JP2000083934A - Blood collection tube - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a blood collection tube which is high in diffusion efficiency to blood, rapidly coagulates the blood and is capable of surely suppressing the coagulation of the blood. SOLUTION: The blood collection tube 1 has a blind tube 2 and is housed with a coagulation accelerator 6 deposited with a fibrinogen protein removing material on the surfaces of inorg. particulate carriers having the sp. gr. larger than the sp. gr. of the blood cells into this blind tube. The blood specimen collection tube 1 may also be constituted by having the blind tube 1 and housing a coagulation suppressor deposited with a blood coagulation fibrinogenolytic factor inhibitor on the surfaces of the inorg. particulate carriers having the sp. gr. larger than the sp. gr. of the blood cells into the blind tube.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a blood collection tube for collecting a blood sample used for a blood test.

[0002]

2. Description of the Related Art In a blood test, collected blood is separated by centrifugation into serum and blood cell components (blood clots), but the blood sample must be sufficiently coagulated before centrifugation. Insufficient coagulation may cause blood cells to rise with a slight impact after centrifugation and contaminate the serum layer, or fibrin may be generated in the serum layer to hinder a test using serum. Conventionally, in view of the speed and efficiency of blood tests,
Various materials and methods have been proposed for promoting coagulation of blood samples. As a first method for promoting blood coagulation, there is a method in which glass powder is placed at the bottom of a blood collection tube. In this method, an extremely fine glass powder is required in order to have an effect of accelerating blood coagulation and to obtain good dispersion in blood.

[0003] As a second method for promoting blood coagulation,
There is a method using a blood collection tube described in JP-B-59-6655. This blood collection tube is made by coating a material obtained by dispersing a blood coagulation accelerator, such as glass powder, on a substance that does not easily adhere to blood components, on the inner surface of a plastic blood collection tube. At this time, the blood clot is contracted without the blood component mainly composed of the blood clot adhering to the tube wall, and the blood coagulation proceeds as in the case of the blood collection tube made of glass.

[0004]

However, the prior art is not sufficient in terms of diffusion efficiency into blood and blood coagulation time.

An object of the present invention is to provide a blood collection tube having a high diffusion efficiency to blood and capable of coagulating blood in a short time.

A second object of the present invention is to provide a blood collection tube having a high diffusion efficiency to blood and capable of reliably suppressing blood coagulation.

[0007]

Means for achieving the above object is to provide a bottomed tube, in which the surface of an inorganic particulate carrier having a specific gravity larger than that of blood cells is placed on a surface of an inorganic particulate carrier. Is a blood collection tube in which a coagulation promoter loaded with is stored.

[0008] It is preferable that the fibrin protein-removing substance is attached to the carrier by a binder. Further, the fibrin protein removing substance is thrombin,
It is preferable to use either a thrombin-like enzyme or a snake venom extract containing a thrombin-like enzyme, or a mixture of two or more thereof. Further, a gel-like blood separating agent having thixotropic property is accommodated in the bottom of the bottomed tube, and the coagulation accelerator is located on the blood separating agent or between the opening of the bottomed tube and the blood separating agent. You may be doing.

In order to achieve the above object, a bottomed tube is provided, in which a blood coagulation / fibrinolytic factor inhibitor is carried on the surface of an inorganic particulate carrier having a specific gravity larger than that of blood cells. This is a blood collection tube containing a coagulation inhibitor.

[0010] The blood coagulation / fibrinolytic factor inhibitor comprises:
Preferably, it is attached to the carrier by a binder. The blood coagulation / fibrinolytic factor inhibitor is preferably one of heparin powder, sodium fluoride, aprotinin, and ethylenediaminetetraacetate, or a mixture of two or more of them. Further, a thixotropic gel-like blood separating agent is stored in the bottom of the bottomed tube, and the coagulation inhibitor is located on the blood separating agent or between the opening of the bottomed tube and the blood separating agent. You may be doing.

The above-mentioned inorganic particle carrier has a particle diameter of 0.1.
It is preferably from 0.05 to 10 mm. Further, the inorganic carrier is, for example, any one of glass particles, ceramic particles or titanium oxide particles, or a mixture of two or more thereof. Further, the ceramic particles are, for example, any one of silica particles, alumina particles, zirconia particles, zeolite particles, and silica-alumina particles, or a mixture of two or more thereof.

[0012]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of a blood collection tube according to the present invention. FIG. 1 is a sectional view of a blood collection tube of the present invention. The blood collection tube 1 of the present invention includes a bottomed tube 2 in which a fibrin proteoprotein removing substance 4 is carried on the surface of an inorganic particulate carrier 3 having a specific gravity greater than that of blood cells. Agent 6 is stored.

