JP2024074252A - Blood collection container - Google Patents

Abstract

[Problem] To provide a blood collection container that can improve the solubility of a serine protease inhibitor and an anticoagulant in blood and can suppress the occurrence of partial coagulation and hemolysis of blood. [Solution] The blood collection container according to the present invention comprises a blood collection container body having a closed end, a serine protease inhibitor, and an anticoagulant, the serine protease inhibitor being disposed on the inner surface of the blood collection container body, and when the blood collection container is in an upright position, at least a portion of the anticoagulant is present on the closed end side of the blood collection container body relative to the area where the serine protease inhibitor is disposed. [Selected Figure] Figure 1

Description

The present invention relates to a blood collection container.

In clinical testing, blood collection containers such as blood collection tubes containing a serine protease inhibitor and an anticoagulant are sometimes used. For example, in tests targeting human atrial natriuretic peptide (HANP) or parathyroid hormone-related protein (PTHrP), blood collection tubes containing aprotinin (a serine protease inhibitor) and an anticoagulant are used.

Conventionally, blood collection tubes in which a drug containing a serine protease inhibitor and an anticoagulant (a mixture of a serine protease inhibitor and an anticoagulant) is applied to the inner surface of the blood collection tube body have been widely used.

In addition, the examples of the following Patent Document 1 describe a blood collection tube obtained by coating the inner surface of a plastic or glass tube with a lithium heparin solution and drying it, then placing an aqueous solution containing a protease inhibitor in the plastic tube and subsequently freeze-drying it.

WO2003/097237A2

In general, in blood collection containers containing drugs such as serine protease inhibitors and anticoagulants, the blood collection container is inverted to mix the collected blood, thereby dissolving the drugs in the blood. However, in conventional blood collection containers, the drugs may not dissolve sufficiently in the blood. When the drugs do not dissolve sufficiently in the blood, partial coagulation of the blood or hemolysis may occur.

The object of the present invention is to provide a blood collection container that can improve the solubility of serine protease inhibitors and anticoagulants in blood and can suppress the occurrence of partial blood coagulation and hemolysis.

The following blood collection containers are disclosed in this specification.

Item 1. A blood collection container comprising a blood collection container body having a closed end, a serine protease inhibitor, and an anticoagulant, the serine protease inhibitor being disposed on the inner surface of the blood collection container body, and when the blood collection container is in an upright position, at least a portion of the anticoagulant is present on the closed end side of the blood collection container body relative to the area where the serine protease inhibitor is disposed.

Item 2. The blood collection container according to Item 1, wherein the serine protease inhibitor includes aprotinin or a DPP-4 inhibitor.

Item 3. The blood collection container according to item 1 or 2, wherein the serine protease inhibitor comprises aprotinin and a DPP-4 inhibitor.

Item 4. The blood collection container according to item 2 or 3, wherein the DPP-4 inhibitor comprises sitagliptin, saxagliptin, linagliptin, alogliptin, vildagliptin, anagliptin, or teneligliptin.

Item 5. The blood collection container according to any one of items 1 to 4, wherein the anticoagulant is EDTA, a metal salt of EDTA, heparin, a heparin salt, citric acid, or a citrate salt.

Item 6. The blood collection container according to any one of items 1 to 5, wherein the anticoagulant is a granular anticoagulant.

Item 7. The blood collection container according to item 6, in which the average particle size of the granular anticoagulant is 200 μm or more and 1000 μm or less.

The blood collection container according to the present invention comprises a blood collection container body having a closed end, a serine protease inhibitor, and an anticoagulant. In the blood collection container according to the present invention, the serine protease inhibitor is disposed on the inner surface of the blood collection container body, and when the blood collection container is in an upright position, at least a portion of the anticoagulant is present on the closed end side of the blood collection container body relative to the area in which the serine protease inhibitor is disposed. Since the blood collection container according to the present invention is provided with the above configuration, it is possible to improve the solubility of the serine protease inhibitor and the anticoagulant in blood, and to suppress the occurrence of partial coagulation and hemolysis of blood.

FIG. 1 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a first embodiment of the present invention. FIG. 2 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a second embodiment of the present invention. FIG. 3 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a third embodiment of the present invention. FIG. 4 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a fourth embodiment of the present invention. FIG. 5 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a fifth embodiment of the present invention. FIG. 6 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a sixth embodiment of the present invention.

The present invention is described in detail below.

(Blood collection container)
The blood collection container according to the present invention comprises a blood collection container body having a closed end, a serine protease inhibitor, and an anticoagulant. In the blood collection container according to the present invention, the serine protease inhibitor is disposed on the inner surface of the blood collection container body, and when the blood collection container is in an upright position, at least a portion of the anticoagulant is present closer to the closed end of the blood collection container body than the area where the serine protease inhibitor is disposed.

The blood collection container according to the present invention has the above-mentioned configuration, which improves the solubility of the serine protease inhibitor and the anticoagulant in blood and suppresses the occurrence of partial coagulation and hemolysis of blood.

Conventionally, blood collection containers in which a drug containing a serine protease inhibitor and an anticoagulant (a mixture of a serine protease inhibitor and an anticoagulant) is applied to the inner surface of the blood collection container body have been widely used. However, in this blood collection container, the serine protease inhibitor and the anticoagulant do not dissolve sufficiently in the blood, and partial coagulation of the blood or hemolysis may occur. For example, in a conventional blood collection container, if the blood is not sufficiently mixed by inversion after collection, the drug may not be distributed throughout the blood, and partial coagulation of the blood may occur. In addition, in a conventional blood collection container, if the blood is not sufficiently mixed by inversion after collection, the drug may remain on the inner surface of the blood collection container body, and blood may adhere to the remaining drug, causing hemolysis.

The inventors have found that by not mixing the serine protease inhibitor and the anticoagulant and by establishing a specific positional relationship between the region where the serine protease inhibitor is present and the region where the anticoagulant is present, the solubility of the serine protease inhibitor and the anticoagulant in blood can be improved and the occurrence of partial coagulation and hemolysis of blood can be suppressed. In other words, the inventors have found that a blood collection container having the above configuration can improve the solubility of the serine protease inhibitor and the anticoagulant in blood and suppress the occurrence of partial coagulation and hemolysis of blood.

Specific embodiments of the present invention will be described below with reference to the drawings. The following Figures 1 to 6 show front cross-sectional views of a blood collection container in an upright position. The upright position is a position in which the closed end of the blood collection container body is positioned downward.

