Blood collection container and method of separating plasma

Abstract

Provided is a blood collection container capable of inhibiting the mixing of leukocytes into plasma. The blood collection container of the present invention is a blood collection container for collecting a given amount of blood, wherein the blood collection container is provided with a blood collection container main body, a plasma separation material housed in the blood collection container main body, an osmotic pressure adjusting agent, and an anticoagulant, the specific gravity of the plasma separation material at 25°C is 1.030 or more and 1.120 or less, and in a case where the osmotic pressure adjusting agent and the anticoagulant housed in the blood collection container main body are dissolved with an amount of physiological saline equivalent to the given amount of blood collected in the blood collection container to obtain an osmotic pressure measurement solution, the specific gravity of the plasma separation material at 25°C and the osmotic pressure of the osmotic pressure measurement solution satisfy a specific relationship.

Description

TECHNICAL FIELD

[0001] The present application relates to a blood collection container. Furthermore, the present application also relates to a method for separating plasma using the blood collection container. BACKGROUND

[0002] In clinical examinations, blood collection containers such as blood collection tubes are widely used for collecting blood. By collecting blood into a blood collection container containing a plasma separation material, and then centrifugally separating the blood collection container, blood can be separated into plasma and blood cells. At this time, the plasma is on the upper side of the plasma separation material, and the blood cells are on the lower side. As a blood collection container containing a plasma separation material, there are known blood collection containers containing a plasma separation composition including resin and inorganic powder or the like (for example, Patent Literature 1), and blood collection containers containing a plasma separation jig (for example, Patent Literature 2).

[0003] PRIOR ART DOCUMENTS

[0004] PATENT LITERATURE

[0005] Patent Literature 1: WO2010 / 053180A1

[0006] Patent Literature 2: WO2010 / 132783A1 SUMMARY

[0007] PROBLEMS TO BE SOLVED BY THE INVENTION

[0008] In clinical examinations, examinations using plasma are performed. In the case of separating plasma from blood using the conventional blood collection container, white blood cells can be mixed in the separated plasma. When white blood cells are mixed in the plasma, the white blood cells can be destroyed, and components such as proteins and nucleic acids in the white blood cells can leak out into the plasma, which can affect the examination results.

[0009] For example, in an examination for detecting extracellular free nucleic acids (for example, cell-free DNA) in plasma, the examination results can greatly fluctuate due to the nucleic acids leaked from the white blood cells.

[0010] An object of the present application is to provide a blood collection container capable of inhibiting the mixing of white blood cells into plasma. Furthermore, an object of the present application is to provide a method for separating plasma using the blood collection container.

[0011] MEANS OF SOLVING THE PROBLEM

[0012] According to a broad aspect of the present application, there is provided a blood collection container which is a blood collection container for collecting a given amount of blood, wherein the blood collection container is provided with: a blood collection container main body, a plasma separation material housed in the blood collection container main body, an osmotic pressure adjusting agent housed in the blood collection container main body, and an anticoagulant housed in the blood collection container main body, the plasma separation material having a specific gravity of 1.030 or more and 1.120 or less at 25°C, in a case where the osmotic pressure adjusting agent and the anticoagulant housed in the blood collection container main body are dissolved with a physiological saline in an amount equivalent to the given amount of blood to be collected in the blood collection container to obtain an osmotic pressure measurement solution, the osmotic pressure of the osmotic pressure measurement solution is 300 mOsm / L or more when the plasma separation material has a specific gravity of 1.030 or more and less than 1.040 at 25°C, the osmotic pressure of the osmotic pressure measurement solution is 330 mOsm / L or more when the plasma separation material has a specific gravity of 1.040 or more and less than 1.050 at 25°C, the osmotic pressure of the osmotic pressure measurement solution is 350 mOsm / L or more when the plasma separation material has a specific gravity of 1.050 or more and less than 1.060 at 25°C, the osmotic pressure of the osmotic pressure measurement solution is 500 mOsm / L or more when the plasma separation material has a specific gravity of 1.060 or more and less than 1.070 at 25°C, and the osmotic pressure of the osmotic pressure measurement solution is 650 mOsm / L or more when the plasma separation material has a specific gravity of 1.070 or more and 1.120 or less at 25°C.

[0013] In one specific aspect of the blood collection container of the present application, the plasma separation material is a plasma separation composition.

[0014] In one specific aspect of the blood collection container of the present application, the plasma separation composition contains an organic component having fluidity at 25°C and inorganic micropowder, the organic component containing a resin, and the inorganic micropowder containing silica micropowder.

[0015] In one specific aspect of the blood collection container of the present application, the silica micropowder contains hydrophilic silica.

[0016] In one specific aspect of the blood collection container of the present application, the content of the hydrophilic silica in the plasma separation composition is 0.01% by weight or more and 2.50% by weight or less in 100% by weight of the plasma separation composition.

[0017] In one specific aspect of the blood collection container of the present application, the silica micropowder contains hydrophilic silica and hydrophobic silica.

[0018] In one specific aspect of the blood collection container of the present application, when the specific gravity of the plasma separation composition at 25°C is 1.05 or more, the inorganic fine powder includes an inorganic fine powder having a specific gravity greater than that of the silica fine powder.

[0019] In one specific aspect of the blood collection container of the present application, the resin includes a petroleum resin, a cyclopentadiene-based resin, a polyester resin, or a (meth)acrylic resin.

[0020] In one specific aspect of the blood collection container of the present application, the osmotic pressure adjusting agent is contained in the blood collection container main body in a powder state or a state dissolved in a liquid, and the anticoagulant is contained in the blood collection container main body in a powder state or a state dissolved in a liquid.

[0021] In one specific aspect of the blood collection container of the present application, the osmotic pressure adjusting agent is disposed on an inner wall surface of the blood collection container main body or on a surface of the plasma separation material, and the anticoagulant is disposed on an inner wall surface of the blood collection container main body or on a surface of the plasma separation material.

[0022] In one specific aspect of the blood collection container of the present application, the osmotic pressure adjusting agent is sodium chloride or glucose.

[0023] In one specific aspect of the blood collection container of the present application, the blood collection container is suitable for detecting extracellular free nucleic acids in blood.

[0024] According to the broad aspect of the present application, there is provided a method for separating plasma, which is a method for separating plasma using the blood collection container, the method comprising: a step of collecting blood into the blood collection container; and a step of centrifugally separating the blood collection container in which the blood is collected.