Conventionally, a fibrin protein-removing substance 4, which is a biologically-derived coagulation-promoting active substance such as thrombin, is dispensed in a liquid state into a blood collection tube, and then the whole blood collection tube is freeze-dried and sealed. Therefore, they existed in one place in the blood collection tube. Therefore, when blood flows into the blood collection tube, the coagulation-promoting active substance is locally dissolved and hardly spreads over the whole blood, and partially coagulates before the whole blood is coagulated, resulting in uneven coagulation.

In the blood collection tube of the present invention, since the carrier 3 carries the fibrin protein-removing substance 4, when the blood flows into the blood collection tube, the carrier 3 is diffused into the blood. The attached living body-derived coagulation promoting active substance also spreads throughout the blood and promotes coagulation of the whole blood. In addition, when only the fibrin protein removing substance 4 is used,
Since the specific gravity is small, it is not easy to enclose because of soaring. However, in this blood collection tube, since it adheres to the carrier 3, it can be prevented from soaring and the enclosing is easy. In addition, since the carrier 3 having a specific gravity larger than that of blood cells is used, the collected blood coagulation accelerator 6 is easily moved in the blood by shaking the blood collection tube after collecting the blood, and the collected coagulation accelerator 6 adheres to the surface of the carrier 3. It is possible to dissolve the fibrin protein removal substance 4 in the whole blood early and surely. For this reason, it becomes possible to coagulate the whole blood uniformly.

Therefore, the blood collection tube of the present invention will be specifically described with reference to the embodiment shown in FIG. Blood collection tube 1 of this embodiment
Is composed of a bottomed tube 2, a coagulation promoter 6 in which a substance for removing fibrin protein 4 is carried on the surface of an inorganic particulate carrier 3, and a sealing member 7 for sealing an opening of the bottomed tube 2. Has been
The inside of the bottomed tube 2 is depressurized by a predetermined blood collection amount.

The bottomed tube 2 is a tubular body having one end opened and the other end closed, and the portion other than the closed end has a substantially cylindrical shape. In addition, in the one shown in FIG. 1, an annular flange is provided at the opening of the bottomed tube 2 so as to protrude outward perpendicularly to the axial direction of the bottomed tube 2.

The material of the bottomed tube 2 is preferably a material having a high gas barrier property in order to maintain a reduced internal pressure. For example, glass, acrylonitrile resin, polyvinyl chloride, polyethylene terephthalate, PMMA (polymethyl (Methacrylate), a polyester resin or the like is preferably used.

When the bottomed tube 2 is formed of a material having a low gas barrier property (for example, polypropylene, polyethylene, polystyrene, etc.), polyvinyl alcohol, ethylene-vinyl, It can be used by coating a film having a gas barrier property such as an alcohol copolymer, and by devising a packaging form in order to maintain a reduced pressure state inside the bottomed tube 2.

When the bottomed tube 2 is made of polyvinyl chloride, the inner surface of the bottomed tube 2 is used to prevent the stabilizer contained in the polyvinyl chloride from being eluted into the collected blood. It is preferable to coat an anti-elution agent on the surface. Furthermore, when the bottomed tube 2 is formed using a hydrophobic synthetic resin, it is preferable that the inner surface is subjected to a hydrophilic treatment to prevent blood cells from adhering to the inner surface of the bottomed tube 2. The hydrophilic treatment can be performed by coating the inner surface of the bottomed tube 2 with a hydrophilic substance (for example, water-soluble silicone, PVA, PVP, or the like).

As shown in FIG. 2, the coagulation accelerator 6 comprises an inorganic particulate carrier 3 having a specific gravity greater than that of blood cells, and a fibrin protein-removing substance 4 carried on the surface thereof.

The inorganic particulate carrier 3 is a particulate material having a specific gravity higher than that of blood cells, specifically, 1.09 to 10.0, preferably 1.1 to 3.0. The granular form is
The shape is not limited to a true sphere, and may be any shape such as an elliptical shape or a rectangular shape, but it is preferable that the surface does not have a sharp edge portion. Further, the particulate matter has a particle size of 0.05-1.
It is preferably 0 mm, and particularly preferably 0.1 to 3 mm.

As the inorganic particulate carrier 3, glass particles,
Either ceramic particles or titanium oxide particles,
Alternatively, a mixture of two or more thereof can be used. Further, as the ceramic particles, any one of silica particles, alumina particles, zirconia particles, zeolite particles, and silica-alumina particles, or a mixture of two or more thereof can be used. As the silica-alumina particles, for example, silica-alumina sintered particles can be used.

As the fibrin protein-removing substance 4, any one of thrombin, a thrombin-like enzyme, or a snake venom extract (relyase) containing a thrombin-like enzyme, or a mixture of two or more thereof is used.

As a method of attaching the fibrin protein-removing substance 4 to the inorganic particulate carrier 3 (adhering method), the substance may be directly attached without using a binder. In this case,
A solution prepared by dissolving the fibrin protein-removing substance 4 in a solvent that dissolves the fibrin protein-removing substance 4 such as water was prepared, the carrier 3 was immersed in the solution, and this was freeze-dried or pulled up. It can be produced by post-drying. After drying, if necessary, it may be crushed so as to have an appropriate particle size.

