JPH0961430A - Test piece for measuring creatinine - Google Patents
Test piece for measuring creatinineInfo
- Publication number
- JPH0961430A JPH0961430A JP22049695A JP22049695A JPH0961430A JP H0961430 A JPH0961430 A JP H0961430A JP 22049695 A JP22049695 A JP 22049695A JP 22049695 A JP22049695 A JP 22049695A JP H0961430 A JPH0961430 A JP H0961430A
- Authority
- JP
- Japan
- Prior art keywords
- test piece
- creatinine
- layer
- alkaline substance
- urine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 238000012360 testing method Methods 0.000 title claims abstract description 55
- 229940109239 creatinine Drugs 0.000 title claims abstract description 43
- 239000000126 substance Substances 0.000 claims abstract description 35
- 210000002700 urine Anatomy 0.000 claims abstract description 33
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims abstract description 24
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 22
- MKWJZTFMDWSRIH-UHFFFAOYSA-N (4-fluoro-3-nitrophenyl)methanol Chemical compound OCC1=CC=C(F)C([N+]([O-])=O)=C1 MKWJZTFMDWSRIH-UHFFFAOYSA-N 0.000 claims description 25
- 238000003892 spreading Methods 0.000 claims description 25
- 230000007480 spreading Effects 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000000523 sample Substances 0.000 claims description 11
- 210000001124 body fluid Anatomy 0.000 claims description 8
- 239000010839 body fluid Substances 0.000 claims description 8
- 239000012488 sample solution Substances 0.000 claims description 8
- 238000006482 condensation reaction Methods 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 239000004202 carbamide Substances 0.000 abstract 1
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 10
- 230000003139 buffering effect Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- VYWYYJYRVSBHJQ-UHFFFAOYSA-N 3,5-dinitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 VYWYYJYRVSBHJQ-UHFFFAOYSA-N 0.000 description 6
- 238000007375 Jaffe assay Methods 0.000 description 6
- 238000011088 calibration curve Methods 0.000 description 5
- 229960003624 creatine Drugs 0.000 description 5
- 239000006046 creatine Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229920000139 polyethylene terephthalate Polymers 0.000 description 5
- 239000005020 polyethylene terephthalate Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical group 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002657 fibrous material Substances 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000008085 renal dysfunction Effects 0.000 description 2
- 229920002799 BoPET Polymers 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004146 energy storage Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000013100 final test Methods 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000000088 plastic resin Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- -1 polyethylene terephthalate Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000012209 synthetic fiber Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 239000012780 transparent material Substances 0.000 description 1
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、体液中のクレアチ
ニン測定用試験片及び測定法に関し、詳しくは、尿のよ
うな緩衝作用の強い体液中のクレアチニンであっても高
精度で測定することが可能な安定性の高い試験片を提供
するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a test piece for measuring creatinine in a body fluid and a measuring method, and more specifically, it can measure creatinine in a body fluid having a strong buffering action such as urine with high accuracy. It is intended to provide a test piece with high stability.
【０００２】[0002]
【従来の技術】クレアチニンは、クレアチン経路の最終
代謝物であり、クレアチンが脱水、環化した構造を有す
る。体内においては、大半はクレアチン又はクレアチン
リン酸として筋肉中に存在する。クレアチンは、ＡＴＰ
から高エネルギーリン酸を受けてクレアチンリン酸とな
り、エネルギー貯蔵物質として機能し、筋収縮などのエ
ネルギー消費時にはＡＤＰに高エネルギーリン酸を転移
してクレアチンに戻るか、非酵素的反応によってクレア
チニンとなる。その後、生成したクレアチニンは、腎臓
を介して尿中へ排泄される。BACKGROUND OF THE INVENTION Creatinine is the final metabolite of the creatine pathway and has a structure in which creatine is dehydrated and cyclized. In the body, most are present in muscle as creatine or creatine phosphate. Creatine is ATP
Receives high-energy phosphoric acid to become creatine phosphate and functions as an energy storage substance. When energy is consumed such as muscle contraction, high-energy phosphoric acid is transferred to ADP to return to creatine, or it becomes creatinine by a non-enzymatic reaction. . Then, the produced creatinine is excreted in the urine via the kidney.