[0025] Effects of the Invention

[0026] The blood collection container of the present application is a blood collection container that collects a given amount of blood, and is provided with a blood collection container main body, a plasma separation material housed in the blood collection container main body, an osmotic pressure adjusting agent housed in the blood collection container main body, and an anticoagulant housed in the blood collection container main body. In the blood collection container of the present application, the specific gravity of the plasma separation material at 25°C is 1.030 or more and 1.120 or less. In the blood collection container of the present application, in a case where the osmotic pressure adjusting agent and the anticoagulant housed in the blood collection container main body are dissolved with an amount of physiological saline equivalent to the given amount of blood collected in the blood collection container to obtain an osmotic pressure measurement solution, the following configurations (1) to (5) are satisfied. (1) When the specific gravity of the plasma separation material at 25°C is 1.030 or more and less than 1.040, the osmotic pressure of the osmotic pressure measurement solution is 300 mOsm / L or more. (2) When the specific gravity of the plasma separation material at 25°C is 1.040 or more and less than 1.050, the osmotic pressure of the osmotic pressure measurement solution is 330 mOsm / L or more. (3) When the specific gravity of the plasma separation material at 25°C is 1.050 or more and less than 1.060, the osmotic pressure of the osmotic pressure measurement solution is 350 mOsm / L or more. (4) When the specific gravity of the plasma separation material at 25°C is 1.060 or more and less than 1.070, the osmotic pressure of the osmotic pressure measurement solution is 500 mOsm / L or more. (5) When the specific gravity of the plasma separation material at 25°C is 1.070 or more and 1.120 or less, the osmotic pressure of the osmotic pressure measurement solution is 650 mOsm / L or more. In the blood collection container of the present application, since the above configurations are provided, the mixing of leukocytes into the plasma can be inhibited. BRIEF DESCRIPTION OF DRAWINGS

[0027] [ Figure 1 ] Figure 1 is a front cross-sectional view of a blood collection container of a first embodiment of the present application.

[0028] [ Figure 2 ] Figure 2 is a front cross-sectional view of a blood collection container of a second embodiment of the present application. DETAILED DESCRIPTION

[0029] Hereinafter, the present application will be described in detail.

[0030] The blood collection container of the present application is a blood collection container that collects a given amount of blood, and is provided with a blood collection container main body, a plasma separation material housed in the blood collection container main body, an osmotic pressure adjusting agent housed in the blood collection container main body, and an anticoagulant housed in the blood collection container main body. In the blood collection container of the present application, the specific gravity of the plasma separation material at 25°C is 1.030 or more and 1.120 or less. In the blood collection container of the present application, in a case where the osmotic pressure adjusting agent and the anticoagulant housed in the blood collection container main body are dissolved with an amount of physiological saline equivalent to the given amount of blood collected in the blood collection container to obtain an osmotic pressure measurement solution, the following configurations (1) to (5) are satisfied.

[0031] (1) When the specific gravity of the plasma separation material at 25°C is 1.030 or more and less than 1.040, the osmotic pressure of the osmotic pressure measurement solution is 300 mOsm / L or more.

[0032] (2) When the specific gravity of the plasma separation material at 25°C is 1.040 or more and less than 1.050, the osmotic pressure of the osmotic pressure measurement solution is 330 mOsm / L or more.

[0033] (3) When the specific gravity of the plasma separation material at 25°C is 1.050 or more and less than 1.060, the osmotic pressure of the osmotic pressure measurement solution is 350 mOsm / L or more.

[0034] (4) When the specific gravity of the plasma separation material at 25°C is 1.060 or more and less than 1.070, the osmotic pressure of the osmotic pressure measurement solution is 500 mOsm / L or more.

[0035] (5) When the specific gravity of the plasma separation material at 25°C is 1.070 or more and 1.120 or less, the osmotic pressure of the osmotic pressure measurement solution is 650 mOsm / L or more.

[0036] In the blood collection container of the present application, since the above configurations are provided, the mixing of leukocytes into plasma can be inhibited.

[0037] Further, in the blood collection container of the present application, since the above configurations are provided, the mixing of red blood cells into plasma can also be inhibited.

[0038] In the case where the plasma is separated from the blood using the conventional blood collection container, white blood cells can be mixed into the separated plasma. When white blood cells are mixed into the plasma, components in the white blood cells can leak into the plasma, affecting the examination of the plasma. In the case of the conventional blood collection container, it is difficult to sufficiently suppress the mixing of white blood cells into the plasma. Note that, in order to suppress the effect on the examination result, a blood collection container that contains a cell stabilizer that stabilizes blood cells is sometimes used, but the cell stabilizer is expensive, and there is a risk that it is harmful to the human body and the environment depending on the kind and concentration thereof.

[0039] On the other hand, the blood collection container of the present application can suppress the mixing of white blood cells into the plasma more than the conventional blood collection container. When blood is collected into the blood collection container of the present application, the osmotic pressure adjusting agent and the anticoagulant are dissolved in the blood, and the osmotic pressure of the blood increases. Therefore, the water in the white blood cells and the water in the red blood cells move outside the blood cells, and the specific gravity of the white blood cells and the red blood cells increases. By centrifuging the blood collection container, the white blood cells and the red blood cells whose specific gravity has increased move well to the lower side of the plasma separation material having a specific gravity. As a result, the mixing of white blood cells and red blood cells into the plasma can be suppressed.

[0040] In the present application, the osmotic pressure adjusting agent and the anticoagulant contained in the main body of the blood collection container are dissolved with physiological saline in an amount equivalent to a given amount of blood collected in the blood collection container, and an osmotic pressure measuring solution is obtained, and the osmotic pressure of the obtained osmotic pressure measuring solution is measured.

[0041] The osmotic pressure measuring solution, specifically, is prepared in the following manner.

[0042] Physiological saline in an amount equivalent to a given amount of blood collected in the blood collection container is added to the blood collection container. For example, in a blood collection container in which 5 mL of blood is collected, 5 mL of physiological saline is added to the blood collection container. After the addition, inversion mixing is performed, and the osmotic pressure adjusting agent and the anticoagulant are dissolved with the physiological saline. Note that, in the case where the blood collection container contains other components in addition to the osmotic pressure adjusting agent and the anticoagulant that are soluble in physiological saline, the other components are also dissolved in the physiological saline. Thus, an osmotic pressure measuring solution can be obtained.

[0043] The osmotic pressure of the osmotic pressure measuring solution is measured using an osmometer (for example, "OM-6060" manufactured by ARKRAY Inc.) by the freezing point depression method.