Further, the substance 3 for removing fibrin protein is added to the carrier 3.
A binder may be used to ensure the adhesion of the binder. The binder is for adhering the fibrin protein-removing substance 4 to the surface of the inorganic particulate carrier 3, and the binder is for ensuring the adhesion of the fibrin protein removing substance 4 to the surface. Those having tackiness and film forming properties are preferred.

As such a binder, PVA is used.
(Polyvinyl alcohol), modified PVA (for example, carboxyl-modified PVA, sulfonic acid group-modified PVA, acrylamide-modified PVA, carion group-modified PVA, long-chain alkyl group-modified PVA), PVP (polyvinylpyrrolidone), vinylpyrrolidone-vinyl acetate copolymer Coalescence, cellulosic substances, for example, carboxymethylcellulose, methylcellulose, oxypropylcellulose, oxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, ethylhydroxyethylcellulose, ethylcellulose, carboxymethylethylcellulose, hydroxyprolylate, 2-hydroxypropylacrylate, etc. Any one of the group consisting of a mixture of water-soluble multi-proteins such as acrylic derivatives, starch, and gelatin Or more of the materials can be used.

Further, the coagulation accelerator 6 may simultaneously carry a blood stabilizing agent such as aprotinin and protamine sulfate, in addition to the above-described fibrinogen protein removing substance 4. Also in this case, it is preferable to use a binder.

When the above-mentioned binder is used, the fibrin protein-removing substance 4 (and blood stabilizer) and the binder are dissolved in a solvent such as water which dissolves the fibrinogen-removing substance 4 (and blood stabilizer). Is prepared, and the carrier 3 is immersed therein, pulled up and dried, or freeze-dried. After drying, if necessary, it may be crushed so as to have an appropriate particle size.

In the blood collection tube 1 of this embodiment, FIG.
As shown in the figure, a bottomed tube 2 made of synthetic resin is used,
A sealing member 7 is fixed to a flange formed at the opening end.

The sealing member 7 is, in this embodiment,
An airtight maintaining member 7a, a sealing member 7b provided on the upper surface of the airtight maintaining member 7a and capable of sealing the piercing portion again after the pierced needle is withdrawn, and a bottomed tube 2 And a tab 7c for further peeling.

The airtight maintenance member 7a has a function of sealing the opening of the bottomed tube 2 and maintaining a reduced pressure inside the bottomed tube 2, and is formed of a substance having a high gas barrier property. Gas barrier film, for example,
It is formed of a metal foil such as an aluminum foil, a resin film material such as an ethylene-vinyl alcohol copolymer, polyvinylidene chloride, or the like.

On the lower surface of the gas barrier film, an adhesive film is provided for fixing to the opening of the bottomed tube 2. A modified polyester resin can be suitably used as the adhesive film. This adhesive film has a heat-fusing property with the resin forming the bottomed tube 2 and has an easy peel property. As the modified polyester resin, dicarboxylic acids such as terephthalic acid and aromatic dicarboxylic acids such as isophthalic acid, and diol components such as ethylene glycol, 1,4-butanediol, diethylene glycol, and neopentyl glycol are used. Softening point 80-170 ° C
(JIS K2531 ring and ball method), glass transition point -30 ° C
Those having a temperature range of -80 ° C (DSC method) are preferred.

Further, on the upper surface of the gas barrier film, there may be provided a printed layer for displaying the product type and the like, and an overcoat (for example, a cellulose-based coating layer) for protecting the printed layer. Further, since the inner surface (adhesive film surface) of the sealing member 7 is a hydrophobic surface, it is preferable to treat at least a portion that comes into contact with blood to prevent blood clots from adhering to the inner surface. In this process, a hydrophilic substance (eg, water-soluble silicone, PVA, PVA) is applied to the inner surface of the sealing member 7.
P etc.).

The sealing member 7b seals a puncture hole formed in the sealing member 7 after the puncture needle provided in the blood collection device is pierced through the sealing member 7 of the blood collection tube 1 and removed. And a function of maintaining a liquid-tight state.
Examples of the sealing member include rubber materials such as natural rubber, isoprene rubber, chloroprene rubber, and silicone rubber,
Alternatively, a resin such as a thermoplastic elastomer such as a styrene-butadiene-styrene (SBS) block copolymer can be used.

The sealing member 7b has a shape as shown in FIG. 1, and the bottom surface of the sealing member 7b is a flat surface forming an adhesive surface with the airtight maintaining member 7a. I have. At the approximate center of the upper part of the sealing member 7b, a concave blood container is provided. The concave blood container has a function of storing and isolating blood attached to the sealing member 7b when the puncture needle of the blood collection device is withdrawn from the sealing member 7.

