WO2024204675A1 - 血液採取容器及び血漿の分離方法 - Google Patents

血液採取容器及び血漿の分離方法 Download PDF

Info

Publication number
WO2024204675A1
WO2024204675A1 PCT/JP2024/012964 JP2024012964W WO2024204675A1 WO 2024204675 A1 WO2024204675 A1 WO 2024204675A1 JP 2024012964 W JP2024012964 W JP 2024012964W WO 2024204675 A1 WO2024204675 A1 WO 2024204675A1
Authority
WO
WIPO (PCT)
Prior art keywords
blood collection
collection container
aqueous solution
weight
blood
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2024/012964
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
嵩也 内山
智雅 井上
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sekisui Medical Co Ltd
Original Assignee
Sekisui Medical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sekisui Medical Co Ltd filed Critical Sekisui Medical Co Ltd
Priority to JP2025511239A priority Critical patent/JPWO2024204675A1/ja
Publication of WO2024204675A1 publication Critical patent/WO2024204675A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers

Definitions

  • the present invention relates to a blood collection container.
  • the present invention also relates to a method for separating plasma using the blood collection container.
  • blood collection containers such as blood collection tubes are widely used to collect blood. After blood is collected in a blood collection container containing a plasma separation material, the blood can be separated into plasma and blood cells by centrifuging the blood collection container. At this time, the plasma is located above the plasma separation material, and the blood cells are located below.
  • blood collection containers containing plasma separation material include blood collection containers containing a plasma separation composition including a resin and an inorganic powder (e.g., Patent Document 1) and blood collection containers containing a plasma separation tool (e.g., Patent Document 2).
  • blood is collected in a blood collection container, stored for a certain period of time, and then separated into plasma and blood cells by centrifugation. For example, if the blood collection container is transported to a testing facility after collection, or if there is a large amount of specimens waiting to be tested at the testing facility, several days may pass between the time the blood is collected in the blood collection container and the time it is centrifuged.
  • miRNA may leak from blood cells during storage after blood collection, or from red blood cells due to hemolysis. If miRNA leaks during storage after blood collection, the miRNA may be mixed into the plasma separated by centrifugation, which may affect the test results.
  • extracellular vesicles may be released from blood cells during storage after blood collection. Since some extracellular vesicles contain miRNA, if extracellular vesicles are released from blood cells during storage after blood collection, the miRNA may be mixed into the plasma separated by centrifugation, which may affect the test results. For example, in a test to detect extracellular free nucleic acids (e.g., cell free RNA) in plasma, the test results may vary depending on the miRNA mixed into the plasma.
  • This specification discloses the following blood collection container and plasma separation method.
  • a blood collection container comprising a blood collection container body, a plasma separation material contained within the blood collection container body, and an aqueous solution contained within the blood collection container body, the aqueous solution including an anticoagulant and an antioxidant.
  • Item 2 The blood collection container according to item 1, wherein the aqueous solution contains a pH adjuster.
  • Item 3 The blood collection container according to item 1, wherein the aqueous solution contains glucose.
  • Item 4 The blood collection container according to item 1, wherein the aqueous solution contains glucose and a pH adjuster.
  • Item 5 The blood collection container according to any one of items 1 to 4, wherein the aqueous solution contains polyethylene glycol.
  • Item 6 The blood collection container according to item 5, in which the content of the polyethylene glycol in the aqueous solution (100% by weight) is 0.1% by weight or more and 10% by weight or less.
  • Item 7 The blood collection container according to any one of items 1 to 6, wherein the aqueous solution contains propylene glycol.
  • Item 8 The blood collection container according to item 7, in which the content of the propylene glycol in the aqueous solution (100% by weight) is 0.1% by weight or more and 30% by weight or less.
  • Item 9 The blood collection container according to any one of items 1 to 8, wherein the aqueous solution contains trehalose.
  • Item 10 The blood collection container according to Item 9, wherein the trehalose content in the aqueous solution (100% by weight) is 0.1% by weight or more and 30% by weight or less.
  • Item 11 The blood collection container according to any one of items 1 to 10, wherein the aqueous solution contains adenine.
  • Item 12 The blood collection container according to item 11, in which the content of the adenine in the aqueous solution (100% by weight) is 0.001% by weight or more and 1% by weight or less.
  • Item 13 The blood collection container according to any one of items 1 to 12, wherein the antioxidant includes ascorbic acid or a salt thereof, or glutathione.
  • Item 14 The blood collection container according to any one of items 1 to 13, wherein the pH of the aqueous solution is 3.0 or more and 6.0 or less.
  • a blood collection container according to any one of items 1 to 14, which is a blood collection container for collecting a predetermined amount of blood, and when an amount of saline equal to the predetermined amount of blood to be collected in the blood collection container is collected in the blood collection container, and a mixed solution is obtained by mixing the saline and the aqueous solution, the osmotic pressure of the mixed solution is 285 mOsm/L or more.
  • Item 16 A blood collection container according to any one of items 1 to 15, in which the specific gravity of the plasma separation material at 25°C is 1.027 or more and 1.060 or less.
  • Item 17 The blood collection container according to any one of items 1 to 16, wherein the plasma separation material is a plasma separation composition.
  • Item 18 The blood collection container according to Item 17, wherein the plasma separation composition comprises an organic component having fluidity at 25°C and an inorganic fine powder, the organic component comprises a resin, and the inorganic fine powder comprises fine silica powder.
  • Item 19 A method for separating plasma, comprising the steps of: collecting blood in a blood collection container according to any one of items 1 to 18; and centrifuging the blood collection container in which the blood has been collected.
  • the blood collection container according to the present invention comprises a blood collection container body, a plasma separation material contained within the blood collection container body, and an aqueous solution contained within the blood collection container body, the aqueous solution containing an anticoagulant and an antioxidant. Since the blood collection container according to the present invention has the above configuration, it is possible to suppress leakage of miRNA and release of extracellular vesicles during storage after blood collection.
