Solution and method for transporting or storing body fluid sample

Abstract

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

Description

Solutions and methods for transporting or storing body fluid samples

[0001] SUMMARY The present disclosure relates to solutions and methods for transporting or storing bodily fluid samples.

[0002] In blood tests, various biomarkers contained in blood are measured using various methods. One example is glycated albumin in the blood. Glycated albumin is a glycation product of albumin. Albumin is a protein that is abundant in the body and has a high glucose binding rate. The glycation degree of glycated albumin (GA) (GA value or GA%) is said to represent the average blood glucose level over the past approximately two weeks. Therefore, the GA value has recently attracted attention as an indicator to be used in blood glucose control and management.

[0003] GA values ​​are measured more frequently than HbA1c. Therefore, one effective method is to perform in-hospital testing rather than in-hospital testing. 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. The testing facility can have a measuring device that can perform testing with high efficiency and accuracy, and can provide test results to the user and related institutions.

[0004] However, once the body fluid leaves the body, glucose and other components may react with proteins such as albumin during transport or storage, causing protein degradation. The degree of glycation may change due to various factors. Therefore, the passage of time may affect the final measurement results of actual glycated proteins.

[0005] In fact, the inventors discovered that albumin reacts with glucose present in the blood during transportation or storage, resulting in glycation, which can cause fluctuations in measurement values. Specifically, the inventors observed increases and decreases in the degree of glycation. The increase in the degree of glycation is thought to be caused by an increase in the frequency of physical contact between albumin and glucose. The inventors discovered that by increasing the dilution ratio, it is possible to suppress the increase in the degree of glycation and substantially prevent it from affecting the measurement value. On the other hand, the decrease in the degree of glycation is thought to be caused by glucose being removed from the protein.

[0006] <Example of Reducing Glycation Degree> Figure 1 shows the effect of temperature on the GA value of glycoalbumin as an example. Serum (BS) and whole blood (WB) were used as blood samples. A serum sample was prepared by diluting pooled serum 20 times. A whole blood sample was prepared by diluting pooled whole blood 10 times. Dilution can suppress the increase in GA value over time. The samples were left standing at 4°C, room temperature (25°C), and a constant temperature bath (37°C and 50°C) for two days ("day 2") immediately after dilution ("day 0"). The GA value of each sample was measured using HPLC. The graph in Figure 1 shows the ratio of the GA value on day 2 to the GA value on day 0, which is set to 100 ("relative GA value").

[0007] The relative GA value remained almost unchanged (approximately 100%) at 4°C. In both serum (BS) and whole blood (WB), the relative GA value decreased from 25°C and decreased with increasing temperature to 37°C and 50°C. In the case of whole blood (WB), the relative GA value was below 98% at 37°C. The relative GA value of whole blood left standing at 50°C for 2 days was not measured ("N.A." in the figure). In the case of serum (BS), the relative GA value was below 97% at 37°C and below 96% at 50°C.

[0008] The relative GA values ​​at 37°C showed that the GA values ​​of serum were more affected by heat than those of whole blood. The cause of 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. That is, some impurities may have increased the GA values ​​due to hemolysis.

[0009] The effect of a high temperature on GA values ​​can be a problem in transport testing. In many cases, the temperature during mailing cannot be controlled. On the other hand, the region where mail-in testing is conducted may have a climate where the temperature can be high. Furthermore, blood samples may be stored in a closed container exposed to sunlight. In such cases, the temperature of the blood sample may rise. If the mailing takes several days, the blood sample may experience a high temperature environment. As a result, an accurate GA value cannot be returned to the subject. Even if this can be controlled by refrigerated transport, the testing business must accept high costs. There is a need for technology that allows transport testing of GA values ​​at low cost, i.e., without temperature control, for example.

[0010] One objective of the present disclosure is to prevent or suppress changes in the degree of glycosylation of proteins contained in a bodily fluid sample, even if the sample is subjected to a high temperature environment during storage or mailing.

