Solution and method for delivering or preserving bodily fluid sample

Abstract

According to one embodiment of the present invention, provided is a solution for transporting or storing a bodily fluid sample, said solution containing, as an active ingredient, a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid, and glucose.

Description

Technical Field

[0001] The present invention relates to solutions and methods for transporting or preserving body fluid samples. Background Art

[0002] Blood tests measure various biomarkers in the blood using various methods. One example is glycated albumin in the blood. Glycated albumin is a glycated product of albumin. Albumin is a protein present in large quantities in the body, with a high glucose binding rate. The glycation degree (GA value or GA%) of glycated albumin (GA) is said to represent the average blood sugar level over the past two weeks. Therefore, the GA value has recently attracted attention as an indicator used in blood sugar control and management.

[0003] Compared to HbA1c, GA values ​​are measured more frequently. Therefore, an effective method is to perform a transport test instead of a hospital test. Specifically, the user collects a small amount of blood, such as fingertip blood, or bodily fluids, such as saliva, and sends it to a testing facility by mail or other means. Testing facilities can utilize measurement equipment capable of performing tests efficiently and accurately, and can provide test results to both the user and relevant agencies.

[0004] However, once outside the body, components such as glucose react with proteins such as albumin during transport or storage, potentially breaking down the proteins. Due to various factors, the glycation degree may change. Therefore, the passage of time may affect the final actual glycated protein measurement results. Summary of the Invention

[0005] In fact, the inventors discovered that during transport or storage, albumin reacts with glucose in the blood and becomes glycated, potentially causing fluctuations in measured values. Specifically, the inventors observed increases and decreases in the glycation level. They believe that the increase in glycation level is due to the frequency of physical contact between albumin and glucose. The inventors discovered that increasing the dilution ratio can suppress the increase in glycation level and prevent a substantial impact on the measured value. On the other hand, they believe that the decrease in glycation level is due to the separation of glucose from the protein.

[0006] <Example of reduced sugar content>

[0007] Figure 1 As an example, the effect of temperature on the GA value of glycated albumin is shown. As blood samples, serum (BS) and whole blood (WB) were used. The serum sample was prepared by diluting the mixed serum 20 times. The whole blood sample was prepared by diluting the mixed whole blood 10 times. By dilution, the increase in GA value over time can be suppressed. Immediately after dilution ("Day 0") and after standing for 2 days at 4°C, room temperature (25°C), and a thermostatic bath (37°C and 50°C) ("Day 2"). For each sample, the GA value was measured using HPLC. Figure 1 The graph shows the ratio of the GA value on day 2 relative to the GA value on day 0, which is set to 100 ("relative GA value").

[0008] The relative GA value remains almost unchanged at 4°C (approximately 100%). The relative GA value for both serum (BS) and whole blood (WB) decreases starting at 25°C and further decreases as the temperature rises to 37°C and 50°C. For whole blood (WB), the relative GA value is less than 98% at 37°C. The relative GA value of whole blood after standing at 50°C for two days was not measured ("NA" in the figure). For serum (BS), the relative GA value is less than 97% at 37°C and less than 96% at 50°C.

[0009] At least from the relative GA values ​​at 37°C, it's clear that serum GA values ​​are more susceptible to a downward trend due to heat than whole blood GA values. The reason for this difference between serum and whole blood is unclear. However, one hypothesis is that it may be due to the influence of blood cell components. Specifically, it's possible that certain impurities produced by hemolysis increase GA values.

[0010] The effect of a high temperature environment on the GA value may cause problems during transport inspections. In most cases, the temperature during mailing cannot be controlled. On the other hand, there are also cases where the area where mail inspections are performed has a climate that may reach high temperatures. Furthermore, blood samples are sometimes stored in closed containers exposed to sunlight. In such cases, the temperature of the blood sample may rise. When mailing takes several days, the blood sample may be exposed to a high temperature environment. As a result, the correct GA value cannot be returned to the subject. Even if it can be controlled through refrigerated transportation, the inspection company has to accept the high cost. There is a need for a technology that can perform GA value transportation inspections at a low cost, for example, without temperature control.

[0011] One object of the present invention is to prevent or suppress substantial changes in the glycation degree of proteins contained in a body fluid sample even if the sample is exposed to a high-temperature environment during storage or mailing.

[0012] Several embodiments of the present invention provide a solution for transporting or storing a body fluid sample. In some embodiments, the body fluid sample may be a blood sample or a saliva sample. In some embodiments, the solution may contain a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, and N-acetylmuramic acid as an active ingredient.

