JP2000241424A - Container for urine specimen - Google Patents

Abstract

PROBLEM TO BE SOLVED: To effectively manufacture products capable of handling a solidified contents in a state of adhering to the bottom and/or a wall of a container, by depressurizing and drying urine precipitation dissolving agent solution stored in the container. SOLUTION: This container contains a urine specimen treating agent, a solid dried without freezing water and a urine specimen treating agent of a dried solid under reduced pressure and a urine specimen treating agent in a wall surface adhesive solid state. Therefore, contents in a test tube, or buffer liquid id dried, the test tube which has solid deposited contents on its wall and/or bottom can be safely, certainly, and stably handled. In other words, even when a storing impact or a weak force is applied to the test tube during transportation of handling, for example, by tilting, oscillating, vibrating, hitting with a finger, or rolling on a floor, the solid contents are adhered onto the wall and/or the bottom and do not substantially separate from it.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is used in fields such as immunoassay and biochemical assay using urine as a sample, and enables urine sample processing to be performed more accurately and easily. The present invention relates to a urine sample container that contains an agent and enables easy handling of a urine sample. According to the container of the present invention, it is possible to dissolve the trace components taken up in the precipitate generated during the storage of urine by the urine sample treating agent contained therein,
Furthermore, the urine sample can be transported in a substantially stable state from the viewpoint of an immunoassay, a biochemical assay, or the like, and can be stored for a long time.

[0002]

2. Description of the Related Art Urine contains end products and intermediate metabolites of protein and nucleic acid metabolism, various organic and inorganic salts, and captures quantitative or qualitative changes of these substances to diagnose various diseases and to diagnose physiological disorders. It is useful for grasping the condition. Urine is clear immediately after urination, but if it is stored and allowed to stand, even in normal urine, various salts may precipitate and become turbid. When the substance (analyte) to be measured is incorporated in the precipitate thus generated, accurate quantification cannot be performed unless the precipitate is dissolved or the adverse effect of the precipitate is removed. In order to use urine as a sample in immunological and biochemical measurements, and to obtain more accurate and reliable results, it is essential to eliminate the formation of such precipitates or eliminate the adverse effects of these precipitates .

[0003] In the field of immunological measurement, biochemical measurement, and the like, inspection of an extremely limited measurement target (item) using fresh urine (generally, only a simple inspection can be performed, Because the analytes to be measured are also limited), the purpose is to handle more measurement objects (items) without necessarily using fresh urine, and mainly to test with various measuring instruments and reagents Recently, the methods used in departments and inspection centers have become important. Furthermore, although urine has a difficult problem in terms of its transportation and storage, it has the advantage that, unlike blood, etc., it can be collected easily and in large quantities without damaging the living body. By measuring and examining the end products and intermediate metabolites of protein and nucleic acid metabolism and various organic and inorganic salts contained, it is very useful for diagnosing illness, understanding the health of living organisms, and understanding the state of drug intake. It is thought to be useful. In such a case, the collected urine (specimen) is usually refrigerated or frozen and stored, and is transported to and stored in the testing unit, testing center, or the like. However, when urine is refrigerated or cryopreserved, it is recognized that a large number of urine precipitates occur as described above.

In recent years, in particular, in a clinical setting, the determination of a specific substance in urine is mainly performed by a test section or a test center as described above. Therefore, it is not possible to use urine without sedimentation immediately after urination. Have difficulty. Since urine transported to the testing department and testing center has precipitates, it is necessary to sample the precipitates after suspending them sufficiently for accurate quantification of specific substances, which is very complicated. I have. In particular, when it is required to process a large amount of sample, it is a serious task to sufficiently suspend the precipitate generated in the sample, and it also becomes a bottleneck for automation. I have. In addition, if the suspension of the precipitate is insufficient, a sampling error occurs, which may affect clinical evaluation, and is a serious problem in terms of reproducibility. In order to process such a large amount of urine sample accurately and efficiently with low labor and to obtain clinically significant data, it is necessary to solve the problem of sedimentation occurring in urine, and WO 98/29745. No. (WO98 / 29745), a urine sample treating agent capable of solving such problems, a urine processing method using the same, a method of solubilizing urine sediment of a sample, etc. There is provided a urine collection container for the purpose of adding the above treatment.

[0005]

SUMMARY OF THE INVENTION The above-mentioned WO 98/297
No. 45 provides a container for urine specimens (ie, a "ureter tube with a urine sedimentation dissolving agent"), which prevents the occurrence of sediment, which may hinder measurement accuracy in a test method using a urine specimen, It is effective for dissolving the precipitate to simplify diagnosis. However, when the urine sample treating agent (that is, the dissolving agent) is a solution, troubles such as leakage and spillage of the solution occur, so that careful handling during transportation and urine collection is required. In WO 98/29745, as a solution to this, solidification of the urine sample treating agent (ie, lysing agent) by freeze-drying is described. However, the resulting solidified urine sample treating agent (ie, lysing agent) is obtained. The urine sample treatment agent, which is a lyophilized solid in the urine sample container product containing the urine sample, has problems in its strength, adhesiveness to the tube wall, and the like. (Product yield) is very low.

That is, the solid-state urine sample treating agent obtained by freeze-drying is partially or mostly peeled off from the wall surface of the container or easily peeled off from the wall surface. It is difficult to keep the contents safely and securely in the container, because it easily breaks due to impact, or the crystal-like matter may be scattered, and the solidified urine sample When transporting or handling urine sample container products containing processing agents,
It is difficult to safely, reliably, and stably maintain the solidified contents in a state of being attached to the bottom surface and / or the wall surface of the container. Even if a urine sample container product containing a solid state urine sample treating agent is manufactured by the freeze-drying method, the solidified content can be handled as it is attached to the bottom and / or wall surface of the container. The rate of obtaining a good product is low, and there is a problem in terms of maintaining uniformity of the product. In addition, there is also a problem that it is difficult to solve the problem because it is impossible to add a substance that hinders the measurement, such as adding a coagulant due to the properties of the product.

[0007]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and in a urine sample container product containing a solid-state urine sample treating agent, the solidified contents of the urine sample container product are contained in a container. Efficiently manufacture products that can be handled while attached to the bottom and / or wall,
An object of the present invention is to provide a urine sample container product containing a solidified and stable urine sample treating agent. The present inventors have conducted intensive studies as a method for solving the above-mentioned conventional method, and as a result of conducting intensive studies, if the urine sediment dissolving agent solution contained in the container is dried under reduced pressure, the resulting solidified urine sample treating agent is obtained. The properties and performance are remarkably improved, the handling properties of the container product containing the solid contents are excellent, the product yield (yield) can be significantly improved, and the uniformity of the product can be maintained. This led to the present invention.

[0008] That is, the present invention provides: [1] a urine sample container characterized by containing a urine sample treatment agent which is a solid dried without freezing water; [2] a reduced-pressure dried solid A urine sample container characterized by containing a urine sample treatment agent; [3] a urine sample container characterized by containing a urine sample treatment agent in a wall-adhesive solid state; [4] A urine sample container containing a solid state urine sample treating agent having a water content of 3 to 50% by weight; [5] a solid state urine sample having a water content of 4 to 45% by weight [6] A urine specimen container containing a urine specimen treating agent; [6] the container is a hollow cylindrical body having one end closed, [1] to [5]. A container according to any one of the above;

[7] The container according to any one of [1] to [5], wherein the container has a test tube or a structure similar thereto; [8] The container is a synthetic resin. The container according to any one of the above [1] to [7];

[9] Synthetic resin is polyethylene such as polyvinyl chloride, high density polyethylene, low density polyethylene, polyolefin resin such as polypropylene, fluorocarbon resin such as Teflon, silicone resin such as silicone,
Polycarbonate, polysulfone, polyphenylene oxide, polyacrylate or polymethacrylate,
The container according to the above [8], which is selected from the group consisting of polyester resins such as polyethylene terephthalate copolymer;

[10] The urine sample treating agent is (a) 6.5 or more
(b) a urine sample treating agent characterized by containing a buffer having a pH as an active ingredient; (b) a urine sample treating agent characterized by containing a buffer having a pH of 6.5 to 9.5 as an active ingredient; a) a urine sample treating agent comprising a buffer having a pH of 7.0 to 8.2 as an active ingredient; and (d) pH 7.
The above-mentioned [1] to [1], which are selected from the group consisting of a urine sample treating agent characterized by containing a buffer having an activity of 4 to 7.8 as an active ingredient.