Figure 1 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a first embodiment of the present invention.

The blood collection container 11 shown in FIG. 1 comprises a serine protease inhibitor 1, an anticoagulant 2, a blood collection container body 3, and a stopper 4. The blood collection container body 3 has a closed end 3a and an open end 3b. The closed end 3a is one end of the blood collection container body 3 in the length direction, and the open end 3b is the other end of the blood collection container body 3 in the length direction. The serine protease inhibitor 1 and the anticoagulant 2 are each contained within the blood collection container body 3. The stopper 4 is attached to the open end 3b of the blood collection container body 3. The blood collection container 11 is tubular and is a vacuum blood collection tube.

The serine protease inhibitor 1 is disposed on the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1 is attached to the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1 is disposed in a layer on the inner surface 3c of the blood collection container body 3.

The region R1 in which the serine protease inhibitor 1 is placed is a circular region. The end 1a on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1 is placed is located above the closed end 3a of the blood collection container body 3. The end 1b on the open end 3b side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1 is placed is located below the open end 3b of the blood collection container body 3.

The anticoagulant 2 is contained in the blood collection container body 3 in granular form. The anticoagulant 2 is a granular anticoagulant. The anticoagulant 2 is present on the closed end 3a side of the blood collection container body 3 from the region R1 in which the serine protease inhibitor 1 is placed. The anticoagulant 2 is present on the closed end 3a side from the end 1a on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1 is placed.

In FIG. 1, all of the granular anticoagulant 2 is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1 is placed. However, in the present invention, it is sufficient that at least a portion of the anticoagulant 2 is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1 is placed. For example, due to vibrations or the like when transporting the blood collection container 11, a portion of the granular anticoagulant 2 may adhere to the region R1 in which the serine protease inhibitor 1 is placed.

Figure 2 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a second embodiment of the present invention.

The blood collection container 11A shown in FIG. 2 comprises a serine protease inhibitor 1A, an anticoagulant 2A, a blood collection container body 3, and a stopper 4. The blood collection container body 3 has a closed end 3a and an open end 3b. The closed end 3a is one end in the length direction of the blood collection container body 3, and the open end 3b is the other end in the length direction of the blood collection container body 3. The serine protease inhibitor 1A and the anticoagulant 2A are each contained within the blood collection container body 3. The stopper 4 is attached to the open end 3b of the blood collection container body 3. The blood collection container 11A is tubular and is a vacuum blood collection tube.

The serine protease inhibitor 1A is disposed on the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1A is attached to the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1A is disposed in a layer on the inner surface 3c of the blood collection container body 3.

The region R1 in which the serine protease inhibitor 1A is disposed is a circular region. In the region R1 in which the serine protease inhibitor 1A is disposed, the end 1Aa on the closed end 3a side of the blood collection container body 3 is located above the closed end 3a of the blood collection container body 3. In the region R1 in which the serine protease inhibitor 1A is disposed, the end 1Ab on the open end 3b side of the blood collection container body 3 is located below the open end 3b of the blood collection container body 3.

The anticoagulant 2A is disposed on the inner surface 3c of the blood collection container body 3. The anticoagulant 2A adheres to the inner surface 3c of the blood collection container body 3. The anticoagulant 2A is disposed in a layer on the inner surface 3c of the blood collection container body 3.

The region R2 in which the anticoagulant 2A is disposed is a circular region. The end 2Aa on the closed end 3a side of the blood collection container body 3 in the region R2 in which the anticoagulant 2A is disposed is located above the closed end 3a of the blood collection container body 3. The end 2Ab on the open end 3b side of the blood collection container body 3 in the region R2 in which the anticoagulant 2A is disposed is located below the open end 3b of the blood collection container body 3.

In the blood collection container 11A, at least a portion of the anticoagulant 2A is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1A is placed. In the blood collection container 11A, at least a portion of the anticoagulant 2A is present on the closed end 3a side, relative to the end 1Aa on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1A is placed.

In the blood collection container 11A, the region R2 in which the anticoagulant 2A is disposed has a region that is located closer to the closed end 3a than the end 1Aa on the closed end 3a side of the region R1 in which the serine protease inhibitor 1A is disposed. The end 2Aa on the closed end 3a side of the region R2 in which the anticoagulant 2A is disposed is located closer to the closed end 3a than the end 1Aa on the closed end 3a side of the region R1 in which the serine protease inhibitor 1A is disposed.

In the blood collection container 11A, the region R1 in which the serine protease inhibitor 1A is disposed has a region that is located closer to the opening end 3b than the end 2Ab on the opening end 3b side of the region R2 in which the anticoagulant 2A is disposed. The end 1Ab on the opening end 3b side of the region R1 in which the serine protease inhibitor 1A is disposed is located closer to the opening end 3b than the end 2Ab on the opening end 3b side of the region R2 in which the anticoagulant 2A is disposed.

In the blood collection container 11A, the end 1Aa on the closed end 3a side of the region R1 in which the serine protease inhibitor 1A is disposed is located closer to the closed end 3a side than the end 2Ab on the open end 3b side of the region R2 in which the anticoagulant 2A is disposed. Therefore, in the blood collection container 11A, there is an overlapping region R12 where the region R1 in which the serine protease inhibitor 1A is disposed and the region R2 in which the anticoagulant 2A is disposed overlap. In the blood collection container 11A, the overlapping region R12 is a circular region.

In overlap region R12, serine protease inhibitor 1A and anticoagulant 2A are present in a mixed state.

Figure 3 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a third embodiment of the present invention.

The blood collection container 11B shown in FIG. 3 comprises a serine protease inhibitor 1B, an anticoagulant 2B, a blood collection container body 3, and a stopper 4. The blood collection container body 3 has a closed end 3a and an open end 3b. The closed end 3a is one end in the length direction of the blood collection container body 3, and the open end 3b is the other end in the length direction of the blood collection container body 3. The serine protease inhibitor 1B and the anticoagulant 2B are each contained within the blood collection container body 3. The stopper 4 is attached to the open end 3b of the blood collection container body 3. The blood collection container 11B is tubular and is a vacuum blood collection tube.

The serine protease inhibitor 1B is disposed on the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1B is attached to the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1B is disposed in a layer on the inner surface 3c of the blood collection container body 3.