  • FIG. 1 is a front cross-sectional view showing a schematic diagram of a blood collection container according to one embodiment of the present invention.
  • the blood collection container comprises a blood collection container body, a plasma separation material contained within the blood collection container body, and an aqueous solution contained within the blood collection container body, the aqueous solution containing an anticoagulant and an antioxidant.
  • the blood collection container according to the present invention has the above-mentioned configuration, and therefore can suppress leakage of miRNA and release of extracellular vesicles during storage after blood collection.
  • the blood and the above-mentioned aqueous solution are mixed.
  • the blood collection container according to the present invention may be stored in a state in which the blood and the above-mentioned aqueous solution are mixed.
  • the blood collection container according to the present invention uses an aqueous solution containing an anticoagulant and an antioxidant, and therefore can suppress leakage of miRNA and release of extracellular vesicles during storage after blood collection.
  • a blood collection container contains a liquid containing dextrose, a compound with hemolysis prevention properties, or a liquid with a low pH, hemolysis is suppressed and the leakage of miRNA from red blood cells due to hemolysis can be suppressed to some extent, but it is not possible to suppress the leakage of miRNA from blood cells or the release of extracellular vesicles.
  • the blood collection container of the present invention uses an aqueous solution containing an anticoagulant and an antioxidant, which can suppress hemolysis during storage after blood collection, and as a result, can suppress leakage of miRNA from red blood cells due to hemolysis.
  • the blood collection container of the present invention uses an aqueous solution containing an anticoagulant and an antioxidant, which can suppress leakage of miRNA from blood cells during storage after blood collection.
  • the blood collection container of the present invention uses an aqueous solution containing an anticoagulant and an antioxidant, which can suppress the release of extracellular vesicles during storage after blood collection. Therefore, with the blood collection container of the present invention, even if the blood collection container is stored for a certain period of time after blood collection, the amount of miRNA mixed in the plasma obtained by centrifugation can be reduced.
  • centrifugation may be performed after blood collection without storing it.
  • (meth)acrylic means either or both of "acrylic” and “methacrylic.”
  • the blood collection container includes a plasma separation material contained in the blood collection container body.
  • a plasma separation material a conventionally known plasma separation material can be used.
  • a plasma separation composition a plasma separation tool, and the like can be mentioned. Since the plasma separation material is easily prepared, the plasma separation material is preferably the plasma separation composition.
  • the specific gravity of the plasma separation material at 25°C is preferably 1.027 or more, more preferably 1.029 or more, even more preferably 1.030 or more, particularly preferably 1.032 or more, and preferably 1.060 or less, more preferably 1.055 or less, and even more preferably 1.050 or less.
  • the specific gravity of the plasma separation material at 25°C is equal to or more than the above lower limit and equal to or less than the above upper limit, plasma can be separated from blood more effectively, and contamination of plasma with white blood cells, red blood cells, and platelets can be more effectively suppressed.
  • the location where the plasma separation material is contained is not particularly limited as long as it is inside the blood collection container body.
  • the plasma separation material may be disposed at the bottom of the blood collection container body, or on the inner wall surface of the blood collection container body.
  • the composition for plasma separation is a composition that moves between the plasma layer and the blood cell layer during centrifugation to form a partition.
  • the plasma separation composition is preferably thixotropic.
  • the plasma separation composition is contained in the bottom of the blood collection container body. In order to more effectively exert the effects of the present invention, the plasma separation composition may be contained in the bottom of the blood collection container body, or may be disposed on the inner wall surface. is preferred.
  • a conventionally known plasma separation composition can be used as the plasma separation composition.
  • the plasma separation composition preferably contains an organic component having fluidity at 25°C and an inorganic fine powder.
  • the organic component having fluidity at 25°C and the inorganic fine powder may each be used alone or in combination of two or more types.
  • the viscosity of the 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, more preferably 100 Pa ⁇ s or less. If the viscosity is equal to or greater than the lower limit and equal to or less than the upper limit, the fluidity of the plasma separation composition is increased, and the strength of the partition wall formed by the centrifugation operation can be increased.
  • the viscosity of the organic component at 25° C. is measured using an E-type viscometer (for example, “TVE-35” manufactured by Toki Sangyo Co., Ltd.) under conditions of 25° C. and a shear rate of 1.0 sec ⁇ 1 .
  • E-type viscometer for example, “TVE-35” manufactured by Toki Sangyo Co., Ltd.
  • the organic component may be a resin, or a mixture of a resin and an organic compound such as a plasticizer. Therefore, the organic component preferably contains the resin, and more preferably contains the resin and the organic compound. When the organic component is a mixture of the resin and the organic compound, the mixture (the organic component) may have fluidity, and the resin or the organic compound may not have fluidity. When the organic component is a mixture of the resin and the organic compound, the resin may be, for example, a resin that is solid at 25°C. Only one type of the resin and the organic compound may be used, or two or more types may be used in combination.
  • the above resins include petroleum resins, cyclopentadiene resins, polyester resins, polyurethane resins, (meth)acrylic resins, silicone resins, ⁇ -olefin-fumaric acid ester copolymers, copolymers of sebacic acid, 2,2-dimethyl-1,3-propanediol, and 1,2-propanediol, polyether polyurethane resins, and polyether polyester resins. Only one of the above resins may be used, or two or more of them may be used in combination.
  • the above resin preferably contains a petroleum resin, a cyclopentadiene resin, a polyester resin, or a (meth)acrylic resin.
  • the above-mentioned cyclopentadiene-based resins include polymers of cyclopentadiene-based monomers, copolymers of cyclopentadiene-based monomers and aromatic monomers, and dicyclopentadiene resins.
  • the above-mentioned cyclopentadiene-based resins may be hydrogenated.
  • the above-mentioned polymers of cyclopentadiene-based monomers and copolymers of cyclopentadiene-based monomers and aromatic monomers may be oligomers.
  • cyclopentadiene monomers include cyclopentadiene, dicyclopentadiene, and alkyl-substituted derivatives of cyclopentadiene.
  • the aromatic monomers include styrene, methylstyrene, indene, and methylindene.