[0011] In some embodiments of the present disclosure, a solution for transporting or storing a bodily fluid sample is provided. In some embodiments, the bodily fluid sample may be a blood sample or a saliva sample. In some embodiments, the solution may include, as an active ingredient, a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, and N-acetylmuramic acid.

[0012]

[0013] Further aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

[0013] Graph showing relative GA values ​​after standing for 2 days at each temperature according to one example. Graph showing relative GA values ​​when each active ingredient is used according to one example. Graph showing relative GA values ​​when each active ingredient is used according to one example. Graph showing relative GA values ​​when each active ingredient is used according to one example. Graph showing relative GA values ​​when each active ingredient is used according to one example.

[0014] <Body Fluid> As used herein, the term "body fluid sample" generally refers to an animal's body fluid itself, a liquid derived from a body fluid, or a liquid that is not a body fluid but is prepared in relation to a body fluid (non-body fluid-derived). A body fluid sample may be a diluted body fluid. A body fluid sample may be a non-body fluid (non-body fluid-derived) solution, or a mixture of a body fluid or a body fluid-derived liquid and a non-body fluid-derived liquid. A body fluid sample may be a lysate of microparticles, cells, extracellular vesicles, etc., a culture medium, etc. A body fluid sample may be a liquid used for sample measurement or a liquid used for calibration measurement. For example, a body fluid sample may be a standard solution or a calibration solution. For example, a body fluid sample may be a liquid that is intentionally or deliberately free of the target substance for use in calibration, etc. A sample to be measured may be a specimen. A body fluid sample may be a liquid containing chemicals.

[0015] The "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 fluid, peritoneal fluid, pericardial fluid, cerebrospinal fluid, synovial fluid, aqueous humor, etc.). The body fluid may be digestive fluid such as saliva, gastric juice, bile, pancreatic juice, or intestinal juice, or may be sweat, tears, nasal mucus, urine, semen, vaginal fluid, amniotic fluid, or milk.

[0016] In some embodiments, the bodily fluid may be a human bodily fluid.

[0017] The "body fluid" may be a solution. The solution may include a physiological buffer solution containing the target substance, such as phosphate buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES). The solution is not particularly limited as long as it contains the target substance.

[0018] The bodily fluid sample may contain a target substance. The bodily fluid sample may have the potential to contain the target substance or may be suspected of containing the target substance. In some embodiments, the target substance may be a molecule, ion, macromolecule, biomolecule, etc. The target substance may comprise a biomolecule. The target substance may be a biological substance. The target substance may be a protein, a glycated protein, etc. The target substance may be a substance related to glycation. For example, the target substance may be a protein that is glycated in the presence of glucose, or a glycated protein whose degree of glycation decreases. 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 bodily fluid sample may be tears, and the target substance may be albumin and / or glycated albumin contained in tears. Albumin may be oxidized albumin (HNA) or reduced albumin (HMA). In some embodiments, the substance of interest may be Advanced Glycation End Products (AGEs). In some embodiments, the substance of interest may be a glycated lipid.

[0019] <Blood> Blood samples can be collected by various techniques. In some embodiments, the blood sample may be capillary blood. In some embodiments, the blood sample may be collected from a vein or artery of a living body. In some embodiments, the blood sample may be collected by a puncture method. The blood sample may be collected from droplets (capillary blood) generated on the skin by puncturing a fingertip, earlobe, sole of the foot, arm, abdomen, etc. In some embodiments, the blood sample may be collected by the subject themselves. In some embodiments, the blood sample may be collected by a doctor, nurse, or clinical laboratory technician. In some embodiments, the blood sample may be collected near a testing device (e.g., a clinic where the testing device is installed).

[0020] In some embodiments, the blood sample taken from the subject may be a small volume, which may comprise a droplet (capillary blood) generated on the skin by a puncture.

[0021] The fingertip blood volume is generally between 0.5 μL and 20 μL. In some embodiments, the fingertip blood volume is 10 μL. A predetermined volume of blood may be collected.

