WO2018230571A1 - Tube de collecte de sang - Google Patents

Tube de collecte de sang Download PDF

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Publication number
WO2018230571A1
WO2018230571A1 PCT/JP2018/022455 JP2018022455W WO2018230571A1 WO 2018230571 A1 WO2018230571 A1 WO 2018230571A1 JP 2018022455 W JP2018022455 W JP 2018022455W WO 2018230571 A1 WO2018230571 A1 WO 2018230571A1
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blood
collection tube
blood collection
added
solution
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PCT/JP2018/022455
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English (en)
Japanese (ja)
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久米　幸夫
恵 清水
信 蔵野
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国立大学法人東京大学
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Publication of WO2018230571A1 publication Critical patent/WO2018230571A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • 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
    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose

Definitions

  • the present invention relates to a blood collection tube.
  • glucose level is widely used in health checkups as an index for various diseases, and is particularly used for diagnosis of diabetes.
  • glucose is broken down by glycolytic enzymes in erythrocytes contained in the collected blood, the blood glucose level in the blood decreases with time.
  • a blood collection tube used for the treatment comprising a blood collection tube main body and a drug contained in the blood collection tube main body, the drug containing maltose, a fluoride salt, and a pH adjusting acid, and having a pH of Disclosed is a blood collection tube containing a liquid reagent in the range of 3.0 to 6.5 and / or containing it in a dry state.
  • Patent Document 2 provides a blood collection tube that prevents hemolysis of collected blood and that can effectively suppress a decrease in blood glucose level and that can stably measure the blood glucose level.
  • a blood collection tube used to measure a blood glucose level in blood and collects a predetermined amount of blood, and has a bottomed cylindrical blood collection tube body that is open at one end and closed at the other end.
  • a particulate drug attached to the inner wall of the blood collection tube main body, the drug being a water-soluble drug containing a glycolysis inhibitor and a blood anticoagulant, wherein the glycolysis inhibitor is collected from the blood Contains 1 to 5 mg D-mannose per 1 mL and 0.3 to 1.0 mg fluoride salt in terms of NaF, the blood anticoagulant is at least one of EDTA and / or heparin, and the drug is a blood collection tube It is attached to the inner wall of the main body by spraying and drying.
  • a blood collection tube in which the osmotic pressure of an aqueous solution when a drug adhering to the inner wall of the blood collection tube main body is dissolved with water equal to a predetermined amount of blood is 30 to 80 mOsm.
  • Blood collection tubes containing sodium fluoride and ethylenediaminetetraacetic acid (EDTA) are widely used at present, but there are individual differences, but when using the blood collection tubes, blood glucose levels in the blood will be increased by 4 hours after blood collection. It is known to decrease by about 10-20%.
  • EDTA ethylenediaminetetraacetic acid
  • the blood glucose level in the blood of a diabetic patient has decreased, for example, even after a lapse of about 4 hours. There are many (false negatives). In this way, when blood glucose is measured using a conventional blood collection tube, if it is determined to be negative in spite of being positive for diabetes, the progression of diabetes progresses and becomes severe without realizing it. There are concerns.
  • An object of the present invention is to provide a blood collection tube capable of suppressing a decrease in blood glucose level in an initial stage after blood collection (for example, after 4 hours from blood collection) and capable of measuring with excellent accuracy.
  • the present inventors have obtained blood collection by using a blood collection tube containing inorganic phosphate or adenosine phosphate.
  • the present inventors have found that it is possible to exert an excellent inhibitory effect on the lowering of blood glucose level in the later initial stage.
  • the present invention is as follows.
  • a cylindrical body having an upper end having an opening and a lower end having a bottom in the longitudinal direction;
  • a plug for closing the opening at the upper end Collection for measuring blood glucose level and / or HbA1c in blood containing at least one selected from the group consisting of inorganic phosphate and adenosine phosphate and salts thereof in the internal space of the cylindrical body.