  • the polyester resins mentioned above include polyalkylene terephthalate resins and polyalkylene naphthalate resins.
  • the polyalkylene terephthalate resins mentioned above include polyethylene terephthalate, polybutylene terephthalate, and poly-1,4-cyclohexanedimethylene terephthalate.
  • the polyurethane resin may be a reaction product of a polyol compound and an isocyanate compound.
  • the above-mentioned (meth)acrylic resins include resins obtained by polymerizing at least one type of (meth)acrylic acid ester monomer, and resins obtained by polymerizing at least one type of (meth)acrylic acid ester monomer and at least one type of monomer other than a (meth)acrylic acid ester monomer.
  • the above-mentioned (meth)acrylic acid ester monomers include (meth)acrylic acid alkyl esters, (meth)acrylic acid polyalkylene glycol esters, (meth)acrylic acid alkoxyalkyl esters, (meth)acrylic acid hydroxyalkyl esters, (meth)acrylic acid glycidyl esters, (meth)acrylic acid dialkylaminoalkyl esters, (meth)acrylic acid benzyl esters, (meth)acrylic acid phenoxyalkyl esters, (meth)acrylic acid cyclohexyl esters, (meth)acrylic acid isobornyl esters, and (meth)acrylic acid alkoxysilylalkyl esters.
  • the number of carbon atoms of the alkyl group is preferably 1 or more and preferably 20 or less.
  • the above-mentioned (meth)acrylic acid alkyl esters are preferably (meth)acrylic acid alkyl esters having an alkyl group having a carbon number of 1 or more and 20 or less.
  • the above-mentioned (meth)acrylic acid ester monomers may be used alone or in combination of two or more.
  • the organic compound may be a benzene polycarboxylic acid alkyl ester derivative.
  • the organic compound is preferably a benzene polycarboxylic acid alkyl ester derivative. Therefore, the organic component is preferably a mixture of the resin and the benzene polycarboxylic acid alkyl ester derivative.
  • the above-mentioned benzene polycarboxylic acid alkyl ester derivatives include phthalic acid esters, trimellitic acid esters, pyromellitic acid esters, etc.
  • the above-mentioned benzene polycarboxylic acid alkyl ester derivatives may be used alone or in combination of two or more kinds.
  • trimellitic acid esters examples include trimellitic acid trimellitate tri-n-octyl, trimellitic acid triisooctyl, and trimellitic acid triisodecyl.
  • the above pyromellitic acid esters include tetraisooctyl pyromellitic acid, etc.
  • trimellitic acid esters Commercially available products of the above trimellitic acid esters include “Monocizer W700” and “Monocizer W-750” manufactured by DIC Corporation, and “Sansocizer TOTM” and “Sansocizer TITM” manufactured by New Japan Chemical Co., Ltd.
  • pyromellitic acid esters include "Monocizer W-7010" manufactured by DIC Corporation.
  • the benzene polycarboxylic acid alkyl ester derivative is preferably a phthalate ester, a trimellitate ester, or a pyromellitate ester, and more preferably a trimellitate ester.
  • the content of the organic components in the plasma separation composition (100% by weight) is preferably 80% by weight or more, more preferably 85% by weight or more, even more preferably 90% by weight or more, and preferably 97% by weight or less.
  • Inorganic fine powder examples include fine silica powder, titanium oxide powder, calcium carbonate powder, zinc oxide powder, alumina powder, fine glass powder, talc powder, kaolin powder, bentonite powder, titania powder, and zirconium powder.
  • the inorganic fine powder is 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.
  • the inorganic fine powder contains fine silica.
  • the inorganic fine powder contains fine silica and an inorganic fine powder other than fine silica (second inorganic fine powder).
  • the specific gravity of the plasma separation composition at 25°C is 1.050 or more
  • the inorganic fine powder does not have to contain the second inorganic fine powder.
  • the specific gravity of the plasma 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 alone or in combination of two or more.
  • the above-mentioned finely powdered silica includes natural silica and synthetic silica.
  • Synthetic silica includes hydrophilic silica and hydrophobic silica.
  • Hydrophilic silica for example, imparts thixotropy to the plasma separation composition by hydrogen bonding between hydroxyl groups on the particle surface, and also has the effect of adjusting the specific gravity.
  • hydrophobic silica has a smaller effect of imparting thixotropy than hydrophilic silica.
  • the finely powdered silica preferably contains hydrophilic silica, and more preferably contains both hydrophilic and hydrophobic silica.
  • the second inorganic fine powder is preferably an inorganic fine powder having a higher specific gravity than fine silica powder, and more preferably an inorganic fine powder having a specific gravity of 3 or more, such as zinc oxide powder, titanium oxide powder, or alumina powder.
  • the specific gravity of the second inorganic fine powder is preferably 3 or more, more preferably 3.5 or more, and even more preferably 4 or more. The higher the specific gravity of the second inorganic fine powder, the better. If the specific gravity is equal to or greater than the lower limit, the specific gravity of the plasma separation composition can be effectively increased.
  • the average particle diameter of the inorganic micropowder, the fine silica powder, and the second inorganic micropowder is not particularly limited.
  • the average particle diameter of the inorganic micropowder, the fine silica powder, and the second inorganic micropowder may be 1 nm or more, 10 nm or more, 500 nm or less, or 100 nm or less.
  • the average particle diameters of the inorganic fine powder, the fine silica powder, and the second inorganic fine powder are average diameters measured on a volume basis (volume average particle diameters), and are the 50% median diameter (D50) values.
  • the volume average particle diameters (D50) can be measured by laser diffraction/scattering method, image analysis method, Coulter method, centrifugal sedimentation method, and the like.
  • the volume average particle diameters (D50) are preferably determined by laser diffraction/scattering method or image analysis method.
  • the specific surface area of the finely powdered silica is not particularly limited.
  • the specific surface area of the finely powdered silica may be 20 m 2 /g or more, 100 m 2 /g or more, 500 m 2 /g or less, or 300 m 2 /g or less.
  • the specific surface area of the above finely powdered silica is measured by the BET method.
  • the content of the hydrophilic silica in 100% by weight of the plasma separation composition 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.
  • content of the hydrophilic silica is equal to or more than the lower limit and equal to or less than the upper limit, both the specific gravity and thixotropy of the plasma separation composition can be maintained within an even more suitable range.
  • the content of the finely powdered silica in 100% by weight of the plasma separation composition is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, preferably 10% by weight or less, more preferably 7% by weight or less.
  • content of the finely powdered silica is equal to or more than the lower limit and equal to or less than the upper limit, both the specific gravity and thixotropy of the plasma separation composition can be maintained within an even more suitable range.