[0044] In the case where the specific gravity of the plasma separation material at 25°C is 1.030 or more and less than 1.040, the osmotic pressure of the osmotic pressure measuring solution is 300 mOsm / L or more, preferably 320 mOsm / L or more, and more preferably 350 mOsm / L or more. When the osmotic pressure is the lower limit or more, the specific gravity of leukocytes and erythrocytes can be effectively increased, and the mixing of leukocytes and erythrocytes into plasma can be further effectively inhibited. Note that the upper limit of the osmotic pressure of the osmotic pressure measuring solution in the case where the specific gravity of the plasma separation material at 25°C is 1.030 or more and less than 1.040 is not particularly limited. The osmotic pressure of the osmotic pressure measuring solution in the case where the specific gravity of the plasma separation material at 25°C is 1.030 or more and less than 1.040 may, for example, be 1500 mOsm / L or less, or 1000 mOsm / L or less.

[0045] In the case where the specific gravity of the plasma separation material at 25°C is 1.040 or more and less than 1.050, the osmotic pressure of the osmotic pressure measuring solution is 330 mOsm / L or more, preferably 350 mOsm / L or more, more preferably 400 mOsm / L or more, and further preferably 500 mOsm / L or more. When the osmotic pressure is the lower limit or more, the specific gravity of leukocytes and erythrocytes can be effectively increased, and the mixing of leukocytes and erythrocytes into plasma can be further effectively inhibited. Note that the upper limit of the osmotic pressure of the osmotic pressure measuring solution in the case where the specific gravity of the plasma separation material at 25°C is 1.040 or more and less than 1.050 is not particularly limited. The osmotic pressure of the osmotic pressure measuring solution in the case where the specific gravity of the plasma separation material at 25°C is 1.040 or more and less than 1.050 may, for example, be 1500 mOsm / L or less, or 1000 mOsm / L or less.

[0046] When the specific gravity of the plasma separation material at 25°C is 1.050 or more and less than 1.060, the osmotic pressure of the osmotic pressure measuring solution is 350 mOsm / L or more, preferably 380 mOsm / L or more, more preferably 450 mOsm / L or more, and further preferably 500 mOsm / L or more. When the osmotic pressure is the lower limit or more, the specific gravity of leukocytes and erythrocytes can be effectively increased, and the mixing of leukocytes and erythrocytes into plasma can be further effectively inhibited. Note that the upper limit of the osmotic pressure of the osmotic pressure measuring solution when the specific gravity of the plasma separation material at 25°C is 1.050 or more and less than 1.060 is not particularly limited. The osmotic pressure of the osmotic pressure measuring solution when the specific gravity of the plasma separation material at 25°C is 1.050 or more and less than 1.060 can be, for example, 1500 mOsm / L or less, or 1000 mOsm / L or less.

[0047] When the specific gravity of the plasma separation material at 25°C is 1.060 or more and less than 1.070, the osmotic pressure of the osmotic pressure measuring solution is 500 mOsm / L or more, preferably 550 mOsm / L or more, more preferably 600 mOsm / L or more, and further preferably 700 mOsm / L or more. When the osmotic pressure is the lower limit or more, the specific gravity of leukocytes and erythrocytes can be effectively increased, and the mixing of leukocytes and erythrocytes into plasma can be further effectively inhibited. Note that the upper limit of the osmotic pressure of the osmotic pressure measuring solution when the specific gravity of the plasma separation material at 25°C is 1.060 or more and less than 1.070 is not particularly limited. The osmotic pressure of the osmotic pressure measuring solution when the specific gravity of the plasma separation material at 25°C is 1.060 or more and less than 1.070 can be, for example, 1000 mOsm / L or less, or 800 mOsm / L or less.

[0048] The osmotic pressure of the osmotic pressure measuring solution is 650 mOsm / L or more, preferably 700 mOsm / L or more, and more preferably 800 mOsm / L or more, when the specific gravity of the plasma separation material is 1.070 or more and 1.120 or less at 25°C. When the osmotic pressure is the lower limit or more, the specific gravity of leukocytes and erythrocytes can be effectively increased, and the mixing of leukocytes and erythrocytes into the plasma can be further effectively inhibited. Note that the upper limit of the osmotic pressure of the osmotic pressure measuring solution when the specific gravity of the plasma separation material is 1.070 or more and 1.120 or less at 25°C is not particularly limited. The osmotic pressure of the osmotic pressure measuring solution when the specific gravity of the plasma separation material is 1.070 or more and 1.120 or less at 25°C can be 1500 mOsm / L or less, or can be 1000 mOsm / L or less, for example.

[0049] (plasma separation material)

[0050] The blood collection container has a plasma separation material housed in the blood collection container main body. The specific gravity of the plasma separation material at 25°C is 1.030 or more and 1.120 or less. As the plasma separation material, a conventionally known plasma separation material can be used. As the plasma separation material, a plasma separation composition and a plasma separation jig, or the like can be given. From the viewpoint of ease of production of the plasma separation material, the plasma separation material is preferably the plasma separation composition.

[0051] The specific gravity of the plasma separation material at 25°C can be 1.040 or more, can be 1.050 or more, can be 1.060 or more, can be more than 1.060, or can be 1.070 or more. The specific gravity of the plasma separation material at 25°C can be less than 1.070, can be less than 1.060, can be less than 1.050, or can be less than 1.040.

[0052] The housing position of the plasma separation material is not particularly limited as long as it is in the blood collection container main body. The plasma separation material can be disposed at the bottom of the blood collection container main body, or can be disposed on an inner wall surface.

[0053] <plasma separation composition>

[0054] The plasma separation composition is a composition that moves to between the plasma layer and the blood cell layer at the time of centrifugal separation and forms a partition wall. Furthermore, the plasma separation composition is used to prevent the transfer of components between the plasma layer and the blood cell layer after centrifugal separation. The plasma separation composition preferably has thixotropy. The plasma separation composition can be housed in the bottom of the blood collection container main body or can be disposed on the inner wall surface. From the viewpoint of further effectively exerting the effects of the present application, the plasma separation composition is preferably housed in the bottom of the blood collection container main body.

[0055] As the plasma separation composition, a plasma separation composition known in the past can be used.

[0056] The plasma separation composition preferably contains an organic component having fluidity at 25°C and inorganic fine powder. The organic component having fluidity at 25°C and the inorganic fine powder can each be used alone or in combination with two or more kinds.

[0057] The organic component having fluidity at 25°C is:

[0058] The "having fluidity at 25°C" means that the viscosity at 25°C is 500 Pa-s or less.

[0059] The viscosity of the organic component at 25°C is preferably 30 Pa-s or more, more preferably 50 Pa-s or more, and preferably 200 Pa-s or less, more preferably 100 Pa-s or less. When the viscosity is the lower limit or more and the upper limit or less, the fluidity of the plasma separation composition can be improved and the strength of the partition wall can be improved.