  • Blood vessels (2)
  • the blood collection tube according to (1) which contains phosphoric acid as inorganic phosphoric acid.
  • the blood collection tube according to any one of (1) to (3) which contains one or more types of adenosine phosphate selected from the group consisting of ATP, ADP, and AMP, and salts thereof.
  • the blood collection tube according to any one of (1) to (4) containing 1 to 100 mg of adenosine phosphate or a salt thereof per 1 mL of collected blood.
  • the blood collection tube according to any one of (1) to (5) further containing a fluoride salt.
  • the blood collection tube of the present invention includes a cylindrical body having an upper end having an opening and a lower end having a bottom in the longitudinal direction, and a plug that closes the opening at the upper end. Further, the internal space of the cylindrical body contains one or more selected from the group consisting of inorganic phosphoric acid, adenosine phosphoric acid, and salts thereof (hereinafter also referred to as “inorganic phosphoric acid etc.”).
  • the upper end having an opening and the lower end having a bottom are both ends in the longitudinal direction of the cylindrical body.
  • the upper end is located above the lower end with respect to the ground so that blood can be drawn from the opening.
  • the lower end is located below the upper end with respect to the ground, and the collected blood is received with a bottom.
  • the cross section of a cylindrical body is cyclic
  • the cross section is circular as long as the cross section is circular or substantially circular.
  • the material of the cylindrical body is not particularly limited, and examples thereof include glass and plastics such as polyethylene terephthalate. In order to make the internal state visible, a colorless and transparent material is preferable.
  • the plug that closes the opening at the upper end of the cylindrical body is not particularly limited, and examples thereof include a rubber plug and a film plug. Further, in the blood collection tube, it is preferable that the stopper closes the opening at the upper end of the cylindrical body, and the internal space of the cylindrical body is decompressed. Since the internal space of the cylindrical body is depressurized, blood collection tends to be easy. The reduced pressure can be appropriately set according to the amount of blood collected and the degree of sealing of the internal space of the cylindrical body by the stopper.
  • the position of the internal space of the cylindrical body containing inorganic phosphate or the like is located on the lower end side of the upper end of the cylindrical body, so that the collected blood may come into contact with the inorganic phosphate or the like. It is preferable because it is easy.
  • inorganic phosphate, adenosine phosphate In order to contain inorganic phosphoric acid or the like in the internal space of the cylindrical body, for example, inorganic phosphoric acid or the like made into a solution may be added from the opening at the upper end, and then the solvent in the solution is dried to obtain a solid state.
  • An inorganic phosphoric acid etc. can be contained in the inside of a cylindrical body with this form. Inorganic phosphoric acid or the like is preferably an aqueous solution from the viewpoint of handleability.
  • the method of adding inorganic phosphoric acid or the like is not particularly limited, and examples thereof include dropping inorganic phosphoric acid or the like in an aqueous solution with a dropper or spraying with a spray coating apparatus.
  • Examples of the inorganic phosphoric acid and salts thereof of the present invention include phosphoric acid, phosphorous acid, hypophosphorous acid and salts thereof, phosphoric acid, phosphorous acid and hypophosphorous acid are preferred, and phosphoric acid is more preferred. . These can be used singly or in combination of two or more.
  • Examples of the inorganic phosphoric acid salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, alkali metal salts are preferable, and sodium salts are more preferable.
  • inorganic phosphoric acid or a salt thereof when inorganic phosphoric acid or a salt thereof is contained, it is preferable to contain inorganic phosphoric acid or a salt thereof in a range of 0.1 to 50 ⁇ L, and 0.5 to 20 ⁇ L per 1 mL of collected blood. More preferably, it is more preferably contained in the range of 1 to 5 ⁇ L, and still more preferably contained in the range of 2.5 to 5 ⁇ L.