  • the content of the second inorganic fine powder in 100% by weight of the plasma separation composition is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, preferably 10% by weight or less, more preferably 7% by weight or less.
  • the specific gravity of the plasma separation composition can be effectively increased.
  • the content of the inorganic fine powder in 100% by weight of the plasma separation composition is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, preferably 10% by weight or less, more preferably 7% by weight or less.
  • the specific gravity of the plasma separation composition can be effectively increased.
  • the plasma separation composition may contain other components in addition to the above-mentioned components, so long as the effects of the present invention are not impaired.
  • the other components include organic gelling agents, thermoplastic elastomers, polyalkylene glycols, silicone oils, auxiliary solvents, antioxidants, colorants, and water.
  • Each of the other components may be used alone or in combination of two or more.
  • the specific gravity of the plasma separation composition at 25°C is preferably 1.027 or more, more preferably 1.029 or more, even more preferably 1.030 or more, particularly preferably 1.032 or more, preferably 1.060 or less, more preferably 1.055 or less, and even more preferably 1.050 or less.
  • the specific gravity of the plasma separation composition at 25°C is equal to or greater than the lower limit and equal to or less than the upper limit, plasma can be separated well from blood, and contamination of plasma with white blood cells, red blood cells, and platelets can be more effectively prevented.
  • the specific gravity of the plasma separation composition at 25°C may be 1.050 or more, or may exceed 1.050.
  • the specific gravity of the above plasma separation composition at 25°C is measured by dropping one drop of the plasma separation composition into saline at 25°C, the specific gravity of which has been adjusted stepwise at intervals of 0.002, and observing whether the composition floats or sinks in the saline.
  • the viscosity of the plasma separation composition at 25°C is preferably 50 Pa ⁇ s or more, more preferably 70 Pa ⁇ s or more, and preferably 500 Pa ⁇ s or less, more preferably 400 Pa ⁇ s or less. If the viscosity is equal to or greater than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively achieved.
  • the viscosity of the plasma separation composition at 25° C. is measured using an E-type viscometer (for example, "TVE-35" manufactured by Toki Sangyo Co., Ltd.) under conditions of 25° C. and a shear rate of 1.0 sec -1 .
  • E-type viscometer for example, "TVE-35” manufactured by Toki Sangyo Co., Ltd.
  • the plasma separation device is a device that moves between the plasma layer and the blood cell layer during centrifugation to form a partition wall, and is used for the purpose of preventing component migration between the plasma layer and the blood cell layer.
  • a conventionally known plasma separation tool can be used as the plasma separation tool.
  • the plasma separation tool include the mechanical separator (plasma separation tool) described in WO2010/132783A1, etc.
  • Examples of materials for the plasma separation tool include elastomers.
  • the blood collection container includes an aqueous solution contained within the blood collection container body, the aqueous solution preferably including an anticoagulant, an antioxidant, and water.
  • the aqueous solution contains an anticoagulant.
  • an anticoagulant a conventionally known anticoagulant can be used.
  • the anticoagulant may be used alone or in combination of two or more kinds.
  • the above anticoagulants include heparin, metal salts of heparin, ethylenediaminetetraacetic acid (EDTA), metal salts of EDTA, and sodium citrate.
  • the anticoagulant is preferably heparin, a metal salt of heparin, EDTA, a metal salt of EDTA, or sodium citrate.
  • the concentration of the anticoagulant in the aqueous solution is preferably 2 mM or more, more preferably 5 mM or more, even more preferably 10 mM or more, preferably 2000 mM or less, more preferably 1000 mM or less, even more preferably 500 mM or less, even more preferably 250 mM or less, even more preferably 100 mM or less, and particularly preferably 50 mM or less.
  • concentration of the anticoagulant is equal to or more than the lower limit and equal to or less than the upper limit, the anticoagulant performance can be satisfactorily exhibited.
  • the aqueous solution contains an antioxidant.
  • an antioxidant By using the antioxidant, leakage of miRNA from red blood cells due to hemolysis, leakage of miRNA from blood cells, and release of extracellular vesicles during storage after blood collection can be effectively suppressed, and the effects of the present invention can be effectively exhibited.
  • the antioxidant may be used alone or in combination of two or more kinds.
  • the antioxidants include ascorbic acid and its salts, lipoic acid, polyphenols, carotenoids, glutathione, acetylsalicylic acid, elamipretide, etc.
  • the ascorbate salts include sodium ascorbate and sodium L-ascorbate phosphate, etc.
  • the antioxidant is preferably ascorbic acid or a salt thereof, lipoic acid, polyphenol, carotenoid, glutathione, acetylsalicylic acid, or elamipretide. In this case, the effect of the present invention can be exerted even more effectively.
  • the antioxidant preferably contains ascorbic acid or a salt thereof, or glutathione, more preferably contains an ascorbate salt, and even more preferably contains sodium ascorbate. In this case, the effect of the present invention can be exerted even more effectively.
  • the glutathione is preferably reduced glutathione.
  • the content of the antioxidant is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, even more preferably 1% by weight or more, preferably 20% by weight or less, more preferably 10% by weight or less, even more preferably 8% by weight or less, and particularly preferably 5% by weight or less.
  • the content of the antioxidant is equal to or more than the lower limit and equal to or less than the upper limit, leakage of miRNA from red blood cells due to hemolysis, leakage of miRNA from blood cells, and release of extracellular vesicles during storage after blood collection can be more effectively suppressed, and the effects of the present invention can be more effectively exhibited.
  • the aqueous solution preferably contains glucose.
  • glucose a nutrient source is supplied to red blood cells and white blood cells, so that the survival rate of blood cells can be increased, and as a result, leakage of miRNA from blood cells during storage after blood collection can be further suppressed.
  • glucose hemolysis during storage after blood collection can be effectively suppressed. Only one type of glucose may be used, or two or more types may be used in combination.
  • the glucose may be dextrose.
  • the glucose content in the aqueous solution (100% by weight) is preferably 0.1% by weight or more, more preferably 0.3% by weight or more, preferably 30% by weight or less, more preferably 10% by weight or less.
  • the glucose content is equal to or more than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively achieved.
  • the aqueous solution preferably contains polyethylene glycol.
  • polyethylene glycol By using polyethylene glycol, the effect of the present invention can be more effectively achieved.