The sealing member 7b is provided substantially at the center of the airtight maintaining member 7a. The shape of the sealing member 7b is not limited to a circular shape, and may be a substantially circular shape including an elliptical shape, a quadrangle, a polygon such as a pentagon,
Moreover, the whole upper surface of the airtight maintenance member 7a may be covered. Further, it is preferable to provide the sealing member 7b and the sealing member 7 on the upper surface,
a may be provided on the lower surface. The sealing member 7b and the airtight maintaining member 7a are adhered using an instant adhesive.

Further, the adhesion between the sealing member 7 and the bottomed tube 2 is performed by attaching the adhesive film of the sealing member 7 to the periphery of the opening of the bottomed tube 2, in the case of FIG. The modified polyester resin film is hermetically adhered by fusion using heat, ultrasonic waves, high frequency, or the like. Further, the attachment of the scattering prevention member 4 to the lower surface of the sealing member 7 may be performed simultaneously with the attachment of the sealing member 7 and the bottomed tube 2. The inside of the bottomed tube 2 can be brought into a reduced pressure state by fixing the sealing member 7 and the opening of the bottomed tube 2 in a reduced pressure atmosphere.

When a glass tube is used as the bottomed tube 2, a rubber material such as natural rubber, isoprene rubber, chloroprene rubber, silicone rubber, or the like may be used as the sealing member.
Alternatively, a plug formed of a thermoplastic elastomer such as a styrene-butadiene-styrene (SBS) block copolymer or the like is used.

As shown in FIG. 3, the bottom of the bottomed tube 2 may contain a thixotropic gel-like blood separating agent. In this case, the coagulation accelerator 6 is stored so as to be located on the blood separating agent or between the opening of the bottomed tube 2 and the blood separating agent.

The gel blood separating agent 8 has an intermediate specific gravity between a blood clot component and a serum component or a blood cell component and a plasma component.

As the gel-like blood separating agent 8, a so-called thixotropic gel-like blood separating agent which forms a gel at normal temperature and pressure and becomes a sol during centrifugation is used. The gel blood separating agent 8 comprises a main component and a viscosity, specific gravity, and thixotropic regulator. Examples of the main component include various polyesters, hydrocarbons such as polybutene, polybutadiene, and liquid polypropylene, and silicone such as methyl. Chlorinated phenyl silicone (Toshiba Silicone TSF44D,
Specific gravity 1.035, viscosity 100-150 cp) and α-
Copolymers of olefins and α, β-unsaturated dicarboxylic acid alkyl esters are exemplified. Particularly good are a viscosity of 5,000 to 200,000 cp (25 ° C.) and a specific gravity of 1.00.
A copolymer of an α-olefin having a molecular weight of up to 1.038 (25 ° C.) and an α, β-unsaturated dicarboxylic acid dialkyl ester. This copolymer is pale yellow, transparent and odorless, is inert to blood, has no risk of causing phenomena such as blood adsorption and elution, and is stable over time. Preferred examples of the copolymer of an α-olefin and an α, β-unsaturated dicarboxylic acid dialkyl ester include those having 2 to 2 carbon atoms.
Copolymers of 22 α-olefins and α, β-unsaturated dicarboxylic acid dialkyl esters having 1 to 20 carbon atoms are exemplified. As the α, β-unsaturated dicarboxylic acid, maleic acid or fumaric acid is particularly preferred.
Preferred examples of the α-olefin / maleic acid dialkyl ester copolymer include an n-α-olefin / α-olefin component wherein the α-olefin component comprises a combination of 12 and 14 carbon atoms.
Maleic acid dimethyl ester copolymer [average molecular weight 20
00 to 5000, specific gravity 1.00 to 1.035 (25
° C), viscosity 10,000-120,000 cp (25
° C)], an n-α-olefin / maleic acid dimethyl ester copolymer in which the α-olefin component is a combination of 6 and 8 carbon atoms [average molecular weight: 2000-4000, specific gravity 1.035 (25 ° C), viscosity] 10000-12000
0 cp (25 ° C.)], n-α-olefin / maleic acid diethyl ester copolymer in which the α-olefin component comprises a combination of 16 and 18 carbon atoms [average molecular weight 300
0-4000, specific gravity 0.995 (28 ° C), viscosity 100
00 cp (25 ° C.)]. Further, α-olefin / fumaric acid dimethyl ester copolymer [average molecular weight: 2,000 to 5,000, specific gravity: 1.00 to 1.035 (2
5 ° C.), viscosity 10,000 to 200,000 cp (25
° C)], α-olefin / fumaric acid dimethyl ester copolymer [average molecular weight: 2,000 to 4,000, specific gravity: 1.03
0 to 1.035 (25 ° C), viscosity 10,000 to 2000
00 cp (25 ° C.)].

As a main component of the gel-like blood separating agent 8, these copolymers can be appropriately mixed and used as required.