[9] The container according to any one of [9]; and [11] the urine sample treating agent is a phosphate buffer, N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid (TES) buffer, N- (2-Hydroxyethyl) piperazine
-N'-ethanesulfonic acid (HEPES) buffer, tris (hydroxymethyl) aminomethane (Tris) -hydrochloric acid buffer, borate buffer, citrate buffer, barbital buffer and imidazole-hydrochloride buffer [1] to [10], wherein the buffer is selected from the group consisting of:
[12] The container according to any one of [1] to [11] above, wherein the urine sample treating agent contains a preservative; [13] The preservative is: Ethylenediaminetetraacetic acid (EDTA),
The container according to the above [12], which is selected from the group consisting of benzalkonium chloride and formaldehyde; and [14] tris (hydroxymethyl) aminomethane (Tris) -hydrochloric acid as a urine sample treating agent The above [1] to [1], wherein the buffer contains ethylenediaminetetraacetic acid (EDTA) and / or benzalkonium chloride as a preservative.
3] The container according to any one of the above items is provided.

Furthermore, the present invention provides: [15] a urine sample treating agent, characterized in that (i) a solubilizing treatment for at least a part of the urine precipitate; ) Urine is a sample used in an immunoassay and / or a biochemical assay, wherein the agent for treating a urine sample according to the above (i); (Iv) the urine sample treating agent according to the above (i) or (ii), wherein at least a part thereof is dissolved so as not to substantially affect the measurement;
The urine sample treatment according to any one of the above (i) to (iii), wherein a trace component taken up in a precipitate generated in the urine sample and serving as an analyte to be measured is solubilized. (V) wherein the precipitate formed in the urine sample is generated during storage of the urine sample;
(iv) the agent for treating a urine sample according to any one of (i) to (vi), wherein the precipitate generated in the urine sample is generated during storage of urine having a pH of less than 7.0. (v) the urine sample treating agent according to any one of (vii) a precipitate generated in the urine sample,
The urine sample treating agent according to any one of the above (i) to (vi), which is generated during storage of urine having a pH of 5.0 to 6.8; (viii) the solubilization treatment is as described in the above [ 10) or [11]
(I) to (v), characterized in that the method is performed by raising the pH of urine with the buffer according to any one of
ii) The urine sample treating agent according to any one of the above; (ix) the solubilization treatment is performed by adding tris (hydroxymethyl) aminomethane (Tri
s)-a urine specimen treating agent according to any one of the above (i) to (viii), which is obtained by adding a hydrochloric acid buffer; (x) a trace component is transferrin in urine, growth hormone in urine, urinary IgG, urinary albumin, chorionic gonadotropin in urine, urinary alpha _{1-microglobulin,} urine beta ₂
Microglobulin, each type of collagen, proline hydroxylase, laminin, matrix metalloproteases (M
MPs), a tissue inhibitor of metalloproteases (TIMPs) and a urine specimen treating agent according to any one of the above (i) to (ix), which is selected from the group consisting of thrombomodulin. And (xi) trace components,
It is selected from the group consisting of the urine sample treating agent according to any one of the above (i) to (x), which is selected from the group consisting of type IV collagen and thrombomodulin. The container according to any one of the above-mentioned [1] to [14]; and

[16] The urine sample treating agent converts (A) urine to pH 6.5.
A urine sample treating agent characterized by the above;
(B) the urine sample treating agent according to the above (A), wherein the urine is adjusted to pH 6.5 to 9.5; (C) the urine is adjusted to pH 6.5 to 8.2.
(A) or (B) the urine sample treating agent according to (A) or (B); (D) urine having a pH of 7.2 to 8.0. C) The urine sample treating agent according to any one of the above (A) to (D), wherein the urine is adjusted to pH 7.4 to 7.8. (F) a urine sample treating agent according to any one of the above (A) to (E), wherein the urine is adjusted to pH 7.4 to 7.6; (G) the above [10] or [11] The buffer according to any one of the above (A) to (F), wherein the pH of urine is increased or the pH of urine is maintained at a predetermined value. Urine sample treatment agent; (H) Tris (hydroxymethyl) aminomethane in urine
(Tris)-a urine sample treating agent according to any one of the above (A) to (G), which is prepared by adding a hydrochloric acid buffer; (I) urine is fresh urine or stored (A) The urine sample treating agent according to any one of the above (A) to (H), which is characterized in that the urine is treated urine; (J) The agent according to any one of the above (15) (i) to (ix). Solubilization of urine in fresh urine to prevent the formation of sediment in the urine from substantially affecting the measurement of the analyte to be measured, or in preserved urine, by the formation of sediment in the urine The above-mentioned, wherein the obstacle in the measurement of the analyte to be measured is substantially removed.
(A) The agent for treating urine specimen according to any one of (A) to (I); and (K)
The urine sample treatment according to any one of the above (A) to (J), wherein the preservation of fresh urine prevents the formation of precipitates generated in the urine or dissolves the precipitates in the stored urine. The container according to any one of the above [1] to [15], which is selected from the group consisting of agents.

[0013] In another aspect, the present invention provides: [17] a urine sample container characterized by containing a solid urine sample treating agent obtained by drying at a temperature of 25 to 70 ° C; [18] A urine sample container characterized by containing a solid urine sample treating agent obtained by drying at a temperature of 30 to 62 ° C; [19] Under a reduced pressure of 600 to 760 mm Hg The urine sample container according to the above [17] or [18], comprising a solid urine sample treating agent obtained by drying in;

[20] The method according to the above [17] or [18], which comprises a solid urine sample treating agent obtained by drying under a reduced pressure of 600 to 730 mmHg. Urine sample container; [21] containing a solid urine sample treating agent obtained by performing vacuum drying at a temperature of 30 to 62 ° C. and a degree of vacuum of 600 to 730 mm Hg for 2 hours to less than 48 hours. A container for urine specimen is provided.

In another aspect, the present invention is characterized in that the present invention contains [22] a solid urine sample treating agent having a property of being less than 70% in a free fall impact test. A urine sample container; [23] a urine sample container characterized by containing a solid urine sample treating agent having a property of being less than 50% in a free fall impact application test; [24] A urine sample container characterized by containing a solid urine sample treating agent having a breakage rate of less than 30% in a free fall impact test; [25] wall adhesion in a shaking impact test A urine sample container characterized by containing a solid urine sample treating agent exhibiting water-repellency; [26] A solid urine sample exhibiting wall adhesion in a shaking impact test at 300 rpm for 20 minutes A urine sample container containing a urine sample treating agent;

[27] A container such as a plastic test tube containing a certain amount of an aqueous solution of the urine sample treating agent is subjected to a drying treatment other than freeze-drying, and the solid urine sample treating agent is removed from the container. The method for producing a urine sample container according to any one of the above-mentioned [1] to [26], wherein the drying treatment is performed by applying any one of the above [17] to [20]. The method according to the above [27], which is performed under the described temperature and pressure; [29] A method such as a plastic test tube containing a fixed amount of an aqueous solution of a urine sample treating agent. The container is dried under reduced pressure,
The method for producing a urine sample container according to any one of the above [1] to [26], wherein the solid state urine sample treating agent is attached to a wall surface of the container; and The production method according to the above [29], which is carried out under the conditions described in the above [21].

