Blood collection container and plasma separation method

Abstract

Provided is a blood collection container capable of suppressing adhesion of a blood separation composition to unintended portions of an inner wall surface of a blood collection container body during centrifugal separation following blood collection.　This blood collection container comprises: a blood collection container body; a blood separation composition that is accommodated in the blood collection container body; and an aqueous solution that is accommodated in the blood collection container body. The blood separation composition includes an organic component that is fluid at 25°C and an inorganic fine powder. The organic component includes a resin. The aqueous solution includes an anticoagulant and water. The combination of the blood separation composition and the aqueous solution is a combination in which the rate of change A of a contact angle represented by a specific formula (A) is greater than the rate of change B of a contact angle represented by a specific formula (B).

Description

Blood collection container and method for separating plasma

[0001] The present invention relates to a blood collection container. The present invention also relates to a method for separating plasma using the above blood collection container.

[0002] In clinical examinations, blood collection containers such as blood collection tubes are widely used to collect blood. As the above blood collection container, as described in Patent Document 1, a blood collection container containing a blood separation composition containing a resin and an inorganic powder and an anticoagulant is known. In this blood collection container, after collecting blood in the blood collection container, the blood collection container can be centrifuged to separate the blood into plasma and blood cell components. At this time, the plasma is located above the blood separation composition, the blood cell components are located below the blood separation composition, and the blood separation composition serves as a partition separating the plasma and the blood cell components.

[0003] WO2010 / 053180A1

[0004] As a blood collection container, a blood collection container in which an anticoagulant is dissolved in water (a blood collection container containing an aqueous solution containing an anticoagulant) may be used inside the blood collection container body.

[0005] However, in a conventional blood collection container containing an aqueous solution containing an anticoagulant, when centrifuged after blood collection, the blood separation composition may adhere in a relatively large amount to an unintended part of the inner wall surface of the blood collection container body. For example, the blood separation composition may adhere in a relatively large amount to the inner wall surface portion of the blood collection container body where the plasma should contact. This state is shown in FIG. 3. The blood collection container 100 shown in FIG. 3 is a blood collection container after collecting blood in the blood collection container and centrifuging it. In the blood collection container 100, the blood separation composition 300 adheres to the inner wall surface portions R1 and R2 of the blood collection container body 200 where the plasma 800 should contact. The adhesion of the blood separation composition 300 to the inner wall surface portions R1 and R2 of the blood collection container body 200 is not originally intended. In FIG. 3, reference numeral 900 is the blood cell component.

[0006] If a relatively large amount of the blood separation composition adheres to an unintended part of the inner wall surface of the blood collection container, the blood separation composition may adhere to the sample aspiration nozzle of the automated analyzer, hindering accurate sample aspiration.

[0007] The object of the present invention is to provide a blood collection container that can suppress the adhesion of the blood separation composition to unintended parts of the inner wall surface of the blood collection container body when the blood is centrifuged after collection. The object of the present invention is also to provide a method for separating plasma using the above blood collection container.

[0008] This specification discloses the following blood collection container and plasma separation method.

[0009] Item 1. A blood collection container comprising a blood collection container body, a blood separation composition contained within the blood collection container body, and an aqueous solution contained within the blood collection container body, wherein the blood separation composition comprises an organic component that is fluid at 25°C and an inorganic fine powder, the organic component comprises a resin, the aqueous solution comprises an anticoagulant and water, and the combination of the blood separation composition and the aqueous solution is such that the rate of change A of the contact angle represented by the following formula (A) is greater than the rate of change B of the contact angle represented by the following formula (B).

[0010] The rate of change of the contact angle A (%) = [(θ1 - θ2) / θ1] × 100 ... (A)

[0011] θ1: Contact angle (°) of the aqueous solution to the blood separation composition 5 seconds after dropping 2 μL of the aqueous solution onto the surface of the blood separation composition. θ2: Contact angle (°) of the aqueous solution to the blood separation composition 100 seconds after dropping 2 μL of the aqueous solution onto the surface of the blood separation composition.

[0012] The rate of change of the contact angle B (%) = [(θ3 - θ4) / θ3] × 100 ... (B)

[0013] θ3: Contact angle (°) of pure water to the blood separation composition 5 seconds after dropping 2 μL of pure water onto the surface of the blood separation composition. θ4: Contact angle (°) of pure water to the blood separation composition 100 seconds after dropping 2 μL of pure water onto the surface of the blood separation composition.

[0014] Item 2. The blood collection container according to Item 1, wherein the absolute value of the difference between the rate of change of the contact angle A and the rate of change of the contact angle B is 5% or more.

[0015] Item 3. The blood collection container according to item 1 or 2, wherein the absolute value of the difference between the rate of change of the contact angle A and the rate of change of the contact angle B is 30% or less.

[0016] Item 4. A blood collection container according to any one of items 1 to 3, wherein the rate of change A of the contact angle is 10% or more.

[0017] Item 5. A blood collection container according to any one of items 1 to 4, wherein the θ2 is 90° or less.

[0018] Item 6. A blood collection container according to any one of items 1 to 5, wherein the θ2 is smaller than the θ4.

[0019] Item 7. A blood collection container according to any one of items 1 to 6, wherein the absolute value of the difference between θ2 and θ4 is 5° or more.

[0020] Item 8. A blood collection container according to any one of items 1 to 7, wherein the aqueous solution contains a wettability modifier.

[0021] Item 9. The blood collection container according to item 8, wherein the wettability modifier is a surfactant.

[0022] Item 10. The blood collection container according to item 8 or 9, wherein the wettability modifier is a silicone-based surfactant.

[0023] Item 11. The blood collection container according to any one of items 1 to 10, wherein the resin comprises a petroleum-based resin, a cyclopentadiene-based resin, a polyester-based resin, or a (meth)acrylic-based resin.

[0024] Item 12. A blood collection container according to any one of items 1 to 11, wherein the specific gravity of the blood separation composition at 25°C is 1.025 or more and 1.090 or less.

[0025] Item 13. A method for separating plasma, comprising the steps of collecting blood in a blood collection container described in any one of items 1 to 12, and centrifuging the blood collection container from which the blood has been collected.