[0060] The viscosity of the organic component at 25°C is measured using an E-type viscometer (for example, "TVE-35" manufactured by Tokimec Inc.) under conditions of 25°C and a shear rate of 1.0 sec -1

[0061] As the organic component, a resin, and a mixture of a resin and an organic compound such as a plasticizer, and the like can be given. Therefore, the organic component preferably contains the resin, and more preferably contains the resin and the organic compound. In the case where the organic component is a mixture of the resin and the organic compound, the mixture (the organic component) can have fluidity, and the resin or the organic compound can not have fluidity. In the case where the organic component is a mixture of the resin and the organic compound, the resin can be, for example, a resin that is solid at 25°C. The resin and the organic compound can each be used alone or in combination with two or more kinds.

[0062] ​As the resin, petroleum resin, cyclopentadiene-based resin, polyester resin, polyurethane resin, (meth)acrylic resin, polysiloxane resin, α-olefin-fumarate copolymer, copolymer of sebacic acid and 2,2-dimethyl-1,3-propanediol and 1,2-propanediol, polyether polyurethane-based resin, and polyether polyester-based resin, etc. can be given. The resin can be used singly or in combination of two or more.

[0063] The resin preferably contains petroleum resin, cyclopentadiene-based resin, polyester resin, or (meth)acrylic resin.

[0064] As the petroleum resin, commercially available products such as "REGALITE S5090" manufactured by EASTMAN CHEMICAL Co. can be given.

[0065] As the cyclopentadiene-based resin, polymer of cyclopentadiene-based monomer, copolymer of cyclopentadiene-based monomer and aromatic monomer, dicyclopentadiene resin, etc. can be given. The cyclopentadiene-based resin can be hydrogenated. The polymer of cyclopentadiene-based monomer and the copolymer of cyclopentadiene-based monomer and aromatic monomer can be oligomer.

[0066] As the cyclopentadiene-based monomer, cyclopentadiene, dicyclopentadiene, and alkyl-substituted derivative of cyclopentadiene, etc. can be given.

[0067] As the aromatic monomer, styrene, methylstyrene, indene, and methylindene, etc. can be given.

[0068] As the dicyclopentadiene resin, commercially available products such as "Sukorettsu (スコレッツ) SU500" and "Sukorettsu SU90" manufactured by COLON Co. can be given.

[0069] As the polyester resin, polyalkylene terephthalate resin and polyalkylene naphthalate resin, etc. can be given. As the polyalkylene terephthalate resin, polyethylene terephthalate, polybutylene terephthalate, and poly-1,4-cyclohexane dimethylene terephthalate, etc. can be given.

[0070] As the polyurethane resin, reaction product of polyhydric alcohol compound and isocyanate compound, etc. can be given.

[0071] As the (meth)acrylic resin, resin obtained by polymerizing at least one (meth)acrylic ester monomer and resin obtained by polymerizing at least one (meth)acrylic ester monomer and at least one monomer other than the (meth)acrylic ester monomer can be given.

[0072] As the (meth)acrylate monomer, for example, an alkyl (meth)acrylate having an alkyl group having a carbon number of 1 or more and 20 or less, a polyalkylene glycol (meth)acrylate, an alkoxyalkyl (meth)acrylate, a hydroxyalkyl (meth)acrylate, a glycidyl (meth)acrylate, a dialkylaminoalkyl (meth)acrylate, a benzyl (meth)acrylate, a phenoxyalkyl (meth)acrylate, a cyclohexyl (meth)acrylate, an isobornyl (meth)acrylate, and an alkoxysilylalkyl (meth)acrylate, and the like can be given. The (meth)acrylate monomer can be used alone or in combination of two or more.

[0073] As the organic compound, a benzene polycarboxylic acid alkyl ester derivative, and the like can be given. The organic compound is preferably a benzene polycarboxylic acid alkyl ester derivative. Thus, the organic component is preferably a mixture of the resin and the benzene polycarboxylic acid alkyl ester derivative.

[0074] As the benzene polycarboxylic acid alkyl ester derivative, a phthalic acid ester, a trimellitic acid ester, and a pyromellitic acid ester, and the like can be given. The benzene polycarboxylic acid alkyl ester derivative can be used alone or in combination of two or more.

[0075] As the trimellitic acid ester, trimellitic acid tri-n-octyl ester, trimellitic acid triisooctyl ester, trimellitic acid triisodecyl ester, and the like can be given.

[0076] As the pyromellitic acid ester, pyromellitic acid tetraisooctyl ester, and the like can be given.

[0077] As the trimellitic acid ester, "MONOSIZER W700" and "MONOSIZER W-750" manufactured by DIC Corporation, "SANSO CIZER TOTM" and "SANSO CIZER TITM" manufactured by Shin Nippon Rika Co., Ltd., and the like can be given.

[0078] As the pyromellitic acid ester, "MONOSIZER W-7010" manufactured by DIC Corporation, and the like can be given.

[0079] The benzene polycarboxylic acid alkyl ester derivative is preferably a phthalic acid ester, a trimellitic acid ester, or a pyromellitic acid ester, and more preferably a trimellitic acid ester.

[0080] Inorganic micropowder:

[0081] As the inorganic micropowder, a silica micropowder, a titanium oxide powder, a zinc oxide powder, an aluminum oxide powder, a glass micropowder, a talc powder, a kaolin powder, a bentonite powder, a titanium dioxide powder, a zirconium powder, and the like can be given.

[0082] In the case where the plasma separation composition having a specific gravity of 1.05 or more at 25°C (preferably, the plasma separation composition having a specific gravity of 1.050 or more at 25°C) is obtained, the inorganic fine powder more preferably contains a silica fine powder and an inorganic fine powder other than the silica fine powder. The inorganic fine powder other than the silica fine powder is preferably an inorganic fine powder having a specific gravity larger than that of the silica fine powder, and more preferably an inorganic fine powder having a specific gravity of 3 or more, such as zinc oxide powder, titanium oxide powder, aluminum oxide powder, and the like.

[0083] From the viewpoint of further effectively exerting the effects of the present application, the inorganic fine powder preferably contains a silica fine powder.

[0084] As the silica fine powder, natural silica and synthetic silica can be given. As the synthetic silica, hydrophilic silica and hydrophobic silica can be given. In the case of the hydrophilic silica, the hydroxyl groups on the surfaces of the particles are hydrogen-bonded to each other, and thus the hydrophilic silica has an effect of adjusting the specific gravity while imparting thixotropy to the plasma separation composition. On the other hand, the hydrophobic silica has a smaller effect of imparting thixotropy than the hydrophilic silica.