In the present invention, the term "weakly acidic or alkaline" means that the measurement of an analyte (eg, an object to be measured, for example, type IV collagen, thrombomodulin, etc.) does not substantially adversely affect the measurement of the target analyte. For the purpose, the pH of normal urine specimens (typically pH 5.0-
6.3) to a pH of 6.5 or higher. Preferably, in the present invention, the term "weakly acidic to alkaline" means that a normally collected urine sample is changed from pH 6.6 or higher to pH 8.2. Particularly preferably, in the present invention, the expression "weakly acidic to alkaline" means that a commonly collected urine sample is adjusted to pH 6.5 to pH 8.2. In particular, it may mean that the urine sample has a pH of 7.5 or a value close to the pH. In another aspect, the term weakly acidic or alkaline in the present invention means that:
In the measurement of an analyte (a measurement object, for example, type IV collagen, thrombomodulin, etc.), a urine sample (fresh urine or stored urine [frozen urine] And refrigerated urine]) and add a buffer to adjust the pH
(Typically pH 5.0-6.3) to a pH of 6.6 or higher. Preferably, in the present invention, the term "weakly acidic to alkaline" means that a urine sample (fresh urine or preserved urine (including frozen urine and refrigerated urine)) is added with a buffer so that a normal collected urine sample has a pH of 6.5 to 6.5. It means that the pH is 8.2. Urine may be brought to a pH at or near pH 7.5 to solubilize the precipitate or prevent the formation of a precipitate. Further, “having substantially no adverse effect on the measurement of the target analyte” means giving a clinically significant result or a measurementally significant result. In addition, it does not substantially affect the measurement, for example, data obtained by measuring fresh urine, after storing the urine for 3 hours or more at room temperature or after storing the urine for 10 hours or more at 10 ° C. It may mean that there is a substantially significant correlation with the data obtained by measuring the stored urine.

Other objects, features, advantages and aspects of the present invention will be apparent to those skilled in the art from the following description. However, it is understood that the description of the present specification, including the following description and the description of the specific examples, shows preferred embodiments of the present invention, and is given only for explanation. I want to. Various changes and / or alterations (or modifications) within the spirit and scope of the present invention disclosed herein will be apparent to those skilled in the art based on the following description and knowledge from other portions of the present specification. Will be readily apparent. All patents and references cited herein are cited for explanatory purposes, which are to be construed as being incorporated herein by reference. is there.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION In the present specification, "wall surface adhesiveness" refers to a container such as a test tube (also simply referred to as "tube") according to the present invention. While standing in a rack, the test tube containing the content of the buffer solution described below is subjected to a drying treatment, and the tube wall of the test tube and / or
Or, for those with solid contents deposited on the bottom of the tube, during transportation, handling, etc., tilting, shaking, shaking, flipping with a finger, or rolling on the floor, etc. Even when a strong impact or a weak force is applied, the solid content remains attached to the tube wall and / or the tube bottom and does not substantially peel therefrom.
Alternatively, the “solid content” refers to a material having such a property that it remains attached to the tube wall and / or the tube bottom of the test tube even after a certain period of time from the production and does not substantially peel from the tube. Is referred to as having "wall surface tackiness", which means that the property is "wall surface tackiness". The wall stickiness can be measured, for example, by using a conventional stirrer, such as a solid content in a liquid in a test tube, for a tube containing solids deposited on the bottom of the test tube and / or in the vicinity of the tube wall. Vibration shock is applied by a vibration applying device or the like used for dissolving the resin, and as a result, the number of solid contents deposited on the vibrated tube is peeled off from the wall surface of the tube by external observation. It can be evaluated by calculating the ratio (breakage rate) to the total number of tubes subjected to the vibration treatment.

[0020] The wall stickiness also means that a pipe containing solid matter deposited on the bottom of the test tube and / or in the vicinity of the tube wall is allowed to freely fall to a floor from a certain height to give an impact. As a result, the appearance of the dropped tube can be observed in the same manner, and the damage ratio can be determined and evaluated. For example, when the test tube is dropped freely from a height of 1.5 m onto a commercially available steel flat table, the appearance of the solid contents adhering to the tube wall of the test tube is observed, and the damage rate is evaluated. If it is less than 70%, it can be regarded as having "wall surface tackiness". More preferably, a similar free fall impact is applied, and the failure rate is less than 50% (more preferably, the free fall impact is applied.
With a failure rate of less than 30%)
There is In another representative example, a test tube having a solid content deposited on the wall and / or bottom of the test tube as described above is used, and the test tube is shaken with a conventional shaker (eg, a reciprocating shaker). Shaker: SR-II (Sanyo Co., Ltd.)] (“shaking impact test”), and shaken at 300 rpm for 20 minutes. If the object detaches from the wall surface, the "solid content" may be defined as having no "wall surface tackiness". In other words, “wall surface adhesiveness” may mean a property in which the solid content is not observed to detach from the wall surface when shaken.

The matters relating to the urine sample treating agent, urine sample processing method, urine sample container, analyte to be measured, etc. of the present invention are described in WO 98/29745 (WO98 / 29745) or It can be selected from those cited in the literature cited therein or those substantially equivalent thereto, particularly the matters described in WO 98/29745 (WO98 / 29745) and the description of the literature cited therein Are included in the disclosure of the present specification by reference thereto. The urine sample treating agent of the present invention is used for treating urine by adding a buffer or the like to urine such as a sample, and more specifically contains a buffer having a pH of 6.5 or more as an active ingredient. For treating urine. The urine sample treating agent is used for solubilizing a precipitate in urine such as a sample, and more specifically, for substantially measuring at least a part of a precipitate generated in a urine sample. It is used to solubilize without affecting. The urine sample container of the present invention is used to make urine a pH of 6.5 or more, and more specifically, to make a urine sample at a pH of 6.5 to 8.2, or to hold a urine sample at a pH of 6.5 to 8.2. used. The urine sample container of the present invention can be intended to perform a predetermined process on urine immediately after urine collection by collecting urine there. Furthermore, for preservation of the urine sample after urine collection, a compound having a preservative effect can be added as a preservative.

The urine sample treating agent of the present invention also includes urine pH
Is maintained at a weakly acidic to alkaline, particularly neutral to weakly alkaline, thereby dissolving urine sediment generated during storage and solubilizing trace components taken up in urine sediment. Thus, the urine sample container of the present invention, by collecting urine there, from immediately after urine collection urine pH slightly acidic to alkaline,
In particular, it can be one aimed at maintaining neutral to weakly alkaline. According to the present invention, the pH of urine is slightly acidic to
In order to maintain the alkalinity, a weakly acidic to alkaline substance, for example, an inorganic compound such as a weakly acidic or alkaline inorganic salt, an organic compound such as a weakly acidic or alkaline organic salt, or a mixture thereof is exemplified. In order to neutralize the pH of urine, there is a method of neutralization using an acid or alkali. In that case, however, it is necessary to neutralize the urine while measuring the pH of each sample, so that it is not always practical. It is not suitable. On the other hand, maintaining the urine pH at a weakly acidic to alkaline, particularly neutral to weakly alkaline, and more preferably at a pH of 6.5 to 9.5 using a buffer keeps the final concentration of the buffer constant. It is preferable because it can be realized only by using the above. Therefore, according to the present invention, to maintain the pH of urine between slightly acidic and alkaline (preferably at pH 6.5-9.5, more preferably at pH 7.2-8.0, even more preferably at pH 7.4-7.8, most preferably at pH 7.4-7.6) , Preferably weakly acidic to alkaline (preferably pH 6.5 to 9.5, more preferably pH 7.0 to 8.2, even more preferably pH 7.4 to 7.8).
Buffering agents. For example, according to the invention, the urine pH
PH 6.5 to 9.5, more preferably pH 7.2 to 8.0, even more preferably pH 7.4 to 7.8, most preferably pH 7.4 to 7.6
PH 6.5-9.5, more preferably pH 7.0-8.
2, more preferably a buffer with a pH of 7.4 to 7.8 is used.