[0026] The blood collection container according to the present invention comprises a blood collection container body, a blood separation composition contained within the blood collection container body, and an aqueous solution contained within the blood collection container body. In the blood collection container according to the present invention, the blood separation composition contains an organic component that is fluid at 25°C and an inorganic fine powder, the organic component contains a resin, and the aqueous solution contains an anticoagulant and water. In the blood collection container according to the present invention, the combination of the blood separation composition and the aqueous solution is such that the rate of change A of the contact angle, represented by a specific formula (A), is greater than the rate of change B of the contact angle, represented by a specific formula (B). Because the blood collection container according to the present invention is provided with the above configuration, when centrifugation is performed after blood collection, adhesion of the blood separation composition to unintended parts of the inner wall surface of the blood collection container body can be suppressed.

[0027] Figure 1 is a schematic front cross-sectional view of a blood collection container according to one embodiment of the present invention. Figure 2 is a schematic front cross-sectional view showing the separation of blood into plasma and blood cell components using the blood collection container shown in Figure 1. Figure 3 is a schematic front cross-sectional view showing the separation of blood into plasma and blood cell components using a conventional blood collection container.

[0028] The details of the present invention will be described below.

[0029] The blood collection container according to the present invention comprises a blood collection container body, a blood separation composition contained within the blood collection container body, and an aqueous solution contained within the blood collection container body. In the blood collection container according to the present invention, the blood separation composition contains an organic component that is fluid at 25°C and an inorganic fine powder, the organic component contains a resin, and the aqueous solution contains an anticoagulant and water.

[0030] In the blood collection container according to the present invention, the combination of the blood separation composition and the aqueous solution is such that the rate of change A of the contact angle, represented by the following formula (A), is greater than the rate of change B of the contact angle, represented by the following formula (B).

[0031] The rate of change of the contact angle A (%) = [(θ1 - θ2) / θ1] × 100 ... (A)

[0032] θ1: Contact angle (°) of the aqueous solution to the blood separation composition 5 seconds after dropping 2 μL of the aqueous solution onto the surface of the blood separation composition. θ2: Contact angle (°) of the aqueous solution to the blood separation composition 100 seconds after dropping 2 μL of the aqueous solution onto the surface of the blood separation composition.

[0033] The rate of change of the contact angle B (%) = [(θ3 - θ4) / θ3] × 100 ... (B)

[0034] θ3: Contact angle (°) of pure water to the blood separation composition 5 seconds after dropping 2 μL of pure water onto the surface of the blood separation composition. θ4: Contact angle (°) of pure water to the blood separation composition 100 seconds after dropping 2 μL of pure water onto the surface of the blood separation composition.

[0035] The blood collection container according to the present invention is equipped with the above configuration, so that when blood is centrifuged after collection, the adhesion of the blood separation composition to unintended parts of the inner wall surface of the blood collection container body can be suppressed.

[0036] In conventional blood collection containers containing an aqueous solution with an anticoagulant, when the blood is centrifuged after collection, a relatively large amount of the blood separation composition may adhere to unintended parts of the inner wall surface of the blood collection container body. The inventors of this invention have conducted thorough research and found the following causes: (1) to (3).

[0037] (1) Due to the presence of an aqueous solution, resin components may migrate from the surface of the blood separation composition into the aqueous solution during storage or transport of the blood collection container.

[0038] (2) During storage or transport of the blood collection container, the blood collection container may be tilted on its side or at an angle, causing resin components that have migrated into the aqueous solution to adhere to the inner wall surface of the blood collection container body or to form a film on the inner wall surface of the blood collection container body.

[0039] (3) When blood is centrifuged after collection, the resin component that adheres to or forms a film on the inner wall surface of the blood collection container body serves as a scaffold, and the blood separation composition further adheres to the resin component, resulting in a relatively large amount of the blood separation composition adhering to unintended parts of the inner wall surface of the blood collection container body.

[0040] Then, the inventors earnestly studied and found that by making the composition for blood separation and the aqueous solution in the above specific combination, when centrifuged after blood collection, the adhesion of the composition for blood separation to the unintended part of the inner wall surface of the blood collection container body can be suppressed. As a reason for this, it is presumed that since the wettability of the composition for blood separation and the aqueous solution is good, the transfer of the resin component from the surface of the composition for blood separation into the aqueous solution is suppressed, and the above cause (1) is less likely to occur, but it is not limited to this.

[0041] Therefore, in the blood collection container according to the present invention, although it is a blood collection container in which an aqueous solution is contained, since the above configuration is provided, when centrifuged after blood collection, the adhesion of the composition for blood separation to the unintended part of the inner wall surface of the blood collection container body can be suppressed. Therefore, the adhesion of the composition for blood separation to the sample suction nozzle of the automatic analyzer can be suppressed. In addition, the appearance of the blood collection container after centrifugation can be improved.

[0042] From the viewpoint of exerting the effects of the present invention, the combination of the composition for blood separation and the aqueous solution is a combination in which the change rate A of the contact angle is larger than the change rate B of the contact angle.

[0043] The absolute value of the difference between the change rate A of the contact angle and the change rate B of the contact angle is preferably 5% or more, more preferably 10% or more, preferably 80% or less, more preferably 50% or less, and still more preferably 30% or less. When the wettability of the composition for blood separation and the aqueous solution is good, the aqueous solution dropped on the surface of the composition for blood separation gradually wets and spreads, so the change rate A of the contact angle becomes large. Therefore, from the viewpoint of more effectively exerting the effects of the present invention, it is preferable that the absolute value of the difference between the change rate A of the contact angle and the change rate B of the contact angle is large.

[0044] The absolute value of the difference between the change rate A of the contact angle and the change rate B of the contact angle is represented by the formula: |change rate A of contact angle - change rate B of contact angle|. Since the unit of the change rate A of the contact angle and the unit of the change rate B of the contact angle are both "%", the unit of the absolute value of the difference is also "%".

[0045] As a method for making the change rate A of the contact angle greater than the change rate B of the contact angle and a method for controlling the absolute value of the difference within the above-mentioned preferable range, there may be mentioned a method of blending a wettability modifier (for example, a surfactant) in the above aqueous solution. If the concentration of the wettability modifier in the above aqueous solution is increased, the absolute value of the above difference is likely to increase.

[0046] The change rate A of the contact angle is preferably 10% or more, more preferably 20% or more, still more preferably 30% or more, further preferably 40% or more, and particularly preferably 50% or more. When the change rate A of the contact angle is at or above the above lower limit, the effects of the present invention can be more effectively exhibited. Incidentally, the change rate A of the contact angle may be 90% or less, 80% or less, or 70% or less.

[0047] The change rate B of the contact angle may be 10% or more, 20% or more, 30% or more, 90% or less, 80% or less, 70% or less, or 60% or less.