The region R1 in which the serine protease inhibitor 1B is disposed is a circular region. The end 1Ba on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1B is disposed is located above the closed end 3a of the blood collection container body 3. The end 1Bb on the open end 3b side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1B is disposed is located below the open end 3b of the blood collection container body 3.

Anticoagulant 2B is disposed on the inner surface 3c of the blood collection container body 3. Anticoagulant 2B adheres to the inner surface 3c of the blood collection container body 3. Anticoagulant 2B is disposed in a layer on the inner surface 3c of the blood collection container body 3.

The region R2 in which the anticoagulant 2B is disposed is a circular region. The end 2Ba on the closed end 3a side of the blood collection container body 3 in the region R2 in which the anticoagulant 2B is disposed is located above the closed end 3a of the blood collection container body 3. The end 2Bb on the open end 3b side of the blood collection container body 3 in the region R2 in which the anticoagulant 2B is disposed is located below the open end 3b of the blood collection container body 3.

In the blood collection container 11B, the entire anticoagulant 2B is present on the closed end 3a side of the blood collection container body 3, rather than the region R1 in which the serine protease inhibitor 1B is placed. In the blood collection container 11B, the entire anticoagulant 2B is present on the closed end 3a side of the end 1Ba on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1B is placed.

Therefore, in the blood collection container 11B, there is no overlapping region between the region R1 in which the serine protease inhibitor 1B is placed and the region R2 in which the anticoagulant 2B is placed.

Figure 4 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a fourth embodiment of the present invention.

The blood collection container 11C shown in FIG. 4 comprises a serine protease inhibitor 1C, an anticoagulant 2C, a blood collection container body 3, and a stopper 4. The blood collection container body 3 has a closed end 3a and an open end 3b. The closed end 3a is one end in the length direction of the blood collection container body 3, and the open end 3b is the other end in the length direction of the blood collection container body 3. The serine protease inhibitor 1C and the anticoagulant 2C are each contained within the blood collection container body 3. The stopper 4 is attached to the open end 3b of the blood collection container body 3. The blood collection container 11C is tubular and is a vacuum blood collection tube.

The serine protease inhibitor 1C is disposed on the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1C is attached to the inner surface 3c of the blood collection container body 3. The serine protease inhibitor 1C is disposed in a layer on the inner surface 3c of the blood collection container body 3. For convenience of illustration, in FIG. 4, the serine protease inhibitor 1C is disposed inside the region in which the anticoagulant 2C is disposed.

The region R1 in which the serine protease inhibitor 1C is disposed is a circular region. The end 1Ca on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1C is disposed is located above the closed end 3a of the blood collection container body 3. The end 1Cb on the open end 3b side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1C is disposed is located below the open end 3b of the blood collection container body 3.

The anticoagulant 2C is disposed on the inner surface 3c of the blood collection container body 3. The anticoagulant 2C adheres to the inner surface 3c of the blood collection container body 3. The anticoagulant 2C is disposed in a layer on the inner surface 3c of the blood collection container body 3.

The region R2 in which the anticoagulant 2C is disposed is a circular region. The end 2Ca on the closed end 3a side of the blood collection container body 3 in the region R2 in which the anticoagulant 2C is disposed is located above the closed end 3a of the blood collection container body 3. The end 2Cb on the open end 3b side of the blood collection container body 3 in the region R2 in which the anticoagulant 2C is disposed is located below the open end 3b of the blood collection container body 3.

In the blood collection container 11C, at least a portion of the anticoagulant 2C is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1C is placed. In the blood collection container 11C, at least a portion of the anticoagulant 2C is present on the closed end 3a side, relative to the end 1Ca on the closed end 3a side of the blood collection container body 3 in the region R1 in which the serine protease inhibitor 1C is placed.

In the blood collection container 11C, the region R2 in which the anticoagulant 2C is disposed has a region that is located closer to the closed end 3a than the end 1Ca on the closed end 3a side of the region R1 in which the serine protease inhibitor 1C is disposed. The end 2Ca on the closed end 3a side of the region R2 in which the anticoagulant 2C is disposed is located closer to the closed end 3a than the end 1Ca on the closed end 3a side of the region R1 in which the serine protease inhibitor 1C is disposed.

In the blood collection container 11C, the end 1Cb on the opening end 3b side of the region R1 in which the serine protease inhibitor 1C is placed and the end 2Cb on the opening end 3b side of the region R2 in which the anticoagulant 2C is placed are in the same position. Therefore, in the blood collection container 11C, there is an overlapping region R12 in which the region R1 in which the serine protease inhibitor 1C is placed and the region R2 in which the anticoagulant 2C is placed overlap. In the blood collection container 11C, the overlapping region R12 is a circular ring-shaped region. The overlapping region R12 coincides with the region R1 in which the serine protease inhibitor 1C is placed.

In overlap region R12, serine protease inhibitor 1C and anticoagulant 2C are present in a mixed state.

Figure 5 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a fifth embodiment of the present invention.

The blood collection container 11D shown in FIG. 5 comprises a serine protease inhibitor 1D, an anticoagulant 2D, a blood collection container body 3, and a stopper 4. The blood collection container body 3 has a closed end 3a and an open end 3b. The closed end 3a is one end in the length direction of the blood collection container body 3, and the open end 3b is the other end in the length direction of the blood collection container body 3. The serine protease inhibitor 1D and the anticoagulant 2D are each contained within the blood collection container body 3. The stopper 4 is attached to the open end 3b of the blood collection container body 3. The blood collection container 11D is tubular and is a vacuum blood collection tube.

The blood collection container 11 shown in FIG. 1 and the blood collection container 11D shown in FIG. 5 differ in the way the anticoagulant is contained. That is, in the blood collection container 11 shown in FIG. 1, the anticoagulant is contained in the blood collection container body 3 in the form of granules, whereas in the blood collection container 11D shown in FIG. 5, the anticoagulant is contained in the blood collection container body 3 in the form of powder. In other respects, the blood collection container 11D is the same as the blood collection container 11.

In FIG. 5, all of the powdered anticoagulant 2D is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1D is placed. However, in the present invention, it is sufficient that at least a portion of the anticoagulant 2D is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1D is placed. For example, due to vibrations or the like when transporting the blood collection container 11D, a portion of the powdered anticoagulant 2D may adhere to the region R1 in which the serine protease inhibitor 1D is placed.

Figure 6 is a front cross-sectional view showing a schematic diagram of a blood collection container according to a sixth embodiment of the present invention.