[0013] Further aspects and advantages of the present invention will be readily apparent to those skilled in the art from the following detailed description, which is intended to illustrate only exemplary embodiments of the present invention. As will be appreciated, the present invention is susceptible of other and different embodiments, and its details may be modified in various obvious respects without departing from the present invention. Accordingly, the drawings and description are to be regarded as illustrative in nature and not as limiting. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is a graph showing relative GA values ​​after standing for 2 days at various temperatures in one example.

[0015] Figure 2 This is a graph showing relative GA values ​​when using each active ingredient in one example.

[0016] Figure 3 This is a graph showing relative GA values ​​when using each active ingredient in one example.

[0017] Figure 4 This is a graph showing relative GA values ​​when using each active ingredient in one example.

[0018] Figure 5 This is a graph showing relative GA values ​​when using each active ingredient in one example. DETAILED DESCRIPTION

[0019] Body fluids

[0020] The "body fluid sample" used in this specification generally refers to the body fluid of an animal itself, a liquid derived from the body fluid, or a liquid that is not a body fluid (not derived from the body fluid) but is adjusted in association with the body fluid. The body fluid sample can be a dilution of the body fluid. The body fluid sample can be a solution that is not a body fluid (not derived from the body fluid), or a mixture of body fluid or a liquid derived from the body fluid and a liquid that is not derived from the body fluid. The body fluid sample can be a disrupted liquid, culture fluid, or the like of microorganisms, cells, extracellular vesicles, etc. The body fluid sample can be a liquid used in sample measurement, or a liquid used in measurement for calibration. For example, the body fluid sample can be a standard solution or a calibration solution. For example, the body fluid sample can be a liquid that intentionally or intentionally does not contain the substance to be measured for calibration, etc. The sample to be measured can be a specimen. The body fluid sample can be a liquid containing chemical substances.

[0021] "Body fluid" may be what is commonly referred to as extra-tissue fluid. Examples of body fluids include, but are not limited to, blood; lymph; tissue fluid (interstitial fluid, intercellular fluid, interstitial fluid, etc.); and body cavity fluid (serous cavity fluid, pleural effusion, ascites, pericardial fluid, cerebrospinal fluid (spinal fluid), joint fluid (synovial fluid), aqueous humor (aqueous humor), etc.). Body fluids may include digestive fluids such as saliva, gastric juice, bile, pancreatic juice, and intestinal fluid; and may include sweat, tears, nasal discharge, urine, semen, vaginal fluid, amniotic fluid, and breast milk.

[0022] In some embodiments, the body fluid can be human body fluid.

[0023] "Body fluid" may be a solution. The solution may include a physiological buffer such as phosphate-buffered saline (PBS) or tris-2-aminoethanesulfonic acid buffer (TES) containing the target substance. The solution is not particularly limited as long as it contains the target substance.

[0024] A body fluid sample may contain a target substance. A body fluid sample may have the possibility of containing a target substance, or may be suspected of containing a target substance. In some embodiments, the target substance may be a molecule, an ion, a polymer, a biomolecule, or the like. The target substance may have a biomolecule. The target substance may be a biological material. The target substance may be a protein, a glycated protein, or the like. The target substance may be a substance related to glycation. For example, it may be a protein that is glycated due to the presence of glucose, or it may be a glycated protein with a reduced degree of glycation. The target substance may be albumin, glycated albumin, hemoglobin, and / or glycated hemoglobin in blood, serum, or plasma. For example, the target sample may be albumin and / or glycated albumin in interstitial fluid, urine, or saliva. For example, the body fluid sample may be tears, and the target substance may be albumin and / or glycated albumin contained in the tears. Albumin may be oxidized albumin (HNA) or reduced albumin (HMA). In some embodiments, the target substance may be AGEs (Advanced Glycation End Products). In some embodiments, the target substance may be glycated lipids.

[0025] Blood

[0026] Blood samples can be collected using various methods. In some embodiments, the blood sample can be capillary blood. In some embodiments, the blood sample can be collected from a vein or artery of a living organism. In some embodiments, the blood sample can be collected by puncture. It can be collected from droplets (capillary blood) generated on the skin by puncturing the fingertips, earlobes, soles of feet, arms, abdomen, etc. In some embodiments, the blood sample can be collected by the subject themselves. In some embodiments, it can be collected by a doctor, nurse, or clinical laboratory technician. In some embodiments, the blood sample can be collected near an inspection device (e.g., a clinic equipped with an inspection device, etc.).