  • polyethylene glycol by using polyethylene glycol, the release of extracellular vesicles and the leakage of miRNA from blood cells can be effectively suppressed during storage after blood collection, and the leakage of miRNA from the released extracellular vesicles can be effectively suppressed.
  • polyethylene glycol can effectively suppress hemolysis during storage after blood collection.
  • polyethylene glycol effectively protects the lipid membrane of the extracellular vesicles and the cell membrane of the blood cells, thereby stabilizing the extracellular vesicles and the blood cells, but is not limited thereto. Only one type of polyethylene glycol may be used, or two or more types may be used in combination.
  • the number average molecular weight of the polyethylene glycol is preferably 500 or more, more preferably 1000 or more, even more preferably 1500 or more, even more preferably 2000 or more, particularly preferably 2500 or more, and preferably 180000 or less, more preferably 170000 or less, even more preferably 150000 or less, even more preferably 120000 or less, and particularly preferably 100000 or less.
  • the number average molecular weight of the polyethylene glycol is equal to or more than the above lower limit and equal to or less than the above upper limit, the effects of the present invention can be exhibited even more effectively.
  • the number average molecular weight of polyethylene glycol is the number average molecular weight calculated using standard polyethylene glycol as measured by gel permeation chromatography (GPC).
  • the content of polyethylene glycol in the aqueous solution (100% by weight) is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, even more preferably 1% by weight or more, preferably 10% by weight or less, more preferably 8% by weight or less, and even more preferably 5% by weight or less.
  • the content of polyethylene glycol is equal to or more than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively exhibited.
  • the aqueous solution preferably contains propylene glycol.
  • propylene glycol By using propylene glycol, the effects of the present invention can be more effectively exhibited.
  • the propylene glycol may be used alone or in combination of two or more kinds.
  • the content of propylene glycol in the aqueous solution (100% by weight) is preferably 0.1% by weight or more, more preferably 1% by weight or more, and preferably 30% by weight or less, more preferably 10% by weight or less.
  • the content of propylene glycol is equal to or more than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively achieved.
  • the aqueous solution preferably contains trehalose.
  • trehalose By using trehalose, the effects of the present invention can be more effectively achieved.
  • the content of trehalose in the aqueous solution (100% by weight) is preferably 0.1% by weight or more, more preferably 0.5% by weight or more, even more preferably 1% by weight or more, preferably 30% by weight or less, more preferably 10% by weight or less, and even more preferably 8% by weight or less.
  • the content of trehalose is equal to or more than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively exhibited.
  • the content of adenine in the aqueous solution (100% by weight) is preferably 0.001% by weight or more, more preferably 0.005% by weight or more, even more preferably 0.01% by weight or more, particularly preferably 0.05% by weight or more, preferably 1% by weight or less, more preferably 0.5% by weight or less, and even more preferably 0.1% by weight or less.
  • the content of adenine is equal to or more than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively exhibited.
  • the aqueous solution preferably contains a pH adjuster.
  • a pH adjuster By using the pH adjuster, the pH of the aqueous solution can be adjusted to a suitable range, and the effects of the present invention can be more effectively achieved.
  • the pH adjuster may be used alone or in combination of two or more.
  • the above pH adjusters include organic acids and inorganic acids. More specifically, the above pH adjusters include citric acid, hydrochloric acid, succinic acid, phosphoric acid, etc.
  • the pH adjuster is preferably an organic acid, more preferably citric acid, hydrochloric acid, succinic acid, or phosphoric acid, and even more preferably citric acid.
  • citric acid when citric acid is used, hemolysis during storage after blood collection can also be effectively suppressed.
  • the amount of the pH adjuster contained in the aqueous solution is not particularly limited as long as the pH of the aqueous solution can be adjusted to the desired pH.
  • the aqueous solution preferably contains water, in which the water serves as a solvent.
  • the content of the water is preferably 30% by weight or more, more preferably 40% by weight or more, even more preferably 60% by weight or more, even more preferably 70% by weight or more, particularly preferably 80% by weight or more, preferably 99% by weight or less, more preferably 95% by weight or less, and even more preferably 90% by weight or less.
  • the aqueous solution may contain other components in addition to the above-mentioned components (anticoagulant, antioxidant, glucose, polyethylene glycol, propylene glycol, trehalose, adenine, pH adjuster, and water).
  • examples of the other components include inorganic salts, sugars, and sugar alcohols. Each of the other components may be used alone or in combination of two or more.
  • the above inorganic salts include sodium salts such as sodium chloride and sodium hydrogen phosphate, and potassium salts such as potassium chloride and potassium hydrogen carbonate.
  • the above sugars include dihydroxyacetone, fructose, galactose, sucrose, maltose, lactulose, and dextran.
  • the sugar alcohols include inositol, D-mannitol, and D-sorbitol.
  • the pH of the aqueous solution is preferably 3.0 or more, more preferably 3.5 or more, even more preferably 4.0 or more, preferably 6.0 or less, more preferably 5.5 or less, and even more preferably 5.0 or less.
  • the pH is equal to or greater than the lower limit and equal to or less than the upper limit, hemolysis can be prevented during storage after blood collection, and leakage of miRNA from red blood cells due to hemolysis can be prevented.
  • the metabolism of blood cells can be suppressed, leakage of miRNA from blood cells and release of extracellular vesicles can be effectively suppressed, and leakage of miRNA from released extracellular vesicles can be effectively suppressed. Therefore, when the pH is equal to or greater than the lower limit and equal to or less than the upper limit, the effects of the present invention can be more effectively exhibited.
  • the pH of the above aqueous solution is measured at 20°C using a pH meter.
  • the osmotic pressure of the aqueous solution is preferably 285 mOsm/L or more, more preferably 350 mOsm/L or more, even more preferably 400 mOsm/L or more, preferably 2,000 mOsm/L or less, more preferably 1,400 mOsm/L or less, and even more preferably 850 mOsm/L or less. If the osmotic pressure of the aqueous solution is above the lower limit, when blood is collected in a blood collection container, the blood and the aqueous solution are mixed, and the osmotic pressure of the blood increases.
  • 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.
  • the white blood cells and the red blood cells with a higher specific gravity move well below the plasma separation material by centrifuging the blood collection container.