As the buffer used in the present invention, those exhibiting a buffering action in a weakly acidic to weakly alkaline state are used.
As the buffer, in measuring an analyte to be measured by applying an immunoassay and / or a biochemical assay,
Those which do not impair the measurement are preferred, but among those commonly used in the art in immunoassays and / or biochemical assays or those which can be easily used, urine specimens can be made weakly acidic to weakly alkaline. (Especially preferably neutral to slightly alkaline)
Can be used. For example, buffers include phosphate or phosphate buffers, tris (hydroxymethyl) aminomethane (Tris) buffers, N- (2-hydroxyethyl) piperazine-N ′-(2-ethanesulfonic acid) ( HEPES)
Liquid, piperazine-N, N'-bis (2-ethanesulfonic acid) (PIPE
S) solution, 3- (cyclohexylamino) -1-propanesulfonic acid (CAPS) solution, 3- (N-morpholino) propanesulfonic acid (M
OPS) solution, N, N'-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid (BES) solution, N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid (TES) solution, N- (2
-Acetamido) -2-aminoethanesulfonic acid (ACES) solution,
Borate buffer, citrate buffer, barbital buffer,
Imidazole-hydrochloric acid buffer and the like. These may be used alone or in any combination. Suitable acids, for example, hydrochloric acid, sulfuric acid, nitric acid, inorganic acids such as phosphoric acid, acetic acid, citric acid, maleic acid, organic acids such as fumaric acid and alkali, for example,
Sodium hydroxide, potassium hydroxide, sodium carbonate,
Potassium carbonate, sodium bicarbonate, alkali hydroxides such as potassium bicarbonate, organic bases such as triethylamine, etc. can be used to adjust the pH to an appropriate value, and they can be used arbitrarily by combining or blending them. be able to.

Preferably, the buffer is phosphate buffer, N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid (TES) buffer, N- (2-hydroxyethyl) piperazine-N'- Propanesulfonic acid (HEPES) buffer, Tris (hydroxymethyl) aminomethane (Tris)-
A hydrochloric acid buffer (Tris-HCl buffer), a borate buffer, a citrate buffer, a barbital buffer and an imidazole-hydrochloride buffer, and examples thereof include those selected from the group consisting of: And preferably a pH of 6.5 or higher
As an active ingredient, more preferably, a buffer having a pH of 6.5 to 9.5 as an active ingredient, and still more preferably, a buffer having a pH of 7.0 to 8.2 as an active ingredient. ,Moreover
Those containing a buffer having a pH of 7.4 to 7.8 as an active ingredient are exemplified. Particularly preferred are Tris-HCl buffers and the like, for example, preferably those having a pH of 6.5 to 9.5, more preferably those having a pH of 7.0 to 8.2,
Even more preferably, those having a pH of 7.4 to 7.8 are mentioned. Typical buffer pH is, for example, from 7.40 to 7.74. The buffer is preferably usually an aqueous solution.

The concentration of the buffer component is not particularly limited as long as a sufficient buffering action can be obtained. For example, the concentration is 0.05 mol to 10.0 mol, preferably 0.1 mol to 5.0 mol, more preferably 1.0 mol to 2.0 mol. No. Buffer pH
Has a pH of 6.5 or more, preferably pH 6.5 to
9.5, more preferably pH 7.0-8.2, even more preferably pH 7.4-7.8. Preferably, 1.5 molar (M) Tris-HCl buffer at pH 7.5 can be used. Since most of normal urine and disease urine are acidic urine, an alkaline buffer, particularly preferably a weakly acidic to alkaline buffer, is used to maintain the urine pH at a weakly acidic to alkaline, particularly neutral to slightly alkaline. It is necessary to add an agent, particularly preferably a buffer having a pH of 6.5 to 9.5. In the case of alkaline urine, in order to dissolve the precipitate formed, to maintain the pH of the urine weakly acidic to alkaline, particularly neutral to weakly alkaline, a weakly alkaline to acidic buffer, particularly preferably pH 6.5-8.2 buffer must be added to urine. The buffering agent of the present invention has a form and concentration that can exert a sufficient buffering action (including a time factor and a temperature factor) on a predetermined amount of urine. Preferably, it is contained in the urine sample treating agent.

The urine sample container of the present invention is suitable for carrying and / or storing a urine sample for each individual, and is preferably portable, and may be made of glass, synthetic resin (plastic), or the like. Can be Examples of the material of the synthetic resin container include polyvinyl chloride, polyethylene such as high density polyethylene and low density polyethylene, polyolefin resin such as polypropylene, fluorocarbon resin such as Teflon, silicone resin such as silicone, polycarbonate, polysulfone, Examples include, but are not limited to, polyester resins such as polyphenylene oxide, polyacrylate or polymethacrylate, and polyethylene terephthalate copolymer. Containers are less susceptible, chemically resistant or better,
Select in consideration of various conveniences such as heat resistance or excellent, easy handling, transparent or translucent, easy to see the sample etc., and low transportation weight. can do. The material of the container preferably includes polyvinyl chloride, polyethylene (including high-density polyethylene and low-density polyethylene), polypropylene, Teflon, polyethylene terephthalate, and silicon.

The shape of the container can be preferably selected from those commonly known in the art, or can be selected from those commonly used in the art or easily used. Particularly suitable for carrying and / or storing liquids, for example,
One having a tubular shape such as a test tube is exemplified. Such shapes may include round bottoms and spitzs (thin ends). Preferably, the container is provided with a sealing means such as a stopper. The size of the container can be freely selected according to the purpose of use and the like, but in the case of a round bottom test tube type, for example, the diameter is 5 to 30 mm, preferably 8 to 20 mm, and the length is 8 to 20 mm. 30-200 mm, preferably 50-15
0 mm. For example, a round-bottom test tube having a diameter of 10 to 18 mm and a length of 70 to 120 mm can be suitably used as the container. In accordance with the present invention, fresh urine is collected in the urine sample container to prevent the formation of sediment in the urine from substantially adversely affecting the measurement of the analyte to be measured, or by storing stored urine (eg, By transferring the refrigerated or frozen urine) to the urine sample container, obstruction in the measurement of the analyte to be measured caused by the formation of a precipitate in the urine can be substantially removed. Fresh urine is collected in the urine sample container of the present invention to prevent the formation of precipitates generated in urine during storage, or stored urine is placed in the urine sample container of the present invention to dissolve the urine precipitate Can be easily done.

