored at −20 ° C. as a sample for initial value.

The remaining half amount of serum was refrigerated at 4 ° C., −20 ° C.,
It was frozen at 80 ° C. and stored for 24 hours. After returning to room temperature after a predetermined time, the separability was again visually observed, and the serum was dispensed into a clean hard glass test tube and used as a specimen stored for 24 hours.
K and LDH were measured for a total of 6 samples. Table 1 shows the results
It was shown to.

As is clear from Table 1, the separability after centrifugation was good, and serum and blood clot were clearly blocked by the serum (plasma) separating material. Also, refrigerated at 4 ° C, -2
There was no change in the separability before and after storage under both conditions of 0 ° C. and -80 ° C. freezing, and K and LDH were kept stable in comparison with the initial values. Furthermore, it was found that the K and LDH obtained in the hard glass test tube of Comparative Example 2 were comparable to each other, and there was no adverse effect on the inspection value.

Comparative Example 1 1.2 g of a thixotropic pasty serum (plasma) separating material (ESCOLECT, manufactured by Sekisui Chemical Co., Ltd.) was housed in the bottom of the same outer cylinder as used in Example 1, and the amount of blood collected. Was reduced to 6 ml and the inside of the container was decompressed and sealed with a stopper made of isoprene-isobutylene rubber. Collection of human fresh blood, evaluation of separability, evaluation of preservability for 24 hours, etc. were carried out in the same manner as in Example 1. The results are shown in Table 1.

As is clear from Table 1, the separability immediately after centrifugation and after refrigerated storage at 4 ° C. was good, but −
The partition walls were destroyed by freezing storage at 20 ° C and -80 ° C, and strong hemolysis occurred when the temperature was returned to room temperature. Moreover, although K and LDH were kept stable at 4 ° C. refrigeration, −20
At 0 ° C and -80 ° C, an abnormally high value was shown due to strong hemolysis, which was significantly different from the initial value.

Comparative Example 2 A clean hard glass test tube with a capacity of 10 ml was used to collect blood of 6 m.
The inside of the container was depressurized to 1 and sealed with a stopper made of isoprene isobutylene rubber. 6 ml of human fresh blood was vacuum-collected, left at room temperature of about 23 ° C. for 1 hour to coagulate the blood, and then centrifuged at 4000 rpm for 10 minutes. Immediately, the whole amount of serum was sampled in a clean hard glass test tube, frozen and stored as a sample for initial value at −20 ° C. for 24 hours, and K and LDH were measured. The results are shown in Table 1.

[0073]

[Table 1]

Example 2 Confirmation of effects of blood coagulation promoting component and anti-adhesion component of blood component Assembly of blood test container Silica fine powder having an average particle diameter of 5 μm (reagent grade, manufactured by Wako Pure Chemical Industries, Ltd.) and silicone nonionic interface Activator (S
H3749, manufactured by Torre Dow Corning) 0.5 each
A suspension prepared in Freon 11/12 mixed medium containing 10 v / v% of isopropyl alcohol at a ratio of w / v% and 0.1 w / v% was prepared. Regarding the inspection container having the same configuration as that used in Example 1, about 200 μ of the suspension was placed in the inner cylinder.
Spray coating and air drying. On the other hand, the serum (plasma) separating material was immersed in a 0.1 w / v% methyl alcohol solution of a silicone nonionic surfactant (SH3749, manufactured by Toray Dow Corning) and naturally dried. The inner cylinder is press-fitted and fixed to the outer cylinder, the serum (plasma) separation material is inserted into the pleated portion near the open end of the inner cylinder, and the inside of the container is decompressed so that the blood collection amount is 6 ml. Isoprene isobutylene rubber It was sealed with a stopper made of.