As the specific gravity, viscosity and thixotropic regulators to be added to the gelled blood separating agent of the present invention, inorganic fine powders such as calcined silica fine powder, precipitated silica fine powder and aliphatic amine derivatives having smectite viscosity can be used. Highly stable organic fine powder used as a nucleating agent for polyolefins such as sorbitols is preferably used. More specifically, silica fine powder (trade name Aerosil, Nippon Aerosil Co., Ltd.), aliphatic primary amine, aliphatic secondary amine, aliphatic tertiary amine, aliphatic quaternary amine of smectite clay
Each derivative of the amine can be used. As the smectite clay, an aliphatic quaternary amine derivative thereof is particularly preferable, and specific examples thereof include Benton 34, Benton 38, Benton 27, and Benton 128 (a derivative of a smectite clay manufactured by NL Industries with a quaternary ammonium salt). aliphatic amine derivatives of C ₈ -C ₂₄ smectite clays such as, furthermore, the sorbitols, dibenzylidene sorbitol, tribenzylidene sorbitol, and alkyl-substituted dibenzylidene sorbitol can be used.

Further, in addition to the α-olefin / maleic acid (or fumaric acid) diester copolymer, a viscosity / specific gravity adjusting agent, a gelling agent, and if necessary, a nonionic surfactant (for example, polyoxyethylene) Hydrogenated castor oil monolaurate, polyoxyethylene hardened castor oil triisostearate, etc.). By adding a small amount of this surfactant (for example, 0.47 to 2.7% by weight), it is possible to prevent phase separation that may be caused by leaving for a long period of time, and it is a non-ionic type, so that hemolysis etc. Does not occur. Particularly, it is useful when only silica is used as a viscosity / specific gravity adjusting agent.

The viscosity of the gel blood separating agent 8 is high,
When it is difficult to float with normal centrifugal force, as shown in FIG. 3, a hollow is formed in advance on the blood separating agent surface,
Floating may be promoted.

Next, the second blood collection tube 50 of the present invention will be described. FIG. 4 is a cross-sectional view of the blood collection tube 50. The second blood collection tube 50 of the present invention includes the bottomed tube 2, and a blood coagulation / fibrinolytic factor inhibitor 54 is provided in the bottomed tube 2 on the surface of the inorganic particulate carrier 3 having a specific gravity larger than that of blood cells. The carried coagulation inhibitor 56 is stored.

Conventionally, a blood coagulation / fibrinolytic factor inhibitor 54 such as lyophilized heparin has been enclosed in a blood collection tube. When blood flows into the blood collection tube, the blood coagulation / fibrinolytic factor inhibitor 54 is locally melted and hardly spreads over the whole blood, and uneven coagulation suppression may occur. In the blood collection tube 50 of the present invention, since the carrier 3 carries the blood coagulation / fibrinolytic factor inhibitor 54, when blood flows into the blood collection tube, the carrier 3
Is diffused into the blood, whereby the blood coagulation / fibrinolytic factor inhibitor 54 attached to the carrier 3 also spreads throughout the blood and suppresses coagulation of the whole blood. Further, when the blood coagulation / fibrinolytic factor inhibitor 54 alone is enclosed in a blood collection tube, the specific gravity is so small that it flies up, so that the encapsulation is not easy. Can be prevented and encapsulation is easy. In addition, since the carrier 3 having a specific gravity larger than that of blood cells is used, the collected blood coagulation inhibitor 56 is easily moved in the blood by shaking the blood collection tube after collecting the blood collection tube, and adheres to the surface of the carrier 3. The blood coagulation / fibrinolytic factor inhibitor 54 can be dissolved in the whole blood early and reliably. For this reason, it is possible to uniformly coagulate the entire blood.

The blood collection tube 50 of this embodiment includes a bottomed tube 2 and
A blood coagulation / fibrinolytic factor inhibitor 54 on the surface of the inorganic particulate carrier 3
And the sealing member 7 for sealing the opening of the bottomed tube 2, and the inside of the bottomed tube 2 is depressurized by a predetermined blood collection amount. Bottomed pipe 2
Are the same as those described above, and reference is made to the above description.

As shown in FIG. 5, the coagulation inhibitor 56 comprises the inorganic particulate carrier 3 having a specific gravity larger than that of blood cells, and the blood coagulation / fibrinolytic factor inhibitor 54 carried on the surface thereof. The inorganic particulate carrier 3 is the same as described above,
Reference is made to the above description.

As the blood coagulation / fibrinolytic factor inhibitor 54, any of heparin powder, sodium fluoride, aprotinin or ethylenediaminetetraacetate, or a mixture of two or more thereof is used.

As a method of attaching the blood coagulation / fibrinolytic factor inhibitor 54 to the inorganic particulate carrier 3 (adhering method), the agent may be directly attached without using a binder. In this case, a solution prepared by dissolving the blood coagulation / fibrinolytic factor inhibitor 54 in a solvent such as water that dissolves the blood coagulation / fibrinolysis factor inhibitor 54 is prepared, the carrier 3 is immersed in the solution, and freeze-dried. thing,
Further, it can be manufactured by lifting and drying it. After drying, if necessary, it may be crushed so as to have an appropriate particle size.