[0048] The contact angle (θ2) of the above aqueous solution is preferably 90° or less, more preferably 70° or less, and still more preferably 50° or less. When the contact angle (θ2) of the above aqueous solution is at or below the above upper limit, the effects of the present invention can be more effectively exhibited. Incidentally, the contact angle (θ2) of the above aqueous solution may be 10° or more.

[0049] The contact angle (θ1) of the above aqueous solution is preferably greater than the contact angle (θ2) of the above aqueous solution.

[0050] The contact angle (θ3) of the above pure water is preferably greater than the contact angle (θ4) of the above pure water.

[0051] The contact angle (θ2) of the above aqueous solution is preferably smaller than the contact angle (θ4) of the above pure water. In this case, the effects of the present invention can be more effectively exhibited.

[0052] The absolute value of the difference between the contact angle (θ2) of the aqueous solution and the contact angle (θ4) of the pure water is preferably 5° or more, more preferably 10° or more. When the absolute value of the difference is above the lower limit, the effects of the present invention can be exhibited even more effectively. The absolute value of the difference between the contact angle (θ2) of the aqueous solution and the contact angle (θ4) of the pure water may be 30° or less, or 20° or less.

[0053] The absolute value of the difference between the contact angle (θ2) of the aqueous solution and the contact angle (θ4) of pure water is expressed by the formula: |θ2 - θ4|. Since the units of θ2 and θ4 are both "°", the unit of the absolute value of the difference is also "°".

[0054] The contact angles (θ1, θ2) of the aqueous solution and the contact angles (θ3, θ4) of the pure water are measured by the static drop method in accordance with JIS-R3527:1999. The contact angles (θ1, θ2) of the aqueous solution and the contact angles (θ3, θ4) of the pure water are static contact angles. The contact angles (θ1, θ2) of the aqueous solution and the contact angles (θ3, θ4) of the pure water are measured using a contact angle measuring device (for example, "DMo-502" manufactured by Kyowa Interface Science Co., Ltd.). Specifically, the measurement is performed as follows.

[0055] At 25°C, 2 μL of the above aqueous solution is dropped perpendicularly onto the surface of the blood separation composition. The angle between the aqueous solution and the surface of the blood separation composition 5 seconds after dropping is measured using the θ / 2 method and is defined as the contact angle of the aqueous solution (θ1). The angle between the aqueous solution and the surface of the blood separation composition 100 seconds after dropping is measured using the θ / 2 method and is defined as the contact angle of the aqueous solution (θ2).

[0056] Similarly, at 25°C, 2 μL of the above-mentioned pure water is dropped perpendicularly onto the surface of the blood separation composition. The angle between the pure water and the surface of the blood separation composition 5 seconds after dropping is measured using the θ / 2 method and is defined as the contact angle of the pure water (θ3). The angle between the pure water and the surface of the blood separation composition 100 seconds after dropping is measured using the θ / 2 method and is defined as the contact angle of the pure water (θ4).

[0057] Furthermore, in the θ / 2 method, the contact angle can be determined by the following equation (1).

[0058] θ=2×arctan(h / r)...(1)

[0059] θ: Contact angle r: Droplet radius h: Droplet height

[0060] The details of the blood collection container according to the present invention will be described below. In this specification, "(meth)acrylic" means either or both of "acrylic" and "methacrylic".

[0061] (Blood Separation Composition) The blood collection container comprises the blood separation composition. The blood separation composition is contained within the blood collection container body. The blood separation composition is a composition that moves between the plasma layer and the blood cell layer during centrifugation to form a partition. The blood separation composition is also used to prevent component migration between the plasma layer and the blood cell layer after centrifugation. Conventional known blood separation compositions can be used as the blood separation composition. The blood separation composition is preferably thixotropic. The blood separation composition may be contained at the bottom of the blood collection container body or placed on the side wall surface of the blood collection container body. It is preferable that the blood separation composition is contained at the bottom of the blood collection container body.

[0062] The above blood separation composition contains an organic component that is fluid at 25°C and an inorganic fine powder. Therefore, the fluidity of the blood separation composition is increased, and the strength of the septum formed by the centrifugation operation can be enhanced. The organic component that is fluid at 25°C may be used alone or in combination of two or more types. The inorganic fine powder may be used alone or in combination of two or more types.

[0063] <Organic components that are fluid at 25°C> The above "fluid at 25°C" means that the viscosity at 25°C is 500 Pa·s or less.

[0064] The viscosity of the above organic component at 25°C is preferably 10 Pa·s or more, more preferably 30 Pa·s or more, preferably 200 Pa·s or less, and more preferably 100 Pa·s or less. When the viscosity is above the lower limit and below the upper limit, the fluidity of the blood separation composition is increased, and the strength of the septum formed after centrifugation can be increased.

[0065] The viscosity of the above organic components at 25°C was determined using an E-type viscometer (for example, "TVE-35" manufactured by Toki Sangyo Co., Ltd.) at 25°C and a shear rate of 1.0 seconds. －１ It is measured under these conditions.

[0066] Examples of the above organic component include resins and mixtures of resins and organic compounds such as plasticizers. The above organic component includes a resin. Preferably, the above organic component includes a resin and an organic compound. Preferably, the above organic component is a mixture of a resin and an organic compound. When the above organic component is a mixture of a resin and an organic compound, it is sufficient that the mixture (the above organic component) has fluidity, and the resin or the organic compound does not need to have fluidity. When the above organic component is a mixture of a resin and an organic compound, the resin may be, for example, a resin that is solid at 25°C. Only one type of resin and one type of organic compound may be used, or two or more types may be used in combination.

[0067] Examples of the above resins include petroleum-based resins, cyclopentadiene-based resins, polyester-based resins, polyurethane-based resins, (meth)acrylic-based resins, silicone-based resins, α-olefin-fumarate copolymers, copolymers of sebacic acid, 2,2-dimethyl-1,3-propanediol, and 1,2-propanediol, polyether polyurethane-based resins, and polyether polyester-based resins. Only one of these resins may be used, or two or more may be used in combination.

[0068] The above resin preferably includes a petroleum-based resin, a cyclopentadiene-based resin, a polyester-based resin, or a (meth)acrylic-based resin, more preferably a petroleum-based resin, a cyclopentadiene-based resin, or a (meth)acrylic-based resin, and even more preferably a (meth)acrylic-based resin. In this case, the fluidity of the blood separation composition can be further increased, and the strength of the partition formed after centrifugation can be further increased. In this case, it becomes easier to adjust the rate of change of the contact angle A and the rate of change of the contact angle B.

[0069] Examples of commercially available petroleum-based resins include Eastman Chemical Company's "Rigalite S5090".