Evaluation Human fresh blood was vacuum-collected in the blood test container. About 23 ℃
When the blood ceased to flow and the serum began to exude, the coagulation time was measured to be about 20
Minutes. Subsequently, centrifugation was performed at 4000 rpm for 10 minutes. After visually observing the separability of the serum by the serum (plasma) separating material, immediately thereafter, half of the serum was dispensed into a clean hard glass test tube and frozen and stored at −20 ° C. as an initial value sample. The remaining half amount of serum was frozen and stored at −20 ° C. for 24 hours while being kept in the test container. After returning to room temperature after a predetermined time, the separability was again visually observed, and the serum was dispensed into a clean hard glass test tube and used as a specimen stored for 24 hours. K and LDH were measured for two samples in total. The results are shown in Table 2. The blood coagulation time was shortened to about 1/3 as compared with the case of not accommodating the blood coagulation accelerating component of Example 1, and as is clear from Table 2, the separability after centrifugation was also good. Furthermore, it was found that there was no change in the separability before and after frozen storage at -20 ° C, K and LDH were comparable to the initial values, and there was no effect on the test values.

[0076]

[Table 2]

Example 3 Confirmation of effect of blood anticoagulant component Assembly of blood test container Heparin Na (reagent grade, Wako Pure Chemical Industries, Ltd.) and silicone nonionic surfactant (SH3749, Toray Dow Corning) 4000 IU / ml,
An aqueous solution containing 0.4 w / v% was prepared. With respect to the inspection container having the same structure as that used in Example 1, about 25 μl of the aqueous solution was spray-coated on the inner cylinder and naturally dried.
On the other hand, silicone-based nonionic surfactant (SH374
9. A serum (plasma) separating material was immersed in a 0.1 w / v% methyl alcohol solution of Toray Dow Corning Co., Ltd.) and naturally dried. The inner cylinder is press-fitted and fixed to the outer cylinder, the serum (plasma) separation material is inserted into the pleated portion near the open end of the inner cylinder, and the inside of the container is decompressed so that the blood collection amount is 6 ml. Isoprene isobutylene rubber It was sealed with a stopper made of.

Evaluation Human fresh blood was vacuum-collected in the blood test container. Mix well by inversion to dissolve heparin Na in blood, then
Centrifugation was performed at 000 rpm for 10 minutes. After visually observing the plasma separability by the serum (plasma) separating material, immediately thereafter, half of the plasma was fractionated into a clean hard glass test tube, and stored frozen at -20 ° C as an initial value sample. The remaining half volume of plasma was stored in the test container and kept at -20 ° C for 2 hours.
It was stored frozen for 4 hours. After returning to room temperature after a predetermined time, the separability was again visually observed, and the plasma was dispensed into a clean hard glass test tube to give a 24-hour storage sample.

K and LDH were measured for a total of 2 specimens. The results are shown in Table 3. As is clear from Table 3, the separability after centrifugation was also good. Furthermore, it was found that there was no change in the separability before and after frozen storage at -20 ° C, K and LDH were comparable to the initial values, and there was no effect on the test values.

Comparative Example 3 Confirmation of effect of blood anticoagulant component Heparin Na was added to a clean hard glass test tube having a capacity of 10 ml.
(Reagent grade, Wako Pure Chemical Industries, Ltd.) 4000 IU /
About 25 μl of an aqueous solution containing it in a proportion of ml was spray-coated and naturally dried. The inside of the container of the obtained test tube was decompressed so that the blood collection amount was 6 ml, and the test tube was sealed with a stopper made of isoprene isobutylene rubber. 6 ml of human fresh blood was collected in a vacuum, mixed thoroughly by inversion to dissolve heparin Na in the blood, and then centrifuged at 4000 rpm for 10 minutes. Immediately, the whole amount of plasma was collected into a clean hard glass test tube, and frozen as a sample at an initial value for 24 hours at −20 ° C.,
K and LDH were measured. The results are shown in Table 3.

[0081]

[Table 3]

Example 4 Preparation of Outer Cylinder, Inner Cylinder, and Serum (Plasma) Separating Material The outer cylinder shown in FIG. 6 was replaced with polyacetal (Young's modulus 1420).
It was prepared by injection molding using kg / mm ² and a specific gravity of 1.4). The inner cylinder shown in FIG. 7 was formed by blow molding using polypropylene (Young's modulus 120 kg / mm ² , specific gravity 0.9). The serum (plasma) separating material shown in FIG. 8 was prepared by injection molding using polyphenylene oxide (Young's modulus 270 kg / mm ² ) having a specific gravity of 1.06.