Urine specimens usually show a value lower than pH 7.0, and often have a pH of 5.0 to 6.9, and storage of such urine specimens (especially when refrigerated or frozen) causes precipitation. It has been observed that analytes are incorporated in such precipitates. According to the urine sample container of the present invention, a buffer is added to the urine sample to adjust the pH thereof to a slightly acidic to weakly alkaline, particularly pH 6.5 to 8.2, more preferably pH 7.2 to 8.0, and even more preferably pH 7.4 to 7.8.
By maintaining the pH at 7.4 to 7.6, even more preferably, the trace components incorporated in the urine sediment are solubilized, and accurate quantification of the trace components in the urine becomes possible. The solubilization treatment of the precipitate may be one that solubilizes a part of the precipitate or one that can dissolve a trace component of the precipitate, as long as there is no problem in measurement. . More preferably, the trace component includes an analyte to be measured.

The urine specimen treating agent of the present invention contains components and / or components which adversely affect the measurement of the analyte to be measured.
Or, it is desirable not to include a component that may cause an obstacle. Further, in order to be able to use the urine sample for various measurements, it is preferable to avoid those that unnecessarily affect substances such as analytes to be measured. However, after the sample urine is added to the urine sample container, a preservative or the like can be added to prevent (suppress) the propagation of various bacteria. Preservatives contained in the urine sample treating agent of the present invention include EDTA, benzalkonium chloride, formaldehyde and the like. These may be used alone or in combination of two or more.
TA is particularly preferred. The preservative is preferably one that does not affect the measurement when the analyte to be measured is measured by applying an immunoassay and / or a biochemical assay. The amount of the preservative added to the urine sample treating agent is set according to the concentration after the sample urine is added, and is generally 0.0001 to 2.0
A range of weight percent is preferred and should be set in each case according to the type of preservative.

The analytes to be measured include those to be examined by immunoassay and / or biochemical assay, and include, for example, hormones, vitamins, bioactive substances, drugs, proteins, Sugars and their metabolites. Typical examples are mentioned and protein components contained in blood, for example, urinary transferrin, urinary growth hormone, urinary IgG, urinary albumin, chorionic gonadotropin in urine, urinary alpha _{1-microglobulin} urinary beta ₂ microglobulin, each type collagen such as type IV collagen, proline hydroxylase, laminin, interstitial collagenase (MMP-1), gelatinase a (MMP-2), stromelysin -1 (MMP-3 ), MMP-7
, Neutrophil collagenase (MMP-8), gelatinase B (MMP-
9), stromlysin-2 (MMP-10), stromlysin-3 (MMP-11), collagenase-3 (MMP-13), MT1-MMP
(MMP-14), MT2-MMP (MMP-15), MT3-MMP (MMP-16), MT4-
MMP (MMP-17), MT5-MMP (MMP-24), Enamelysin (MM
P-20) and other matrix metalloproteases (MMP
s), tissue inhibitors of metalloproteases (TIMPs) (eg, TIMP-1, TIMP-2, TIMP-3, TIMP
-4), thrombomodulin and the like.

Since sediment easily forms in urine, when time is required from urine collection to testing (for example, when performing various tests) or when a sample is transported to an inspection center or the like during refrigeration, sedimentation may occur. Is thought to cause uptake of urine trace components. Especially when storing acidic urine (for example, refrigerated or frozen stored urine), the analyte to be measured may be adversely affected by the above-mentioned analyte to be taken therein. Is recognized. Generally, a plurality of dispensing operations are performed until the target component is determined from urine collection. That is,
Dispensing from a urine collection cup to a transport test tube, dispensing from the transport test tube to transport to the inspection site where each item is measured,
After being sampled at each measurement site, the amount is determined. When performing the above dispensing and sampling operations, if the target component is incorporated in the urine sediment, a sufficient suspending operation is required for each dispensing and sampling operation. Become. If non-uniformity occurs in this suspension operation, accurate quantification of the target component becomes impossible. However, since this suspension operation is a mechanical treatment, it is sufficient to ensure uniformity. Turbidity is very difficult, which hinders automation of the measurement. Perform the above dispensing and sampling operations on a large number of samples,
Further, there is a problem that it is too complicated when a large number and many types of tests are performed.

By using the urine sample container of the present invention, it is possible to add a buffer to a fixed amount of urine at a fixed rate.
(This is made possible by adding a certain amount of urine to a container with a certain amount of buffer added), as a result of which the final concentration of the buffer can be kept constant. For example, type IV collagen (IVC) and thrombomodulin (TM) in urine
In the measurement, by adding 0.1 volume of 1.5 M Tris-HCl buffer, pH 7.5 to 1 volume of urine, IV.C and TM incorporated in urine sediment are solubilized. This makes it possible to easily and accurately quantify trace components in urine simply by performing a sample processing method that can be easily performed without being affected by urine sedimentation. Accordingly, the present invention provides a urine collection container or the like containing a characteristic solid urine sample treating agent designed to achieve such an object.

In addition, a plurality of dispensing operations are performed, various tests, measurements, and analyzes are performed on a urine sample.
In order to be able to handle urine samples in a large number of samples by performing sampling operations, etc., and to handle urine samples in testing units and testing centers equipped with various measuring instruments and reagents that perform a large number and various types of tests. It is considered that it is sufficient to add sufficient components to the urine to avoid the influence of the urinary sediment, and it is desirable to avoid adding unnecessary components. In addition, for example, it is preferable that IV.C or TM can be measured and tested efficiently using a urine sample to avoid problems associated with urine sedimentation or its formation. In particular, for example, those which can achieve such a purpose without adding benzamidinium chloride, sodium azide and the like to urine are preferable. Therefore, in the present invention, a urine collection container containing a characteristic solid urine sample treating agent designed to achieve such an object is preferably provided, and it is possible to simplify the processing of urine. Making it possible.

A urine sample container containing the solid-state urine sample treating agent of the present invention is characterized by being prepared by a person skilled in the art by which an aqueous solution is dried to leave the non-volatile components constituting the solution. It will be understood that they can be prepared using methods known to those skilled in the art or by evaporation to dryness. There are so many methods that can be employed that they cannot be exhaustively posted, but are described in detail in basic reference books and more detailed papers as well as in many research literatures, which are well known to those skilled in the art. . A typical method for producing a urine sample container comprising the solid state urine sample treating agent of the present invention is, for example, a urine sample treating agent (or typically a urine sediment dissolving agent). It is characterized by dispensing a certain amount of the aqueous solution into a dedicated container, preferably a plastic test tube, and drying it, and in particular, once freezing the water in the aqueous solution and then sublimating the generated ice, from there, It is characterized in that no processing such as removal is performed. Although the production can be carried out at about 25 ° C., a preferred drying treatment is carried out while heating, preferably at a temperature of 30 to 70 ° C. The processing temperature is
Although it is possible to perform the test at a higher temperature, when a plastic test tube is used, an appropriate temperature is selected in consideration of the heat resistance of the plastic material. When the processing temperature is increased, the processing time can be shortened. In addition, the drying treatment can be performed under normal pressure, but is preferably performed under reduced pressure. A preferred method for producing the urine sample container of the present invention is a method of drying under reduced pressure. The drying under the reduced pressure,
It is preferably performed under a reduced pressure of 600 to 760 mmHg, more preferably at a reduced pressure of 600 to 730 mmHg. Here, the degree of pressure reduction is expressed in millimeters of mercury (mm Hg) and indicates how much pressure is reduced from normal pressure (whether the pressure is reduced). The degree of pressure reduction can be made higher, but in this case, it is necessary to operate the aqueous solution to be treated so as not to bump.
If the degree of pressure reduction is increased, the processing time can be shortened. However, an appropriate temperature is selected so that the problem such as bumping does not occur. Further, the time for the drying treatment is not limited, and any one can be adopted as long as a solid-state urine sample treating agent having desired properties can be obtained. For example, from the viewpoint of production efficiency, it is preferably 1 hour or more, more preferably 2 hours or more, and further preferably 4 hours or more to less than 48 hours. A typical drying method is, for example, at a temperature of 30 to 62 ° C and a reduced pressure of 600 to 730 mmHg,
2 hours or more to less than 48 hours.