[0027] In some embodiments, the blood sample collected from the subject may be a minute amount of blood. The minute amount of blood may have a volume similar to that of a minute droplet of blood (capillary blood) generated on the skin by puncture.

[0028] The volume of the fingertip blood is typically between 0.5 μL and 20 μL. In some embodiments, the volume of the fingertip blood is 10 μL. A predetermined volume of blood can be collected.

[0029] The volume can be the same as or greater than 0.1 μL, 0.2 μL, 0.3 μL, 0.4 μL, 0.5 μL, 0.6 μL, 0.7 μL, 0.8 μL, 0.9 μL, 1.0 μL, 1.1 μL, 1.2 μL, 1.3 μL, 1.4 μL, 1.5 μL, 1.6 μL, 1.7 μL, 1.8 μL, 1.9 μL, 2.0 μL, etc.

[0030] The volume can be the same as or smaller than 1.0 μL, 1.5 μL, 2 μL, 3 μL, 4 μL, 5 μL, 6 μL, 7 μL, 8 μL, 9 μL, 10 μL, 15 μL, etc.

[0031] In some embodiments, the blood sample mixed with the diluent may be whole blood. In some embodiments, the blood sample mixed with the diluent may be plasma or serum.

[0032] <Saliva>

[0033] In some embodiments, the body fluid sample can be saliva. Saliva can be obtained using various methods. For example, the subject can spit saliva secreted naturally or stimulated in the mouth into a cup (casting method, PD). For example, an absorbent such as cotton wool can be placed in the mouth to absorb the saliva. For example, a dropper can be used to absorb the saliva accumulated in the mouth. For example, a funnel or straw can be used to guide the saliva from the mouth into a tube. For example, a mouthwash can be contained in the mouth, and the mixture of the mouthwash and saliva can be guided into a tube.

[0034] <Solution>

[0035] The "solution" used in this specification means a solution that is mixed with a body fluid sample to dilute the sample unless otherwise specified, and can be used interchangeably with "diluent".

[0036] In some embodiments, the diluent may contain a substance (active ingredient) that substantially has the ability to inhibit the change in the glycation degree of a protein caused by glycation over time. In some embodiments, the active ingredient may be selected from the group consisting of kanamycin (C 18 H 36 N4O 11 )、G418(C 20 H 40 N4O 10 ), Streptomycin (C 21 H 39 N7O 12 ), maltotriose (C 18 H 32 O 16 ), N-acetylmuramic acid (C 11 H 19 NO8) and glucose (C6H 12 (06). In some embodiments, the active ingredient may contain a single active ingredient. In some embodiments, the active ingredient may contain two or more active ingredients. In some embodiments, the active ingredient may be a salt. Examples of salts include, but are not limited to, sulfates and hydrochlorides. Examples of active ingredients include, but are not limited to, kanamycin monosulfate, G418 disulfate, and streptomycin sulfate.

[0037] The concentration of the active ingredient in the solution can be set so as not to significantly affect the measured value of the glycated protein of the subject from the time of blood collection or solution mixing to the time of measurement. For example:

[0038] The concentration of kanamycin can be set to 0.1% or more.

[0039] The concentration of G418 can be set to 0.1-0.5%.

[0040] The concentration of streptomycin can be set to 0.1% or less.

[0041] The concentration of maltotriose can be set to 0.2% or less.

[0042] The concentration of N-acetylmuramic acid can be set to 0.3% or less.

[0043] Regarding these, it was confirmed that a period of 2 days until the measurement had an effective effect (see the following Examples).

[0044] <Dilution ratio>

[0045] The term "dilution ratio" or "N×" used in this specification, when using a volume V1 of dilution solution relative to a collected body fluid volume V0, means (V0 + V1) / V0. For example, if 10 μL of a transport solution or storage solution is prepared by mixing 9 μL of dilution solution with 1 μL of collected body fluid, the dilution ratio is "10-fold" or "10×."

[0046] Dilution of body fluid samples is effective for the increase in glycation level. It is believed that the reason for the increase in glycation level is the physical contact between albumin and glucose. Dilution helps to reduce this frequency and inhibit the rate of glycation. Through the action of dilution and active ingredients, GA values ​​can be obtained within the required accuracy within the actual delivery time (e.g., several hours, 2 days, several days, 1 week) and temperature (e.g., room temperature, normal temperature, etc.). In some embodiments, such a sufficient dilution rate can be adopted. When the dilution rate is too low, that is, when a sufficient dilution rate is not adopted, the GA value fluctuates during delivery, and the GA value of the object cannot be determined with good accuracy.