The blood collection container 11E shown in FIG. 6 comprises a serine protease inhibitor 1E, a liquid 2E containing an anticoagulant, a blood collection container body 3, and a stopper 4. The blood collection container body 3 has a closed end 3a and an open end 3b. The closed end 3a is one end in the length direction of the blood collection container body 3, and the open end 3b is the other end in the length direction of the blood collection container body 3. The serine protease inhibitor 1E and the liquid 2E containing an anticoagulant are each contained within the blood collection container body 3. The stopper 4 is attached to the open end 3b of the blood collection container body 3. The blood collection container 11E is tubular and is a vacuum blood collection tube.

The blood collection container 11 shown in FIG. 1 and the blood collection container 11E shown in FIG. 6 differ in the way the anticoagulant is stored. That is, in the blood collection container 11 shown in FIG. 1, the anticoagulant is stored in the blood collection container body 3 in the form of granules, whereas in the blood collection container 11E shown in FIG. 6, the anticoagulant is stored in the blood collection container body 3 in the form of a solution in liquid. In other respects, the blood collection container 11E is the same as the blood collection container 11.

In FIG. 6, all of the anticoagulant-containing liquid 2E is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1E is placed. However, in the present invention, it is sufficient that at least a portion of the anticoagulant-containing liquid 2E is present on the closed end 3a side of the blood collection container body 3, relative to the region R1 in which the serine protease inhibitor 1E is placed. For example, due to vibrations or the like when transporting the blood collection container 11E, a portion of the anticoagulant-containing liquid 2E may adhere to the region R1 in which the serine protease inhibitor 1E is placed.

The blood collection container according to the present invention will be described in more detail below.

<Serine protease inhibitors>
The serine protease inhibitor is disposed on the inner surface of the blood collection container body. The serine protease inhibitor is preferably disposed in a layer on the inner surface of the blood collection container body. The serine protease inhibitor is preferably attached to the inner surface of the blood collection container body. In this case, the serine protease inhibitor may be attached to the inner surface of the blood collection container body via, for example, a water-soluble binder described below. By using the serine protease inhibitor, it is possible to prevent the measurement substance in the blood from being decomposed by serine proteases.

As the serine protease inhibitor, a conventionally known serine protease inhibitor can be used. Examples of the serine protease inhibitor include aprotinin, DPP-4 inhibitor (dipeptidyl peptidase 4 inhibitor), antitrypsin, antithrombin, AEBSF (4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride), and benzamidine. Only one type of the serine protease inhibitor may be used, or two or more types may be used in combination.

The above DPP-4 inhibitors include sitagliptin, saxagliptin, linagliptin, alogliptin, vildagliptin, anagliptin, and teneligliptin.

The serine protease inhibitor preferably contains aprotinin or a DPP-4 inhibitor, more preferably contains aprotinin and a DPP-4 inhibitor, and even more preferably is aprotinin. In this case, tests targeting human atrial natriuretic peptide (HANP) and parathyroid hormone-related protein (PTHrP), etc., can be performed with high accuracy. The aprotinin may be aprotinin derived from bovine lung.

The DPP-4 inhibitor preferably includes sitagliptin, saxagliptin, linagliptin, alogliptin, vildagliptin, anagliptin, or teneligliptin. In this case, tests targeting human atrial natriuretic peptide (HANP) and parathyroid hormone-related protein (PTHrP), etc., can be performed with high accuracy.

In the blood collection container, the content of the serine protease inhibitor is preferably 200 KIU or more, more preferably 300 KIU or more, preferably 5000 KIU or less, more preferably 2000 KIU or less per mL of collected blood. When the content of the serine protease inhibitor is equal to or more than the lower limit and equal to or less than the upper limit, the measurement substance in the blood can be effectively prevented from being decomposed by serine proteases.

In the blood collection container, the aprotinin content is preferably 200 KIU or more, more preferably 300 KIU or more, and preferably 5000 KIU or less, more preferably 2000 KIU or less per mL of collected blood. When the aprotinin content is equal to or more than the lower limit and equal to or less than the upper limit, the measurement substance in the blood can be effectively prevented from being decomposed by serine proteases.

<Anticoagulant>
The anticoagulant is contained within the blood collection container body, and when the blood collection container is in an upright position, at least a portion of the anticoagulant is present within the blood collection container body on the closed end side of the blood collection container body relative to a region in which the serine protease inhibitor is disposed.

As the anticoagulant, a conventionally known anticoagulant can be used. Examples of the anticoagulant include ethylenediaminetetraacetic acid (EDTA), metal salts of EDTA, heparin, heparin salts, citric acid, and citrate salts. Examples of the heparin salts include metal salts of heparin. Examples of the citrate salts include sodium citrate. Only one type of the anticoagulant may be used, or two or more types may be used in combination.

From the viewpoint of exhibiting good anticoagulant performance, the anticoagulant is preferably EDTA, a metal salt of EDTA, heparin, a heparin salt, citric acid or a citrate salt, and more preferably EDTA, a metal salt of EDTA, heparin, a metal salt of heparin or sodium citrate. From the viewpoint of exhibiting even better anticoagulant performance, the anticoagulant is preferably EDTA or a metal salt of EDTA. From the viewpoint of suitable combination with a test reagent for human atrial natriuretic peptide (HANP) and parathyroid hormone-related protein (PTHrP), etc., the serine protease inhibitor is preferably aprotinin, and the anticoagulant is preferably EDTA or a metal salt of EDTA.

The form in which the anticoagulant is contained in the blood collection container body is not particularly limited. The anticoagulant may be disposed on the inner surface of the blood collection container body. The anticoagulant may be attached to the inner surface of the blood collection container body. The anticoagulant may be disposed in a layer on the inner surface of the blood collection container body. The anticoagulant may be contained in the blood collection container body in a granular state, or in a powdered state. The anticoagulant may be a granular anticoagulant, or in a powdered state. The anticoagulant may be contained in the blood collection container body in a dissolved state in a liquid, or in a dissolved state in water. The anticoagulant may be contained in the blood collection container body as a solute of a solution.

In this specification, "granular" means that the average particle size is 200 μm or more and 2000 μm or less, and "powder" means that the average particle size is 0.1 μm or more and less than 200 μm.

The granular anticoagulant and the powdered anticoagulant may each be composed of an anticoagulant hydrate. That is, when the anticoagulant is contained in the blood collection container body in a granular state, the anticoagulant may be a hydrate. Also, when the anticoagulant is contained in the blood collection container body in a powdered state, the anticoagulant may be a hydrate.