[0022] The volume may be greater than or equal to 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.

[0023] The volume may be equal to or less 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.

[0024] In some embodiments, the blood sample mixed with the diluent may be whole blood, hi some embodiments, the blood sample mixed with the diluent may be plasma or serum.

[0025] <Saliva> In some embodiments, the body fluid sample may be saliva. Saliva can be obtained by various methods. For example, a subject may spit saliva secreted naturally or in response to stimulation into a cup (spraying method, PD). For example, an absorbent material such as cotton may be placed in the oral cavity and allowed to absorb the saliva. For example, saliva accumulated in the oral cavity may be sucked up with a dropper. For example, saliva may be introduced from the oral cavity into a tube using a funnel or straw. For example, mouthwash may be placed in the oral cavity, and the mixture with the saliva may be introduced into the tube.

[0026] <Solution> Unless otherwise specified, the term "solution" used in this specification refers to a solution that is mixed with a body fluid sample to dilute it, and is used interchangeably with "diluting solution."

[0027] In some embodiments, the diluent may contain a substance (active ingredient) that has the ability to substantially inhibit the temporal change in the degree of glycosylation of proteins due to glycation. In some embodiments, the active ingredient is kanamycin (C １８ H ３６ N ４ O １１ ), G418(C ２０ H ４０ N ４ O １０ ), streptomycin (C ２１ H ３９ N ７ O １２ ), maltotriose (C １８ H ３２ O １６ ), N-acetylmuramic acid (C １１ H １９ NO ８ ), and glucose (C ６ H １２ O ６ In some embodiments, the active ingredient may be selected from the group consisting of: 1) an active ingredient; 2) an active ingredient; 3) an active ingredient; 4) an active ingredient; 5) an active ingredient; 6) an active ingredient; 7) an active ingredient; 8) an active ingredient; 9) an active ingredient; 10) an active ingredient; 11) an active ingredient; 12) an active ingredient; 13) an active ingredient; 14) an active ingredient; 15) an active ingredient; 16) an active ingredient; 17) an active ingredient; 18) an active ingredient; 19) an active ingredient; 20) an active ingredient; 21) an active ingredient; 22) an active ingredient; 23) an active ingredient; 24) an active ingredient; 25) an active ingredient; 26) an active ingredient; 27) an active ingredient; 28) an active ingredient; 29) an active ingredient; 30) an active ingredient; 31) an active ingredient; 32) an active ingredient; 33) an active ingredient; 34) an active ingredient; 35) an active ingredient; 36) an active ingredient; 37) an active ingredient; 38) an active ingredient; 39) an active ingredient; 40) an active ingredient; 41) an active ingredient; 42) an active ingredient; 43) an active ingredient; 44) an active ingredient; 45) an active ingredient; 46) an active ingredient; 47) an active ingredient; 48) an active ingredient; 49) an active ingredient; 50) an active ingredient; 51) an active ingredient; 52) an active ingredient; 53) an active ingredient; 54) an active ingredient; 55) an active ingredient; 56) an active ingredient; 57) an active ingredient; 58) an active ingredient; 59) an active ingredient; 60) an active ingredient; 60) an active ingredient; 61) an active ingredient; 62) an active ingredient;

[0028] The concentrations of the active ingredients in the solution may be set so as not to significantly affect the measured value of the subject's glycated protein from the time of blood collection or solution mixing to the time of measurement. For example: The kanamycin concentration may be set to 0.1% or more. The G418 concentration may be set to 0.1-0.5%. The streptomycin concentration may be set to 0.1% or less. The maltotriose concentration may be set to 0.2% or less. The N-acetylmuramic acid concentration may be set to 0.3% or less. These have been confirmed to be effective when the time until measurement is within two days (see the Examples below).