In the above-mentioned drying treatment, the buffer solution is usually prepared in a state where a container such as a test tube (also simply referred to as a “tube”) is a test tube, for example, standing in a test tube rack as usual. The test tube containing the contents is subjected to a drying treatment to deposit solid contents on the tube wall and / or the bottom of the test tube. Preferably, the drying under reduced pressure employed in the present invention can be performed using a commonly used vacuum dryer. In a preferred example, the vacuum dryer is provided with a water ring type vacuum pump to reduce the pressure. As the vacuum dryer,
For example, vacuum drying equipment DQ-70 of Sato Vacuum Machinery Co., Ltd.
S modification. When examining the properties of the urine sample container containing the solid-state urine sample treating agent obtained by the drying treatment as described above, for example, a plastic test tube, it may be tilted. Even if strong impact or weak force is applied to the tube wall and / or the tube bottom such as a test tube by shaking, shaking, playing with a finger, or rolling on the floor, the solid content The object remains adhered to the tube wall and / or tube bottom and does not substantially peel therefrom, or remains attached to the tube wall and / or tube bottom even after a certain period of time from the time of manufacture. so,
It has the property that it is not substantially peeled off or hardly peeled off. Therefore, it is observed that the solid content (urine sample treating agent deposit) is a wall sticky solid. Further examination of the water content of the solid state contents reveals that the water content of 3 to 50% by weight ((w / w)%) is determined to be suitable for the purpose of the present invention. 4 to 45% by weight ((w /
w)%), more preferably 4.6-42% by weight for the solid state contents of the preferred nature. A typical moisture content of the contents is, for example, 8-41.7% by weight.

It is considered that, because a certain amount of moisture remains in the contents, the contents can be prevented from being scattered even when an impact or the like is applied. Thus, in the urine sample container of the present invention, the retention of the content is further improved. It is conceivable that the content becomes as if a film is formed on the surface, and that the moisture is retained and the adhesiveness to the tube wall surface is retained. The contents are unlikely to be peeled off from the tube wall even when the tube bottom is flipped, shaken, or turned upside down, but on the other hand, it is observed that the contents can be rapidly dissolved and does not adversely affect the measurement. Has been issued. The use of the urine sample container of the present invention can prevent dilution of urine trace components. The container is also in a ready-to-use form that receives fresh urine and at the same time prevents or prevents the formation of urine precipitates upon storage.

By employing the above-mentioned vacuum drying method, drying in a container having a low thermal conductivity (that is, changing the liquid content to a solid content), which was difficult with the conventional method (freeze-drying method or the like). ) Can be implemented with good yield (rate of accepted products). Further, the productivity of the urine sample container which can withstand use as a product and contains the solid state urine sample treating agent is also improved, and for example, a yield (product acceptance rate) of 95% or more can be obtained. By the reduced-pressure drying method of the present invention, it is possible to produce a dried product having a high content retention even in a solution containing a urine specimen treating agent (typically a precipitation dissolving agent) having various concentrations and various compositions. . In the drying under reduced pressure,
Containers of various materials and shapes can be processed, and most container shapes (unsealed ones) can be dried. According to the reduced-pressure drying method of the present invention, it is possible to uniformly coagulate a buffer solution contained in a plastic container without adding a coagulant, and furthermore, a container made of a material having a low thermal conductivity such as plastic is used. If a large amount of lyophilization is performed, the yield of acceptable products will decrease (30% or less),
There is no such thing. The vacuum drying method of the present invention enables a large amount of the urine sedimentation dissolving agent to be dried in the container, and the product yield (rate of acceptable products) is excellent at 95% or more. However, it is possible to avoid deformation due to heat, and it is possible to obtain a dried body in a short time. Kit The present invention further includes the urine sample container of the present invention and a device for handling liquid such as urine related thereto, such as a plastic dropper, a pipette, and the like.
And / or other diagnostic component-based packs and kits that are combined with one or more containers filled with one or more other reagent component compositions. Precautionary statements in the form prescribed by governmental agencies that regulate the manufacture, use or sale of medical or non-medical diagnostic or measurement drugs or biological products, together with such container (s). (Document), which may be accompanied by a notice (attachment) indicating the approval of the government agency for the manufacture, use or sale of the product.

[0038]

The present invention will be described in more detail with reference to the following examples, which are provided merely for explanation of the present invention and for reference to specific embodiments thereof. .
These exemplifications are intended to illustrate certain specific embodiments of the present invention, but are not intended to limit or limit the scope of the invention disclosed herein. It is to be understood that the invention is capable of various embodiments based on the teachings herein. All examples, unless otherwise described in detail, are performed or can be performed using standard techniques, which are well known and routine to those skilled in the art. .

Example 1 Tris-hydrochloric acid buffer (pH 7.5) was selected and used as a urine sample treating agent, and a urine collection tube containing the constituents thereof as a solid was prepared. Was evaluated by five male and five female panelists. Prepare 1.5 M Tris-hydrochloric acid buffer (pH 7.5) and place it in a special tube [plastic round bottom test tube made of polyethylene terephthalate of 1.5 cm in diameter and 10 cm in height: PET9 (Tokuyama Sekisui Industry Co., Ltd.)]. Dispensed mLs were prepared and treated as follows.

(1) A dedicated tube containing 0.5 mL each of a urine sample treating agent as a solution is treated by a freeze-drying method disclosed in WO 98/29745. A special tube containing 0.5 mL of the urine sample treatment liquid as a liquid is treated using a freeze-drying apparatus (vacuum freeze-dryer MODEL TRI-6-5SMP: manufactured by FST, USA). Processing conditions are from normal pressure to shelf temperature minus
Perform freezing treatment at 40 ° C for 2 hours, then reduce the pressure and maintain the vacuum at a shelf temperature minus 40 ° C for 5 hours. To remove). Next, in a vacuum state, the shelf temperature was set to plus 10 ° C., kept at the same temperature for 10 hours, and further treated at the same temperature for 5 hours with the shelf temperature set to plus 20 ° C. The lyophilization treatment was performed 10 times with changing the conditions as a group of 10 tubes.
In any case, the solid content in the tube is in the form of solidified crystalline powder with a smooth appearance,
Some fine powders were also observed. Also, if you apply a shock, such as flipping the bottom of the obtained tube with your finger,
In most cases, the contents are observed to peel off from the tube wall, and the solid contents to be broken and scattered. In this freeze-drying method, the product is in a state where the content adheres to the tube wall (the solidified content does not break into pieces, or the solidified content It was observed by panelists that the rate (yield) at which no part of the sample could be scattered) was obtained (yield: 50% or less). When manufactured on an industrial production line, the yield of acceptable products whose contents are considered to be acceptable for processing urine samples is less than 30% in freeze-drying methods, as observed by panelists. Was evaluated.

(2) A dedicated tube containing 0.5 mL each of the urine sample treating agent as a liquid is subjected to drying under reduced pressure, and the properties of the solidified contents in the tube are evaluated by a panelist. A dedicated tube containing 0.5 mL each of the urine sample treatment liquid as a liquid is used as a drying device [vacuum drying device DQ-70S modified:
Sato Vacuum Machinery Co., Ltd.], temperature 57 ° C, decompression 70
The solution was dried under reduced pressure at 0 mm Hg for 22 hours. This treatment allowed the translucent Tris-HCl buffer solids to be deposited as if coated on the bottom of the dedicated tube. As a result of 100 tubes, the solid contents in each tube had a somewhat transparent or translucent appearance, the surface was somewhat shiny, and the fine powder was almost or less. No content was observed, and the contents had deposited as if coated on the bottom of the tube. For the most part, the contents remained approximately uniformly applied to the tube wall of the tube in the form of a coating, and the yield of acceptable products was evaluated by panelists as 95% or more.