From the viewpoint of further increasing the solubility in blood, the anticoagulant is preferably a granular anticoagulant or a powdered anticoagulant, and more preferably a granular anticoagulant. From the viewpoint of further increasing the solubility in blood, the anticoagulant is preferably contained in the blood collection container body in a granular or powdered state, and more preferably contained in the blood collection container body in a granular state. Furthermore, when the anticoagulant is a granular anticoagulant, the manufacturing efficiency of the blood collection container can be improved and the solidification of the anticoagulant due to moisture absorption can be effectively prevented compared to when the anticoagulant is a powdered anticoagulant.

The average particle size of the granular anticoagulant is 200 μm or more and 2000 μm or less, preferably 300 μm or more, more preferably 400 μm or more, even more preferably 450 μm or more, particularly preferably 500 μm or more, preferably 1000 μm or less, more preferably 970 μm or less, even more preferably 850 μm or less, even more preferably 750 μm or less, even more preferably 700 μm or less, and particularly preferably 650 μm or less. If the average particle size is equal to or greater than the lower limit, solidification upon moisture absorption can be effectively prevented. If the average particle size is equal to or less than the upper limit, solubility in blood can be further improved.

The average particle size of the powdered anticoagulant is 0.1 μm or more and less than 200 μm, preferably 1 μm or more, more preferably 10 μm or more, even more preferably 20 μm or more, particularly preferably 40 μm or more, preferably 100 μm or less, more preferably 80 μm or less, even more preferably 70 μm or less.

The median diameter (d50) at 50% is used as the average particle size of the anticoagulant. The average particle size can be measured using a laser diffraction scattering type particle size distribution measuring device (e.g., Malvern Panalytical's "Mastersizer 3000"). The analysis conditions can be, for example, particle refractive index: 1.490, dispersion medium refractive index: 1.330, and laser scattering intensity: 5.68%.

When the anticoagulant is dissolved in a liquid and contained in the blood collection container body, the amount of the liquid containing the anticoagulant contained in the blood collection container body is preferably 0.01 mL or more, more preferably 0.2 mL or more, preferably 2 mL or less, more preferably 1 mL or less. When the amount of the liquid containing the anticoagulant is equal to or more than the lower limit and equal to or less than the upper limit, the blood is not excessively diluted and the effects of the present invention can be more effectively achieved.

In the blood collection container, the content of the anticoagulant is preferably 2 mg or more, more preferably 4 mg or more, and preferably 6 mg or less, and more preferably 5 mg or less per mL of collected blood. When the content of the anticoagulant is equal to or more than the lower limit and equal to or less than the upper limit, the anticoagulant performance can be satisfactorily exhibited, and the effects of the present invention can be exhibited even more effectively.

<Blood collection container body>
The shape of the blood collection container body is not particularly limited. The blood collection container body is preferably a tubular container with a bottom.

The material of the blood collection container body is not particularly limited. Examples of materials for the blood collection container body include thermoplastic resins such as polyethylene, polypropylene, polystyrene, polyethylene terephthalate, polymethyl methacrylate, and polyacrylonitrile; thermosetting resins such as unsaturated polyester resins, epoxy resins, and epoxy-acrylate resins; modified natural resins such as cellulose acetate, cellulose propionate, ethyl cellulose, and ethyl chitin; and glass such as silicate glass, such as soda-lime glass, phosphosilicate glass, and borosilicate glass, and quartz glass. Only one type of material may be used for the blood collection container body, or two or more types may be used in combination.

From the viewpoint of increasing the strength and oxygen barrier properties of the blood collection container body, and from the viewpoint of improving the visibility of the contents, it is preferable that the material of the blood collection container body is polyethylene terephthalate. The blood collection container body is preferably a polyethylene terephthalate container (PET container), and more preferably a polyethylene terephthalate tube (PET tube).

<Plug>
The blood collection container preferably includes a stopper. The stopper is preferably attached to the open end of the blood collection container body. A conventionally known stopper can be used as the stopper. The stopper is preferably made of a material and has a shape that allows it to be attached to the open end of the blood collection container body in an airtight and liquidtight manner. The stopper is preferably configured to be pierced by a blood collection needle.

Examples of the stopper include a stopper shaped to fit into the open end of the blood collection container body, a sheet-shaped seal stopper, etc.

The stopper may also be a stopper comprising a stopper body such as a rubber stopper and a cap member made of plastic or the like. In this case, the risk of blood coming into contact with the human body can be reduced when the stopper body is pulled out from the open end of the blood collection container body after blood collection.

Examples of the material of the stopper (or the stopper body) include synthetic resin, elastomer, rubber, metal foil, etc. Examples of the rubber include butyl rubber and halogenated butyl rubber, etc. Examples of the metal foil include aluminum foil, etc. From the viewpoint of improving the sealing performance, the material of the stopper (or the stopper body) is preferably butyl rubber. The stopper (or the stopper body) is preferably a butyl rubber stopper.

<Other details of blood collection container>
The length of the blood collection container body is designated as L. L is usually the distance between the closed end and the open end of the blood collection container body.

When the anticoagulant is a granular anticoagulant, when the anticoagulant is a powdered anticoagulant, or when the anticoagulant is dissolved in a liquid and contained in the blood collection container body, the region (region R1) in which the serine protease inhibitor is disposed is preferably present in at least a portion of the region between the 0.1 L position and the 1 L position from the closed end toward the open end of the blood collection container body, and more preferably present in at least a portion of the region between the 0.2 L position and the 0.9 L position. In this case, the effect of the present invention can be exerted even more effectively.

When the anticoagulant is a granular anticoagulant, when the anticoagulant is a powdered anticoagulant, or when the anticoagulant is dissolved in a liquid and contained in the blood collection container body, the end of the closed end side of the blood collection container body in the region (region R1) where the serine protease inhibitor is arranged is preferably located closer to the open end than the position of 0.1 L from the closed end toward the open end of the blood collection container body, more preferably located closer to the open end than the position of 0.2 L, preferably located closer to the closed end than the position of 0.9 L, and more preferably located closer to the closed end than the position of 0.8 L. In this case, the effect of the present invention can be exerted even more effectively.