[0070] Examples of the cyclopentadiene resins mentioned above include polymers of cyclopentadiene monomers, copolymers of cyclopentadiene monomers and aromatic monomers, and dicyclopentadiene resins. The cyclopentadiene resins may be hydrogenated. The polymers of cyclopentadiene monomers and copolymers of cyclopentadiene monomers and aromatic monomers may be oligomers.

[0071] Examples of the cyclopentadiene monomers mentioned above include cyclopentadiene, dicyclopentadiene, and alkyl-substituted derivatives of cyclopentadiene.

[0072] Examples of the above-mentioned aromatic monomers include styrene, methylstyrene, indene, and methylindene.

[0073] Examples of commercially available dicyclopentadiene resins include "Scorets SU500" and "Scorets SU90" manufactured by Colon Co., Ltd.

[0074] Examples of the above-mentioned polyester resins include polyalkylene terephthalate resins and polyalkylene naphthalate resins. Examples of the above-mentioned polyalkylene terephthalate resins include polyethylene terephthalate, polybutylene terephthalate, and poly-1,4-cyclohexanedimethylene terephthalate.

[0075] Examples of the polyurethane resins mentioned above include reaction products of polyol compounds and isocyanate compounds.

[0076] Examples of the (meth)acrylic resins mentioned above include resins obtained by polymerizing at least one (meth)acrylic acid ester monomer, and resins obtained by polymerizing at least one (meth)acrylic acid ester monomer with at least one monomer other than a (meth)acrylic acid ester monomer.

[0077] Examples of the above (meth)acrylic acid ester monomers include alkyl (meth)acrylates, polyalkylene glycol (meth)acrylates, alkoxyalkyl (meth)acrylates, hydroxyalkyl (meth)acrylates, glycidyl (meth)acrylates, dialkylaminoalkyl (meth)acrylates, benzyl (meth)acrylates, phenoxyalkyl (meth)acrylates, cyclohexyl (meth)acrylates, isobornyl (meth)acrylates, and alkoxysilylalkyl (meth)acrylates. When the above (meth)acrylic acid ester monomer has an alkyl group, the number of carbon atoms in the alkyl group is preferably 1 or more, and preferably 20 or less. The above alkyl (meth)acrylic acid ester is preferably an alkyl (meth)acrylic acid ester having an alkyl group with 1 to 20 carbon atoms. The above (meth)acrylic acid ester monomer may be used alone or in combination of two or more.

[0078] Examples of the above organic compound include benzenepolycarboxylate alkyl ester derivatives. Preferably, the above organic compound is a benzenepolycarboxylate alkyl ester derivative. Therefore, it is preferable that the above organic component is a mixture of the above resin and the above benzenepolycarboxylate alkyl ester derivative.

[0079] Examples of the above-mentioned alkyl benzene polycarboxylate derivatives include phthalate esters, trimellitic acid esters, and pyromellitic acid esters. The above-mentioned alkyl benzene polycarboxylate derivatives may be used individually or in combination of two or more.

[0080] Examples of the trimellitic acid esters mentioned above include tri-n-octyl trimellitic acid, triisooctyl trimellitic acid, and triisodecyl trimellitic acid.

[0081] Examples of the pyromellitic acid esters mentioned above include tetraisooctyl pyromellitic acid.

[0082] Examples of commercially available trimellitic acid esters include DIC Corporation's "Monosizer W700" and "Monosizer W-750," and Shin Nippon Rika Co., Ltd.'s "Sansosizer TOTM" and "Sansosizer TITM."

[0083] Examples of commercially available pyromellitic acid esters include DIC Corporation's "Monosizer W-7010".

[0084] The above-mentioned alkyl benzene polycarboxylate derivative is preferably a phthalate ester, trimellitic acid ester, or pyromellitic acid ester, and more preferably a trimellitic acid ester.

[0085] In 100% by weight of the blood separation composition, the content of the above organic component is preferably 80% by weight or more, more preferably 85% by weight or more, even more preferably 90% by weight or more, and preferably 98% by weight or less. In this case, the fluidity of the blood separation composition is further increased, and the strength of the partition formed after centrifugation can be further increased. In this case, it becomes easier to adjust the rate of change of the contact angle A and the rate of change of the contact angle B.

[0086] <Inorganic Fine Powders> Examples of the above inorganic fine powders include fine silica powder, titanium oxide powder, calcium carbonate powder, zinc oxide powder, alumina powder, glass fine powder, talc powder, kaolin powder, bentonite powder, titania powder, and zirconium powder.

[0087] The inorganic fine powders mentioned above are preferably fine silica powder, titanium oxide powder, calcium carbonate powder, zinc oxide powder, alumina powder, glass fine powder, talc powder, kaolin powder, bentonite powder, titania powder, or zirconium powder.

[0088] From the viewpoint of maintaining both the specific gravity and thixotropy of the blood separation composition within a suitable range, it is preferable that the inorganic fine powder contains fine silica. When obtaining a blood separation composition with a specific gravity of 1.050 or higher at 25°C, it is more preferable that the inorganic fine powder contains fine silica and an inorganic fine powder other than fine silica (a second inorganic fine powder). However, even if the specific gravity of the blood separation composition at 25°C is 1.050 or higher, the inorganic fine powder does not have to contain the second inorganic fine powder. Also, even if the specific gravity of the blood separation composition at 25°C is less than 1.050, the inorganic fine powder may contain the second inorganic fine powder. The inorganic fine powder, the fine silica, and the second inorganic fine powder may each be used individually or in combination of two or more.

[0089] Examples of the fine silica powder mentioned above include natural silica and synthetic silica. Examples of synthetic silica include hydrophilic silica and hydrophobic silica. Hydrophilic silica, for example, imparts thixotropy to blood separation compositions and adjusts specific gravity by hydrogen bonding between hydroxyl groups on the particle surface. On the other hand, hydrophobic silica has a smaller effect on imparting thixotropy compared to hydrophilic silica.

[0090] From the viewpoint of maintaining both the specific gravity and thixotropy of the blood separation composition within a suitable range, the above-mentioned fine silica powder preferably contains hydrophilic silica, and more preferably contains both hydrophilic silica and hydrophobic silica.

[0091] The second inorganic fine powder is preferably an inorganic fine powder with a higher specific gravity than the fine silica powder, and more preferably an inorganic fine powder such as zinc oxide powder, titanium oxide powder, alumina powder, and calcium carbonate powder with a specific gravity of 2.5 or higher. The specific gravity of the second inorganic fine powder may be 10 or less, or 6 or less.