[0047] The dilution ratio can be the same as or greater than 5×, 6×, 7×, 8×, 9×, 10×, etc. In some embodiments, the dilution ratio can be greater than 5×. In some embodiments, the dilution ratio can be greater than 8×. In some embodiments, the dilution ratio can be greater than 10×.

[0048] If the dilution rate is too high, that is, if the concentration of the target protein (e.g., albumin) is too low, measurement cannot be performed. At least the measurement method and measurement device have concentration limits. The concentration of albumin in the mixed solution must be greater than this. The amount of blood collected from the subject may be small. The concentration must be within a range that is at least theoretically or practically measurable.

[0049] The dilution ratio may be the same as or less than 10×, 15×, 20×, 25×, 30×, 40×, 50×, 60×, 70×, 80×, 90×, 100×, etc. In some embodiments, the dilution ratio may be 100× or less. In some embodiments, the dilution ratio may be 90× or less. In some embodiments, the dilution ratio may be 80× or less. In some embodiments, the dilution ratio may be 50× or less. In some embodiments, the dilution ratio may be 20× or less.

[0050] In some embodiments, the dilution ratio may be between 5× and 100×. In some embodiments, the dilution ratio may be between 8× and 100×. In some embodiments, the dilution ratio may be between 9× and 100×. In some embodiments, the dilution ratio may be between 10× and 100×.

[0051] <Chelating agents>

[0052] In some embodiments, the solution may contain a chelating agent. In some embodiments, the solution may contain a substance capable of capturing divalent cations. Divalent cations such as calcium are known to inhibit the binding of albumin to kanamycin (an aminoglycoside antibiotic). It is believed that the addition of divalent cations inhibits the binding of kanamycin to albumin, thereby reducing the effect of kanamycin on reducing the degree of saccharification. In some embodiments, the chelating agent may be EDTA. Examples of chelating agents include, but are not limited to, EDTA, EDTA-2Na, EDTA-4Na, EDTA-2K, EGTA (GEDTA), EGTA-AM, BAPTA, BAPTA-4Na, HEDTA, HEDTA-3Na, NTA, NTA-2Na, NTA-3Na , CyDTA, BAPTA, BAPTA-4Na, BAPTA-AM, DTPA, DTPA-3Na, DTPA-5Na, TTHA, TTHA-6Na, HIDS, HIDS-3Na, EDDS, EDDS-3Na, DOTA, HEDP, phytic acid, cyclotenine, etc.

[0053] Buffer

[0054] In some embodiments, the solution may contain a buffer. In some embodiments, the buffer may be selected from the group consisting of HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), sodium acetate, and PBS (phosphate buffered saline).

[0055] Salt

[0056] In some embodiments, the solution may contain a salt. The salt may be, for example, but not limited to, NaCl, KCl, etc. In some embodiments, the salt may be NaCl.

[0057] In some embodiments, the solution can be adjusted to be isotonic with respect to blood cell components. This can suppress hemolysis. Hemolysis generally has no effect on HPLC measurements. However, if components such as hemoglobin that appear due to hemolysis are denatured or modified by heat or over time, this can sometimes affect HPLC measurements. Alternatively, hemolysis can affect optical measurements such as absorbance measurements. Therefore, suppressing hemolysis during transport or storage reduces the risk of measurement failure or inaccurate measurements.

[0058] GA measurement

[0059] In the present invention, the method for measuring GA is not limited. In some embodiments, GA value can be measured using HPLC. In some embodiments, GA value can be measured using an enzymatic method or the like.

[0060] Absorbance measurement devices using enzymatic methods are generally low-cost and do not require a large space. Furthermore, commercially available reagents can be used, eliminating the need for setup and reagent preparation. Pretreatment procedures are also simple. Simply place the blood collection tube directly after centrifugation. However, these methods rely on optical measurements, such as absorbance, and cannot accurately measure the presence of pigments such as hemoglobin, such as when measuring whole blood. In other words, accurate measurements cannot be performed in the presence of hemolysis.