  • adenosine phosphoric acid and salts thereof of the present invention examples include ATP (Adenosine TriPhosphate), ADP (Adenosine DiPhosphate), AMP (Adenosine MonoPhosphate) and salts thereof, and ATP and its salts are preferred. These can be used singly or in combination of two or more.
  • Examples of the salt of adenosine phosphate include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, alkali metal salts are preferable, and sodium salts are more preferable.
  • the salt of ATP is preferably a disodium salt.
  • the salt species such as alkali metals and alkaline earth metal salts mentioned above as salts of inorganic phosphoric acid can be similarly applied to the fluoride salt, acid for pH adjustment, and salt species of anticoagulant described later. It is.
  • adenosine phosphate or a salt thereof when adenosine phosphate or a salt thereof is contained, it is preferable to contain adenosine phosphate or a salt thereof in the range of 0.1 to 1000 mg, and 0.5 to 200 mg per 1 mL of collected blood. More preferably, it is contained in the range of 1 to 100 mg, more preferably in the range of 5 to 50 mg, still more preferably in the range of 10 to 20 mg, and in the range of 12 to 17 mg. It is very preferable to contain.
  • adenosine phosphoric acid or a salt thereof By containing 0.1 mg or more of adenosine phosphoric acid or a salt thereof, a decrease in blood glucose level in the initial stage after blood collection tends to be reliably suppressed.
  • containing 1000 mg or less of adenosine phosphoric acid or a salt thereof there is a tendency that errors in blood glucose level measurement can be suppressed.
  • the blood collection tube of the present invention may contain inorganic phosphoric acid or a salt thereof, and adenosine phosphoric acid or a salt thereof at the same time, or may contain only one of them.
  • the blood collection tube can contain known components used for blood collection tubes in addition to inorganic phosphoric acid and the like, if necessary.
  • a known glycolysis inhibitor a substance having an action of inhibiting glycolysis other than inorganic phosphoric acid (fluoride, D-mannose, monoiodoacetic acid, etc.) is used in combination with inorganic phosphoric acid, etc.
  • fluoride, D-mannose, monoiodoacetic acid, etc. is used in combination with inorganic phosphoric acid, etc.
  • the blood collection tube preferably further contains a fluoride salt.
  • the fluoride salt is not particularly limited, and examples thereof include sodium fluoride and potassium fluoride, and sodium fluoride is preferable. These can be used singly or in combination of two or more.
  • the fluoride salt is preferably contained in the range of 0.2 to 3.0 mg, more preferably in the range of 1.0 to 2.5 mg per 1 mL of collected blood. More preferably, it is contained in the range of -2.0 mg.
  • the blood collection tube may further contain a pH adjuster.
  • a pH adjuster For example, an acid for adjusting pH may be further contained in order to suppress metabolism of red blood cells in the collected blood, and for example, hemolysis of the collected blood (which may occur when the pH is 4 or less) is inhibited. Therefore, an acid for pH adjustment may be further contained, and a base for pH adjustment may further be contained.
  • a pH adjusting agent when it is in the pH range where the metabolism and hemolysis of red blood cells are suppressed, it is not necessary to further contain a pH adjusting agent.
  • the acid for adjusting the pH is not particularly limited, and examples thereof include ethylenediaminetetraacetic acid (EDTA), citric acid, succinic acid and salts thereof.
  • EDTA ethylenediaminetetraacetic acid
  • the salt of EDTA sodium salt, potassium salt
  • citric acid and salts thereof are also preferable. These can be used singly or in combination of two or more.
  • the blood collection tube may further contain an anticoagulant in order to more directly inhibit hemolysis of the collected blood.
  • an anticoagulant a known anticoagulant can be used, and is not particularly limited, but heparin and a salt thereof are preferable. These can be used singly or in combination of two or more.
  • the aqueous solution is preferably an aqueous solution using physiological saline from the viewpoint of stability of blood components such as hemolysis suppression.