【０００３】従って、クレアチニンの尿中排泄量すなわ
ち尿中濃度は、筋肉疾患や腎機能障害の指標に用いられ
ている。また、腎機能障害がある場合等、血中のクレア
チニン濃度が疾患の指標となり得る。Therefore, the amount of creatinine excreted in urine, that is, the concentration in urine, is used as an index of muscle disease and renal dysfunction. In addition, blood creatinine concentration can be an index of disease, such as when there is renal dysfunction.
【０００４】体液中のクレアチニンの検出方法として公
知の「ヤッフェ(Jaffe) 反応」は、強アルカリ性条件下
におけるクレアチニンとピクリン酸との縮合物による呈
色反応を利用したものであり、簡便かつ経済的な検出方
法として広く一般的に使用されている。またヤッフェ反
応は、ピクリン酸の代わりに３，５−ジニトロ安息香酸
を使用する、ベネディクト−ベーレ(Benedict-Bhere)の
方法が応用化されている。The "Jaffe reaction" known as a method for detecting creatinine in body fluids utilizes a color reaction due to a condensate of creatinine and picric acid under strongly alkaline conditions, and is simple and economical. It is widely and commonly used as a simple detection method. For the Jaffe reaction, the method of Benedict-Bhere, which uses 3,5-dinitrobenzoic acid instead of picric acid, is applied.
【０００５】上記のヤッフェ反応は、主に溶液系として
使われているが、その一方でこの反応を簡便な乾式の試
験片へ応用した技術が開示されている（特開平１−１２
９１６４号、特開平１−１２９１６５号、特開平５−２
８１２３５号各公報）。しかしながら、尿を対象とした
場合、これらに記載の方法はいずれもある程度のクレア
チニンを測定できるものの、精度のよい方法とは言いが
たいものであった。The above-mentioned Jaffe reaction is mainly used as a solution system, while a technique in which this reaction is applied to a simple dry test piece is disclosed (Japanese Patent Laid-Open No. 1-12).
9164, JP-A-1-129165, JP-A 5-2
No. 81235). However, in the case of urine, all of the methods described above can measure creatinine to some extent, but it is hard to say that they are accurate methods.
【０００６】というのは、尿は広いpH域を有し、しかも
緩衝作用が非常に強いため、強アルカリ性下が必須条件
であるヤッフェ反応あるいはベネディクト−ベーレの方
法において、アルカリ性物質を加えても尿の緩衝作用に
よって反応ｐＨの低下が引き起こされ、結果的にクレア
チニンの検出・測定に大きな誤差を与えてしまうからで
ある。Since urine has a wide pH range and has a very strong buffering action, urine is added even if an alkaline substance is added in the Jaffe reaction or the Benedict-Bere method, which is essential under strongly alkaline conditions. This is because the pH of the reaction causes a decrease in the reaction pH, resulting in a large error in the detection and measurement of creatinine.
【０００７】よって、上記方法を利用した尿中クレアチ
ニンの測定において誤差を少なくするためには、強力な
アルカリ性物質（例えば水酸化ナトリウムや水酸化リチ
ウム等の水酸化物）を、尿の緩衝能を上回る程度に多量
に添加する必要がある。本発明者らの実験によれば、尿
の緩衝能を上回って強アルカリ性を確保・維持するに
は、尿以外の検体を用いる場合の約５倍量以上のアルカ
リ性物質を添加しなけらばならないことが判明してい
る。Therefore, in order to reduce the error in the measurement of creatinine in urine using the above-mentioned method, a strong alkaline substance (for example, a hydroxide such as sodium hydroxide or lithium hydroxide) should be used for buffering the urine. It is necessary to add a large amount to exceed. According to the experiments conducted by the present inventors, in order to maintain and maintain strong alkalinity by exceeding the buffer capacity of urine, it is necessary to add an alkaline substance in an amount of about 5 times or more that in the case of using a sample other than urine. It turns out.