When the anticoagulant is disposed on the inner surface of the blood collection container body (when the anticoagulant is attached to the inner surface of the blood collection container body), the region where the serine protease inhibitor is disposed (region R1) is preferably present in at least a portion of the region between the 0.1 L position and the 0.9 L position from the closed end toward the open end of the blood collection container body, and more preferably present in at least a portion of the region between the 0.2 L position and the 0.8 L position. In this case, the effect of the present invention can be exerted even more effectively.

When the anticoagulant is disposed on the inner surface of the blood collection container body (when the anticoagulant is attached to the inner surface of the blood collection container body), the end of the closed end side of the blood collection container body in the region (region R1) where the serine protease inhibitor is disposed is preferably located closer to the open end than the position of 0.4 L from the closed end of the blood collection container body toward the open end, and more preferably located closer to the open end than the position of 0.6 L. In this case, the effect of the present invention can be exerted even more effectively.

When the anticoagulant is disposed on the inner surface of the blood collection container body (when the anticoagulant is attached to the inner surface of the blood collection container body), the region in which the anticoagulant is disposed (region R2) is preferably present in at least a portion of the region between the 0L position and the 0.9L position from the closed end toward the open end of the blood collection container body, and more preferably present in at least a portion of the region between the 0.1L position and the 0.8L position. In this case, the effect of the present invention can be exerted even more effectively.

When the anticoagulant is disposed on the inner surface of the blood collection container body (when the anticoagulant is attached to the inner surface of the blood collection container body), the end of the blood collection container body on the closed end side in the region where the anticoagulant is disposed (region R2) is preferably located closer to the open end than the 0L position from the closed end toward the open end of the blood collection container body, more preferably closer to the open end than the 0.1L position, preferably closer to the closed end than the 0.9L position, and more preferably closer to the closed end than the 0.8L position. In this case, the effect of the present invention can be exerted even more effectively.

When the anticoagulant is disposed on the inner surface of the blood collection container body (when the anticoagulant is attached to the inner surface of the blood collection container body), the end of the blood collection container body on the opening end side in the region where the anticoagulant is disposed (region R2) is preferably located closer to the opening end than the position of 0.1L from the closed end toward the opening end of the blood collection container body, more preferably closer to the opening end than the position of 0.2L, preferably closer to the closed end than the position of 0.9L, and more preferably closer to the closed end than the position of 0.8L. In this case, the effect of the present invention can be exerted even more effectively.

The blood collection container is a blood collection container from which a predetermined amount of blood is collected. The predetermined amount of blood is changed as appropriate depending on the size and internal pressure of the blood collection container. The predetermined amount of blood may be 1 mL or more, 2 mL or more, 4 mL or more, 12 mL or less, 11 mL or less, or 10 mL or less.

In the blood collection container, a plasma separation material may or may not be contained in the blood collection container body. In the blood collection container, it is preferable that a plasma separation material is not contained in the blood collection container body. The plasma separation material is a composition (plasma separation composition) or a tool (plasma separation tool) that moves between the plasma layer and the blood cell layer during centrifugation to form a partition. Examples of the plasma separation composition include a composition containing an organic component having fluidity at 25°C and an inorganic fine powder (for example, a composition described in WO2010/053180A1). Examples of the plasma separation tool include a mechanical separator described in WO2010/132783A1, etc.

The blood collection container is preferably a blood collection tube.

The internal pressure of the blood collection container is not particularly limited. It is preferable that the internal pressure of the blood collection container is reduced. When the blood collection container is a reduced pressure container, a predetermined amount of blood can be easily collected in the blood collection container. The blood collection container can also be used as a vacuum blood collection tube in which the inside is evacuated and sealed with the stopper. When it is a vacuum blood collection tube, a constant amount of blood can be easily collected regardless of the skill level of the blood collector.

To prevent bacterial infection, it is preferable that the inside of the blood collection container be sterilized in accordance with ISO or JIS standards.

The blood collection container containing a granular or powdered anticoagulant can be manufactured, for example, as follows.

A first composition containing a serine protease inhibitor is prepared. The first composition is placed on the inner surface of the blood collection container body. Before or after placing the first composition on the inner surface of the blood collection container body, a granular or powdered anticoagulant is placed in the bottom of the blood collection container body. Next, a stopper is attached to the opening of the blood collection container body. For example, when two types of serine protease inhibitors are used, the first composition containing the two types of serine protease inhibitors may be placed on the inner surface of the blood collection container body, or a first composition A containing a first type of serine protease inhibitor and a first composition B containing a second type of serine protease inhibitor may be placed on the inner surface of the blood collection container body.

The blood collection container in which the anticoagulant is dissolved in liquid and contained within the blood collection container body can be manufactured, for example, as follows.

A first composition containing a serine protease inhibitor is prepared. The first composition is placed on the inner surface of the blood collection container body. Before or after placing the first composition on the inner surface of the blood collection container body, a liquid containing an anticoagulant (preferably a mixture of an anticoagulant and water) is placed in the bottom of the blood collection container body. Next, a stopper is attached to the opening of the blood collection container body. For example, when two types of serine protease inhibitors are used, the first composition containing the two types of serine protease inhibitors may be placed on the inner surface of the blood collection container body, or a first composition A containing a first type of serine protease inhibitor and a first composition B containing a second type of serine protease inhibitor may be placed on the inner surface of the blood collection container body.

The blood collection container in which the anticoagulant is disposed on the inner surface of the blood collection container body can be manufactured, for example, as follows.

A first composition containing a serine protease inhibitor and a second composition containing an anticoagulant are prepared. The first composition and the second composition are each placed on the inner surface of the blood collection container body. Next, a stopper is attached to the opening of the blood collection container body. For example, when two types of serine protease inhibitors are used, the first composition containing the two types of serine protease inhibitors may be placed on the inner surface of the blood collection container body, or a first composition A containing a first type of serine protease inhibitor and a first composition B containing a second type of serine protease inhibitor may be placed on the inner surface of the blood collection container body.

The region where the first composition is placed corresponds to the region (region R1) where the serine protease inhibitor is placed in the blood collection container. The region where the second composition is placed corresponds to the region (region R2) where the anticoagulant is placed in the blood collection container.

The first and second compositions can be placed on the inner surface of the blood collection container body by known techniques such as coating and spraying. The coating method is not particularly limited. Examples of the coating method include spray coating and dipping coating. After the first and second compositions are applied to the inner surface of the blood collection container body, it is preferable to dry them.

The application order (arrangement order) of the first composition and the second composition is not particularly limited.

Each of the first composition and the second composition may contain other components such as water, an organic solvent, a water-soluble binder, and a clot detachment component. In this case, each of the regions R1 and R2 may also contain the other components described above.