[0029] <Dilution ratio> As used herein, the expression "dilution ratio" or "Nx" refers to (V0 + V1) / V0 when a volume V1 of diluted solution is used for a volume V0 of collected body fluid. For example, if 9 μL of diluted solution is mixed with 1 μL of collected body fluid to prepare 10 μL of transport solution or storage solution, the dilution ratio is "10 times" or "10x."

[0030] Dilution of a body fluid sample is effective in preventing an increase in glycation level. The increase in glycation level is thought to be caused by physical contact between albumin and glucose. Dilution reduces this frequency and contributes to suppressing the rate of glycation. The dilution and the effect of the active ingredient make it possible to obtain a GA value within the required accuracy within a realistic range of transportation time (e.g., several hours, two days, several days, one week) and temperature (e.g., room temperature, ambient temperature, etc.). In some embodiments, such a sufficient dilution rate can be adopted. If the dilution rate is too low, i.e., if a sufficient dilution rate is not adopted, the GA value will fluctuate during transportation, making it impossible to accurately determine the subject's GA value.

[0031] The dilution factor may be equal to or greater than 5x, 6x, 7x, 8x, 9x, 10x, etc. In some embodiments, the dilution factor may be 5x or greater. In some embodiments, the dilution factor may be greater than 8x. In some embodiments, the dilution factor may be 10x or greater.

[0032] If the dilution rate is too high, i.e., if the concentration of the target protein (e.g., albumin) is too low, measurement is not possible. At least the measurement method and measurement device have a concentration limit. The concentration of albumin in the mixed solution must be greater than this. Depending on the subject, the amount of blood collected may be small. The concentration must be at least within a range that is measurable, either in principle or practically.

[0033] The dilution factor may be equal to or less than 10x, 15x, 20x, 25x, 30x, 40x, 50x, 60x, 70x, 80x, 90x, 100x, etc. In some embodiments, the dilution factor may be 100x or less. In some embodiments, the dilution factor may be 90x or less. In some embodiments, the dilution factor may be 80x or less. In some embodiments, the dilution factor may be 50x or less. In some embodiments, the dilution factor may be 20x or less.

[0034] In some embodiments, the dilution factor may be between 5x and 100x. In some embodiments, the dilution factor may be between 8x and 100x. In some embodiments, the dilution factor may be between 9x and 100x. In some embodiments, the dilution factor may be between 10x and 100x.

[0035] <Chelating Agent> 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 effectiveness of kanamycin in reducing glycation levels. 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, cyclen, and the like.

[0036] Buffering Agent In some embodiments, the solution may contain a buffering agent, which may be selected from the group consisting of HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), sodium acetate, and PBS (phosphate buffered saline).

[0037] Salt In some embodiments, the solution may include a salt. The salt may be, for example, but not limited to, NaCl, KCl, etc. In some embodiments, the salt may be NaCl.

[0038] In some embodiments, the solution may be adjusted to be isotonic with respect to blood cell components, thereby suppressing hemolysis. Hemolysis generally does not affect HPLC measurements. However, if components such as hemoglobin released by hemolysis are denatured or modified due to heat or the passage of time, they may affect HPLC measurements. Alternatively, hemolysis may affect optical measurements such as absorbance measurements. Therefore, suppressing hemolysis during transportation or storage reduces the risk of measurements becoming impossible or inaccurate.

[0039] <GA Measurement> The present disclosure does not limit the method for measuring GA. In some embodiments, GA levels may be measured using HPLC. In some embodiments, GA levels may be measured using an enzymatic method or the like.

[0040] Enzyme-based absorbance measurement devices are generally low-cost and do not require large spaces. Furthermore, commercially available reagents can be used, eliminating the need for condition setting or reagent preparation. Furthermore, pretreatment procedures are simple; the centrifuged blood collection tubes simply need to be placed on the device. However, these methods rely on optical measurements such as absorbance measurement, and therefore cannot provide accurate measurements when samples contain pigmented substances such as hemoglobin, for example, when measuring whole blood. In other words, accurate measurements cannot be obtained in the case of hemolysis.