【０００８】ところが、上記のようなクレアチニンの測
定に使用されるピクリン酸や３，５−ジニトロ安息香
酸、特にこれらの反応生成物は、尿の緩衝作用を上回る
程の量のアルカリ性物質を添加すると極めて不安定であ
り、生成物の呈色にも大きな影響を与える。However, picric acid and 3,5-dinitrobenzoic acid, which are used for the determination of creatinine as described above, and particularly the reaction products thereof, are added with an alkaline substance in an amount exceeding the buffering effect of urine. It is extremely unstable and greatly affects the coloration of the product.
【０００９】反応系が液系である場合には、測定する直
前に大量のアルカリ性物質を添加することによって、ピ
クリン酸や３，５−ジニトロ安息香酸の安定性を保つこ
とはできるが、使用する全ての試薬類をあらかじめ仕込
んである乾式の試験片では、これらの安定性を保つこと
はできない。したがって、希釈されていない尿を対象と
して、クレアチニンを精度よく測定する試験片を作製す
ることは、非常に困難であった。When the reaction system is a liquid system, the stability of picric acid and 3,5-dinitrobenzoic acid can be maintained by adding a large amount of an alkaline substance immediately before measurement, but it is used. These stability cannot be maintained in a dry type test piece in which all reagents are pre-loaded. Therefore, it has been very difficult to produce a test piece for measuring creatinine with high precision in undiluted urine.
【００１０】[0010]
【発明が解決しようとする課題】本発明は、上記観点か
らなされたものであり、非希釈尿のような緩衝作用の強
い体液であっても、クレアチニンを精度よく測定できる
安定な試験片を提供することを課題とする。The present invention has been made from the above viewpoint, and provides a stable test piece capable of measuring creatinine with high accuracy even in a body fluid having a strong buffering action such as undiluted urine. The task is to do.
【００１１】[0011]
【課題を解決するための手段】上記課題を解決するため
に鋭意研究した結果、３，４−ジニトロ安息香酸が、尿
の緩衝作用を上回る程に増量したアルカリ性物質の存在
下でも安定して、クレアチニンとの縮合反応により呈色
することを見出し、本発明を完成させた。[Means for Solving the Problems] As a result of earnest research to solve the above problems, 3,4-dinitrobenzoic acid was stable even in the presence of an alkaline substance whose amount was increased to exceed the buffering effect of urine. The present invention has been completed by finding that a color is produced by a condensation reaction with creatinine.
【００１２】すなわち本発明は、展開層と、この展開層
の全部又は少なくとも一部に接する３，４−ジニトロ安
息香酸及び強アルカリ性物質とを含む、体液中のクレア
チニン測定用試験片である。That is, the present invention is a test piece for measuring creatinine in a body fluid, which comprises a spreading layer and 3,4-dinitrobenzoic acid and a strongly alkaline substance in contact with all or at least a part of the spreading layer.
【００１３】また本発明は、上記試験片の好ましい態様
として、展開層を支持するための支持体をさらに有し、
この支持体上に３，４−ジニトロ安息香酸を含む試薬層
が設けられ、この試薬層上に強アルカリ性物質を含む展
開層が設けられた試験片を提供する。In a preferred embodiment of the above test piece, the present invention further comprises a support for supporting the spreading layer,
There is provided a test piece in which a reagent layer containing 3,4-dinitrobenzoic acid is provided on the support, and a developing layer containing a strong alkaline substance is provided on the reagent layer.
【００１４】本発明はさらに、試料液中のクレアチニン
濃度を測定する方法であって、試料液中に、試料液のｐ
Ｈが１２〜１３となる量の強アルカリ性物質と、３，４
−ジニトロ安息香酸とを溶解させ、試料中に含まれるク
レアチニンと３，４−ジニトロ安息香酸との縮合反応に
よる呈色を測定することを特徴とするクレアチニンの測
定法を提供する。The present invention further provides a method for measuring the creatinine concentration in a sample solution, wherein the sample solution contains p
A strong alkaline substance with an amount of H of 12 to 13,
-Providing a method for measuring creatinine, which comprises dissolving dinitrobenzoic acid and measuring the coloration due to a condensation reaction between creatinine contained in a sample and 3,4-dinitrobenzoic acid.