[0092] The average particle size of the inorganic fine powder, the fine silica powder, and the second inorganic fine powder is not particularly limited. The average particle size of the inorganic fine powder, the fine silica powder, and the second inorganic fine powder may be 1 nm or more, 10 nm or more, 500 nm or less, or 100 nm or less.

[0093] The average particle diameter of the above inorganic fine powder, the above fine silica powder, and the above second inorganic fine powder is the average diameter measured on a volume basis (volume-average particle diameter), and is the value of the median diameter (D50) at which 50% is reached. The above volume-average particle diameter (D50) can be measured by laser diffraction / scattering, image analysis, Coulter method, and centrifugal sedimentation method, etc. Preferably, the above volume-average particle diameter (D50) is determined by laser diffraction / scattering or image analysis.

[0094] The specific surface area of ​​the above-mentioned fine silica powder is not particularly limited. The specific surface area of ​​the above-mentioned fine silica powder is 20 m². ２ It may be more than / g, and 100m ２ It may be more than / g, and 500m ２ It may be less than / g, and 300m ２ It may be less than / g.

[0095] The specific surface area of ​​the above-mentioned fine silica powder is measured by the BET method.

[0096] In 100% by weight of the above blood separation composition, the content of the hydrophilic silica is preferably 0.01% by weight or more, more preferably 0.10% by weight or more, even more preferably 0.30% by weight or more, preferably 2.50% by weight or less, and more preferably 2.00% by weight or less. When the content of the hydrophilic silica is above the lower limit and below the upper limit, both the specific gravity and thixotropy of the blood separation composition can be maintained within a more favorable range.

[0097] In 100% by weight of the blood separation composition, the content of the fine silica powder is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, preferably 10% by weight or less, and more preferably 7% by weight or less. When the content of the fine silica powder is above the lower limit and below the upper limit, both the specific gravity and thixotropy of the blood separation composition can be maintained within a more favorable range.

[0098] In 100% by weight of the blood separation composition, the content of the second inorganic fine powder is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, preferably 10% by weight or less, and more preferably 7% by weight or less. When the content of the second inorganic fine powder is above the lower limit and below the upper limit, the specific gravity of the blood separation composition can be effectively increased.

[0099] In 100% by weight of the above blood separation composition, the content of the above inorganic fine powder is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, preferably 10% by weight or less, and more preferably 8% by weight or less. When the content of the above inorganic fine powder is above the lower limit and below the upper limit, the specific gravity of the blood separation composition can be effectively increased.

[0100] <Other Components> The blood separation composition described above may contain other components besides those described above, as long as they do not impair the effects of the present invention. Examples of these other components include organic gelling agents, thermoplastic elastomers, polyalkylene glycols, silicone oils, auxiliary solvents, antioxidants, colorants, and water. Each of these other components may be used individually or in combination of two or more.

[0101] The specific gravity of the blood separation composition at 25°C is preferably 1.025 or higher, more preferably 1.030 or higher, even more preferably 1.035 or higher, preferably 1.090 or lower, more preferably 1.085 or lower, and even more preferably 1.080 or lower. When the specific gravity of the blood separation composition at 25°C is above the lower limit and below the upper limit, plasma can be separated well from blood, and the contamination of plasma with leukocytes, erythrocytes, and platelets can be effectively suppressed.

[0102] The specific gravity of the blood separation composition at 25°C is measured by sequentially adding one drop of the blood separation composition to saline solution at 25°C, with the specific gravity adjusted in increments of 0.002, and observing its buoyancy. The specific gravity of the saline solution at 25°C is measured using a hydrometer (for example, a "DA-130N" manufactured by Kyoto Electronics Manufacturing Co., Ltd.).

[0103] The viscosity of the above blood separation composition at 25°C is preferably 50 Pa·s or more, more preferably 70 Pa·s or more, preferably 500 Pa·s or less, and more preferably 400 Pa·s or less. When the viscosity is above the lower limit and below the upper limit, the effects of the present invention can be exhibited even more effectively.

[0104] The viscosity of the above blood separation composition at 25°C was determined using an E-type viscometer (e.g., "TVE-35" manufactured by Toki Sangyo Co., Ltd.) at 25°C and a shear rate of 1.0 seconds. －１ It is measured under these conditions.

[0105] (Aqueous solution) The blood collection container described above is equipped with the aqueous solution described above. The aqueous solution is contained within the body of the blood collection container described above. The aqueous solution contains an anticoagulant and water.

[0106] <Anticoagulant> Conventional known anticoagulants can be used as the above anticoagulant. One type of anticoagulant may be used, or two or more types may be used in combination.

[0107] Examples of the above-mentioned anticoagulants include heparin, metal salts of heparin, ethylenediaminetetraacetic acid (EDTA), metal salts of EDTA, citric acid, and sodium citrate. Examples of the above-mentioned sodium citrate include trisodium citrate.

[0108] From the viewpoint of exhibiting good anticoagulant performance, the above anticoagulant is preferably EDTA, a metal salt of EDTA, heparin, a metal salt of heparin, or sodium citrate.

[0109] The concentration of the anticoagulant in the aqueous solution is not particularly limited, as long as it is a concentration at which anticoagulant performance is exhibited.

[0110] <Water> The above aqueous solution contains water. In the above aqueous solution, water acts as a solvent. The water may be pure water.

[0111] In the above aqueous solution at 100% by weight, the water content is preferably 40% by weight or more, more preferably 70% by weight or more, even more preferably 80% by weight or more, particularly preferably 90% by weight or more, preferably 99% by weight or less, and more preferably 98% by weight or less.

[0112] <Wettability Modifier> The aqueous solution preferably contains a wettability modifier. The wettability modifier refers to a component that modifies the wettability of the blood separation composition to the aqueous solution. Only one type of wettability modifier may be used, or two or more types may be used in combination.

[0113] Examples of the above-mentioned wettability modifiers include surfactants and water-soluble polymers.

[0114] Examples of the above-mentioned surfactants include silicone-based surfactants, polysorbate 20, nonylphenyl polyethylene glycol, and sodium dodecyl sulfate.

[0115] Examples of the water-soluble polymers mentioned above include polyoxyethylene polyoxypropylene glycol, dextrin, and collagen peptides.

[0116] The above wettability modifier is preferably a surfactant, more preferably a nonionic surfactant, and even more preferably a silicone-based surfactant. The above aqueous solution preferably contains a surfactant, more preferably a nonionic surfactant, and even more preferably a silicone-based surfactant. In this case, it becomes easier to adjust the rate of change A of the contact angle, and therefore the effects of the present invention can be exhibited even more effectively.