[0085] From the viewpoint of keeping both the specific gravity and the thixotropy of the plasma separation composition in the appropriate ranges, the silica fine powder preferably contains hydrophilic silica, and more preferably contains both hydrophilic silica and hydrophobic silica. The silica fine powder preferably contains at least hydrophilic silica.

[0086] The content of the hydrophilic silica in the plasma separation composition 100% by weight is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, and further preferably 0.3% by weight or more, and is preferably 2.50% by weight or less, and more preferably 2.00% by weight or less. When the content of the hydrophilic silica is the lower limit or more and the upper limit or less, both the specific gravity and the thixotropy of the plasma separation composition can be kept in the appropriate ranges.

[0087] The average particle diameter of the silica fine powder is not particularly limited. The average particle diameter of the silica fine powder can be 1 nm or more, and can be 10 nm or more. The average particle diameter of the silica fine powder can be 500 nm or less, and can be 100 nm or less.

[0088] The average particle diameter of the silica fine powder is an average diameter measured on a volume basis, and is a value of a median particle diameter (D50) at 50%. The volume average particle diameter (D50) can be measured by a laser diffraction / scattering method, an image analysis method, a Coulter method, a centrifugal sedimentation method, and the like. The volume average particle diameter (D50) is preferably measured by a method based on a laser diffraction / scattering method or an image analysis method.

[0089] The plasma separation composition can contain other components than the components described above, within a range not impairing the effects of the present application. For example, as the other components, the plasma separation composition can contain an organic gelling agent, a thermoplastic elastomer, a polyalkylene glycol, a silicone oil, an auxiliary solvent, an antioxidant, a coloring agent, water, and the like. The other components can be used singly, or two or more kinds thereof can be used in combination.

[0090] The specific gravity of the plasma separation composition at 25°C is 1.030 or more and 1.120 or less.

[0091] The specific gravity of the plasma separation composition at 25°C is measured by sequentially adding one drop of the plasma separation composition to a 25°C saline solution in which the specific gravity is adjusted in stages at intervals of 0.002, and measuring by floatation and sinking in the saline solution.

[0092] The viscosity of the plasma separation composition at 25°C is preferably 100 Pa-s or more, more preferably 150 Pa-s or more, and is preferably 500 Pa-s or less, more preferably 400 Pa-s or less. When the viscosity is the lower limit or more and the upper limit or less, the effects of the present application can be further effectively exerted.

[0093] The viscosity of the plasma separation composition at 25°C is measured using an E-type viscometer (for example, "TVE-35" manufactured by Tokimec Inc.) under conditions of 25°C and a shear rate of 1.0 second -1 .

[0094] <Plasma separation jig>

[0095] The plasma separation jig is a jig that moves to a space wall between a plasma layer and a blood cell layer at the time of centrifugal separation. Furthermore, the plasma separation jig is used to prevent the transfer of components between the plasma layer and the blood cell layer.

[0096] As the plasma separation jig, a conventionally known plasma separation jig can be used. As the plasma separation jig, for example, a mechanical septum (plasma separation jig) described in WO2010 / 132783A1 and the like can be cited.

[0097] As the material of the plasma separation jig, for example, an elastomer and the like can be cited.

[0098] (Osmotic pressure adjusting agent)

[0099] The blood collection container is provided with an osmotic pressure adjusting agent housed in the blood collection container main body. As the osmotic pressure adjusting agent, a conventionally known osmotic pressure adjusting agent can be used. The osmotic pressure adjusting agent can be used singly, or two or more kinds thereof can be used in combination.

[0100] As the osmotic pressure adjusting agent, sodium chloride, potassium chloride, glucose, dihydroxyacetone, and sugar alcohols such as D-mannitol and D-sorbitol can be mentioned.

[0101] From the viewpoint of further effectively exerting the effects of the present application, the osmotic pressure adjusting agent is preferably sodium chloride or glucose.

[0102] The osmotic pressure adjusting agent can be contained in the blood collection container main body in a state of a powder, or can be contained in the blood collection container main body in a state of being dissolved in a liquid. Note that the osmotic pressure adjusting agent can exist in the blood collection container main body in both a state of a powder and a state of being dissolved in a liquid.

[0103] As the liquid, water and ethanol, and the like can be mentioned.

[0104] Further, the osmotic pressure adjusting agent is preferably disposed on the inner wall surface of the blood collection container main body or on the surface of the plasma separation material. Note that the osmotic pressure adjusting agent can be disposed on the inner wall surface of the blood collection container main body, can be disposed on the surface of the plasma separation material, or can be disposed on both the inner wall surface of the blood collection container main body and the surface of the plasma separation material.

[0105] In the case where the osmotic pressure adjusting agent is contained in a state of a powder, the osmotic pressure adjusting agent in a powder form is preferably attached to the inner wall surface of the blood collection container main body or is disposed on the surface of the plasma separation material.

[0106] The amount of the osmotic pressure adjusting agent contained in the blood collection container main body is not particularly limited as long as the osmotic pressure of the osmotic pressure measuring solution satisfies the range.

[0107] (Anticoagulant)

[0108] The blood collection container is provided with an anticoagulant contained in the blood collection container main body. As the anticoagulant, conventionally known anticoagulants can be used. The anticoagulant can be used alone or two or more kinds can be used in combination.

[0109] As the anticoagulant, heparin, ethylenediaminetetraacetic acid (EDTA), citric acid, and the like can be mentioned.

[0110] The anticoagulant can be contained in the blood collection container main body in a state of a powder, or can be contained in the blood collection container main body in a state of being dissolved in a liquid. Note that the anticoagulant can exist in the blood collection container main body in both a state of a powder and a state of being dissolved in a liquid.

[0111] As the liquid, water and alcohol, etc. can be given.

[0112] Further, the anticoagulant is preferably disposed on the inner wall surface of the blood collection container main body or on the surface of the plasma separation material. Note that the anticoagulant can be disposed on the inner wall surface of the blood collection container main body, on the surface of the plasma separation material, or on both the inner wall surface of the blood collection container main body and the surface of the plasma separation material.

[0113] In the case where the anticoagulant is housed in a powder state, the powder-like anticoagulant is preferably attached to the inner wall surface of the blood collection container main body or disposed on the surface of the plasma separation material.

[0114] The amount of the anticoagulant housed in the blood collection container main body is not particularly limited as long as the effects of the present application are not hindered.

[0115] (Blood collection container main body)

[0116] The shape of the blood collection container main body is not particularly limited, and a bottomed tubular container is preferable.