【００１５】前記体液としては、尿、血清等が適用され
得るが、特に非希釈尿が好適に適用される。その際、前
記強アルカリ性物質は、試験片に非希釈尿を吸収させた
ときに反応ｐＨを１２〜１３に維持することができるこ
とが好ましい。この強アルカリ性物質として、具体的に
は水酸化リチウムが挙げられる。As the body fluid, urine, serum and the like can be applied, but undiluted urine is particularly preferably applied. At that time, it is preferable that the strong alkaline substance can maintain the reaction pH at 12 to 13 when the test strip absorbs the undiluted urine. Specific examples of the strong alkaline substance include lithium hydroxide.
【００１６】以下、本発明を詳細に説明する。本発明の
試験片は、展開層と、この展開層の全部又は少なくとも
一部に接する３，４−ジニトロ安息香酸及び強アルカリ
性物質とを有し、好ましくは支持体をさらに備える。The present invention will be described in detail below. The test piece of the present invention has a spreading layer, 3,4-dinitrobenzoic acid and a strongly alkaline substance in contact with all or at least a part of the spreading layer, and preferably further comprises a support.
【００１７】前記展開層は、尿などの検体を吸収して液
相の反応系を作るためのものであり、素材としては濾
紙、織布、不織布、ガラス繊維、ニトロセルロース、親
水性高分子等、多孔性の素材が挙げられる。また、形状
としては、ストリップ（細片）状、棒状等が挙げられ
る。これらの内では、濾紙などのようなセルロース等の
天然由来の繊維素材は、強アルカリ条件下では加水分解
や劣化することがあるため、化学合成繊維生地等が好ま
しい。The spreading layer is for absorbing a sample such as urine to form a liquid phase reaction system, and its material is filter paper, woven cloth, non-woven cloth, glass fiber, nitrocellulose, hydrophilic polymer, etc. , And porous materials. Further, examples of the shape include a strip shape and a rod shape. Of these, chemically-derived fiber materials and the like are preferable because naturally-derived fiber materials such as cellulose such as filter paper may be hydrolyzed or deteriorated under strongly alkaline conditions.
【００１８】展開層の物理的な強度が弱い場合には、本
発明の試験片は、展開層を支持するための支持体を有し
ていてもよい。支持体は、展開層と一体となり得る形状
であってもよいし、展開層の一部のみを支持するもので
あってもよい。支持体の素材としては、乾式試験片を作
製する際に通常用いられるプラスチック樹脂、例えばポ
リエチレンテレフタレート（以下、「ＰＥＴ」と省略す
る）等が挙げられる。支持体に光透過性の素材を用いる
と、試験片を使用する際に、呈色を支持体側から観察、
測定することが可能となる。When the physical strength of the spreading layer is weak, the test piece of the present invention may have a support for supporting the spreading layer. The support may have a shape that can be integrated with the spreading layer, or may support only a part of the spreading layer. Examples of the material of the support include a plastic resin that is usually used in producing a dry test piece, such as polyethylene terephthalate (hereinafter abbreviated as “PET”). When a transparent material is used for the support, the coloration is observed from the support side when the test piece is used,
It becomes possible to measure.
【００１９】３，４−ジニトロ安息香酸及び強アルカリ
性物質は、上記のような展開層の全部又は少なくとも一
部に接する。ここで「接する」とは、３，４−ジニトロ
安息香酸及び強アルカリ性物質が展開層の表面上に接し
ていることのみを意味するものではなく、展開層の内部
で展開層を構成する素材に接していることも含む。ま
た、上記の物質は間接的に展開層に接していてもよく、
例えばマイクロカプセルに封入された状態で接していて
もよい。さらには、展開層上に３，４−ジニトロ安息香
酸及び強アルカリ性物質の一方の物質が層状に設けら
れ、他方の物質がその上に接するように担持されていて
もよい。The 3,4-dinitrobenzoic acid and the strongly alkaline substance are in contact with all or at least a part of the spreading layer as described above. Here, "contacting" does not mean that 3,4-dinitrobenzoic acid and a strongly alkaline substance are in contact with each other on the surface of the spreading layer. Including being in contact. Further, the above substances may be in contact with the spreading layer indirectly,
For example, they may be in contact with each other while being enclosed in microcapsules. Furthermore, one of the 3,4-dinitrobenzoic acid and the strongly alkaline substance may be provided in a layered form on the spreading layer, and the other substance may be supported so as to be in contact therewith.