  • the contamination of the white blood cells and the red blood cells into the plasma can be effectively suppressed.
  • the osmotic pressure of the aqueous solution is equal to or higher than the lower limit and equal to or lower than the upper limit, excessive stress on the blood cells is suppressed, the blood cells can be further stabilized, and leakage of miRNA from the blood cells can be effectively suppressed.
  • hemolysis can be effectively suppressed.
  • the osmotic pressure of the above aqueous solution is measured by the freezing point depression method using an osmometer (e.g., Arkray's "OM-6060").
  • the amount of aqueous solution contained in the blood collection container body is changed as appropriate depending on the size of the blood collection container body, the amount of blood to be collected, etc.
  • the amount of aqueous solution contained in the blood collection container body is preferably 0.1 mL or more, more preferably 0.5 mL or more, even more preferably 0.7 mL or more, preferably 5 mL or less, more preferably 3 mL or less, and even more preferably 2.5 mL or less.
  • the shape of the blood collection container body is not particularly limited.
  • the blood collection container body is preferably a tubular container with a bottom.
  • the blood collection container body preferably has an open end at one end and a closed bottom (closed end) at the other end.
  • the material of the blood collection container body is not particularly limited.
  • 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 resin, epoxy resin, and epoxy-acrylate resin; modified natural resins such as cellulose acetate, cellulose propionate, ethyl cellulose, and ethyl chitin; and glass such as silicate glass, such as soda-lime glass, phosphosilicate glass, and borosilicate glass, and quartz glass. Only one type of material may be used for the blood collection container body, or two or more types may be used in combination.
  • the blood collection container preferably includes a stopper.
  • the stopper is preferably attached to the open end of the blood collection container body.
  • a conventionally known stopper can be used as the stopper.
  • the stopper is preferably made of a material and has a shape that allows it to be attached to the open end of the blood collection container body in an airtight and liquidtight manner.
  • the stopper is preferably configured to be pierced by a blood collection needle.
  • stopper examples include a stopper shaped to fit into the open end of the blood collection container body, a sheet-shaped seal stopper, etc.
  • the stopper may also be a stopper comprising a stopper body such as a rubber stopper and a cap member made of plastic or the like. In this case, the risk of blood coming into contact with the human body can be reduced when the stopper body is pulled out from the open end of the blood collection container body after blood collection.
  • the material of the stopper examples include synthetic resin, elastomer, rubber, metal foil, etc.
  • the rubber examples include butyl rubber and halogenated butyl rubber.
  • the metal foil examples include aluminum foil, etc. From the viewpoint of improving the sealing performance, the material of the stopper is preferably butyl rubber.
  • the stopper (or the stopper main body) is preferably a butyl rubber stopper.
  • the blood collection container is a blood collection container in which a predetermined amount of blood is collected.
  • the predetermined amount of blood is appropriately changed depending on the size and internal pressure of the blood collection container.
  • the predetermined amount of blood may be 1 mL or more, 2 mL or more, 4 mL or more, 12 mL or less, 11 mL or less, or 10 mL or less.
  • the physiological saline solution is collected in the blood collection container in an amount equal to the predetermined amount of blood collected in the blood collection container, and a mixed solution is obtained in which the physiological saline solution and the aqueous solution are mixed.
  • a mixed solution is obtained in which the physiological saline solution and the aqueous solution are mixed.
  • 5 mL of physiological saline solution is collected in the blood collection container, and the physiological saline solution and the aqueous solution are mixed by inversion to obtain a mixed solution.
  • the osmotic pressure of the mixed solution in which the physiological saline solution and the aqueous solution are mixed is preferably 285 mOsm/L or more, more preferably 300 mOsm/L or more, even more preferably 320 mOsm/L or more, preferably 500 mOsm/L or less, more preferably 450 mOsm/L or less, and even more preferably 400 mOsm/L or less. If the osmotic pressure of the mixed solution is above the lower limit, when blood is collected in the blood collection container, the blood and the aqueous solution are mixed, and the osmotic pressure of the blood increases.
  • the water in the white blood cells and the water in the red blood cells move out of the blood cells, and the specific gravity of the white blood cells and the red blood cells increases.
  • the white blood cells and the red blood cells with increased specific gravity move well below the plasma separation material by centrifuging the blood collection container.
  • the contamination of the white blood cells and the red blood cells into the plasma can be effectively suppressed.
  • the osmotic pressure of the above-mentioned mixture is equal to or higher than the lower limit and equal to or lower than the upper limit, excessive stress on the blood cells can be suppressed, the blood cells can be further stabilized, and the leakage of miRNA from the blood cells can be effectively suppressed.
  • hemolysis can be effectively suppressed.
  • the osmotic pressure of the mixture is measured by the freezing point depression method using an osmometer (e.g., Arkray's "OM-6060").
  • the blood collection container it is preferable that 3 mL or more of blood is collected per 1 mL of the aqueous solution contained therein, more preferably 4 mL or more, more preferably 11 mL or less, and even more preferably 10 mL or less.
  • the blood is not excessively diluted, and the effects of the present invention can be exerted even more effectively.
  • the blood collection container is preferably a blood collection tube.
  • the blood collection container body is preferably a blood collection tube body.
  • the blood collection container is preferably used to separate plasma from blood.
  • the blood collection container can be manufactured, for example, as follows:
  • an anticoagulant and an antioxidant are dissolved in water to obtain an aqueous solution. If necessary, other components are also dissolved in water to obtain an aqueous solution.
  • the aqueous solution obtained is added to the main body of the blood collection container. Before or after adding the aqueous solution, the plasma separation material is placed in the main body of the blood collection container.
  • FIG. 1 is a schematic front cross-sectional view of a blood collection container according to one embodiment of the present invention.
  • the blood collection container 1 shown in FIG. 1 comprises a blood collection container body 2, a plasma separation composition 3, an aqueous solution 4, and a stopper 5.
  • the blood collection container body 2 has an opening at one end and a bottom that is closed at the other end.
  • the plasma separation composition 3 is contained in the bottom of the blood collection container body 2.