Further, a binder may be used to ensure that the blood coagulation / fibrinolytic factor inhibitor 54 adheres to the carrier 3. The binder is for attaching the blood coagulation / fibrinolytic factor inhibitor 54 to the surface of the inorganic particulate carrier 3, and the binder is for ensuring the attachment of the blood coagulation / fibrinolysis factor inhibitor 54. Further, those having adhesiveness and film forming property are preferable.

As such a binder, those described above can be used. When a binder is used, a blood coagulation / fibrinolytic factor inhibitor 54 such as water (and a blood stabilizer)
Is prepared by dissolving the blood coagulation / fibrinolytic factor inhibitor 54 (and blood stabilizer) and the binder in a solvent that dissolves the carrier 3, immersing the carrier 3 in the solution, and freeze-drying the carrier 3. It can be produced by post-drying. After drying, if necessary, it may be crushed so as to have an appropriate particle size.

In the blood collection tube 50 of this embodiment, the bottom tube 2 made of synthetic resin is used, and the sealing member 7 is fixed to a flange formed at the opening end. The sealing member 7 is the same as described above, and reference is made to the above description. When a glass tube is used as the bottomed tube 2, a rubber material such as natural rubber, isoprene rubber, chloroprene rubber, silicone rubber, or a styrene-butadiene-styrene (SBS) block copolymer is used as the sealing member. A plug formed of a thermoplastic elastomer such as the above is used.

As in the blood collection tube shown in FIG. 3, the bottom of the bottomed tube 2 may contain a thixotropic gel-like blood separating agent. In this case, the coagulation inhibitor 56 is stored so as to be located above the blood separating agent or between the opening of the bottomed tube 2 and the blood separating agent. The gel blood separating agent is the same as described above, and reference is made to the above description.

[0056]

Example 1 Example 1 Thrombin (derived from bovine plasma: Mochida Pharmaceutical Co., Ltd.) 1000 which is a fibrin protein-removing substance
A thrombin aqueous solution was prepared by dissolving 0 IU in 200 ml of water, and glass beads (about 0.2 m in diameter) were added to this aqueous solution.
m) 160 g were added, mixed and lyophilized. Crush the lyophilizate and sieve to a particle size of 30-70mes
The coagulation accelerator in which the substance for removing fibrin protein was supported on the surface of the inorganic particulate carrier of h was obtained. As a bottomed tube, it has a shape as shown in FIG. 1 and the outer diameter of the opening of the blood collection tube is 13.4 m.
m, having a thickness of 1.0 mm, a taper of 15/1000, and an opening having an outer diameter of 17.3 mm and a thickness of 2.0 mm were produced by injection molding polyethylene terephthalate. As an airtight maintenance member forming a sealing member, a printed surface for distinguishing types is provided on the upper surface, an aluminum foil layer (40 μ) having a gas barrier property on the lower surface, and a modified polyester layer (5 μm) serving as an adhesive film is provided on the lower surface. (Elitel UE3500, manufactured by Unitika Ltd.). Then, using the laminated film for a sealing member, the sealing member has a shape as shown in FIG.
An airtight maintenance member having a length of 8 mm, a tab length of 9 mm, and a width of 8 mm was produced. Using a natural rubber member as the sealing member, a member having a diameter of 7.0 mm, a thickness of 2.0 mm, and a concave blood container having a diameter of 3.0 mm and a depth of 0.3 mm in the upper central portion is produced. Then, it was bonded to the upper surface of the airtight maintenance member using an instant adhesive. Further, 10 mg of a coagulation accelerator carrying the above-mentioned fibrin proteoprotein-removing substance was placed in the bottomed tube, and then reduced pressure (580 Torr)
Then, the sealing member was heat-sealed to the flange of the bottomed tube (sealing temperature: 130 ° C.) to produce a reduced-pressure blood collection tube of the present invention having a blood collection amount of about 5 cc.

Example 2 Thrombin (derived from bovine plasma: Mochida Pharmaceutical Co., Ltd.) 100, which is a substance for removing fibrin protein
00IU, polyvinylpyrrolidone (PVP) 100mg
Was dissolved in 200 ml of water to prepare an aqueous solution of thrombin containing polyvinylpyrrolidone, 160 g of glass beads (about 0.2 mm in diameter) were added to the aqueous solution, mixed, and freeze-dried. Crush the lyophilized material, sieve it,
A coagulation accelerator in which a fibrin proteolytic substance was carried on the surface of an inorganic particulate carrier having a particle size of 30 to 70 mesh was obtained. A vacuum blood collection tube of the present invention having a blood collection amount of about 5 cc was prepared in the same manner as in Example 1 except that 10 mg of this coagulation accelerator was used.