Preparation of a suspension of a blood coagulation promoting component and a blood component anti-adhesion component A fine silica powder having an average particle size of 5 μm (reagent grade, manufactured by Wako Pure Chemical Industries, Ltd.) and a silicone nonionic surfactant (S
H3749, manufactured by Torre Dow Corning) 0.5 each
Those suspended in methanol at a ratio of w / v% and 0.1 w / v% were prepared.

Preparation of Solution of Anti-adhesion Component of Blood Component A silicone nonionic surfactant (SH3749, manufactured by Toray Dow Corning) was dissolved in methanol at a ratio of 0.1 w / v% to prepare a solution.

Assembly of blood test container About 200 μl of a suspension of a blood coagulation promoting component and a blood component anti-adhesion component was spray-coated on the inner cylinder and naturally dried. A serum (plasma) separating material was spray-coated with a solution of a blood component anti-adhesion component and naturally dried. Thereafter, these were assembled in the same manner as in Example 1 to prepare a blood test container.

Evaluation Human fresh blood was vacuum-collected in the blood test container. About 23 ℃
It was allowed to stand at room temperature for about 25 hours when blood ceased to flow and serum began to exude as coagulation time.
Minutes. Then, centrifugation was performed at 5000 rpm for 10 minutes. After visually observing the separability of the serum by the serum (plasma) separating material, immediately thereafter, half of the serum was dispensed into a clean hard glass test tube and frozen and stored at −20 ° C. as an initial value sample. The remaining half amount of serum was frozen and stored at −20 ° C. for 24 hours while being kept in the test container. After returning to room temperature after a predetermined time, the separability was again visually observed, and the serum was dispensed into a clean hard glass test tube and used as a specimen stored for 24 hours. K and LDH were measured for two samples in total. The results are shown in Table 4.

The blood coagulation time was equal to or more than the value of 30 minutes in the test tube made of hard glass, which was carried out at the same time, and the separability after centrifugation was also good. Furthermore, it was found that there was no change in the separability before and after frozen storage at -20 ° C, K and LDH were comparable to the initial values, and there was no effect on the test values.

[0088]

[Table 4]

Example 5 Preparation of Outer Cylinder, Inner Cylinder, and Serum (Plasma) Separation Material The outer cylinder shown in FIG. 6 was prepared by using an acrylonitrile-styrene copolymer (Young's modulus 340 kg / mm ² , specific gravity 1.07). It was created by injection molding. The inner cylinder shown in FIG. 7 was formed by blow molding using low density polyethylene (Young's modulus 20 kg / mm ² , specific gravity 0.92). FIG.
The polystyrene (Young's modulus 350 kg / mm ² ) having a specific gravity of 1.04 was used for the serum (plasma) separation material shown in
It was created by injection molding.

Assembly of blood test container At the bottom of the outer cylinder, ethylenediaminetetraacetic acid dipotassium salt 4 m
g, after accommodating 3 mg of sodium fluoride, the inner cylinder is press-fitted and fixed to the outer cylinder, and the serum (plasma) separating material is inserted inside the pleated portion near the open end of the inner cylinder, and the blood collection amount is 2 ml Thus, the inside of the container was depressurized and sealed with a stopper made of isoprene-isobutylene rubber to prepare a blood test container.

Evaluation Human fresh blood was vacuum-collected in the blood test container. Mix well by inversion to dissolve ethylenediaminetetraacetic acid dipotassium salt and sodium fluoride in blood, and then 5000 rp
Centrifugation was performed for 10 minutes. After visually observing the plasma separability by the serum (plasma) separating material, immediately thereafter, half of the plasma was fractionated into a clean hard glass test tube, and stored frozen at -20 ° C as an initial value sample. The remaining half amount of plasma was frozen and stored at −20 ° C. for 24 hours while being kept in the test container. After returning to room temperature after a predetermined time, the separability was again visually observed, and the plasma was dispensed into a clean hard glass test tube to give a 24-hour storage sample.

Blood glucose levels were measured for a total of 2 samples. Table 5 shows the results. As is clear from Table 5, the separability after centrifugation was also good. Furthermore, it was found that there was no change in the separability before and after cryopreservation at −20 ° C., the blood glucose level was comparable to the initial value, and the test value was not affected.