[0117] The raw material of the blood collection container main body is not particularly limited. As the raw material of the blood collection container main body, thermoplastic resins such as polyethylene, polypropylene, polystyrene, polyethylene terephthalate, polymethyl methacrylate, and polyacrylonitrile; thermosetting resins such as unsaturated polyester resin, epoxy resin, and epoxy-acrylate resin; modified natural resins such as cellulose acetate, cellulose propionate, ethyl cellulose, and ethyl chitin; silicate glasses such as soda lime glass, phosphosilicate glass, and borosilicate glass; and glass such as quartz glass can be given. The raw material of the blood collection container main body can be used alone or in combination with two or more kinds.

[0118] (Plug)

[0119] The blood collection container preferably has a plug. As the plug, a conventionally known plug can be used. The plug is preferably a plug made of a raw material that can be installed at the opening of the blood collection container main body in airtight and liquid-tight manner, and a shape. The plug is preferably configured in such a manner that the blood collection needle can be pierced.

[0120] As the plug, plugs having a shape that fits into the opening of the blood collection container main body, sheet-like sealing plugs, and the like can be given.

[0121] Further, the stopper can be a stopper having a stopper main body such as a rubber stopper and a cap member made of plastic or the like. In this case, when the stopper is pulled out from the opening of the blood collection container main body after blood collection, the risk of blood contacting the human body can be suppressed.

[0122] As the material of the stopper (or the stopper main body), for example, synthetic resin, elastomer, rubber, metal foil, or the like can be mentioned. As the rubber, butyl rubber, halogenated butyl rubber, or the like can be mentioned. As the metal foil, aluminum foil, or the like can be mentioned. From the viewpoint of improving the sealing property, the material of the stopper is preferably butyl rubber. The stopper (or the stopper main body) is preferably a butyl rubber stopper.

[0123] (Other details of the blood collection container)

[0124] The blood collection container is preferably a blood collection tube. The blood collection container main body is preferably a blood collection tube main body.

[0125] The blood collection container is used for separating plasma from blood. The blood collection container is particularly suitable for detecting extracellular free nucleic acid in blood. In the present application, since the mixing of leukocytes into plasma can be suppressed, the detection of extracellular free nucleic acid in the blood of a subject can be performed with good accuracy by detecting extracellular free nucleic acid in plasma. As the extracellular free nucleic acid, cell-free DNA (cfDNA), cell-free RNA (cfRNA), or the like can be mentioned.

[0126] The blood collection container in which the osmotic pressure adjusting agent and the anticoagulant are contained in a state of being dissolved in a liquid, for example, can be manufactured in the following manner.

[0127] The osmotic pressure adjusting agent, the anticoagulant, and other components used as necessary are dissolved in a solvent such as water to obtain a mixed solution. The obtained mixed solution is added to the inside of the blood collection container main body. Further, before or after the addition of the mixed solution, the plasma separation composition is contained in the blood collection container main body.

[0128] Note that the blood collection container in which the osmotic pressure adjusting agent and the anticoagulant are disposed on the surface of the plasma separation composition in a state of powder can be obtained by, for example, volatilizing the solvent in the mixed solution or adding the osmotic pressure adjusting agent and the anticoagulant or the like in a state of powder to the surface of the plasma separation composition.

[0129] The blood collection container in which the osmotic pressure adjusting agent and the anticoagulant are disposed on the inner wall surface of the blood collection container main body in a state of powder, for example, can be manufactured in the following manner.

[0130] The osmotic pressure adjusting agent, the anticoagulant, and other components as needed are dissolved in a solvent such as water to obtain a mixed solution. The mixed solution is applied to the inner wall surface of the blood collection container main body and dried. Further, before or after the mixed solution is applied, the plasma separation composition is housed in the blood collection container main body.

[0131] Figure 1 is a front cross-sectional view of a blood collection container of Embodiment 1 of the present application.

[0132] Figure 1 The blood collection container 1 shown in the figure is provided with a blood collection container main body 2, a plasma separation composition 3, a mixed solution 4 containing the osmotic pressure adjusting agent, the anticoagulant, and water, and a plug 5. The blood collection container main body 2 has an opening at one end and a closed bottom at the other end. The plasma separation composition 3 is housed in the bottom of the blood collection container main body 2. The plug 5 is inserted into the opening of the blood collection container main body 2.

[0133] The mixed solution 4 containing the osmotic pressure adjusting agent, the anticoagulant, and water is disposed on the surface of the plasma separation composition 3, more specifically, on the upper face (the surface on the one end side) of the plasma separation composition 3. In the case of the mixed solution 4, it is disposed on the surface of the plasma separation composition 3 when the blood collection container is in an upright state. In the case of the osmotic pressure adjusting agent and the anticoagulant, they are housed in the blood collection container main body 2 in a state dissolved in a liquid.

[0134] Figure 2 is a front cross-sectional view of a blood collection container of Embodiment 2 of the present application.

[0135] Figure 2 The blood collection container 1A shown in the figure is provided with a blood collection container main body 2, a plasma separation composition 3, a mixed powder 4A of the osmotic pressure adjusting agent and the anticoagulant, and a plug 5. The blood collection container main body 2 has an opening at one end and a closed bottom at the other end. The plasma separation composition 3 is housed in the bottom of the blood collection container main body 2. The plug 5 is inserted into the opening of the blood collection container main body 2.

[0136] The mixed powder 4A of the osmotic pressure adjusting agent and the anticoagulant is disposed on the inner wall surface 2a of the blood collection container main body 2. The mixed powder 4A is adhered to the inner wall surface 2a of the blood collection container main body 2. That is, the osmotic pressure adjusting agent and the anticoagulant are adhered to the inner wall surface 2a of the blood collection container main body 2. The osmotic pressure adjusting agent and the anticoagulant are housed in the blood collection container main body 2 in a state of powder. The mixed powder 4A is disposed on the one end side of the plasma separation composition 3.

[0137] In the blood collection container of the present application, the plasma separation composition can be disposed on the inner wall surface of the blood collection container main body, and the mixed liquid can be disposed at the bottom of the blood collection container main body when the blood collection container is in an upright state. In addition, in the blood collection container of the present application, the plasma separation composition can be disposed on the inner wall surface of the blood collection container main body, and the mixed powder can be disposed on the inner wall surface of the blood collection container main body or on the surface of the plasma separation composition. In the blood collection container of the present application, the plasma separation composition can be disposed on the inner wall surface of the blood collection container main body, and the mixed powder can be disposed at the bottom of the blood collection container main body. In addition, the plasma separation jig can be used instead of the plasma separation composition.

[0138] The internal pressure of the blood collection container is not particularly limited. In the case of the blood collection container, a vacuum blood collection tube sealed by the sealing member can be used after the inside is evacuated. In the case of the vacuum blood collection tube, a certain amount of blood collection can be easily performed regardless of the skill of the blood collector.