[0117] In 100% by weight of the above aqueous solution, the content of the above wettability modifier is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, even more preferably 0.007% by weight or more, preferably 30% by weight or less, more preferably 10% by weight or less, even more preferably 5% by weight or less, even more preferably 1% by weight or less, even more preferably 0.5% by weight or less, and particularly preferably 0.1% by weight or less. When the content of the above wettability modifier is above the lower limit and below the upper limit, it becomes easier to adjust the rate of change A of the contact angle, and therefore the effects of the present invention can be exhibited more effectively.

[0118] In 100% by weight of the above aqueous solution, the content of the surfactant is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, even more preferably 0.007% by weight or more, preferably 10% by weight or less, more preferably 5% by weight or less, even more preferably 1% by weight or less, even more preferably 0.5% by weight or less, and particularly preferably 0.1% by weight or less. When the content of the surfactant is above the lower limit and below the upper limit, it becomes easier to adjust the rate of change A of the contact angle, and therefore the effects of the present invention can be exhibited more effectively.

[0119] In 100% by weight of the above aqueous solution, the content of the above silicone-based surfactant is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, even more preferably 0.007% by weight or more, preferably 5% by weight or less, more preferably 1% by weight or less, and even more preferably 0.5% by weight or less. When the content of the above silicone-based surfactant is above the lower limit and below the upper limit, it becomes easier to adjust the rate of change A of the contact angle, and therefore the effects of the present invention can be exhibited even more effectively.

[0120] <Other Components> The above aqueous solution may contain other components besides those listed above (anticoagulant, water, and wettability modifier). Examples of these other components include inorganic salts, sugars, pH adjusters, and sugar alcohols. Each of these other components may be used individually or in combination of two or more.

[0121] (Blood collection container body) The shape of the blood collection container body is not particularly limited. Preferably, the blood collection container body is a tubular container with a bottom. Preferably, the blood collection container body has an open end and a closed end. The open end of the blood collection container body is one end in the longitudinal direction of the blood collection container body, and the closed end of the blood collection container body is the other end in the longitudinal direction of the blood collection container body. In the blood collection container body, the distance between the open end and the closed end is the length of the blood collection container body.

[0122] The material of the blood collection container body described above 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, ethylcellulose, and ethyl chitin; silicate glass such as soda-lime glass, phosphate glass, and borosilicate glass; and glass such as quartz glass. The blood collection container body may be made of only one type of material, or two or more types may be used in combination.

[0123] The blood collection container body is preferably a resin container, more preferably a thermoplastic resin container, and even more preferably a polyethylene terephthalate container. When the blood collection container body is a resin container (particularly a polyethylene terephthalate container), a relatively large amount of the blood separation composition tends to adhere to unintended parts of the inner wall surface of the blood collection container body. In contrast, with the blood collection container of the present invention, the effects of the present invention can be effectively demonstrated even if the blood collection container body is a resin container. Furthermore, since the resin container is less prone to breakage than a glass container, when the blood collection container body is a resin container (particularly a polyethylene terephthalate container), the risk of the collected blood scattering due to breakage or other reasons can be reduced.

[0124] (Stopper) 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 so that a blood collection needle can be inserted through it.

[0125] Examples of the above-mentioned stoppers include stoppers having a shape that fits onto the open end of the blood collection container body, and sheet-shaped sealing stoppers.

[0126] The above-mentioned stopper may comprise 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 is pulled out from the open end of the blood collection container body after blood collection.

[0127] Examples of materials for the stopper body (or plug body) include synthetic resin, elastomer, rubber, and metal foil. Examples of rubber include butyl rubber and halogenated butyl rubber. Examples of metal foil include aluminum foil. From the viewpoint of improving sealing performance, the material of the stopper body is preferably butyl rubber. The stopper body (or plug body) is preferably a butyl rubber stopper.

[0128] (Further details of the blood collection container) The blood collection container is preferably a blood collection container from which a predetermined amount of blood is collected. The predetermined amount of blood can be appropriately changed depending on the size and internal pressure of the blood collection container. The predetermined amount of blood (the amount of blood collected in the blood collection container) 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.

[0129] In the blood collection container described above, it is preferable that 3 mL or more of blood is collected per 1 mL of the aqueous solution contained in the blood collection container body, more preferably 4 mL or more, preferably 11 mL or less, and more preferably 10 mL or less. In this case, the blood is not excessively diluted, and the effects of the present invention can be exhibited even more effectively.

[0130] It is preferable that the aqueous solution is contained within the blood collection container body at a position closer to the open end of the blood collection container body than to the blood separation composition. It is preferable that the aqueous solution is contained within the blood collection container body at a position closer to the open end of the blood collection container body than to the blood separation composition. It is preferable that the blood separation composition and the aqueous solution are in contact when the blood collection container is in an upright position. The upright position is a state in which the closed end of the blood collection container body is located on the lower side and the open end of the blood collection container body is located on the upper side. It is preferable that the aqueous solution is placed on the upper surface of the blood separation composition.

[0131] The blood collection container is preferably a blood collection tube. The blood collection container body is preferably a blood collection tube body.

[0132] The internal pressure of the blood collection container is not particularly limited. Preferably, 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 into the blood collection container. The blood collection container can also be used as a vacuum blood collection tube, which is sealed with the stopper after the inside has been evacuated. When it is a vacuum blood collection tube, a fixed amount of blood can be easily collected regardless of the skill level of the blood collector.

[0133] From the standpoint of preventing bacterial infection, it is preferable that the inside of the blood collection container be sterilized in accordance with ISO or JIS standards. Conventional known methods can be used for sterilization. Examples of sterilization methods include radiation sterilization such as gamma ray sterilization and electron beam sterilization, as well as autoclaving.

[0134] The blood collection container described above can be manufactured, for example, as follows:

[0135] An aqueous solution is obtained by dissolving the anticoagulant and the wettability modifier in water. If necessary, other components may also be dissolved in water to obtain an aqueous solution. The obtained aqueous solution is added to the blood collection container body. The blood separation composition is placed in the blood collection container body either before or after adding the aqueous solution.

[0136] Figure 1 is a schematic front cross-sectional view showing a blood collection container according to one embodiment of the present invention.