[0061] HPLC devices are generally capable of performing relatively accurate measurements even in the presence of hemolysis. These are specialized devices, resulting in high unit costs, a large footprint, and lengthy measurement times. However, multiple HPLC devices can be installed within an organization and operated consistently under appropriate management. This allows for high precision, overall efficiency, and low costs.

[0062] <Other ingredients>

[0063] In some embodiments, the solution may contain a chelating agent, a buffer, and a salt as active ingredients. In some embodiments, the solution may contain an active ingredient consisting of a chelating agent, a buffer, and a salt as active ingredients. In some embodiments, the solution may contain a chelating agent, a buffer, a salt, and water. In some embodiments, the solution may consist essentially of a chelating agent, a buffer, a salt, and water.

[0064] In some embodiments, the solution may contain ingredients other than chelating agents, buffers, and salts. In some embodiments, the solution preferably does not contain albumin and glycated albumin, or ingredients that have a substantial effect on the determination. For example, when performing HPLC determination, it is preferred not to use some preservatives. For example, it is preferred not to use ProClin (registered trademark). It is preferred not to use CMIT and / or MIT. It is preferred not to use meropenem trihydrate. The inventors have found that these ingredients tend to give GA values ​​higher than the actual value, at least when measured by HPLC (not shown).

[0065] <Example>

[0066] The following describes an example: Blood samples were diluted with diluents containing each active ingredient according to an embodiment of the present invention, and their GA values ​​were measured using HPLC on the same day and two days later.

[0067] <Preparation of diluent>

[0068] First, prepare a solution containing 10 mM HEPES and 150 mM NaCl at a pH of 8.0. Each active ingredient is mixed with this solution to prepare a dilution solution.

[0069] <Preparation of measurement samples>

[0070] In Examples 1 to 4, a serum pool was used as a blood sample. The serum pool was prepared by separating and mixing venous blood from multiple healthy individuals. The serum was then mixed with the aforementioned diluent. A 10-fold (10x) diluted measurement sample was prepared by adding 10 μL of serum to 90 μL of the diluent.

[0071] In Example 5, 1000 mg / dL of glucose was added to the above dilution solution. Healthy human whole blood was used as the blood sample. The whole blood sample was introduced into the above dilution solution to prepare a 2×, 10×, and 40× dilution series of measurement samples.

[0072] The samples were measured on the same day ("Day 0") or stored in a 37°C thermostat for 2 days ("Day 2") and then measured.

[0073] <HPLC measurement>

[0074] The measurement conditions were based on "Detection of GA by HPLC," J Chromatogr 597, 271-275 (1992). The columns used were Shodex-Asahipak ES-502N (7.5 mm ID × 100 mm) (Showa Denko K.K.) and TSKgel Boronate-5PW (4.6 mm ID × 100 mm) (Tosoh Corporation). The eluents used were glycine (JIS special grade), magnesium chloride hexahydrate (JIS special grade), D(-)-sorbitol (Wako grade 1), ethanol (99.5%, JIS special grade), tris(hydroxymethyl)aminomethane (Tris, biotechnology grade), and EDTA-2Na. Analysis was performed using a Prominence HPLC system equipped with a system controller (Shimadzu Corporation).

[0075] <Description of the Figure>

[0076] Figures 2 to 5 In the graph shown, the vertical axis represents the ratio (relative GA value) of the GA value measured 2 days later (Day 2) to the GA value measured on the day of preparation (Day 0). When multiple measurements were performed, the average value is shown.

[0077] The horizontal axis represents the active ingredient group in each example. Figures 2 to 5 are the same.

[0078] <Example 2: Addition of Kanamycin and EDTA>

[0079] The following dilution series containing kanamycin as the active ingredient was prepared.

[0080] No Additives;

[0081] 0.1 w / v% kanamycin (0.1% KAN);

[0082] 0.2 w / v% kanamycin (0.2% KAN);

[0083] 0.5 w / v% kanamycin (0.5% KAN); and

[0084] 0.1 w / v% kanamycin and 2 mM EDTA (2 mM EDTA + 0.1% KAN).

[0085] Each additive was dissolved in a diluent at a predetermined w / v concentration (0.1% to 0.5%). Specifically, 570 μL of the diluent containing each additive was added to 30 μL of mixed serum to prepare a 20× dilution. HPLC was used to measure the GA% of the sample taken on day 0 and the sample taken on day 2 after standing in a 37°C thermostat for two days.