[0041] HPLC systems generally provide relatively accurate measurements, even in the case of hemolysis. Because these systems are specialized, they are expensive per unit, require a large footprint, and require long measurement times. However, multiple HPLC systems can be installed in a facility and operated under constant, appropriate management. This allows for high accuracy, as well as overall high efficiency and low costs.

[0042] <Other Ingredients> In some embodiments, the solution may include a chelating agent, a buffering agent, and a salt as active ingredients. In some embodiments, the solution may include an active ingredient consisting of a chelating agent, a buffering agent, and a salt as active ingredients. In some embodiments, the solution may include a chelating agent, a buffering agent, a salt, and water. In some embodiments, the solution may consist essentially of a chelating agent, a buffering agent, a salt, and water.

[0043] In some embodiments, the solution may contain components other than the chelating agent, buffer, and salt. In some embodiments, the solution preferably does not contain albumin, glycoalbumin, or components that substantially affect the measurement. For example, when performing HPLC measurement, it is preferable to avoid the use of certain preservatives. For example, it is preferable to avoid the use of ProClin®. It is preferable to avoid the use of CMIT and / or MIT. It is preferable to avoid the use of meropenem trihydrate. The inventors have discovered that these components tend to give higher GA values ​​than the actual values, at least in HPLC measurement (not shown).

[0044] Examples Examples will be described below. Blood samples were diluted with diluents containing each active ingredient according to an embodiment of the present disclosure, and the GA values ​​were measured using HPLC on the same day and two days later.

[0045] <Preparation of Dilution Solution> First, a solution containing 10 mM HEPES and 150 mM NaCl was prepared. The pH was 8.0. Each active ingredient was mixed with this solution to prepare a dilution solution.

[0046] <Preparation of Measurement Sample> In Examples 1 to 4, pooled serum was used as the blood sample. The pooled serum was prepared by separating the serum from venous blood collected from multiple healthy individuals and then mixing the serum. The serum was then mixed with the diluent described above. 10 μL of serum was added to 90 μL of diluent to prepare a 10-fold (10x) diluted measurement sample.

[0047] In Example 5, 1000 mg / dL of glucose was added to the diluent. Whole blood from a healthy subject was used as a blood sample. The whole blood sample was introduced into the diluent to prepare measurement samples in a dilution series of 2x, 10x, and 40x.

[0048] The samples were measured on the same day (day 0), or stored in a 37°C incubator for two days (day 2), and then measured.

[0049] <HPLC Measurement> The measurement conditions were determined based on "GA Detection by HPLC Method," J. Chromatogr. 597, 271-275 (1992). The columns used were Shodex-Asahipak ES-502N (7.5 mm ID x 100 mm) (Showa Denko K.K.) for AEX and TSKgel Boronate-5PW (4.6 mm ID x 100 mm) (Tosoh Corporation) for BAC. 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. For the analysis, a Prominence HPLC system (Shimadzu Corporation) equipped with a system controller was used.

[0050] 2 to 5, the vertical axis indicates the ratio (relative GA value) of the GA value measured on the day after (day 2) to the GA value measured on the same day as preparation (day 0). When multiple measurements were taken, the average value is shown.

[0051] The horizontal axis indicates the active ingredient group in each example. "No additive" is common to all of Figures 2 to 5.

[0052] Example 2: Addition of Kanamycin and EDTA The following dilution series containing kanamycin as an active ingredient were prepared: no additive (No Additive); 0.1 w / v% kanamycin (0.1% KAN); 0.2 w / v% kanamycin (0.2% KAN); 0.5 w / v% kanamycin (0.5% KAN); and 0.1 w / v% kanamycin and 2 mM EDTA (2 mM EDTA + 0.1% KAN).

[0053] Each additive was dissolved in a diluent to a specified w / v concentration (0.1% to 0.5%). Specifically, 570 μL of the diluent containing each additive was added to 30 μL of pooled serum to prepare a 20x diluent. The GA% of the day 0 sample and the day 2 sample, which had been left in a 37°C incubator for 2 days, was measured using HPLC.