  • the blood collection tube of the present invention is used to measure blood glucose level and / or HbA1c (Hemoglobin A1c) in blood, and suppresses a decrease in blood glucose level in the initial stage after blood collection (for example, 4 hours after blood collection). In addition to being able to do so, fluctuations in HbA1c can also be suppressed. Further, it is possible to measure with excellent accuracy by suppressing the occurrence of errors such as a positive error in blood glucose level.
  • HbA1c Hemoglobin A1c
  • Blood collection tubes and reagents used in Reference Examples, Examples and Comparative Examples were prepared as follows.
  • each blood collection tube contains physiological saline and various home-made additive solutions (EDTA-2K, sodium fluoride (NaF), mannose, 3.2% citric acid solution, phosphoric acid, monoiodoacetic acid, ATP-2Na, NADH , Adenosine, guanosine, cytosine, cytidine, hydroxyurea, ADP-1K, AMP) are added in the types and amounts shown in the experiment below, and the total solution volume is set to be constant, and the blood dilution rate is set. Aligned to certain conditions.
  • Blood centrifugation was performed at 3000 rpm (1710 g) for 3 minutes unless otherwise specified.
  • Blood collection tube Sekisui Medical Co., Ltd. II blood collection tube for blood glucose test (453557: 12.7 ⁇ 75.6mm EDTA-2K + NaF) used for blood glucose measurement was used. Called blood vessels.
  • Blood collection tube for serum Blood collection using Sekisui Medical Co., Ltd. Insepack (registered trademark) II-D high-speed coagulation type blood collection tube (473470: 12.7 ⁇ 75.6mm with high-speed coagulation accelerator / separator) Centrifugation was performed within 5 minutes, and the supernatant (serum) was used to separate blood cells for glycolysis.
  • the serum was used as a comparative control (an index for confirming that there was no blood glucose fluctuation due to a change in the state of the measuring device itself).
  • Blood collection tubes for blood count Antiglycolytic agents (inorganic phosphate) using blood collection tubes (NP-EK0255-2: 12.8 ⁇ 75mm EDTA-2K granules) for hematology test (EK) ⁇ EDTA-2K> from Nipro Corporation , Adenosine phosphate, mannose, citric acid, monoiodoacetic acid and other substances having an action to block the glycolytic system) were used as comparative controls.
  • Heparin blood collection tube Terumo Corporation Venoject II vacuum blood collection tube A heparin blood collection tube (VP-H050K: 13.2 ⁇ 78 mm sodium heparin) was used as a comparative control when no glycolysis inhibitor was contained.
  • Homemade blood collection tubes Various additive solutions (EDTA-2K additive solution, sodium fluoride (NaF) additive solution, mannose additive solution, citric acid additive) prepared in-house on YS Tube No. 7 (14910) of Toyo Equipment Science Co., Ltd. Solution, phosphoric acid addition solution, monoiodoacetic acid addition solution, ATP addition solution) were added and used in the types and amounts shown in the following experiment.
  • EDTA-2K additive solution sodium fluoride (NaF) additive solution, mannose additive solution, citric acid additive
  • EDTA-2K addition solution Wako Pure Chemical Industries EDTA-2K (340-01511) was used for addition, and a solution was prepared by adding 110 mg of EDTA-2K to 1 mL of purified water.
  • Mannose added solution Wako Pure Chemical Industries D-mannose (130-00872) was used for addition, and a solution was prepared by adding 110 mg of D-mannose to 1 mL of purified water.
  • Citric acid added solution Muto Chemical Co., Ltd. 3.2% citric acid solution (86231) was used.
  • Phosphoric acid addition solution Wako Pure Chemical Industries, Ltd. Phosphoric acid (164-02176) was used for addition, and a solution was prepared that was diluted 10 times with purified water.
  • Monoiodoacetic acid addition solution Wako Pure Chemical Industries, Ltd. Iodoacetic acid (91-00492) was used for addition, and a solution was prepared by adding 110 mg of monoiodoacetic acid to 1 mL of purified water.