[0086] like Figure 2 As shown, when no kanamycin was added (No Additive), the relative GA value was less than 97%. In contrast, the addition of kanamycin reduced this reduction (0.1% to 0.5% KAN). Furthermore, as the kanamycin concentration increased, the decrease in the relative GA value was further suppressed.

[0087] It was also found that the addition of EDTA enhanced this effect. The relative GA value (approximately 99%) of "2 mM EDTA + 0.1% KAN" was not only greater than that of "0.1% KAN" (approximately 97.6%), but also greater than that of "0.5% KAN" (approximately 98.2%). This indicates that the addition of EDTA can reduce the amount of kanamycin added.

[0088] <Example 3: Streptomycin, G418>

[0089] Prepare the dilution series of streptomycin and G418 shown below.

[0090] No Additives;

[0091] 0.2 w / v% kanamycin (0.2% KAN);

[0092] 0.1 w / v% streptomycin (0.1% STR);

[0093] 0.2 w / v% streptomycin (0.2% STR);

[0094] 0.1 w / v% G418 (0.1% G418); and

[0095] 0.2w / v% G418 (0.2% G418).

[0096] like Figure 3 As shown, the relative GA value of "0.1% STR" is approximately 100%. This indicates a sufficient effect in suppressing the decrease in GA value. On the other hand, the relative GA value of "0.2% STR" is approximately 102%. This excessively increases the GA value. Therefore, it is clear that excessive addition of STR has the opposite effect.

[0097] The relative GA value of 0.1% G418 was approximately 98.2, indicating a comparable effect in suppressing the decrease in GA values ​​as 0.2% KAN. The relative GA value of 0.2% G418 was also approximately 98.2, demonstrating a nearly identical effect to 0.1% G418. This indicates that the addition of G418 suppresses the decrease in GA values. Meanwhile, no effect of G418 concentration was observed at least in the 0.1% and 0.2% concentrations.

[0098] <Example 4: Maltotriose, N-acetylmuramic acid>

[0099] Prepare the dilution series of maltotriose and N-acetylmuramic acid shown below.

[0100] No Additives;

[0101] 0.1w / v% maltotriose (0.1%MT);

[0102] 0.2w / v% maltotriose (0.2%MT);

[0103] 0.5w / v% maltotriose (0.5%MT);

[0104] 0.1 w / v% N-acetylmuramic acid (0.1% NAM);

[0105] 0.2 w / v% N-acetylmuramic acid (0.2% NAM); and

[0106] 0.5 w / v% N-acetylmuramic acid (0.5% NAM).

[0107] like Figure 4 As shown, the relative GA value of "0.1% MT" is approximately 98.2, indicating a comparable effect in suppressing the decrease in GA value as "0.2% KAN." The relative GA value of "0.2% MT" is approximately 99.8, demonstrating a sufficient effect in suppressing the decrease in GA value. Meanwhile, the relative GA value of "0.5% MT" is extremely high (outside the figure). This excessively increases the GA value. Therefore, it is clear that excessive addition of MT has the opposite effect.

[0108] The relative GA value of 0.1% NAM was approximately 98.5, indicating a greater effect in suppressing the decrease in GA values ​​than 0.2% KAN. The relative GA value of 0.2% NAM was approximately 99.0, demonstrating a sufficient effect in suppressing the decrease in GA values. Meanwhile, the relative GA value of 0.5% MT was extremely high (outside the figure), indicating an excessive increase in GA values. Therefore, it is clear that excessive addition of NAM has the opposite effect.

[0109] <Example 5: Glucose>

[0110] Prepare the dilution series of glucose shown below.

[0111] dilution with 0.03% glucose added (1 / 40 (0.03% GLU));

[0112] Add 0.1% glucose dilution (1 / 10 (0.1% GLU)); and

[0113] A dilution of 0.5% glucose (1 / 2 (0.5% GLU)) was added.

[0114] like Figure 5 As shown, the relative GA value of "1 / 40 (0.03% GLU)" was approximately 97.7, indicating an effect of suppressing the decrease in GA value. The relative GA value of "1 / 10 (0.1% GLU)" was approximately 98.7, indicating a high effect of suppressing the decrease in GA value. On the other hand, the relative GA value of "1 / 2 (0.5% GLU)" was extremely high (outside the figure). This excessively increased the GA value. Therefore, it was found that excessive addition of glucose had the opposite effect.