【００２０】本発明の試験片の好ましい態様としては、
３，４−ジニトロ安息香酸を含む層が表面上に形成され
た支持体と、強アルカリ性物質を含む層が表面上に形成
された展開層とが、３，４−ジニトロ安息香酸層と強ア
ルカリ性物質層が接するようにして圧着等の手法により
積層化させた試験片（図１参照）が挙げられる。このよ
うに多層化することで、３，４−ジニトロ安息香酸の安
定性を一層高めることができる。その際、支持体として
プラスチック素材等の非多孔性素材を用いるときは、
３，４−ジニトロ安息香酸を支持体上に固定するため
に、バインダーを用いて試薬層として支持体上に担持さ
せてもよい。また、強アルカリ性物質は、展開層中に含
浸させてもよい。尚、３，４−ジニトロ安息香酸と強ア
ルカリ性物質の試験片中の存在部位は、上記と逆であっ
てもよいが、反応環境を強アルカリにすることが必要で
あるので、展開層及び支持層のうち、先に検体試料が触
れる展開層側に水酸化物を含ませることが好ましい。ま
た、強アルカリ性物質は、強アルカリ性条件を強化する
ために、試薬層及び展開層の両方に含有させてもよい。As a preferred embodiment of the test piece of the present invention,
A support on which a layer containing 3,4-dinitrobenzoic acid is formed on the surface and a spreading layer on which a layer containing a strong alkaline substance is formed are a 3,4-dinitrobenzoic acid layer and a strong alkaline. An example is a test piece (see FIG. 1) that is laminated by a method such as pressure bonding so that the material layers are in contact with each other. By thus forming multiple layers, the stability of 3,4-dinitrobenzoic acid can be further enhanced. At that time, when a non-porous material such as a plastic material is used as the support,
In order to fix 3,4-dinitrobenzoic acid on the support, a binder may be used to support it on the support as a reagent layer. Further, the strong alkaline substance may be impregnated in the spreading layer. The sites where 3,4-dinitrobenzoic acid and the strongly alkaline substance are present in the test piece may be the opposite of the above, but since it is necessary to make the reaction environment a strong alkali, the development layer and the support are supported. Of the layers, it is preferable to include a hydroxide on the side of the spreading layer that the specimen sample comes into contact with first. Further, the strong alkaline substance may be contained in both the reagent layer and the developing layer in order to strengthen the strong alkaline condition.
【００２１】強アルカリ性物質としては、試料に溶解さ
せたときに強アルカリ性の環境を誘導することができる
ものであればよく、特に、試験片に非希釈尿を吸収させ
たときに、試験片での反応ｐＨを１２〜１３に維持する
ことができることが好ましい。具体的には、水酸化アル
カリ金属であれば、大抵の物質が使用できる。試験片の
作製・保存中に、水酸化アルカリ金属の二酸化炭素を吸
着する性質により炭酸が生じるため、試験片のｐＨが低
下することが知られている。この観点から、使用する水
酸化アルカリ金属としては、炭酸を生じにくい水酸化リ
チウムが望ましい。水酸化リチウムを用いる場合には、
例えば展開層が厚さ１５０μｍ、面積が１００ｃｍ2 の
場合、１９〜３１ｇ含有されていることが好ましい。The strong alkaline substance may be any substance that can induce a strong alkaline environment when dissolved in a sample, and particularly when the test piece absorbs undiluted urine, It is preferable that the reaction pH can be maintained at 12 to 13. Specifically, almost any substance can be used as long as it is an alkali metal hydroxide. It is known that the pH of the test piece is lowered because carbonic acid is generated due to the property of the alkali metal hydroxide to adsorb carbon dioxide during the production and storage of the test piece. From this point of view, as the alkali metal hydroxide to be used, lithium hydroxide, which hardly produces carbonic acid, is desirable. When using lithium hydroxide,
For example, when the developed layer has a thickness of 150 μm and an area of 100 cm 2 , it is preferable that 19 to 31 g is contained.