  • ATP-2Na addition solution Oriental Yeast Co., Ltd. Adenosine-5′-triphosphate disodium (309-50513) was used for addition, and a solution was prepared by adding 250 mg of ATP-2Na to 1 mL of purified water.
  • ADP-1K addition solution Wako Pure Chemical Industries, Ltd.
  • Adenosine 5′-dipotassium monophosphate (303-50751) was used for addition, and a solution was prepared by adding 50 mg of ADP-1K to 1 mL of purified water.
  • AMP addition solution Wako Pure Chemical Industries Adenosine 5'-monophosphate (303-50491) was used for addition, and a solution was prepared by adding 50 mg of AMP to 1 mL of purified water.
  • NADH addition solution Wako Pure Chemical Industries ⁇ -diphosphopyridine nucleotide disodium (046-16231) was used for addition, and a solution was prepared by adding 110 mg of NADH to 1 mL of purified water.
  • Adenosine addition solution Wako Pure Chemical Industries Adenosine (015-24591) was used for addition, and a solution in which 110 mg of adenosine was added to 1 mL of purified water was prepared.
  • Guanosine addition solution Tokyo Chemical Industry Guanosine (015-12303) was used for addition, and a solution was prepared by adding 110 mg of guanosine to 1 mL of purified water.
  • Cytosine addition solution Wako Pure Chemical Industries cytosine (015-12303) was used for addition, and a solution was prepared by adding 110 mg of cytosine to 1 mL of purified water.
  • Cytidine addition solution Wako Pure Chemical Industries Cytidine (035-23231) was used for addition, and a solution was prepared by adding 110 mg of cytidine to 1 mL of purified water.
  • Hydroxyurea addition solution Wako Pure Chemical Industries, Ltd. Hydroxyurea (085-06653) was used for addition, and a solution was prepared by adding 110 mg of hydroxyurea to 1 mL of purified water.
  • each blood collection tube in Reference Example 1 and Comparative Examples 1 and 2 was prepared as follows, and the blood glucose level at each elapsed time at room temperature was measured. It was measured.
  • Reference example 1 serum blood collection tube: Comparative sample 1 using serum from which blood cells were removed by adding 200 ⁇ L of physiological saline and 2 mL of whole blood to the blood collection tube for serum (blood collection tube for blood count): 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood vessels.
  • Comparative Example 2 Heparin blood collection tube: 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the heparin blood collection tubes.
  • the serum of Reference Example 1 was centrifuged within 5 minutes after blood collection. Then, the blood glucose level was measured over time using a sample obtained by transferring the supernatant (serum) to another Spitz (the blood serum subjected to glycolysis was left at room temperature).
  • the blood glucose level was measured immediately after mixing, the supernatant (plasma) and blood cell layer were mixed and returned to whole blood, added to the blood collection tube, and allowed to stand at room temperature.
  • each blood collection tube in Comparative Examples 3 to 13 is prepared as follows, and the blood glucose level at each elapsed time at room temperature is measured. did.
  • Reference example 2 serum blood collection tube
  • Comparative example 3 blood glucose test blood collection tube
  • serum blood collection tube blood glucose test collection 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood vessels.
  • Comparative Example 4 Homemade blood collection tube: 180 ⁇ L of physiological saline, 20 ⁇ L of EDTA-2K added solution and 2 mL of whole blood were added to the homemade blood collection tube.