[0139] From the viewpoint of preventing bacterial infection, the inside of the blood collection container is preferably sterilized in accordance with the standards of ISO and JIS.

[0140] (Method for separating plasma)

[0141] The method for separating plasma of the present application is a method for separating plasma using the blood collection container, and includes a step of collecting blood into the blood collection container and a step of centrifugally separating the blood collection container in which the blood is collected.

[0142] The centrifugal separation conditions in the step of centrifugally separating are not particularly limited as long as the blood plasma and blood cells can be separated by the plasma separation material forming a partition wall. As the centrifugal separation conditions, for example, conditions in which centrifugal separation is performed at 400 G or more and 4000 G or less for 10 minutes or more and 120 minutes or less can be mentioned.

[0143] Hereinafter, the present application will be described in more detail by exemplifying embodiments. The present application is not limited to the following embodiments.

[0144] As the material of the plasma separation composition, the following was prepared.

[0145] (Material of the organic component having fluidity at 25°C)

[0146] (Meth)acrylic resin:

[0147] A (meth)acrylate polymer having fluidity at 25°C was obtained by free radical polymerization of 2-ethylhexyl acrylate and butyl acrylate by a solution polymerization method in the presence of an azo-based polymerization initiator.

[0148] Other resins:

[0149] Petroleum resin ("REGALITE S5090" manufactured by EASTMAN CHEMICAL Co.)

[0150] Dicyclopentadiene resin 1 ("MALCOM SU500" manufactured by COLON Co.)

[0151] Dicyclopentadiene resin 2 ("MALCOM SU90" manufactured by COLON Co.)

[0152] Organic compound:

[0153] Trimellitate (phenyl polycarboxylic acid alkyl ester derivative, "MONOSIZER W700" manufactured by DIC Co.)

[0154] (Inorganic fine powder)

[0155] Hydrophilic silica (silica fine powder, "200 CF" manufactured by AEROSIL Co., Japan)

[0156] Hydrophobic silica (silica fine powder, "R974" manufactured by AEROSIL Co., Japan)

[0157] Titanium oxide powder ("A-100" manufactured by ISHIHARA SANGYO KAISHA, LTD.)

[0158] (Other components)

[0159] Silicone oil ("SF8410" manufactured by DOW CORNING TORAY CO., LTD.)

[0160] Organic gelling agent ("GELOLD" manufactured by SHIN NIPPON RIKO CO., LTD.)

[0161] 1-methyl-2-pyrrolidone (auxiliary solvent)

[0162] Preparation of compositions A to I for plasma separation:

[0163] The compositions A to I for plasma separation were prepared by mixing the organic components having fluidity at 25°C, the inorganic fine powder and the other components in the mixing proportions described in Tables 1 and 2.

[0164] Preparation of composition J for plasma separation:

[0165] An organic component having fluidity at 25°C was prepared by dissolving and mixing materials described in Table 2 in an organic component having fluidity at 25°C under heating at 130°C. Next, the organic component having fluidity at 25°C and inorganic fine powder and other components were mixed in the proportions described in Table 2 to prepare a blood plasma separation composition J.

[0166]

[0167]

[0168] (osmotic pressure adjusting agent)

[0169] sodium chloride

[0170] glucose

[0171] (anticoagulant)

[0172] ethylenediaminetetraacetic acid dipotassium salt dihydrate (EDTA 2K-2H2O)

[0173] (Example 1)

[0174] An osmotic pressure adjusting agent and an anticoagulant were dissolved in water to obtain a mixed solution. The kinds and amounts of the components of the obtained mixed solution are shown in Table 3.

[0175] A PET bottomed tube (blood collection container main body) having a length of 100 mm and an inner diameter of 14 mm at the opening portion was prepared. 1.0 g of the blood plasma separation composition A was contained in the bottom of the blood collection container main body. Further, 1.0 mL of the obtained mixed solution was added to the surface of the blood plasma separation composition A. The inside of the blood collection container was depressurized and sealed by a butyl rubber plug. Thus, a blood collection container was prepared. In the obtained blood collection container, the osmotic pressure adjusting agent and the anticoagulant were disposed on the surface of the blood plasma separation composition in a state of being dissolved in a liquid. Further, the obtained blood collection container was a container for collecting 4 mL of blood.

[0176] (Examples 2 to 12 and Comparative Examples 2 to 5)

[0177] The kinds and compositions of the blood plasma separation composition, the osmotic pressure adjusting agent, and the anticoagulant were changed as shown in Tables 3 to 6, and otherwise, a blood collection container was prepared in the same manner as in Example 1.

[0178] (Comparative Example 1)

[0179] An anticoagulant was dissolved in water to obtain a mixed solution. The kinds and amounts of the components of the obtained mixed solution are shown in Table 6.

[0180] A PET bottomed tube (blood collection container main body) having a length of 100 mm and an inner diameter of 14 mm at the opening portion was prepared. 1.0 g of the plasma separation composition B was contained in the bottom of the blood collection container main body. Further, 30 mg of the resulting mixture was coated on the inner wall surface of the blood collection container main body and allowed to dry. The inside of the blood collection container was depressurized and sealed by a butyl rubber plug. Thus, a blood collection container was prepared. In the resulting blood collection container, the anticoagulant was disposed on the inner wall surface of the blood collection container main body in a powder state. Further, the resulting blood collection container was a container for collecting 4 mL of blood.

[0181] (Evaluation)

[0182] (1) Specific gravity of the plasma separation composition at 25°C

[0183] In 25°C saline, the specific gravity of which was adjusted in stages at intervals of 0.002, 1 drop of the resulting plasma separation composition was added dropwise in order, and the specific gravity was determined by the floatation and sinking in the saline.

[0184] (2) Osmotic pressure of the osmotic pressure measurement solution

[0185] Physiological saline 4 mL was added to the resulting blood collection container. After the addition, decanting mixing was performed, and the osmotic pressure adjusting agent and the anticoagulant were dissolved in the physiological saline to obtain an osmotic pressure measurement solution. The osmotic pressure of the resulting osmotic pressure measurement solution was determined by the freezing point depression method using an osmometer (ARKRAY Co., Ltd. "OM-6060").

[0186] (3) Forming property of the partition wall

[0187] The blood of three persons was prepared, and the following procedures were performed in order.

[0188] Blood collection procedure:

[0189] Blood 4 mL was collected into the resulting blood collection container.

[0190] Centrifugal separation procedure:

[0191] The blood collection container was centrifugally separated at 1500 G for 15 minutes.