【００２２】本発明の試験片は、クレアチニンとの縮合
反応により呈色する物質として３，４−ジニトロ安息香
酸を用いる以外は、従来の試験片と同様にして製造する
ことができる。例えば、バインダーと３，４−ジニトロ
安息香酸とを溶媒中に溶解又は分散させることによって
粘性の高い塗工液を調製し、この塗工液を支持体表面に
一定の厚さに塗工した後乾燥させて、試薬層を形成させ
る。バインダーとしては、メチルセルロース等の非活性
かつ親水性のポリマーが挙げられる。上記のようにして
得られる支持体と、強アルカリ性物質溶液を含浸、乾燥
させた展開層とを、試薬層と展開層が接するようにして
圧着することによって、全体を積層化する。これらの操
作は、最終製品と同じ大きさの素材を用いて行ってもよ
いが、大きい素材を用いて積層化したものを適宜裁断し
てもよい。The test piece of the present invention can be manufactured in the same manner as the conventional test piece except that 3,4-dinitrobenzoic acid is used as a substance that develops a color by a condensation reaction with creatinine. For example, a binder and 3,4-dinitrobenzoic acid are dissolved or dispersed in a solvent to prepare a highly viscous coating liquid, and the coating liquid is applied to the surface of a support at a constant thickness. It is dried to form a reagent layer. Examples of the binder include inactive and hydrophilic polymers such as methyl cellulose. The support obtained as described above and the developing layer impregnated with the strongly alkaline substance solution and dried are pressure-bonded so that the reagent layer and the developing layer are in contact with each other, whereby the whole is laminated. These operations may be performed using a raw material having the same size as the final product, or a laminate obtained by using a large raw material may be appropriately cut.
【００２３】試薬を担持させた展開層又は展開層と支持
体とを積層化したものを、そのまま試験片として用いて
もよいが、これを細片化したものをＰＥＴ等からなる把
持部の先端に固定して用いてもよい。The developing layer supporting the reagent or the laminated layer of the developing layer and the support may be used as a test piece as it is, but the fragmented piece is a tip of a gripping part made of PET or the like. You may fix and use it.
【００２４】本発明の試験片を使用する際には、展開層
の上へ試料（非希釈尿等）を滴下して、試薬層の色変化
を、目視あるいは分光色差計、反射率測定装置（例えば
スポットケムＳＰ−４４１０（（株）京都第一科学の商
標）等の装置を用いて読み取る。装置を用いて定量分析
する場合には、試料液を試験片の展開層へ滴下した後、
クレアチニンと３，４−ジニトロ安息香酸の縮合物の吸
収波長（５５０ｎｍ）における反射率の変化速度を測定
し、あらかじめ既知濃度系列のクレアチニン溶液を滴下
して測定しておいた結果から作成した検量線を用いて、
前記変化速度から濃度を算出する。支持体に光透過性の
素材を用いたときは、呈色を支持体側から測定してもよ
い。When the test piece of the present invention is used, a sample (undiluted urine or the like) is dropped on the spreading layer, and the color change of the reagent layer is visually or spectrally measured by a color difference meter or a reflectance measuring device ( For example, it is read using an apparatus such as Spotchem SP-4410 (trademark of Kyoto Daiichi Kagaku Co., Ltd.) When quantitative analysis is performed using the apparatus, after dropping the sample solution into the spreading layer of the test piece,
A calibration curve prepared from the results of measuring the rate of change of reflectance at the absorption wavelength (550 nm) of a condensate of creatinine and 3,4-dinitrobenzoic acid and measuring the concentration of creatinine solution of known concentration in advance. Using,
The concentration is calculated from the rate of change. When a light-transmissive material is used for the support, coloration may be measured from the support side.