[0137] The blood collection container 1 shown in Figure 1 comprises a blood collection container body 2, a blood separation composition 3, an aqueous solution 4, and a stopper 5. The blood separation composition 3 and the aqueous solution 4 are each housed within the blood collection container body 2. The blood collection container body 2 has an open end and a closed end. The blood separation composition 3 is housed at the bottom of the blood collection container body 2. The aqueous solution 4 contains an anticoagulant and water. When the blood collection container 1 is in an upright position, the aqueous solution 4 is positioned on the upper surface of the blood separation composition 3. The stopper 5 is inserted into the open end of the blood collection container body 2. The combination of the blood separation composition 3 and the aqueous solution 4 is such that the rate of change A of the contact angle is greater than the rate of change B of the contact angle.

[0138] Figure 2 is a schematic front cross-sectional view showing how blood is separated into plasma and blood cell components using the blood collection container shown in Figure 1.

[0139] The blood collection container 1 shown in Figure 2 is the blood collection container after blood has been collected in it and centrifuged. By collecting blood in the blood collection container 1 and centrifuging it, the blood cell components 9 are located below the partition formed by the blood separation composition 3, and the plasma 8 is located above the partition formed by the blood separation composition 3.

[0140] (Method for separating plasma) Plasma can be separated from blood using the blood collection container described above. The plasma separation method according to the present invention comprises the steps of collecting blood into the blood collection container described above and centrifuging the blood collection container in which the blood has been collected.

[0141] In the plasma separation method according to the present invention, it is preferable to include a step of mixing the collected blood with the aqueous solution between the step of collecting the blood and the step of centrifugation. Examples of methods for mixing the collected blood with the aqueous solution include inversion mixing.

[0142] The centrifugal separation conditions in the above-mentioned centrifugal separation process are not particularly limited, as long as the blood separation composition can form a partition and separate the plasma from the blood cells. Examples of such centrifugal separation conditions include centrifugation at 400 G to 4000 G for 10 minutes to 120 minutes.

[0143] After the centrifugal separation process described above, the blood cell components are located below the septum formed by the blood separation composition, and the plasma is located above the septum formed by the blood separation composition.

[0144] The present invention will be described in more detail below with reference to examples. The present invention is not limited to the following examples.

[0145] The following materials were prepared for the blood separation composition.

[0146] (Organic component material that is fluid at 25°C) (Meth)acrylic resin (synthesized by synthesis example 1 below) Petroleum resin (Eastman Chemical Company's "Rigalite S5090") Dicyclopentadiene resin 1 (Colon's "Scorets SU500") Dicyclopentadiene resin 2 (Colon's "Scorets SU90") Trimellit acid ester

[0147] Synthesis Example 1: 2-ethylhexyl acrylate and butyl acrylate were radically polymerized by solution polymerization in the presence of an azo polymerization initiator to obtain a (meth)acrylic ester polymer ((meth)acrylic resin) that is fluid at 25°C. The specific gravity of the (meth)acrylic resin at 25°C was 1.034.

[0148] (Inorganic fine powders) Hydrophilic silica (fine powder silica, "200CF" manufactured by Nippon Aerosil Co., Ltd.) Hydrophobic silica (fine powder silica, "RX200" manufactured by Nippon Aerosil Co., Ltd.) Calcium carbonate powder (specific gravity 2.7, "Socal UP-G" manufactured by IMERYS Co., Ltd.)

[0149] (Other ingredients) Silicone oil (SF8410 manufactured by Toray Dow Corning Co., Ltd.) Organic gelling agent (Gelol D manufactured by Shin Nippon Rika Co., Ltd.) 1-methyl-2-pyrrolidone (auxiliary solvent)

[0150] The following materials were prepared for the aqueous solution.

[0151] (Anticoagulant) Trisodium citrate

[0152] (Wettability modifiers) Polysorbate 20 (Tween 20, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. as "Polyoxyethylene (20) Sorbitan Monolaurate") Silicone-based surfactant A (manufactured by Dow Toray Industries, Ltd. as "DOWSIL SF8410 Fluid") Silicone-based surfactant B (manufactured by Shin-Etsu Chemical Co., Ltd. as "KF-615A")

[0153] water

[0154] (Example 1) Preparation of blood separation composition: A blood separation composition was prepared by mixing organic components, inorganic fine powders, and other components that are fluid at 25°C according to the mixing ratios shown in Table 1. One drop of the obtained blood separation composition was sequentially added to saline solution at 25°C, with the specific gravity adjusted in increments of 0.002, and the specific gravity was measured by buoyancy in the saline solution. The specific gravity of the obtained blood separation composition at 25°C was 1.075.

[0155] Preparation of aqueous solutions: Aqueous solutions were obtained by mixing the components shown in Table 1 in the proportions indicated in Table 1. The amounts shown in the table are the pure amounts, and the content (concentration) of each component in the aqueous solution is the content (concentration) in the anhydrous state.

[0156] Preparation of the blood collection container: A tubular polyethylene terephthalate container (PET closed-bottom tube) with a length of 100 mm and an inner diameter of 14 mm at the open end was prepared as the blood collection container body. 1.2 g of the blood separation composition was placed in the bottom of the blood collection container body. In addition, 1 mL of the obtained aqueous solution was added to the surface of the blood separation composition. The inside of the blood collection container was reduced in pressure so that the blood collection volume would be 8 mL, and it was sealed with a butyl rubber stopper. After sealing, it was irradiated with gamma rays at a dose of 15 kGy. The blood collection container was thus prepared.

[0157] (Examples 2, 3 and Comparative Example 1) An aqueous solution and a blood collection container were prepared in the same manner as in Example 1, except that the composition of the aqueous solution was changed as shown in Table 1.

[0158] (Example 4) Preparation of blood separation composition: The organic components that are fluid at 25°C as described in Table 2 were blended, heated and dissolved at 130°C, and mixed to prepare an organic component that is fluid at 25°C. Next, the organic component that is fluid at 25°C, inorganic fine powder, and other components were mixed in the blending ratios described in Table 2 to prepare a blood separation composition. One drop of the obtained blood separation composition was sequentially added to saline solution at 25°C, with the specific gravity adjusted in increments of 0.002, and the specific gravity was measured by buoyancy in the saline solution. The specific gravity of the obtained blood separation composition at 25°C was 1.045.

[0159] Preparation of aqueous solutions: Aqueous solutions were obtained by mixing the components shown in Table 2 in the proportions indicated in Table 2. The amounts shown in the table are the pure amounts, and the content (concentration) of each component in the aqueous solution is the content (concentration) in the anhydrous state.