[0054] As shown in Figure 2, without the addition of kanamycin (No Additive), the relative GA value was below 97%. In contrast, the rate of decrease was small with the addition of kanamycin (0.1% to 0.5% KAN). Furthermore, the decrease in the relative GA value was more suppressed as the kanamycin concentration increased.

[0055] Furthermore, the addition of EDTA was found to enhance this effect. The relative GA value of "2 mM EDTA + 0.1% KAN" (approximately 99%) was not only higher than that of "0.1% KAN" (approximately 97.6%), but also higher than that of "0.5% KAN" (approximately 98.2%). This indicates that the addition of EDTA makes it possible to reduce the amount of kanamycin added.

[0056] Example 3: Streptomycin, G418 The following dilution series of streptomycin and G418 were prepared: no additive (No Additive), 0.2 w / v% kanamycin (0.2% KAN), 0.1 w / v% streptomycin (0.1% STR), 0.2 w / v% streptomycin (0.2% STR), 0.1 w / v% G418 (0.1% G418), and 0.2 w / v% G418 (0.2% G418).

[0057] As shown in Figure 3, the relative GA value of "0.1% STR" was nearly 100%. In other words, it showed a sufficient effect of suppressing the decrease in GA value. On the other hand, the relative GA value of "0.2% STR" was nearly 102%. This resulted in an excessive increase in GA value. Therefore, it was found that adding excessive STR had the opposite effect.

[0058] The relative GA value of "0.1% G418" was about 98.2, i.e., it showed the same effect of suppressing the decline in GA value as "0.2% KAN". The relative GA value of "0.2% G418" was about 98.2, showing almost the same effect as "0.1% G418". In other words, it was found that the addition of G418 has the effect of suppressing the decline in GA value. On the other hand, the effect of its concentration was not observed at least at 0.1% and 0.2%.

[0059] Example 4: Maltotriose, N-acetylmuramic acid The following dilution series of maltotriose and N-acetylmuramic acid were prepared: no additive, 0.1 w / v % maltotriose (0.1% MT), 0.2 w / v % maltotriose (0.2% MT), 0.5 w / v % maltotriose (0.5% MT), 0.1 w / v % N-acetylmuramic acid (0.1% NAM), 0.2 w / v % N-acetylmuramic acid (0.2% NAM), and 0.5 w / v % N-acetylmuramic acid (0.5% NAM).

[0060] As shown in Figure 4, the relative GA value of "0.1% MT" was approximately 98.2, which means that it had the same effect of suppressing the decline in GA value as "0.2% KAN." The relative GA value of "0.2% MT" was approximately 99.8, which showed a sufficient effect of suppressing the decline in GA value. On the other hand, the relative GA value of "0.5% MT" was extremely high (not shown). This, in turn, excessively increased the GA value. Therefore, it was found that adding excessive MT had the opposite effect.

[0061] The relative GA value of "0.1% NAM" was approximately 98.5, i.e., it showed a higher effect of suppressing the decline in GA value than "0.2% KAN." The relative GA value of "0.2% NAM" was approximately 99.0, showing a sufficient effect of suppressing the decline in GA value. On the other hand, the relative GA value of "0.5% MT" was extremely high (not shown). This, in turn, excessively increased the GA value. Therefore, it was found that adding excessive NAM had the opposite effect.

[0062] Example 5: Glucose The following dilution series of glucose were prepared: a dilution solution containing 0.03% glucose (1 / 40 (0.03% GLU)); a dilution solution containing 0.1% glucose (1 / 10 (0.1% GLU)); and a dilution solution containing 0.5% glucose (1 / 2 (0.5% GLU)).

[0063] As shown in Figure 5, 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 (not shown in the figure). This actually excessively increased the GA value. Therefore, it was found that adding excessive glucose has the opposite effect.