(3) A shock is applied to the product obtained by freeze-drying and the product obtained by drying under reduced pressure to observe the broken state of the solid content in the tube. 1.5m height
Was allowed to fall freely on a commercially available steel flat desk, and the state of the solid contents adhering to the tube wall was visually observed by a panelist. Each tube was tested using 10 tubes. As a result, in the product obtained by freeze-drying, the content was damaged, and the rate at which the content was scattered and it was difficult to maintain its content (breakage rate) was 70.0%. In the case of the material obtained by drying under reduced pressure, the damage ratio was only 20.0%. In the case of the vacuum drying method, even if it was damaged, the contents were not shattered, the scattering was prevented, and it was judged by the panelists that the content could be maintained.
In the vacuum drying method according to the present invention, a coagulant can be uniformly coagulated on the tube bottom or on the tube wall without adding a coagulant to a buffer used as a urine sample treating agent, and used as a product with confidence. It is evaluated that a large number of acceptable products can be stably obtained (high productivity).

Example 2 Tris-hydrochloric acid buffer (pH 7.5) was selected and used as a urine sample treating agent, and a tube dedicated to urine containing the components constituting the same was prepared. The contents were evaluated for performance. 1.5 M Tris-HCl buffer (pH
7.5) is prepared, and 0.5 mL is dispensed into a special tube (the same plastic round bottom test tube used in Example 1). The tube was dried by a drying device (Example 1).
At the same temperature, 57 ° C, 700 mm decompression
The mixture was dried under reduced pressure at Hg for 22 hours. This process makes the translucent
Tris-HCl buffer solids were obtained which were deposited as if coated on the bottom of the dedicated tube. After placing 5 mL of urine in a tube (ureter tube) and mixing to completely dissolve the dissolving agent, urine type IV collagen measurement kit [Panauria uIV · C “plate”: manufactured by Fuji Pharmaceutical Co., Ltd., under development] The amount of type IV collagen in urine was measured. The results are shown in Table 1.

[0044]

[Table 1]

As a result, the urine sample treatment agent was dried under reduced pressure to obtain a T
In a tube (urine collection tube) accommodating the ris-hydrochloric acid buffer as a solidified content, the same value as that measured using a freeze-dried tube could be confirmed. In other words, it is recognized that the performance of the contents of the tube after drying under reduced pressure is good in measuring a urine sample.

Example 3 The permissible conditions of the drying under reduced pressure are examined. Tris-HCl buffer (pH 7.5) is selected and used as a urine sample treatment agent, and a urine collection tube containing its components as a solid is dried and dried under reduced pressure, and the contents of the tube are prepared. The properties and performance of the product were evaluated. Prepare 1.5 M Tris-HCl buffer (pH 7.5), and place 0.5 mL in a special tube (the same plastic round bottom test tube used in Example 1).
Prepare one dispensed at a time. Next, the tube 6480
Using a drying device (the same as that used in Example 1),
It was dried under reduced pressure at a temperature of 57 ° C. and a reduced pressure of 700 mm Hg for 0 to 50 hours. At regular intervals, from any place on the drying device, a total of 1
Take 0 tubes at a time and check the contents of the tubes,
Performance evaluation was performed by five male and five female panelists.

The evaluation criteria are as follows. Pass: The coating is deposited on the bottom surface inside the tube (or the inner wall near the bottom) as if coated. No movement of the contents is immediately observed even when the tube is inverted, and the bottom outside the tube is touched with a finger. Solids do not move when flipped Fail: The contents are observed to move when the tube is inverted, or some of the solids are broken, and the outer bottom of the tube is lightly rubbed with a finger. A part of which is observed to peel off or move even if played

[0048] As a result, when the drying under reduced pressure was performed for 4 hours or less, there were many cases where the solution dripped when the tube was inverted, but the buffer solution in the tube became thicker each time the tube was dried, and the buffer was placed on the bottom of the tube. Although it was located, it was observed that it became difficult to flow even when the tube was inverted. However, when the drying under reduced pressure was performed for about 8 hours, it was observed that the flow rate was considerably slow and the viscosity was considerably high. As the drying time becomes longer, the number of accepted products increases,
At 20 and 22 hours, the appearance was translucent, and 95% or more of the acceptable products were obtained. Also, those dried for 48 hours or more were almost rejected because solids were broken or peeled off from the tube wall. The water content of the acceptable products was measured by the Karl Fischer method and found to be 4.6 to 33.5 (w / w)% in all cases.

Examples 4 to 9 The same procedure as in Example 3 was carried out except that the same buffer solution as in Example 3 was dispensed in 0.5 mL tubes, and the processing temperature, the degree of vacuum and the processing time shown in Table 2 were employed. Similarly, the tube was dried under reduced pressure, and the properties and performance of the content of the obtained tube were evaluated by panelists. The evaluation criteria are the same as in the third embodiment. The results are shown in Table 2.

[0050]

[Table 2]

Examples 10 to 12 Tubes in which 0.5 mL of the same buffer solution as in Example 3 above was dispensed were dried at the treatment temperature and reduced pressure shown in Table 3 for 16 hours in the same manner as in Example 3. The properties and performance of the treated tube were evaluated by panelists according to the same evaluation criteria as in Example 3. The water content was measured by the Karl Fischer method. The results are shown in Table 3.

[0052]

[Table 3]

If the drying temperature is 60 ° C. or higher, the plastic container may be deformed, so that its use is avoided. Further, when the degree of pressure reduction was increased to near a complete vacuum state, bumping occurred and drying was impossible. On the other hand, drying is possible even at a low degree of reduced pressure (600 mmHg or less), but it takes a long time. Buffer pH 6.5-9.0 and citrate buffer,
Similar products can be obtained using a buffer selected from the group consisting of phosphate buffers and other Tris-HCl buffers.

Example 13 A 1.5 M Tris-hydrochloric acid buffer solution (pH 7.5) was prepared and dispensed in a dedicated tube (the same plastic round bottom test tube used in Example 1) by 0.5 mL each. Except for the drying treatment time, the same treatment as in Example 3 was carried out at the temperature and the degree of reduced pressure adopted in Example 3, and the solid-state urine sample treating agent having the following water content was used as the content and the tube wall of the tube and / or Or reciprocating shaker: SR deposited on the bottom of the pipe
-II (Sanyo Co., Ltd.) and shaken at 300 rpm for 20 minutes. In a state where the shaken test tube is inverted,
The "wall surface tackiness" of the "solid content" was evaluated based on whether or not the solid content detached from the wall surface. The water content is measured by the Karl Fischer method. At the same time, Example 1
The product prepared by freeze-drying in the same manner as (1) was also examined. Table 4 shows the results. Table 4 shows the number of the solid contents detached from the wall surface in the test using four test tubes.