[0160] Preparation of the blood collection container: A tubular polyethylene terephthalate container (PET closed-bottom tube) with a length of 100 mm and an inner diameter of 14 mm at the open end was prepared as the blood collection container body. 1.2 g of the blood separation composition was placed in the bottom of the blood collection container body. In addition, 1 mL of the obtained aqueous solution was added to the surface of the blood separation composition. The inside of the blood collection container was reduced in pressure so that the blood collection volume would be 8 mL, and it was sealed with a butyl rubber stopper. After sealing, it was irradiated with gamma rays at a dose of 15 kGy. The blood collection container was thus prepared.

[0161] (Example 5 and Comparative Example 2) The aqueous solution and blood collection container were prepared in the same manner as in Example 4, except that the composition of the aqueous solution was changed as shown in Table 2.

[0162] (Evaluation) (1) In combinations of blood separation compositions and aqueous solutions using contact angle measurement, the contact angle was measured using a contact angle measuring device (DMo-502 manufactured by Kyowa Interface Science Co., Ltd.) as follows: At 25°C, 2 μL of aqueous solution was dropped perpendicularly onto the surface of the blood separation composition. The angle between the aqueous solution and the surface of the blood separation composition 5 seconds after dropping was measured by the θ / 2 method and was defined as the contact angle of the aqueous solution (θ1). The angle between the aqueous solution and the surface of the blood separation composition 100 seconds after dropping was measured by the θ / 2 method and was defined as the contact angle of the aqueous solution (θ2). Similarly, at 25°C, 2 μL of the above pure water was dropped perpendicularly onto the surface of the blood separation composition. The angle between the pure water and the surface of the blood separation composition 5 seconds after dropping was measured by the θ / 2 method and was defined as the contact angle of the pure water (θ3). The angle between the pure water and the surface of the blood separation composition 100 seconds after dropping was measured using the θ / 2 method and defined as the contact angle of the pure water (θ4).

[0163] The rate of change A of the contact angle was determined from equation (A) above, and the rate of change B of the contact angle was determined from equation (B) above.

[0164] (2) Amount of blood separation composition adhering to unintended parts of the inner wall surface of the blood collection container The obtained blood collection container was placed on a mix rotor ("MR-5" manufactured by AS ONE Corporation) and oscillated for 2 hours at a rotation speed of 48 rpm. This oscillating operation is a transport model operation that severely represents the transport conditions of the blood collection container. Next, 8 mL of blood was collected in the blood collection container. The blood collection container from which the blood was collected was centrifuged at 20°C and 1500 × g for 10 minutes. After centrifugation, the blood cell components were located below the partition formed by the blood separation composition. The plasma layer was located above the partition formed by the blood separation composition.

[0165] The area R of the portion of the inner wall surface of the blood collection container body where the blood separation composition adheres to an unintended area was determined. The area R is the area of ​​the inner wall surface of the blood collection container body where the blood separation composition exists between the plasma layer and the blood collection container body in a direction perpendicular to the longitudinal direction of the blood collection container body (radial direction of the blood collection container body). In addition, the area S of the inner wall surface of the blood collection container body where the plasma layer and the blood collection container body are in direct contact was determined. The adhesion area ratio X was calculated using the following formula (X).

[0166] Adhesion area ratio X (%) = [R / (R + S)] × 100 ... (X) R: Area R S: Area S

[0167] <Criteria for determining the amount of adhesion of blood separation composition> ○○: Adhesion area ratio X is 0% or more and less than 25% ○: Adhesion area ratio X is 25% or more and less than 50% ×: Adhesion area ratio X is 50% or more

[0168] The configuration and results are shown in Tables 1 and 2 below.

[0169]

[0170]

[0171] 1...Blood collection container 2...Blood collection container main body 3...Blood separation composition 4...Aqueous solution 5...Blug body 8...Plasma 9...Blood cell component

Claims

1. A blood collection container comprising: a blood collection container body; a blood separation composition contained within the blood collection container body; and an aqueous solution contained within the blood collection container body, wherein the blood separation composition comprises an organic component that is fluid at 25°C and an inorganic fine powder; the organic component comprises a resin; the aqueous solution comprises an anticoagulant and water; and the combination of the blood separation composition and the aqueous solution is such that the rate of change A of the contact angle represented by the following formula (A) is greater than the rate of change B of the contact angle represented by the following formula (B). Change rate of contact angle A (%) = [(θ1 - θ2) / θ1] × 100 ... (A) θ1: Contact angle of the aqueous solution to the blood separation composition (°) 5 seconds after dropping 2 μL of the aqueous solution onto the surface of the blood separation composition θ2: Contact angle of the aqueous solution to the blood separation composition (°) 100 seconds after dropping 2 μL of the aqueous solution onto the surface of the blood separation composition Change rate of contact angle B (%) = [(θ3 - θ4) / θ3] × 100 ... (B) θ3: Contact angle of the pure water to the blood separation composition (°) 5 seconds after dropping 2 μL of pure water onto the surface of the blood separation composition θ4: Contact angle of the pure water to the blood separation composition (°) 100 seconds after dropping 2 μL of pure water onto the surface of the blood separation composition 2. The blood collection container according to claim 1, wherein the absolute value of the difference between the rate of change of the contact angle A and the rate of change of the contact angle B is 5% or more.

3. The blood collection container according to claim 1 or 2, wherein the absolute value of the difference between the rate of change of the contact angle A and the rate of change of the contact angle B is 30% or less.

4. The blood collection container according to any one of claims 1 to 3, wherein the rate of change A of the contact angle is 10% or more.

5. The blood collection container according to any one of claims 1 to 4, wherein the θ2 is 90° or less.

6. The blood collection container according to any one of claims 1 to 5, wherein θ2 is smaller than θ4.

7. The blood collection container according to any one of claims 1 to 6, wherein the absolute value of the difference between θ2 and θ4 is 5° or more.

8. The blood collection container according to any one of claims 1 to 7, wherein the aqueous solution contains a wettability modifier.

9. The blood collection container according to claim 8, wherein the wettability modifier is a surfactant.

10. The blood collection container according to claim 8 or 9, wherein the wettability modifier is a silicone-based surfactant.

11. The blood collection container according to any one of claims 1 to 10, wherein the resin comprises a petroleum-based resin, a cyclopentadiene-based resin, a polyester-based resin, or a (meth)acrylic-based resin.

12. The blood collection container according to any one of claims 1 to 11, wherein the specific gravity of the blood separation composition at 25°C is 1.025 or more and 1.090 or less.

13. A method for separating plasma, comprising the steps of: collecting blood in a blood collection container according to any one of claims 1 to 12; and centrifuging the blood collection container from which the blood has been collected.

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