【００２５】本発明の試験片は、上記のような構成を有
しているので、試験片に試料液を吸収させたときに、試
料液中のｐＨを高く維持することができ、試料中に含ま
れるクレアチニンと３，４−ジニトロ安息香酸との縮合
反応による呈色を安定化させることができる。その結
果、高い測定精度を有し、簡便にクレアチニンを定量す
ることができる。Since the test piece of the present invention has the above-mentioned constitution, when the test piece absorbs the sample solution, the pH in the sample solution can be kept high, and It is possible to stabilize the coloration due to the condensation reaction between the contained creatinine and 3,4-dinitrobenzoic acid. As a result, creatinine can be easily quantified with high measurement accuracy.
【００２６】[0026]
【発明の実施の形態】以下に、本発明をさらに具体的に
説明する。下記の塗工液成分を混合した後、支持体（１
２５μｍのＰＥＴ製白色フィルム）上に、濡れ厚さ１５
０μｍの厚さで塗工し、４０℃で１０分間乾燥させる。BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in more detail below. After mixing the following coating liquid components, the support (1
25μm PET white film), wet thickness 15
It is applied to a thickness of 0 μm and dried at 40 ° C. for 10 minutes.
【００２７】 （試薬層の塗工液成分） ３，４−ジニトロ安息香酸 （（株）東京化成） １．６９６ｇ 水酸化リチウム１水和物 （（株）ナカライテスク） ０．３３６ｇ メチルセルロース （（株）ナカライテスク） ０．２３ｇ 蒸留水 ５．０ｇ(Components of Reagent Layer Coating Liquid) 3,4-Dinitrobenzoic Acid (Tokyo Kasei Co., Ltd.) 1.696 g Lithium hydroxide monohydrate (Nacalai Tesque, Inc.) 0.336 g Methylcellulose ((shares) ) Nakarai Tesque) 0.23g Distilled water 5.0g
【００２８】一方、下記の含浸液成分を混合し３７℃で
溶解させた後、化学合成繊維生地（ポリエステル編み物
「ザヴィーナ・ミニマックス」（株）鐘紡の商標）へ１
３０ｍｌ／m2吸収、含浸させた後、４０℃で１５分間乾
燥させる。On the other hand, the following impregnation liquid components were mixed and melted at 37 ° C., and then chemically synthesized fiber fabric (polyester knitting “Zavina Minimax” (trademark of Kanebo Co., Ltd.) 1
After absorbing and impregnating with 30 ml / m 2 , it is dried at 40 ° C. for 15 minutes.
【００２９】 （展開層の含浸液成分） 水酸化リチウム （（株）東京化成） ２９．３７２ｇ 蒸留水 ２００．００ｇ(Impregnating liquid component of spreading layer) Lithium hydroxide (Tokyo Kasei Co., Ltd.) 29.372 g Distilled water 200.00 g
【００３０】次に、０．１％トリトンＸ−１００を含む
蒸留水で湿らせた展開層を、試薬層の上にのせて圧着さ
せることによりラミネートした後、この積層物を裁断機
で５mm×７mmになるように裁断する。裁断して得られた
パッドを、面積が５mm×７０mm，厚さが０．２５mmのス
ティック状の白色ＰＥＴ片の先端部分に貼り付け、最終
的な試験片を得る。Next, a developing layer moistened with distilled water containing 0.1% Triton X-100 was placed on the reagent layer and pressure-bonded to laminate, and then this laminate was cut with a cutting machine to a size of 5 mm ×. Cut to 7 mm. The pad obtained by cutting is attached to the tip portion of a stick-shaped white PET piece having an area of 5 mm × 70 mm and a thickness of 0.25 mm to obtain a final test piece.
【００３１】このようにして得られる試験片の側面図を
図１に示す。A side view of the test piece thus obtained is shown in FIG.
【００３２】[0032]
【実施例】以下に、本発明を実施例によりさらに具体的
に説明する。EXAMPLES The present invention will be described more specifically with reference to the following examples.