[0093]

[Table 5]

Example 6 Preparation of Outer Cylinder, Inner Cylinder, and Serum (Plasma) Separation Material The outer cylinder shown in FIG.
It was prepared by injection molding using kg / mm ² and a specific gravity of 1.2). The inner cylinder shown in FIG. 9 was prepared by blow molding using an olefin-based thermoplastic elastomer (Young's modulus 1 kg / mm ² , specific gravity 1.0). The serum (plasma) separation material shown in FIG. 8 was prepared by injection molding using polystyrene (Young's modulus 350 kg / mm ² ) having a specific gravity of 1.04.

Preparation of Suspension of Blood Coagulation Promoting Component and Blood Component Anti-Adhesion Component A suspension of blood coagulation promoting component and blood component anti-adhesion component similar to Example 4 was prepared.

Preparation of Solution of Anti-Adhesion Component of Blood Component A solution of anti-adhesion component of blood component similar to that in Example 4 was prepared.

Assembly of blood test container About 200 μl of a suspension of a blood coagulation promoting component and a blood component anti-adhesion component was spray-coated on the inner cylinder and naturally dried. A serum (plasma) separating material was spray-coated with a solution of a blood component anti-adhesion component and naturally dried. Thereafter, these were assembled in the same manner as in Example 1 to prepare a blood test container.

Evaluation Human fresh blood was vacuum-collected in the blood test container. About 23 ℃
It was allowed to stand at room temperature for about 25 hours when blood ceased to flow and serum began to exude as coagulation time.
Minutes. Then, centrifugation was performed at 5000 rpm for 10 minutes. After visually observing the separability of the serum by the serum (plasma) separating material, immediately thereafter, half of the serum was dispensed into a clean hard glass test tube and frozen and stored at −20 ° C. as an initial value sample. The remaining half amount of serum was frozen and stored at −20 ° C. for 24 hours while being kept in the test container. After returning to room temperature after a predetermined time, the separability was again visually observed, and the serum was dispensed into a clean hard glass test tube and used as a specimen stored for 24 hours. K and LDH were measured for two samples in total. The results are shown in Table 6.

The blood coagulation time was equal to or more than the value of 30 minutes in the test tube made of hard glass, which was carried out at the same time, and the separability after centrifugation was also good. Furthermore, it was found that there was no change in the separability before and after frozen storage at -20 ° C, K and LDH were comparable to the initial values, and there was no effect on the test values.

Example 7 Preparation of Outer Cylinder, Inner Cylinder, and Serum (Plasma) Separation Material The outer cylinder shown in FIG.
270 kg / mm ^Two, Specific gravity 1.4), injection
It was created by molding. The inner cylinder shown in FIG.
Plastic elastomer (Young's modulus 2 kg / mm ^Two,specific gravity
1.2) was used to prepare by blow molding. In Figure 8
The serum (plasma) separation material shown is made of poly with a specific gravity of 1.06.
Phenylene oxide (Young's modulus 270 kg / mm^Two)
Was prepared by injection molding.

Preparation of Suspension of Blood Coagulation Promoting Component and Blood Component Anti-Adhesion Component The same suspension of the blood coagulation promoting component and blood component anti-adhesion component as in Example 4 was prepared.

Preparation of Solution of Anti-Adhesion Component of Blood Component A solution of anti-adhesion component of blood component similar to that in Example 4 was prepared.

Assembly of Blood Test Container About 200 μl of a suspension of the blood coagulation accelerating component and the blood component anti-adhesion component was spray-applied to the inner cylinder and naturally dried. A serum (plasma) separating material was spray-coated with a solution of a blood component anti-adhesion component and naturally dried. Thereafter, these were assembled in the same manner as in Example 1 to prepare a blood test container.

Evaluation Human fresh blood was vacuum-collected in the blood test container. About 23 ℃
It was allowed to stand at room temperature for about 25 hours when blood ceased to flow and serum began to exude as coagulation time.
Minutes. Then, centrifugation was performed at 5000 rpm for 10 minutes. After visually observing the separability of the serum by the serum (plasma) separating material, immediately thereafter, half of the serum was dispensed into a clean hard glass test tube and frozen and stored at −20 ° C. as an initial value sample. The remaining half amount of serum was frozen and stored at −20 ° C. for 24 hours while being kept in the test container. After returning to room temperature after a predetermined time, the separability was again visually observed, and the serum was dispensed into a clean hard glass test tube and used as a specimen stored for 24 hours. K and LDH were measured for two samples in total. The results are shown in Table 6.