[0115] <Body fluid storage / transport kit>

[0116] In some embodiments, a kit for preserving / transporting body fluids (sometimes referred to as a "transport kit" in this specification) is provided. In some embodiments, the kit may include a solution containing the active ingredient of the present invention and a tube containing the solution. The kit may also include an apparatus for obtaining body fluids. In some embodiments, the tube may contain the active ingredient in a solid state inside it. For example, a liquid may be added to the tube to prepare a prescribed solution containing the active ingredient. A body fluid sample may be introduced into the adjusted solution containing the active ingredient. For example, a body fluid sample may be introduced into a tube containing a solid-state active ingredient. The active ingredient may be mixed with the body fluid sample without dilution. The solid active ingredient may be maintained, indicated, or housed in the tube in a manner suitable for preservation and / or transportation.

[0117] In some embodiments, a blood transfusion kit is provided. In some embodiments, the kit may include a solution containing the active ingredient of the present invention and a tube containing the solution. The kit may also include a blood collection tube. The blood collection tube may include a capillary tube for collecting blood. The kit may include a plunger configured to be inserted into the blood collection tube and squeeze out the blood within the capillary tube. The kit may also include a puncture device for blood collection.

[0118] In some embodiments, a saliva delivery kit is provided. In some embodiments, the kit may include a solution containing the active ingredient of the present invention and a tube containing the solution. Saliva can be added directly to the tube containing the solution. The kit may include cotton wool, a funnel, a pipette, a dropper, etc. for collecting saliva.

[0119] The present invention includes the following embodiments:

[0120] A001

[0121] A solution for transporting or storing a body fluid sample, comprising a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid, and glucose as an active ingredient.

[0122] A001b

[0123] A solution for transporting or storing a body fluid sample, comprising a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, and N-acetylmuramic acid as an active ingredient.

[0124] A001c

[0125] A solution for transporting or storing a body fluid sample, comprising kanamycin as an active ingredient.

[0126] A001d

[0127] A solution for transporting or storing a body fluid sample, comprising an active ingredient selected from the group consisting of kanamycin, aminoglycoside, and monosaccharide / polysaccharide, and having the ability to inhibit a decrease in the degree of glycation of a glycated protein.

[0128] A001e

[0129] A solution for transporting or storing a body fluid sample, comprising an active ingredient capable of inhibiting a decrease in the degree of glycation of a glycated protein.

[0130] A005

[0131] The solution according to any one of A001 to A001c or any one of embodiments, wherein

[0132] The concentration of the above-mentioned kanamycin is 0.1% to 0.3%;

[0133] The concentration of the above-mentioned G418 is 0.1 to 0.3%;

[0134] The concentration of the streptomycin is less than 0.1%;

[0135] The concentration of the maltotriose is 0.1% to 0.2%; and

[0136] The concentration of the above-mentioned N-acetylmuramic acid is 0.1% to 0.3%.

[0137] A006

[0138] The solution according to any one of A001 to A005 or any one of the embodiments, further comprising a chelating agent.

[0139] A007

[0140] A solution for transporting or storing a body fluid sample, comprising kanamycin and a chelating agent as active ingredients.

[0141] A008

[0142] The solution according to A007 or any one of the embodiments, wherein the concentration of the kanamycin is 0.1% to 0.3%, and the chelating agent is EDTA.

[0143] A011

[0144] The solution according to A001 or any one of the embodiments, wherein the body fluid sample is blood, saliva, or tears, or a solution derived therefrom.

[0145] A012

[0146] A001 or the solution according to any one of the embodiments, wherein the body fluid sample is suspected of containing glycated protein.

[0147] A013

[0148] The solution according to A012 or any one of the embodiments, wherein the glycated protein is glycated albumin.

[0149] B001

[0150] A substance or solution for inhibiting a decrease in the degree of glycation of a glycated protein, comprising as an active ingredient a substance selected from the group consisting of kanamycin, N-acetylmuramic acid, maltotriose, streptomycin, G418, and glucose.

[0151] B002

[0152] The substance or solution according to B001 or any one of the embodiments, which is used for transporting or preserving a body fluid sample.

[0153] B011

[0154] The solution according to any one of B001 or B002 or any one of embodiments, wherein the body fluid sample is suspected of containing glycated protein.

[0155] C001

[0156] Use of a substance selected from the group consisting of kanamycin, N-acetylmuramic acid, maltotriose, streptomycin, G418 and glucose for inhibiting the decrease in the glycation degree of glycated protein.