[0064] <Kit for Preserving and Transporting Body Fluids> In some embodiments, a kit for preserving and transporting body fluids (sometimes simply referred to herein as a "transport kit") is provided. In some embodiments, the kit may include a solution containing an active ingredient of the present disclosure and a tube containing the solution. The kit may further include a device for obtaining the body fluid. In some embodiments, the tube may contain the active ingredient in a solid state therein. For example, a predetermined solution containing the active ingredient may be prepared by adding a liquid to the tube. A body fluid sample may be introduced into the prepared solution containing the active ingredient. For example, a body fluid sample may be introduced into a tube containing the active ingredient in a solid state. The active ingredient may be mixed with the body fluid sample undiluted. The solid active ingredient may be held, directed, or contained within the tube in a manner suitable for storage and / or transport.

[0065] In some embodiments, a blood transport kit is provided. In some embodiments, the kit may include a solution containing an active ingredient of the present disclosure and a tube containing the solution. The kit may further include a blood collection tube. The blood collection tube may have a capillary tube for collecting blood. The kit may include a plunger configured to be inserted into the blood collection tube and push the blood in the capillary tube. The kit may include a blood collection lancing device.

[0066] In some embodiments, a saliva transfer kit is provided. In some embodiments, the kit may include a solution containing an active ingredient of the present disclosure and a tube containing the solution. Saliva may be directly added to the tube containing the solution. The kit may also include a cotton ball, funnel, straw, dropper, etc. for collecting saliva.

[0067] The present disclosure includes the following embodiments: A001: A solution for transporting or storing a body fluid sample, comprising as an active ingredient a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid, and glucose. A001b: A solution for transporting or storing a body fluid sample, comprising as an active ingredient a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, and N-acetylmuramic acid. A001c: A solution for transporting or storing a body fluid sample, comprising kanamycin as an active ingredient. A001d: A solution for transporting or storing a body fluid sample, comprising as an active ingredient a substance selected from the group consisting of kanamycin, aminoglycosides, and mono / polysaccharides, which has the ability to inhibit a decrease in the glycosylation degree of glycated proteins. A001e: A solution for transporting or storing a body fluid sample, comprising, as an active ingredient, an agent capable of inhibiting a decrease in the glycosylation degree of a glycated protein. A005: The solution according to any one of A001 to A001c or any embodiment, wherein the concentration of the kanamycin is 0.1% to 0.3%; the concentration of the G418 is 0.1 to 0.3%; the concentration of the streptomycin is 0.1% or less; the concentration of the maltotriose is 0.1% to 0.2%; and the concentration of the N-acetylmuramic acid is 0.1% to 0.3%. A006: The solution according to any one of A001 to A005 or any embodiment, further comprising a chelating agent. A007: A solution for transporting or storing a body fluid sample, comprising, as active ingredients, kanamycin and a chelating agent. A008: The solution according to A007 or any of the embodiments, wherein the concentration of the kanamycin is 0.1% to 0.3%, and the chelating agent is EDTA. A011: The solution according to A001 or any of the embodiments, wherein the body fluid sample is blood, saliva, or tears, or a solution derived therefrom.A012: The solution of A001 or any of the embodiments, wherein the body fluid sample is suspected of containing a glycated protein. A013: The solution of A012 or any of the embodiments, wherein the glycated protein is glycoalbumin.

[0068] B001 A substance or solution used to inhibit a decrease in the degree of glycosylation of glycated proteins, comprising as an active ingredient a substance selected from the group consisting of kanamycin, N-acetylmuramic acid, maltotriose, streptomycin, G418 and glucose. B002 The substance or solution according to B001 or any of the embodiments, used for transporting or storing a body fluid sample. B011 The solution according to B001 or B002 or any of the embodiments, wherein the body fluid sample is suspected of containing glycated proteins.

[0069] C001 Use of a substance selected from the group consisting of kanamycin, N-acetylmuramic acid, maltotriose, streptomycin, G418 and glucose for inhibiting a decrease in the degree of glycation of a glycated protein.