Example 3 Thrombin (derived from bovine plasma: Mochida Pharmaceutical Co., Ltd.) 100 which is a fibrin protein-removing substance
00IU, snake venom extract substance (Recerase, PENTAPH)
ARM LTD. Was prepared by dissolving about 15000 μl of polyvinylpyrrolidone (PVP) in 200 ml of water to prepare an aqueous solution of thrombin containing polyvinylpyrrolidone and reserase. 160 g of glass beads (about 0.2 mm in diameter) were added to this aqueous solution and mixed. Then, it was freeze-dried. Crush the lyophilized material, sieve it,
A coagulation accelerator having a 70 mesh inorganic particulate carrier carrying a fibrin proteolytic substance and a snake venom extract substance on the surface was obtained.
A vacuum blood collection tube of the present invention having a blood collection amount of about 5 cc was prepared in the same manner as in Example 1 except that 10 mg of this coagulation accelerator was used.

Example 4 Thrombin (derived from bovine plasma: Mochida Pharmaceutical Co., Ltd.) 100 which is a substance for removing fibrin protein
A solution of thrombin containing 00IU, about 100000 IU of aprotinin and 100 mg of polyvinylpyrrolidone (PVP) in 200 ml of water was prepared, and 160 g of glass beads (about 0.2 mm in diameter) were added to the aqueous solution, followed by mixing. After doing
Lyophilized. The freeze-dried product was crushed and sieved to obtain a coagulation accelerator in which a fibrin protein-removing substance and a snake venom extract substance were supported on the surface of an inorganic particulate carrier having a particle size of 30 to 70 mesh. A vacuum blood collection tube of the present invention having a blood collection amount of about 5 cc was prepared in the same manner as in Example 1 except that 10 mg of this coagulation accelerator was used.

Example 5 As a gel-like blood separating agent, an α-olefin / maleic acid diester copolymer having a viscosity of 60,000 cp (25 ° C.) was used as a base polymer.
As a specific gravity adjusting agent, silica fine powder (trade name Aerosil R)
972, manufactured by Nippon Aerosil Co., Ltd.) and modified smectite clay powder (trade name: Benton 38, manufactured by NL Industries Co., Ltd.) as a thixotropic agent were prepared. Blood was collected in the same manner as in Example 1 except that 1.5 g of the gel-like blood separating agent was injected into the bottom of the bottomed tube, and 10 mg of the coagulation accelerator prepared in Example 2 was added thereto. A vacuum blood collection tube of the present invention having a volume of about 5 cc was prepared.

Example 6 The same gel blood separating agent as in Example 5 was used as the gel blood separating agent, and 1.5 g of the gel blood separating agent was injected into the bottom of the bottomed tube. A reduced-pressure blood collection tube of the present invention having a blood collection amount of about 5 cc was prepared in the same manner as in Example 1, except that 10 mg of the coagulation accelerator prepared in Example 3 was added.

Example 7 The same gel blood separating agent as in Example 5 was used as the gel blood separating agent, and 1.5 g of this gel blood separating agent was injected into the bottom of the bottomed tube. A reduced-pressure blood collection tube of the present invention having a blood collection amount of about 5 cc was prepared in the same manner as in Example 1, except that 10 mg of the coagulation accelerator prepared in Example 4 was added.

Comparative Example 1 A blood collection tube having a blood collection amount of about 5 cc was prepared using a glass bottomed tube.

Comparative Example 2 A blood collection tube having a blood collection amount of about 5 cc was prepared in the same manner as in Example 1 except that the addition of the coagulation accelerator was not performed.

(Experiment) Using the blood collection tubes of Examples 1 to 7 and Comparative Examples 1 and 2, blood was collected from a collaborator of the experiment. The clotting time of each blood collection tube was as shown in Table 1.

[0066]

[Table 1]

[0067]

The blood collection tube of the present invention has a bottomed tube, in which a fibrin proprotein-removing substance is carried on the surface of an inorganic particulate carrier having a specific gravity larger than that of blood cells. It contains an accelerator. Therefore, when blood flows into the blood collection tube, the carrier diffuses into the blood, whereby the coagulation-promoting active substance derived from a living body attached to the carrier also spreads throughout the blood, and promotes coagulation of the whole blood. further,
It is not easy to enclose in a blood collection tube when enclosing it in a blood collection tube by using only the fibrin protein-removing substance, but it is difficult to enclose the blood collection tube because it adheres to the carrier. Easy. In addition, since a carrier having a specific gravity larger than that of blood cells is used, the blood coagulation accelerator is shaken after blood collection, so that the stored coagulation accelerator easily moves in the blood, and the fibrous substances adhering to the surface of the carrier are removed. The proteoprotein-removing substance can be dissolved in the whole blood early and surely, and the whole blood can be uniformly coagulated.