  • Comparative Example 5 (Mannose 2.2 mg) : Saline 160 ⁇ L, mannose added solution 20 ⁇ L, EDTA-2K added solution 20 ⁇ L and whole blood 2 mL added to homemade blood collection tube
  • Comparative Example 6 (Mannose 4.4 mg): Saline 140 ⁇ L, mannose added solution 40 ⁇ L, homemade blood collection tube Add 20 ⁇ L of EDTA-2K and 2 mL of whole blood Comparative Example 7 (Mannose 6.6 mg): Add 120 ⁇ L of physiological saline, 60 ⁇ L of mannose, 20 ⁇ L of EDTA-2K, and 2 mL of whole blood to homemade blood collection tube Comparative Example 8 (Mannose 8.8mg): 100 ⁇ L of physiological saline in homemade blood collection tube, 80 ⁇ m of mannose added solution L,
  • Comparative Example 12 (citric acid 2.56 mg): 100 ⁇ L of physiological saline, 80 ⁇ L of citric acid added solution, 20 ⁇ L of EDTA-2K added solution and whole blood Add 2 mL Comparative Example 13 (citric acid 5.12 mg): Add 20 ⁇ L of physiological saline, 160 ⁇ L of citric acid added solution, 20 ⁇ L of EDTA-2K added solution, and 2 mL of whole blood to homemade blood collection tube
  • the homemade blood collection tube (Comparative Example 4) showed the same results as the blood collection tube for blood count (Comparative Example 1).
  • Glycolytic inhibitor D-mannose was found to have a positive error in blood glucose levels as the amount of addition was increased, and in addition to the glycolysis inhibitor D-mannose, it was confirmed that the blood glucose level decreased over time.
  • “positive error” means that the blood glucose level is measured as a value larger than the true value.
  • each blood collection tube in Reference Examples 3 to 9 was prepared as described below, and the blood glucose level was measured at each elapsed time at room temperature.
  • Reference Example 3 (Clotting Blood Collection Tubes): 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood sampling blood collection tube
  • Reference Example 4 (NADH): Saline 180 ⁇ L, NADH added solution 20 ⁇ L and Add 2 mL of whole blood Reference Example 5
  • Adenosine Add 180 ⁇ L of physiological saline to blood collection tube for blood count, add 20 ⁇ L of adenosine-added solution and 2 mL of whole blood Reference Example 6 (Guanosine): Add 180 mL of physiological saline to blood collection tube for blood count Add 20 ⁇ L of guanosine-added solution and 2 mL of whole blood Reference Example 7 (cytosine): Add 180 ⁇ L of physiological saline, 20
  • Comparative Example 14 blood glucose test blood collection tube: 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood glucose test blood collection tube
  • Example 1 physiological saline 160 ⁇ L, phosphate added to the blood glucose test blood collection tube Add 40 ⁇ L of solution (10-fold phosphate) and 2 mL of whole blood
  • Example 2 Blood collection tube for blood glucose test 140 ⁇ L of saline, phosphate-added solution (10-fold phosphate) 60 ⁇ L and whole blood Add 2mL
  • Example 3 Phosphate 8 ⁇ L: Add 160 ⁇ L of physiological saline, 80 ⁇ L of phosphate-added solution (10X phosphoric acid) and 2mL of whole blood to blood
  • each blood collection tube in Comparative Example 15 and Examples 4 to 9 is prepared as follows, and blood glucose at each elapsed time at room temperature. The value was measured.
  • Comparative Example 15 blood glucose test blood collection tube: 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood glucose test blood collection tube.
  • Example 4 (phosphate 2 ⁇ L, EDTA-2K): physiological saline 140 ⁇ L to blood glucose test blood collection tube , 20 ⁇ L of phosphate-added solution (10-fold phosphoric acid), 40 ⁇ L of EDTA-2K-added solution and 2 mL of whole blood were added
  • Example 5 (phosphate 4 ⁇ L, EDTA-2K): 120 ⁇ L of physiological saline in a blood glucose test tube 40 ⁇ L of phosphate-added solution (10-fold phosphoric acid), 40 ⁇ L of EDTA-2K-added solution and 2 mL of whole blood were added.
  • Example 6 (phosphate 6 ⁇ L, EDTA-2K): 100 ⁇ L of physiological saline in a blood glucose test tube 60 ⁇ L of acid-added solution (10-fold phosphoric acid), 40 ⁇ L of EDTA-2K-added solution and 2 mL of whole blood were added.