The organic solvents include methanol, ethanol, butanol, isopropanol, hexane, etc. The organic solvents may be used alone or in combination of two or more.

Examples of the water-soluble binder include polyvinyl alcohol, polyvinylpyrrolidone, acrylic acid copolymers, and polyoxyalkylene block copolymers. Only one type of the water-soluble binder may be used, or two or more types may be used in combination.

The clot detaching component may be silicone oil, polyvinylpyrrolidone, polyvinyl alcohol, polyoxyalkylene, or derivatives thereof. The clot detaching component may be used alone or in combination of two or more. The silicone oil may be a water-soluble modified silicone oil, which is preferably used. The polyoxyalkylene and its derivatives may be polyoxypropylene butyl ether, polyoxyethylene butyl ether, polyoxypropylene glyceryl ether, polyoxyethylene glyceryl ether, etc., which are preferably used.

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

The following blood collection containers were prepared:

A blood collection container body having the shape shown in FIG. 1. Inner diameter 10.5 mm x length 75.6 mm (length: distance between closed end and open end)
Material: Polyethylene terephthalate

The following stoppers were prepared:

A stopper having the shape shown in FIG. 1 Rubber stopper (material: butyl rubber)

The following medications were prepared:

(Serine protease inhibitors)
Aprotinin ("Aprotinin" manufactured by BIOSYNTH Carbosynth)
DPP-4 inhibitor-containing solution (Merck Millipore's "DPP IV Inhibitor")

(Anticoagulant)
EDTA granules: granular disodium ethylenediaminetetraacetate dihydrate (EDTA2Na.2H ₂ O) ("EDTA2Na Granules" manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., average particle size: 570 μm)
EDTA powder: powdered disodium ethylenediaminetetraacetate dihydrate (EDTA2Na.2H ₂ O) ("EDTA2Na" manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., average particle size: 66 μm)

Example 1
3.73 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition. The obtained first composition was sprayed onto the inner surface of the blood collection container body, and then dried. The area where the first composition was sprayed is shown in the table below. Next, 2.0 mg of EDTA granules per 1 mL of blood to be collected was placed in the bottom of the blood collection container body. Next, the blood collection container body was decompressed to 52 kPa, and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube).

Example 2
A blood collection container (vacuum blood collection tube) was produced in the same manner as in Example 1, except that 1.5 mg of EDTA granules per 1 mL of blood to be collected was placed in the bottom of the blood collection container body.

Example 3
3.73 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition. 783 mg of EDTA powder was completely dissolved in 9.217 g of water to obtain a second composition. The obtained second composition was sprayed onto the inner surface of the blood collection container body and then dried. Next, the obtained first composition was sprayed onto the inner surface of the blood collection container body and then dried. The areas where the first composition and the second composition were sprayed are shown in the table below. Next, the blood collection container body was depressurized to 52 kPa and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube).

Example 4
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 3, except that the areas to which the first composition and the second composition were sprayed were changed as shown in the table below.

Example 5
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 1, except that EDTA powder was used and 1.5 mg of EDTA powder was placed in the bottom of the blood collection container body for each 1 mL of blood to be collected.

Example 6
3.73 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition. 783 mg of EDTA powder was completely dissolved in 9.217 g of water to obtain a second composition. The obtained first composition was sprayed onto the inner surface of the blood collection container body and then dried. Next, 40 μL of the obtained second composition was added to the bottom of the blood collection container body. The area where the first composition was sprayed is shown in the table below. Next, the blood collection container body was depressurized to 52 kPa and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube).

(Example 7)
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 1, except that 37.3 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition.

(Example 8)
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 3, except that 37.3 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition.

Example 9
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 4, except that 37.3 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition.

Example 10
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 5, except that 37.3 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition.

(Example 11)
A blood collection container (vacuum blood collection tube) was prepared in the same manner as in Example 6, except that 37.3 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition.

(Comparative Example 1)
3.73 mg of aprotinin and 783 mg of EDTA powder were completely dissolved in 9.217 g of water to obtain composition X. The obtained composition X was sprayed onto the inner surface of the blood collection container body and then dried. The area where composition X was sprayed is shown in the table below. Next, the blood collection container body was depressurized to 52 kPa and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube).

(Comparative Example 2)
37.3 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition. 783 mg of EDTA powder was completely dissolved in 9.217 g of water to obtain a second composition. The obtained first composition was sprayed onto the inner surface of the blood collection container body and then dried. Next, the obtained second composition was sprayed onto the inner surface of the blood collection container body and then dried. The areas where the first composition and the second composition were sprayed are shown in the table below. Next, the blood collection container body was depressurized to 52 kPa and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube).

(Examples 12 to 15)
A blood collection container (vacuum blood collection tube) was produced in Example 12 in the same manner as Example 1, in Example 13 in the same manner as Example 3, in Example 14 in the same manner as Example 4, and in Example 15 in the same manner as Example 6, except that 10 μL of a DPP-4 inhibitor-containing liquid (first composition) per 1 mL of blood to be collected was sprayed onto the inner surface of the blood collection container body and then dried.

(Examples 16 to 19)
A blood collection container (vacuum blood collection tube) was produced in Example 16 in the same manner as Example 1, in Example 17 in the same manner as Example 3, in Example 18 in the same manner as Example 4, and in Example 19 in the same manner as Example 6, except that 100 μL of a DPP-4 inhibitor-containing liquid (first composition) per 1 mL of blood to be collected was sprayed onto the inner surface of the blood collection container body and then dried.

(Example 20)
3.73 mg of aprotinin was completely dissolved in 10 g of water to obtain a first composition A. The obtained first composition A was sprayed onto the inner surface of the blood collection container body, and then dried. Next, 10 μL of a DPP-4 inhibitor-containing liquid (first composition B) per 1 mL of blood to be collected was sprayed onto the inner surface of the blood collection container body, and then dried. The areas sprayed with the first composition A and the first composition B are shown in the table below. Next, 2.0 mg of EDTA granules per 1 mL of blood to be collected were placed in the bottom of the blood collection container body. Next, the blood collection container body was decompressed to 52 kPa, and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube). In the obtained blood collection container, aprotinin and a DPP-4 inhibitor were disposed on the inner surface of the blood collection container body.