The blood coagulation time was equal to or more than the value of 30 minutes in the test tube made of hard glass which was carried out at the same time, and the separability after centrifugation was also good. Furthermore, it was found that there was no change in the separability before and after frozen storage at -20 ° C, K and LDH were comparable to the initial values, and there was no effect on the test values.

[0106]

[Table 6]

[0107]

EFFECTS OF THE INVENTION Since the blood test containers of the present invention 1 to 4 have the above-mentioned structure, they are suitable for vacuum blood sampling, and serum (plasma)
Is excellent in separability, and the specimen can be kept stable by cryopreservation at -20 ° C or -80 ° C, which contributes to rapid clinical examination and improved reliability.

[Brief description of drawings]

FIG. 1 is a view showing an example of a nested structure of a blood test container of the first invention.

FIG. 2 is a diagram showing a perspective view, a lateral surface, and an upper surface of an example of a serum (plasma) separating material of the blood test container of the present invention 1.

FIG. 3 is a diagram showing an example of a pleated structure of the inner cylinder of the blood test container of the first invention.

FIG. 4 is a view showing an example of a nested structure of a blood test container of the third invention.

FIG. 5 is a view showing an example of a pleated structure of the inner cylinder of the blood test container of the third invention.

FIG. 6 is a view showing an outer cylinder of the embodiment.

FIG. 7 is a diagram showing an inner cylinder of Examples 1 to 5.

FIG. 8 is a view showing a serum (plasma) separating material of an example.

FIG. 9 is a view showing an inner cylinder of Examples 6 and 7.

[Explanation of symbols]

 1 outer cylinder 2 inner cylinder 3 pleated structure 4 outer cylinder 5 inner cylinder 6 pleated structure

Claims (4)

[Claims] 1. An outer cylinder, which is a bottomed tubular container having an opening at one end, an inner cylinder that is locked to an inner wall of the outer cylinder to form a nested structure that is not in contact with the outer cylinder, and the inner cylinder. A blood test container comprising a blood serum (plasma) separating material provided in a cylinder and an airtight stopper, wherein the inner cylinder has an opening at one end, and the opening has a peripheral edge. A bottomed tubular container having a pleated structure, the rigidity of which is less than the rigidity of the outer cylinder, and the serum (plasma) separation material is blood-impermeable. It is active, has a specific gravity of 1.03 or more, a rigidity of at least the rigidity of the inner cylinder, and the serum (plasma) separating material is a centrifuge. A blood test container, which slides on the inner wall surface of the inner cylinder during separation. 2. At least one of the inner surface of the inner cylinder, the surface of the blood serum (plasma) separating material, and the inner space formed by the inner cylinder independently comprises a blood coagulation promoting component and / or a blood component. The blood test container according to claim 1, wherein an anti-adhesion component or a blood anticoagulant component is present. 3. A bottomed tubular container having an opening at one end, the outer cylinder having a tapered shape with a diameter decreasing from the opening end toward the bottom, and the outer container being locked to the inner wall of the outer cylinder. A blood test container comprising an inner cylinder forming a nested structure that is not in contact with the cylinder, a blood serum (plasma) separating material provided in the inner cylinder, and an airtight stopper, wherein the inner cylinder is A tubular structure having openings at both ends thereof and having a pleated structure at the edges of the opening on the opening side of the outer cylinder, wherein It is locked to the inner wall and has a rigidity less than that of the outer cylinder. The serum (plasma) separating material is inactive to blood and has a specific gravity of 1 0.03 or more, the magnitude of rigidity is greater than or equal to the magnitude of rigidity of the inner cylinder, and the serum (blood The blood test container, wherein the (serum) separating material slides on the inner wall surface of the inner cylinder during centrifugation. 4. At least one of the inner surface of the inner cylinder, the surface of the serum (plasma) separating material, and the inner space formed by the inner cylinder independently comprises a blood coagulation promoting component and / or a blood component. The blood test container according to claim 3, wherein an anti-adhesion component or a blood anticoagulant component is present.