  • Example 7 (8 ⁇ L of phosphate, EDTA-2K): 80 ⁇ L of physiological saline in blood collection tube for blood glucose test Addition solution (10-fold phosphoric acid) 80 ⁇ L, EDTA-2K addition solution 40 ⁇ L and whole blood 2 mL were added.
  • Example 8 (ATP-2Na 12.5 mg): Saline 150 ⁇ L, ATP-2Na addition solution to blood collection tube for blood glucose test 50 Add ⁇ L and 2 mL of whole blood
  • Example 9 (ATP-2Na 25 mg): Add 100 ⁇ L of physiological saline, 100 ⁇ L of ATP-2Na added solution, and 2 mL of whole blood to blood collection tube for blood glucose test
  • Example 10 100 ⁇ L of physiological saline, 100 ⁇ L of ATP-2Na added solution and 2 mL of whole blood were added to a blood collection tube for blood glucose test
  • Example 11 Blood collection tube for blood glucose test 75 ⁇ L of physiological saline, 125 ⁇ L of ATP-2Na added solution and 2 mL of whole blood were added.
  • Example 12 (ATP-2Na 37.5 mg): 50 ⁇ L of physiological saline, 150 ⁇ L of ATP-2Na added solution and 2 mL of whole blood were added to the blood glucose test tube.
  • Addition Example 13 (ATP-2Na 50 mg): Add 200 ⁇ L of ATP-2Na added solution and 2 mL of whole blood to blood collection tube for blood glucose test
  • each blood collection tube in Comparative Examples 16 to 17 and Examples 14 to 19 was prepared as follows, and at each elapsed time at room temperature. The blood glucose level was measured.
  • Comparative Example 16 (Clotting blood collection tube): 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood sampling tube.
  • Example 14 (AMP 10 mg): 200 ⁇ L of AMP-added solution and the whole blood sampling tube.
  • Example 15 (ADP-1K 10 mg): 200 ⁇ L of ADP-1K added solution and 2 mL of whole blood were added to the blood collection tube for blood count test
  • Example 16 (ATP-2Na 50 mg): Blood collection tube for blood count test 200 ⁇ L of ATP-2Na added solution and 2 mL of whole blood added Comparative Example 17 (blood collection tube for blood count test): 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood glucose test tube
  • Example 17 (AMP 10 mg): Blood glucose test
  • Example 18 (ADP-1K 10 mg): 200 ⁇ L of ADP-1K added solution and 2 mL of whole blood were added to a blood glucose test tube
  • Example 19 (ATP-2Na 50 mg) ) : Add 200 ⁇ L of ATP-2Na added solution and 2mL of whole blood to blood collection tube for blood glucose test
  • ATP-2Na, ADP-1K, and AMP were all confirmed to have a glycolytic inhibitory effect.
  • the effect of inhibiting glycolysis was strong in the order of ATP-2Na, ADP-1K, and AMP.
  • sodium fluoride contained in blood glucose blood collection tubes it was confirmed that the glycolytic inhibitory effect of ATP-2Na, ADP-1K, and AMP became stronger. Hemolysis was not observed in any blood collection tube (Comparative Examples 16-17, Examples 14-19) until at least 8 hours later.
  • Comparative Example 18 blood glucose test blood collection tube: 2 mL of whole blood was added to the blood glucose test blood collection tube Comparative Example 19 (blood glucose test blood collection tube): 200 ⁇ L of physiological saline and 2 mL of whole blood were added to the blood glucose test blood collection tube
  • Example 20 (2 ⁇ L of phosphate): 100 ⁇ L of physiological saline, 20 ⁇ L of phosphate-added solution (10-fold phosphoric acid), 80 ⁇ L of EDTA-2K-added solution, and 2 mL of whole blood are added to a blood glucose test tube.