  • the aqueous solution 4 contains an anticoagulant and an antioxidant.
  • the stopper 5 is inserted into the opening of the blood collection container body 2.
  • the aqueous solution 4 is disposed on the surface of the plasma separation composition 3, more specifically, on the upper surface (surface at one end) of the plasma separation composition 3.
  • the aqueous solution 4 is disposed on the surface of the plasma separation composition 3 when the blood collection container 1 is in an upright position.
  • the aqueous solution is disposed on the upper surface of the plasma separation composition (the surface at one end of the blood collection container body) when the blood collection container is in an upright position.
  • the plasma separation composition may be disposed on the side wall surface of the blood collection container body, and the aqueous solution may be disposed on the bottom of the blood collection container body when the blood collection container is in an upright position.
  • the plasma separation tool may be used instead of the plasma separation composition.
  • the internal pressure of the blood collection container is not particularly limited.
  • the blood collection container can also be used as a vacuum blood collection tube, with the interior evacuated and sealed with the stopper. When used as a vacuum blood collection tube, a fixed amount of blood can be easily collected regardless of the skill level of the blood collector.
  • the inside of the blood collection container is sterilized in accordance with ISO or JIS standards.
  • the blood collection container can be used to separate plasma from blood.
  • a method for separating plasma according to the present invention includes the steps of collecting blood in the blood collection container and centrifuging the blood collection container in which the blood has been collected.
  • the plasma separation method according to the present invention preferably includes a step of mixing the collected blood with the aqueous solution between the step of collecting the blood and the step of centrifuging.
  • Methods for mixing the collected blood with the aqueous solution include mixing by inversion, etc.
  • the centrifugation conditions in the centrifugation step are not particularly limited, so long as a partition can be formed using the plasma separation material to separate the plasma from the blood cells.
  • Examples of the centrifugation conditions include centrifugation at 400 G or more and 4000 G or less for 10 minutes or more and 120 minutes or less.
  • PET bottomed tube polyethylene terephthalate tube 100 mm long, 14 mm inside diameter at the open end
  • Glucose Polyethylene glycol (number average molecular weight: 4,000) Propylene glycol Trehalose Adenine Citric acid (pH adjuster) Sodium chloride (osmolality adjuster)
  • Hydrophilic silica fine silica powder, "200CF” manufactured by Nippon Aerosil Co., Ltd.
  • Hydrophobic silica fine silica powder, "RX200” manufactured by Nippon Aerosil Co., Ltd.
  • Preparation of plasma separation composition 14.50 parts by weight of petroleum resin, 18.0 parts by weight of dicyclopentadiene resin 1, 19.70 parts by weight of dicyclopentadiene resin 2, and 44.90 parts by weight of trimellitic acid ester were mixed and melted by heating at 130 ° C. to prepare an organic component having fluidity at 25 ° C.
  • the obtained organic component having fluidity at 25 ° C. was mixed with 0.70 parts by weight of hydrophilic silica, 1.80 parts by weight of hydrophobic silica, 0.06 parts by weight of an organic gelling agent, and 0.34 parts by weight of 1-methyl-2-pyrrolidone to prepare a composition for plasma separation.
  • the specific gravity of the obtained composition for plasma separation at 25 ° C. was 1.045.
  • Example 1 Preparation of aqueous solution: The components shown in Table 1 were dissolved in water (water for injection) to obtain aqueous solutions. The types and concentrations of the components in the obtained aqueous solutions are shown in Table 1.
  • Preparation of blood collection container 1.2 g of the plasma separation composition was placed in the bottom of the blood collection container body. 1.5 mL of the obtained aqueous solution was added onto the surface of the plasma separation composition. The inside of the blood collection container was decompressed so that the blood collection volume was 8.5 mL, and the container was sealed with a butyl rubber stopper. In this way, a blood collection container was prepared.
  • Examples 2 to 14 and Comparative Examples 1 to 4 Blood collection containers were produced in the same manner as in Example 1, except that the compositions of the aqueous solutions were changed as shown in Tables 1 to 4.
  • Osmotic pressure of the mixed solution 8.5 mL of physiological saline was collected into the obtained blood collection container. After collecting the physiological saline, the container was inverted to mix the physiological saline and the aqueous solution contained in the blood collection container, to obtain a mixed solution. The osmotic pressure of the obtained mixed solution was measured by the freezing point depression method using an osmometer ("OM-6060" manufactured by Arkray, Inc.).
  • the blood collection container containing the mixed blood and aqueous solution was centrifuged at 1900 G for 15 minutes.
  • the plasma located above the partition formed by the plasma separation composition was collected.
  • the collected plasma was transferred to another container, and the container was centrifuged at 16,000 G for 10 minutes.
  • the supernatant plasma was collected from the vessel.
  • plasma collected in (iv) above using the blood collection container on the day the blood and aqueous solution were mixed will be referred to as “plasma (D0).”
  • plasma collected in (iv) above using the blood collection container stored at 37°C for three days after mixing the blood and aqueous solution will be referred to as “plasma (D3).”
  • evaluation results are the average values obtained by evaluating the blood of two people.
  • Plasma absorbance 100 ⁇ L of plasma (D0) and 100 ⁇ L of plasma (D3) were dispensed into a 96-well plate, and the absorbance at a wavelength of 415 nm was measured using a plate reader (SpectraMax iD5 manufactured by MOLECULAR DEVICES).
  • the increase rate of absorbance was calculated using the following formula. A larger increase rate of absorbance indicates that hemolysis occurred during storage.
  • A0 Absorbance of plasma (D0)
  • A3 Absorbance of plasma (D3)
  • the total miRNA concentration is a concentration including both miRNA derived from blood cells and miRNA derived from extracellular vesicles.
  • the above-mentioned miRNA derived from blood cells includes both miRNA leaked from red blood cells and miRNA leaked from blood cells other than red blood cells.
  • Total miRNA concentration (ng/1 mL of plasma) A ⁇ B/C
  • the rate of increase in total miRNA concentration was calculated using the following formula. Total miRNA concentration in plasma was evaluated according to the following criteria. The smaller the rate of increase in total miRNA concentration, the more suppressed the leakage of miRNA during storage after blood collection.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
PCT/JP2024/012964 2023-03-29 2024-03-29 血液採取容器及び血漿の分離方法 Ceased WO2024204675A1 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2025511239A JPWO2024204675A1 (https=) 2023-03-29 2024-03-29