[0070] D001: A method for transporting or storing a body fluid sample, comprising: providing a body fluid sample suspected of containing a glycated protein; mixing a component that inhibits a decrease in the glycosylation degree of the glycated protein with the target solution; and transporting or storing the mixed solution. D002: The method according to D001 or any embodiment, wherein the body fluid sample is a body fluid. D003: The method according to D001 or D002 or any embodiment, wherein the glycated protein is glycoalbumin.

[0071] E001 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 embodiment. E011 A kit comprising: a) the solution according to any one of A001 to A013 and B001 to B011 or any embodiment; b) a tube containing the solution and configured to receive the body fluid sample. E012 A kit according to E011 or any embodiment, further comprising: c) a capillary tube configured to collect a predetermined volume of the body fluid sample. E012b A kit according to E011 or any embodiment, further comprising: c0) a collection device for collecting the body fluid sample. E013 A kit according to E011 or E012 or any embodiment, wherein the amount of the solution is 90 μL, and the volume of body fluid that the capillary tube can collect is 10 μL. E014 The kit according to any one of E001 to E013 or any embodiment, further comprising: d) a plunger configured to be inserted into the capillary tube and push out the bodily fluid in the capillary tube. E021 The kit according to any one of E001 to E013 or any embodiment, wherein the bodily fluid sample is blood. E022 The kit according to E021 or any embodiment, further comprising: e1) a blood sampling lancing device. E023 The kit according to E021 or E022 or any embodiment, wherein the amount of the solution is 90 μL, and the blood is obtained by lancing. E031 The kit according to any one of E001 to E013 or any embodiment, wherein the bodily fluid sample is saliva. E032 The kit according to E031 or any embodiment, further comprising: e2) at least one of cotton, a funnel, a straw, and a dropper.

[0072] Several embodiments and examples of the present disclosure have been described above, but these embodiments and examples exemplify the present disclosure. For example, the above embodiments have been described in detail to clearly explain the present disclosure, and additional changes in dimensions, configurations, materials, and circuits may be made as necessary. Note that embodiments that combine any one or more features of the present disclosure described above are also within the scope of the present disclosure. The claims encompass numerous modifications to the embodiments without departing from the technical spirit of the present disclosure. Therefore, the embodiments and examples disclosed herein are provided for illustrative purposes and should not be considered to limit the scope of the present disclosure.

Claims

1. 1. A solution for transporting or storing a body fluid sample, comprising: The present invention comprises, as an active ingredient that inhibits a decrease in the degree of glycation of a glycated protein, a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid, and glucose. solution.

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

3. 3. The solution according to claim 1 or 2, The solution further comprising a chelating agent.

4. 4. The solution of claim 3, The chelating agent is EDTA. solution.

5. 2. The solution of claim 1 , The body fluid sample is blood, saliva, or tears or a solution derived therefrom. solution.

6. 5. The solution according to claim 1, wherein The glycated protein is glycoalbumin. solution.

7. 1. A method for transporting or storing a body fluid sample, comprising: 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 as an active ingredient that inhibits the decrease in the degree of glycation of glycated proteins with the target solution; and transporting or storing the mixed solution; A method for providing the above.

8. 1. A kit for transporting or storing a body fluid sample, comprising: a) a solution comprising, as an active ingredient that inhibits the reduction in the degree of glycation of a glycated protein, a substance selected from the group consisting of kanamycin, G418, streptomycin, maltotriose, N-acetylmuramic acid, and glucose; and b) a tube containing the solution and configured to receive the bodily fluid sample; A kit comprising:

9. 9. The kit of claim 8, c) a collection device for collecting the body fluid sample; The kit further comprises:

10. 10. The kit of claim 9, The body fluid sample is blood, The tool includes a capillary tube. kit.

11. 11. The kit of claim 10, The kit further comprises a blood collection lancing device.

12. 10. The kit of claim 9, The body fluid sample is saliva, The tool includes at least one of a cotton ball, a funnel, a straw, and a dropper. kit.