  • Example 21 (phosphate) 4 ⁇ L): 100 ⁇ L of physiological saline, 40 ⁇ L of phosphate-added solution (10-fold phosphoric acid), 60 ⁇ L of EDTA-2K-added solution and 2 mL of whole blood were added to the blood glucose test tube.
  • Example 22 Blood glucose 100 ⁇ L of physiological saline, 100 ⁇ L of ATP-2Na added solution, and 2 mL of whole blood are added to the blood collection tube for examination
  • Example 23 (ATP-2Na 50 mg): 200 ⁇ L of ATP-2Na added solution and 2 mL of whole blood are added to the blood collection tube for blood glucose testing
  • the specimens in the blood collection tubes of Comparative Examples 18 to 19 and Examples 20 to 23 were measured for HbA1c with Tosoh Corporation automatic glycohemoglobin analyzer HLC-723G9. The results are summarized below.

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Abstract

L'invention concerne un tube de collecte de sang permettant de mesurer les taux de glucose sanguin et/ou les taux de HbAlc dans le sang, ledit tube de collecte de sang comprenant un corps tubulaire possédant une extrémité supérieure comprenant une ouverture et une extrémité inférieure à fond le long de la direction longitudinale, ainsi qu'un capuchon fermant l'ouverture à l'extrémité supérieure, de l'acide phosphorique inorganique et/ou du phosphate d'adénosine étant logés dans l'espace à l'intérieur du corps tubulaire.
PCT/JP2018/022455 2017-06-16 2018-06-12 Tube de collecte de sang WO2018230571A1 (fr)

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JP2024065530A (ja) * 2022-10-31 2024-05-15 国立大学法人 東京大学 赤血球へのグルコース取り込み阻害剤並びに採血管におけるグルコース濃度低下抑制剤およびそれを備えた採血管

Citations (7)

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JPS61258174A (ja) * 1985-05-10 1986-11-15 Kyoto Ikagaku Kenkyusho:Kk 血液中の解糖阻止方法
JPS63106563A (ja) * 1986-06-26 1988-05-11 Yatoron:Kk 解糖阻止剤
JPH0295261A (ja) * 1988-09-30 1990-04-06 Sekisui Chem Co Ltd 解糖阻止剤
US5204267A (en) * 1991-12-17 1993-04-20 Osborn Laboratories, Inc. Method of glucose stabilization and analysis in dried blood spot samples
JPH085629A (ja) * 1994-06-16 1996-01-12 Terumo Corp 血液または血球の保存方法
JP5435797B2 (ja) * 2010-02-26 2014-03-05 積水メディカル株式会社 採血管及び血糖値及び／またはヘモグロビンＡ１ｃ値測定用薬剤組成物
US20150208644A1 (en) * 2012-08-09 2015-07-30 Petra Weser-Bisse Composition and use of substances for the in vitro stabilization of glucose, lactate and homocysteine in blood

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61258174A (ja) * 1985-05-10 1986-11-15 Kyoto Ikagaku Kenkyusho:Kk 血液中の解糖阻止方法
JPS63106563A (ja) * 1986-06-26 1988-05-11 Yatoron:Kk 解糖阻止剤
JPH0295261A (ja) * 1988-09-30 1990-04-06 Sekisui Chem Co Ltd 解糖阻止剤
US5204267A (en) * 1991-12-17 1993-04-20 Osborn Laboratories, Inc. Method of glucose stabilization and analysis in dried blood spot samples
JPH085629A (ja) * 1994-06-16 1996-01-12 Terumo Corp 血液または血球の保存方法
JP5435797B2 (ja) * 2010-02-26 2014-03-05 積水メディカル株式会社 採血管及び血糖値及び／またはヘモグロビンＡ１ｃ値測定用薬剤組成物
US20150208644A1 (en) * 2012-08-09 2015-07-30 Petra Weser-Bisse Composition and use of substances for the in vitro stabilization of glucose, lactate and homocysteine in blood

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