[0157] D001

[0158] A method for transporting or storing a body fluid sample comprises the following steps:

[0159] Providing body fluid samples suspected of containing glycated proteins;

[0160] mixing a component that inhibits a decrease in the degree of glycation of the glycated protein with the target solution; and

[0161] Transport or store the mixed solution.

[0162] D002

[0163] The method according to D001 or any one of the embodiments, wherein the body fluid sample is body fluid.

[0164] D003

[0165] The method according to D001 or D002 or any one of embodiments, wherein the glycated protein is glycated albumin.

[0166] E001

[0167] A kit for transporting a body fluid sample, comprising the solution according to any one of A001 to A013 and B001 to B011 or any one embodiment.

[0168] E011

[0169] A kit comprising:

[0170] a) the solution of any one or any embodiment of A001 to A013 and B001 to B011;

[0171] b) A tube configured to contain the solution and receive the body fluid sample.

[0172] E012

[0173] The kit according to E011 or any one of the embodiments further comprises c) a capillary tube configured to collect a predetermined volume of the body fluid sample.

[0174] E012b

[0175] The kit according to E011 or any one of the embodiments further comprises c0) a collection tool for collecting the body fluid sample.

[0176] E013

[0177] The kit according to E011 or E012 or any one of the embodiments, wherein the amount of the solution is 90 μL, and the volume of body fluid that can be collected by the capillary tube is 10 μL.

[0178] E014

[0179] The kit according to any one of E001 to E013 or any one of the embodiments, wherein d) the plunger is configured to be inserted into the capillary tube and squeeze out the body fluid in the capillary tube.

[0180] E021

[0181] The kit according to any one of E001 to E013 or any one of embodiments, wherein the body fluid sample is blood.

[0182] E022

[0183] The kit according to E021 or any one of the embodiments, further comprising e1) a puncture tool for blood collection.

[0184] E023

[0185] The kit according to E021 or E022 or any one of the embodiments, wherein the amount of the solution is 90 μL, and the blood is puncture blood.

[0186] E031

[0187] The kit according to any one of E001 to E013 or any one of embodiments, wherein the body fluid sample is saliva.

[0188] E032

[0189] The kit according to E031 or any one of the embodiments, further comprising e2) at least one of cotton wool, a funnel, a pipette, and a dropper.

[0190] Several embodiments and examples of the present invention have been described above, but these embodiments and examples are illustrative of the present invention. For example, the above embodiments are described in detail in order to easily explain the present invention, and the size, structure, material, and circuit can be added and changed as needed. It should be noted that the embodiment of any combination of one or more of the above-mentioned features of the present invention is also included in the scope of the present invention. Without departing from the technical idea of ​​the present invention, the claims include a variety of variations of the embodiments. Therefore, the embodiments and examples disclosed in this specification are shown for illustration and should not be considered to limit the scope of the present invention.

Claims

1. A solution for transporting or storing a body fluid sample, The invention comprises a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid and glucose as an active ingredient.

2. The solution according to claim 1, wherein The concentration of kanamycin is 0.1% to 0.3%; The concentration of G418 is 0.1-0.3%; The concentration of streptomycin is below 0.1%; The concentration of maltotriose is 0.1% to 0.2%; and The concentration of the N-acetylmuramic acid is 0.1% to 0.3%.

3. The solution according to claim 1 or 2, wherein It also contains a chelating agent.

4. The solution according to claim 3, wherein The chelating agent is EDTA.

5. The solution according to claim 1, wherein The body fluid sample is blood, saliva or tears, or a solution derived therefrom.

6. The solution according to any one of claims 1 to 4, wherein The body fluid sample is suspected to contain glycated albumin.

7. A method for transporting or storing a body fluid sample, comprising the following steps: providing a subject solution suspected of containing glycated albumin; mixing a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid, and glucose with the subject solution; and The mixed solution is transported or stored.

8. A kit for transporting or storing a body fluid sample, comprising: a) a solution having as an active ingredient a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid and glucose; and b) A tube configured to enclose the solution and receive the body fluid sample.

9. The kit according to claim 8, wherein The device further comprises c) a collecting tool for collecting the body fluid sample.

10. The kit according to claim 9, wherein The body fluid sample is blood, The deployment tool comprises a capillary tube.

11. The kit according to claim 10, wherein It also has a puncture device for blood collection.

12. The kit according to claim 9, wherein The body fluid sample is saliva, The use tool comprises at least one of cotton wool, a funnel, a straw and a dropper.

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