[0192] Visual observation:

[0193] Whether or not the plasma separation composition contained in the bottom of the blood collection container main body before centrifugal separation moved to between the blood cell layer and the plasma layer after centrifugal separation to form a partition wall well was confirmed by visual observation. Specifically, the forming property of the partition wall was evaluated by the following method.

[0194] Test (1): The blood collection container after centrifugal separation was observed with the naked eye. The case where the plasma separation composition was positioned between the blood cell layer and the plasma layer was determined to be good. On the other hand, the case where the entire amount of the plasma separation composition was positioned below the blood cell layer was determined to be poor.

[0195] Test (2): The blood collection container after centrifugal separation was left standing with the bottom of the blood collection container turned upward by 90°. At this time, with respect to the blood cell component positioned on the bottom side of the blood collection container main body with respect to the plasma separation composition, the blood cell component was moved to the opening end side of the blood collection container main body closer to the plasma separation composition, and whether or not the blood cell component was mixed with the plasma was observed with the naked eye. The case where the blood cell component was not mixed with the plasma was determined to be good. On the other hand, the case where the blood cell component was mixed with the plasma was determined to be poor.

[0196] [Criteria for determining the formation of the partition wall]

[0197] O: The determination results of Test (1) and Test (2) were both good

[0198] X: The determination result of Test (1) or Test (2) was poor

[0199] Note that in Comparative Examples 4 and 5, the results of the formation of the partition wall were poor, and therefore the evaluation of (4) the mixing of white blood cells in the plasma below was not performed.

[0200] (4) Mixing of white blood cells in the plasma

[0201] The blood of three people was prepared, and the following procedures were performed in order.

[0202] Blood collection procedure:

[0203] 4 mL of blood was collected into the obtained blood collection container.

[0204] Centrifugal separation procedure:

[0205] The blood collection container was centrifugally separated at 1500 G for 15 minutes.

[0206] After centrifugal separation, the plasma positioned above the partition wall formed by the plasma separation composition was stirred by pipetting to suspend the blood cells accumulated and remaining on the partition wall formed by the plasma separation composition, and then recovered.

[0207] The recovered plasma was analyzed using a multi-item automatic blood cell analyzer (XE5000 manufactured by SYSMEX Corporation) to measure the number of white blood cells in the plasma. In addition, the number of white blood cells in the prepared blood (whole blood sample) was also measured in the same manner. Note that the number of white blood cells is an average of the results obtained from the evaluation of the blood of three persons.

[0208] The residual rate of white blood cells was calculated by the following equation.

[0209] Residual rate of white blood cells (%) = (number of white blood cells contained in the separated plasma) / (number of white blood cells contained in the whole blood sample) x 100

[0210] [Criterion for determination of the mixing of white blood cells in the plasma]

[0211] O: Residual rate of white blood cells is less than 10%

[0212] X: Residual rate of white blood cells is 10% or more

[0213] The composition and results are shown in Tables 3 to 6 below.

[0214]

[0215]

[0216]

[0217]

[0218] Explanation of symbols

[0219] 1, 1A... blood collection container

[0220] 2... blood collection container main body

[0221] 2a... inner wall surface

[0222] 3... composition for plasma separation

[0223] 4... mixed solution

[0224] 4A... mixed powder

[0225] 5... plug

Claims

1. A blood collection container for collecting a given amount of blood, wherein, The blood collection container includes: Blood collection container body, Plasma separation material contained within the main body of the blood collection container Osmotic pressure regulator contained within the main body of the blood collection container, and The anticoagulant contained within the main body of the blood collection container. The plasma separation material has a specific gravity of 1.030 to 1.120 at 25°C. The plasma separation material is a composition for plasma separation. The plasma separation composition comprises organic components and inorganic microparticles that are free-flowing at 25°C. The organic components include petroleum resins, cyclopentadiene resins, polyester resins, or (meth)acrylic resins. The inorganic micro powder includes silica micro powder. In the case where an osmotic pressure measuring solution is obtained by dissolving the osmotic pressure regulator and the anticoagulant contained within the main body of the blood collection container in physiological saline with a given volume of saline equal to the amount of blood collected in the blood collection container,... When the specific gravity of the plasma separation material at 25°C is greater than or equal to 1.030 and less than 1.040, the osmotic pressure of the solution used for osmotic pressure measurement is greater than or equal to 300 mOsm / L. When the specific gravity of the plasma separation material at 25°C is greater than or equal to 1.040 and less than 1.050, the osmotic pressure of the solution used for osmotic pressure measurement is greater than or equal to 330 mOsm / L. When the specific gravity of the plasma separation material at 25°C is greater than or equal to 1.050 and less than 1.060, the osmotic pressure of the solution used for osmotic pressure measurement is greater than or equal to 350 mOsm / L. When the specific gravity of the plasma separation material at 25°C is greater than or equal to 1.060 and less than 1.070, the osmotic pressure of the solution used for osmotic pressure measurement is greater than or equal to 500 mOsm / L. When the specific gravity of the plasma separation material at 25°C is 1.070 or higher and 1.120 or lower, the osmotic pressure of the solution used for osmotic pressure measurement is 650 mOsm / L or higher.

2. The blood collection container according to claim 1, wherein, The silica micropowder contains hydrophilic silica.

3. The blood collection container according to claim 2, wherein, In the plasma separation composition, the content of hydrophilic silica is 0.01% to 2.50% by weight in 100% by weight.

4. The blood collection container according to any one of claims 1 to 3, wherein, The silica micropowder comprises hydrophilic silica and hydrophobic silica.

5. The blood collection container according to any one of claims 1 to 3, wherein, When the specific gravity of the plasma separation composition is 1.05 or higher at 25°C, the inorganic micropowder comprises inorganic micropowder with a specific gravity greater than that of the silica micropowder.

6. The blood collection container according to any one of claims 1 to 3, wherein, The osmotic pressure regulator is contained within the body of the blood collection container in either powder or liquid form. The anticoagulant is contained within the body of the blood collection container in either powder or dissolved in a liquid state.

7. The blood collection container according to any one of claims 1 to 3, wherein, The osmotic pressure regulator is disposed on the inner wall surface of the blood collection container body or on the surface of the plasma separation material. The anticoagulant is disposed on the inner wall of the blood collection container body or on the surface of the plasma separation material.

8. The blood collection container according to any one of claims 1 to 3, wherein, The osmotic pressure regulator is sodium chloride or glucose.

9. The blood collection container according to any one of claims 1 to 3, used for detecting extracellular free nucleic acids in blood.

10. A method for separating plasma, wherein the method uses the blood collection container according to any one of claims 1 to 9. The separation method comprises: The process of centrifuging blood collection containers containing blood.

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