(Examples 21 and 22)
3.73 mg of aprotinin was completely dissolved in 10 g of water to obtain the first composition A. 783 mg of EDTA powder was completely dissolved in 9.217 g of water to obtain the second composition. The obtained second composition was sprayed onto the inner surface of the blood collection container body and then dried. Next, the obtained first composition A was sprayed onto the inner surface of the blood collection container body and then dried. Next, 10 μL of a DPP-4 inhibitor-containing liquid (first composition B) per 1 mL of blood to be collected was sprayed onto the inner surface of the blood collection container body and then dried. The areas sprayed with the first composition A, first composition B, and second composition are shown in the table below. Next, the blood collection container body was depressurized to 52 kPa and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube). In the obtained blood collection container, aprotinin and a DPP-4 inhibitor are disposed on the inner surface of the blood collection container body.

(Example 23)
3.73 mg of aprotinin was completely dissolved in 10 g of water to obtain the first composition A. 783 mg of EDTA powder was completely dissolved in 9.217 g of water to obtain the second composition. The obtained first composition A was sprayed onto the inner surface of the blood collection container body and then dried. Next, 10 μL of a DPP-4 inhibitor-containing liquid (first composition B) per 1 mL of blood to be collected was sprayed onto the inner surface of the blood collection container body and then dried. Next, 40 μL of the obtained second composition was added to the bottom of the blood collection container body. The areas sprayed with the first composition A and the first composition B are shown in the table below. Next, the blood collection container body was depressurized to 52 kPa and sealed with a stopper to prepare a blood collection container (vacuum blood collection tube). In the obtained blood collection container, aprotinin and a DPP-4 inhibitor are disposed on the inner surface of the blood collection container body.

(Examples 24 and 25)
A blood collection container (vacuum blood collection tube) was prepared in Example 24 in the same manner as in Example 20, and in Example 25 in the same manner as in Example 21, except that 100 μL of the DPP-4 inhibitor-containing liquid (first composition B) was used per 1 mL of blood to be collected.

(evaluation)
(1) Solubility After 2 mL of physiological saline was collected in the obtained blood collection container, it was mixed by inversion. After mixing by inversion 2 or 5 times, it was visually confirmed whether the drugs (serine protease inhibitor and anticoagulant) were dissolved in the physiological saline. Solubility was evaluated according to the following criteria.

[Solubility criteria]
◯: The drug was dissolved in physiological saline by mixing by inversion twice. △: The drug was not dissolved in physiological saline by mixing by inversion twice, but was dissolved in physiological saline by mixing by inversion five times. ×: The drug was not dissolved in physiological saline by mixing by inversion five times.

(2) Partial coagulation of blood After 2 mL of blood was collected in the obtained blood collection container, it was inverted twice to mix and left to stand for 5 minutes. Then, the blood in the blood collection container was removed. The blood collection container from which the blood had been removed was visually confirmed. Partial coagulation of blood was evaluated according to the following criteria.

[Criteria for determining partial blood coagulation]
○: No blood clots were observed in the blood collection container (no partial blood clots were observed)
×: Blood clots are observed in the blood collection container (partial blood coagulation is observed)

(3) Hemolysis After 2 mL of blood was collected in the obtained blood collection container, it was inverted 5 times to mix. Next, the blood collection container was centrifuged under the conditions of 1,500 G, 10 minutes and 20°C. 200 μL of separated plasma was collected, and the absorbance of the plasma at a wavelength of 415 nm was measured using a "SpectraMax ^TM iD5" manufactured by MOLECULAR DEVICES. In addition, the separated plasma was visually confirmed. The presence or absence of hemolysis was comprehensively judged from the absorbance and visual observation. Hemolysis was evaluated according to the following criteria.

[Criteria for determining hemolysis]
○: No hemolysis was observed ×: Hemolysis was observed (absorbance at a wavelength of 415 nm was 2.0 or more and the plasma was reddish when visually observed)

The configurations and results are shown in Tables 1 to 4. Tables 1 to 4 also show diagrams with similar configurations. As shown in the examples in Tables 1 to 4, good results were observed in all evaluation items (solubility, partial blood coagulation, hemolysis) regardless of whether the anticoagulant was contained in granular, powdered, liquid, or attached to the inner surface of the blood collection container body. Among the granular, powdered, and liquid forms, from the viewpoint of the manufacturing efficiency of the blood collection container and the viewpoint of effectively preventing the anticoagulant from adhering to unintended areas due to vibration during transportation, etc., the preferred anticoagulant containment forms are 1) granular, 2) powdered, and 3) liquid, in that order.

1, 1A, 1B, 1C, 1D, 1E...Serine protease inhibitor 1a, 1b, 1Aa, 1Ab, 1Ba, 1Bb, 1Ca, 1Cb, 1Da, 1Db, 1Ea, 1Eb...End 2, 2A, 2B, 2C, 2D...Anticoagulant 2E...Liquid containing anticoagulant 2Aa, 2Ab, 2Ba, 2Bb, 2Ca, 2Cb...End 3...Blood collection container body 3a...Closed end 3b...Open end 3c...Inner surface 4...Plug 11, 11A, 11B, 11C, 11D, 11E...Blood collection container R1...Region in which serine protease inhibitor is arranged R2...Region in which anticoagulant is arranged R12...Overlapping region

Claims (7)

a blood collection container body having a closed end;
A serine protease inhibitor,
and an anticoagulant;
the serine protease inhibitor is disposed on an inner surface of the blood collection container body;
A blood collection container, wherein when the blood collection container is in an upright position, at least a portion of the anticoagulant is present closer to the closed end of the blood collection container body than the area in which the serine protease inhibitor is disposed. The blood collection container according to claim 1, wherein the serine protease inhibitor comprises aprotinin or a DPP-4 inhibitor. The blood collection container according to claim 2, wherein the serine protease inhibitor comprises aprotinin and a DPP-4 inhibitor. The blood collection container according to claim 2 or 3, wherein the DPP-4 inhibitor comprises sitagliptin, saxagliptin, linagliptin, alogliptin, vildagliptin, anagliptin, or teneligliptin. The blood collection container according to any one of claims 1 to 3, wherein the anticoagulant is EDTA, a metal salt of EDTA, heparin, a heparin salt, citric acid or a citrate salt. The blood collection container according to any one of claims 1 to 3, wherein the anticoagulant is a granular anticoagulant. The blood collection container according to claim 6, wherein the average particle size of the granular anticoagulant is 200 μm or more and 1000 μm or less.

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