[0055]

[Table 4]

Example 14 The antiseptic effect of the compound was evaluated. A test compound (EDTA, benzalkonium chloride or formaldehyde) was added to 1.5 M Tris-hydrochloric acid buffer (pH 7.5), and the urine collection tube (the same plastic round bottom test tube used in Example 1) was added. Each 0.5 mL aliquot was dried under reduced pressure at a temperature of 50 ° C. and a reduced pressure of 700 mmHg for 24 hours. After adding 5 mL of E. coli culture solution (LB) to the obtained tube and completely dissolving the contents, 5 μL of E. coli (JM109, BL21, ATCC 8739) cultured overnight in E. coli culture solution was added. Cultivation was performed overnight at ℃, and turbidity indicating the presence or absence of growth was visually inspected. EDTA
Showed no growth of E. coli JM109 and ATCC 8739 at a concentration of 0.186 to 0.744% by weight (when 5 mL of Escherichia coli culture solution was added), and the antiseptic effect was confirmed. Benzalkonium chloride is
0.0002 to 0.01% by weight (when 5 mL of E. coli culture solution is added)
No growth of Escherichia coli JM109, BL21 and ATCC 8739 was observed, and the antiseptic effect was confirmed. Formaldehyde is 0.00
At a concentration of 6 to 0.03% by weight (when 5 mL of Escherichia coli culture solution was added), growth of Escherichia coli JM109, BL21 and ATCC 8739 was not observed, and the antiseptic effect was confirmed.

Example 15 The effect of the addition of EDTA and / or benzalkonium chloride on the measured value of urinary type IV collagen was examined. 1.5M Tri
EDTA was added to s-hydrochloric acid buffer (pH 7.5) to a concentration of 0.372% by weight (when 5 mL of urine was added), and a dedicated tube for urine collection (the same plastic round-bottom test tube used in Example 1) 0.5 mL each at a temperature of 50 ° C and a reduced pressure of 7
It was dried under reduced pressure at 00 mmHg for 24 hours. Also, without adding EDTA, only 1.5 M Tris-HCl buffer (pH 7.5) was dispensed in 0.5 mL portions into a dedicated urine collection tube, and dried under reduced pressure in the same manner. After placing 5 mL of urine in each of the obtained tubes and mixing to completely dissolve the dissolving agent, a urine type IV collagen measurement kit [Panauria uIV · C “Plate”: developed by Fuji Pharmaceutical Co., Ltd. Medium], the amount of urinary type IV collagen was measured. When comparing the measured values for 50 urine samples, the average
It was 100.4% (EDTA added / EDTA not added), and the measured value was not affected by the addition of EDTA. When 0.186% by weight of EDTA and 0.001% by weight of benzalkonium chloride (each at the concentration of 5 mL of urine) were added, the ratio of the measured values of urinary type IV collagen was 100.8% on average (EDTA and benzalkonium chloride). (Addition of ruconium / no addition of EDTA and benzalkonium chloride), and the addition of EDTA and benzalkonium chloride did not affect the measured values. Benzalkonium chloride
When 0.001% by weight (concentration when 5 mL of urine was added) was added, the ratio of the urinary type IV collagen measured value was 103.3% on average.
(Addition of benzalkonium chloride / no addition of benzalkonium chloride), and addition of benzalkonium chloride did not affect the measured values.

Obviously, the present invention can be practiced other than as specifically described in the foregoing description and examples. Many modifications and variations of the present invention are possible in light of the above teachings, and so are within the scope of the appended claims.

[0059]

According to the urine sample container of the present invention, the solid-state urine sample treating agent that has been dried by vacuum drying or the like is accommodated. It can be handled safely, reliably, and stably without crushing or scattering of crystalline substances. According to the present invention, there is provided a urine sample container product containing a solid-state urine sample treating agent, wherein the solidified content can be handled while being attached to the bottom and / or wall surface of the container. Provided is a container product for a urine sample that is manufactured efficiently and contains a solidified urine sample treating agent having excellent properties. In the vacuum drying method adopted in the present invention,
The obtained solid-state content adheres to the bottom and / or tube wall of the bottom portion of a test tube or the like that is a container, and the solid-state content may be broken or damaged by a slight impact applied to the container. Also, it does not collapse, or part or all of the contents are not peeled off from the bottom and / or the wall of the tube, and the contents are securely scattered without being scattered. A product that can hold the contents and can be used efficiently as a urine sample container without problems in terms of handleability and reliability in use (approximately 95% in production yield) The solid product, which can be obtained and the product obtained (a urine sample container containing a solid state urine sample treating agent) can be used safely with normal handling precautions during transportation, test use, etc. Objects that are durable (use Product).

Claims (17)

[Claims] 1. A urine sample container comprising a urine sample treatment agent which is a solid which is dried without freezing water. 2. A urine sample container containing a urine sample treating agent which is a solid dried under reduced pressure. 3. A urine sample container comprising a urine sample treating agent in a wall-adhesive solid state. 4. A urine sample container containing a solid urine sample treating agent having a water content of 3 to 50% by weight. 5. A urine sample container containing a solid urine sample treating agent having a water content of 4 to 45% by weight. 6. The container according to claim 1, wherein the container comprises a hollow cylindrical body having one end closed. 7. The container according to claim 1, wherein the container has a test tube or a structure similar thereto. 8. The container according to claim 1, wherein the container is made of a synthetic resin. 9. The synthetic resin is a polyethylene such as polyvinyl chloride, high density polyethylene, low density polyethylene, etc.
Selected from the group consisting of polyolefin resins such as polypropylene, fluorocarbon resins such as Teflon, silicone resins such as silicon, polycarbonate, polysulfone, polyphenylene oxide, polyacrylate or polymethacrylate, and polyester resins such as polyethylene terephthalate copolymer. 9. The container according to claim 8, wherein the container is provided. 10. A urine sample treating agent characterized in that the urine sample treating agent comprises (a) a buffer having a pH of 6.5 or more as an active ingredient; and (b) a buffer having a pH of 6.5 to 9.5. A urine sample treating agent characterized by containing it as an active ingredient;
(c) a urine sample treating agent comprising a buffer having a pH of 7.0 to 8.2 as an active ingredient; and (d) a pH of 7.4 to
The container according to any one of claims 1 to 9, characterized in that the container is selected from the group consisting of a urine sample treating agent, which comprises a buffer having a pH of 7.8 as an active ingredient. 11. The method according to claim 1, wherein the urine sample treating agent is for solubilizing a trace component which is taken up in a precipitate generated in the urine sample and is an analyte to be measured. The container according to any one of the above. 12. The urine transferrin, wherein the trace component is:
Growth hormone in urine, urinary IgG, urinary albumin, chorionic gonadotropin in urine, urinary alpha _{1-microglobulin,} urine beta ₂ microglobulin, each type collagen prolyl hydroxylase, laminin, matrix metalloproteinases (MMPs ), Tissue inhibitors of metalloproteases (TIMPs) and thrombomodulin.
The container as described. 13. The container according to claim 11, wherein the trace component is selected from the group consisting of type IV collagen and thrombomodulin. 14. The urine sample treating agent is a phosphate buffer, N-
Tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid (TES) buffer, N- (2-hydroxyethyl) piperazine-N'-ethanesulfonic acid (HEPES) buffer, tris (hydroxymethyl) aminomethane (Tris) 2.) providing a buffer selected from the group consisting of hydrochloric acid buffer, borate buffer, citrate buffer, barbital buffer and imidazole-hydrochloride buffer.
14. The container according to any one of claims 13 to 13. 15. The container according to claim 1, wherein the urine sample treating agent contains a preservative. 16. The container according to claim 15, wherein the preservative is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), benzalkonium chloride, and formaldehyde. 17. A urine specimen treating agent comprising tris (hydroxymethyl) aminomethane (Tris) -hydrochloric acid buffer and ethylenediaminetetraacetic acid (EDTA) and / or benzalkonium chloride as a preservative. Item 1
17. The container according to any one of 16 above.