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2023053036 2023-03-29
JP2023-053036 2023-03-29

Publications (1)

Publication Number Publication Date
WO2024204675A1 true WO2024204675A1 (ja) 2024-10-03

Family

ID=92905835

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2024/012964 Ceased WO2024204675A1 (ja) 2023-03-29 2024-03-29 血液採取容器及び血漿の分離方法

Country Status (2)

Country Link
JP (1) JPWO2024204675A1 (https=)
WO (1) WO2024204675A1 (https=)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019207229A (ja) * 2018-05-29 2019-12-05 東ソー株式会社 血液試料保存剤
WO2021182575A1 (ja) * 2020-03-11 2021-09-16 積水メディカル株式会社 白血球濃縮分離デバイス、血液採取容器及び白血球の分離方法
JP7169608B1 (ja) * 2022-01-28 2022-11-11 積水メディカル株式会社 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法
WO2022250142A1 (ja) * 2021-05-28 2022-12-01 積水メディカル株式会社 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法
WO2023026725A1 (ja) * 2021-08-25 2023-03-02 積水メディカル株式会社 細胞含有液用保存液及び細胞含有液用保存容器

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019207229A (ja) * 2018-05-29 2019-12-05 東ソー株式会社 血液試料保存剤
WO2021182575A1 (ja) * 2020-03-11 2021-09-16 積水メディカル株式会社 白血球濃縮分離デバイス、血液採取容器及び白血球の分離方法
WO2022250142A1 (ja) * 2021-05-28 2022-12-01 積水メディカル株式会社 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法
WO2023026725A1 (ja) * 2021-08-25 2023-03-02 積水メディカル株式会社 細胞含有液用保存液及び細胞含有液用保存容器
JP7169608B1 (ja) * 2022-01-28 2022-11-11 積水メディカル株式会社 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法

Also Published As

Publication number Publication date
JPWO2024204675A1 (https=) 2024-10-03

Similar Documents

Publication Publication Date Title
JP6901194B1 (ja) 血液採取容器及び血漿の分離方法
JP7803493B2 (ja) 白血球濃縮分離デバイス、血液採取容器及び白血球の分離方法
JP7169608B1 (ja) 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法
KR102852716B1 (ko) 혈청 또는 혈장 분리용 조성물, 혈액 채취 용기, 및 혈청 또는 혈장의 분리 방법
US20250073703A1 (en) Blood collection container, method for separating plasma, method for separating extracellular free nucleic acid, and method for separating extracellular vesicle
JP7601359B2 (ja) 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法
WO2024204675A1 (ja) 血液採取容器及び血漿の分離方法
JP7355473B1 (ja) 循環腫瘍細胞分離キット、循環腫瘍細胞分離容器及び循環腫瘍細胞の分離方法
JP7768638B1 (ja) 血液採取容器、血漿の分離方法、細胞外遊離核酸の分離方法及び細胞外小胞の分離方法
WO2020235544A1 (ja) 単核球含有血漿分離用組成物及び血液採取容器
JP7609510B1 (ja) 血液採取容器及び単核球の分離方法
JP7670408B1 (ja) 血液採取容器
CA3157473C (en) Blood collection container and plasma separation method
JP7779617B1 (ja) 血液採取容器及び血漿の分離方法
WO2026054038A1 (ja) 血球分離用水溶液、血液採取容器及び単核球の分離方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24780770

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2025511239

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 24780770

Country of ref document: EP

Kind code of ref document: A1