The blood collection tube of the present invention has a bottomed tube, in which a blood coagulation / fibrinolytic factor inhibitor is carried on the surface of an inorganic particulate carrier having a specific gravity greater than that of blood cells. The agent is stored. Therefore, when blood flows into the blood collection tube, the carrier diffuses into the blood, whereby the blood coagulation / fibrinolytic factor inhibitor attached to the carrier also spreads throughout the blood and suppresses coagulation of the whole blood. Furthermore, when only blood coagulation / fibrinolytic factor inhibitor is used,
Since the specific gravity is small, it is not easy to enclose because of its soaring. However, in this blood collection tube, it is possible to prevent soaring and the like because it adheres to the carrier, and it is easy to enclose. In addition, since a carrier having a specific gravity larger than that of blood cells is used, the collected blood coagulation inhibitor is easily moved in the blood by shaking the blood collection tube after collecting the blood, and the blood coagulation adhering to the surface of the carrier is collected. The fibrinolytic factor inhibitor can be dissolved in the whole blood early and surely, and the whole blood can be uniformly inhibited from coagulation.

[Brief description of the drawings]

FIG. 1 is a sectional view of a blood collection tube according to an embodiment of the present invention.

FIG. 2 is a cross-sectional view of a coagulation promoter used for a blood collection tube of the present invention.

FIG. 3 is a sectional view of a blood collection tube according to another embodiment of the present invention.

FIG. 4 is a sectional view of a blood collection tube according to another embodiment of the present invention.

FIG. 5 is a cross-sectional view of a coagulation accelerator used for a blood collection tube according to another embodiment of the present invention.

[Explanation of symbols]

 Reference Signs List 1 blood collection tube 2 bottomed tube 3 inorganic particulate carrier 4 fibrin protein removing substance 6 coagulation accelerator 50 blood collection tube 54 blood coagulation / fibrinolytic factor inhibitor 56 coagulation inhibitor

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor, Meguro Takashi 1800, 431, Hirano, Urari-cho, Naka-gun, Ibaraki Pref. Yasuhiro 1727-1 Tsukiji-Arai, Showa-cho, Nakakoma-gun, Yamanashi Prefecture Inside Terumo Corporation (72) Inventor Takato Murashita 17271-1 Tsukiji-Arai, Showa-machi, Nakakoma-gun, Yamanashi Prefecture Terumo Corporation F-term (reference) 2G045 BA04 BA08 BA10 BA10 BB34 CA25 HA06 HA14 HB12 HB16 HB17 4C038 UA02 UA05 UA06 UC04

Claims (11)

[Claims] 1. A bottomed tube, wherein a coagulation promoter in which a substance for removing fibrin protein is carried on a surface of an inorganic particulate carrier having a specific gravity larger than that of blood cells is stored in the bottomed tube. A blood collection tube, characterized in that: 2. The blood collection tube according to claim 1, wherein the substance for removing fibrin protein is attached to the carrier with a binder. 3. The fibrin proteolytic substance according to claim 1 or 2, wherein the substance is a thrombin, a thrombin-like enzyme, a snake venom extract containing a thrombin-like enzyme, or a mixture of two or more thereof. Blood collection tube. 4. A thixotropic gel-like blood separating agent is stored in the bottom of the bottomed tube, and the coagulation promoter is placed on the blood separating agent or in the opening of the bottomed tube and the blood separating agent. 4. The blood collection tube according to claim 1, which is located between the blood collection tubes. 5. A bottomed tube, wherein a coagulation inhibitor in which a blood coagulation / fibrinolytic factor inhibitor is carried on the surface of an inorganic particulate carrier having a specific gravity larger than that of blood cells is housed in the bottomed tube. A blood collection tube, characterized in that: 6. The blood collection tube according to claim 5, wherein the blood coagulation / fibrinolytic factor inhibitor is attached to the carrier with a binder. 7. The method according to claim 5, wherein the blood coagulation / fibrinolytic factor inhibitor is heparin powder, sodium fluoride, aprotinin, or ethylenediaminetetraacetate, or a mixture of two or more thereof. Blood collection tube. 8. A thixotropic gel-like blood separating agent is stored in the bottom of the bottomed tube, and the coagulation inhibitor is placed on the blood separating agent or in the opening of the bottomed tube and the blood separating agent. The blood collection tube according to any one of claims 5 to 7, which is located between the blood collection tubes. 9. The inorganic particle carrier having a particle size of 0.05 to 0.05.
The blood collection tube according to any one of claims 1 to 8, which is 10 mm. 10. The blood collection tube according to claim 1, wherein the inorganic carrier is one of glass particles, ceramic particles, and titanium oxide particles, or a mixture of two or more thereof. 11. The ceramic particles include silica particles, alumina particles, zirconia particles, zeolite particles,
Any of silica-alumina particles or their 2
The blood collection tube according to claim 10, which is a mixture of at least one species.