【００３３】[0033]
【実施例１】上記実施の形態と同様にして試験片を製造
した。得られた試験片を用いて、尿中のクレアチニンを
測定した。ヒトプール尿へクレアチニンを１００〜５０
０ｍｇ／ｄｌとなるように添加したものを試料とし、ヤ
ッフェ反応を用いた市販の溶液系自動分析装置用試薬
（「クリニメイト」（株）第一化学の商標）と、本発明
による試験片の各々を用いて、クレアチニン定量値の相
関をとった。Example 1 A test piece was manufactured in the same manner as in the above embodiment. The obtained test piece was used to measure creatinine in urine. 100-50 creatinine in human pool urine
Each of the test pieces according to the present invention and a reagent for a commercially available solution-type automatic analyzer using the Jaffe reaction (a trademark of "Clinimate" Co., Ltd. Daiichi Kagaku) was used as a sample by adding 0 mg / dl. Was used to correlate quantitative creatinine values.
【００３４】試験片の展開層へ滴下する試料の量は５μ
ｌとし、３７℃の環境下で、スポットケムＳＰ−４４１
０（（株）京都第一科学製）を使用して、クレアチニン
と３，４−ジニトロ安息香酸の縮合物の吸収波長（５５
０ｎｍ）における反射率を展開層側から測定した。得ら
れた反射率は、化１式に示すクベルカ−ムンク(Kubelka
-Munk)の式に従ってＫ／Ｓ値に換算し、その２０〜３０
秒間の増加量（ΔＫ／Ｓ）から１分間あたりの増加量を
求めた。The amount of the sample dropped on the spreading layer of the test piece was 5 μm.
1 and under the environment of 37 ° C, Spotchem SP-441
0 (manufactured by Kyoto Daiichi Kagaku Co., Ltd.) using an absorption wavelength of a condensate of creatinine and 3,4-dinitrobenzoic acid (55
The reflectance at 0 nm) was measured from the spreading layer side. The obtained reflectance is represented by Kubelka-Munk (Formula 1).
-Munk) converted into K / S value according to the formula, 20-30
The amount of increase per minute was calculated from the amount of increase (ΔK / S) per second.
【００３５】[0035]
【化１】Ｋ／Ｓ値＝（１−Ｒ）2／２Ｒ Ｒ ：反射率（％）## EQU1 ## K / S value = (1-R) 2 / 2RR: reflectance (%)
【００３６】上記のようにして本発明の試験片を用いて
測定された各クレアチニン濃度と１分間あたりのΔＫ／
Ｓとの関係を図２に示す。これを検量線とした。検量線
は、上記測定範囲で良好な直線性を示した。Each creatinine concentration measured using the test piece of the present invention as described above and ΔK / minute per minute
The relationship with S is shown in FIG. This was used as a calibration curve. The calibration curve showed good linearity in the above measurement range.
【００３７】また、市販の溶液系自動分析装置用試薬を
用いて測定された結果と、本発明による試験片を用いて
測定された結果との相関を、化２式に示す。Further, the correlation between the result measured by using the commercially available reagent for solution type automatic analyzer and the result measured by using the test piece according to the present invention is shown in Chemical formula 2.
【００３８】[0038]
【化２】ｒ＝０．９９９ ｙ＝１．６６×１０-3＋０．９９９ｘ （ｘ＝自動分析装置用試薬、ｙ＝本発明による試験片）Embedded image r = 0.999 y = 1.66 × 10 −3 + 0.999x (x = reagent for automatic analyzer, y = test piece according to the present invention)
【００３９】随時尿中に含まれるクレアチニン排泄量
（濃度）は、個人差があるものの、一般的に３００ｍｇ
／ｄｌまでの範囲であり、本発明によって得られる検量
線は５００ｍｇ／ｄｌまでの直線性を示しており、尿中
クレアチニンの定量に十分な測定範囲を有している。The amount of creatinine excreted (concentration) in urine at any time is generally 300 mg, although it varies from person to person.
/ Dl, the calibration curve obtained by the present invention shows linearity up to 500 mg / dl, and has a measurement range sufficient for quantifying creatinine in urine.
【００４０】[0040]
【実施例２】実尿を試料として、ヤッフェ反応を用いた
溶液系自動分析装置用試薬と、本発明による試験片を用
い、クレアチニンを定量した。これらの値の相関を化３
式に示す。このように、両者は、実尿に対しても良好な
相関関係を示した。[Example 2] Using real urine as a sample, creatinine was quantified using a reagent for a solution-type automatic analyzer using the Jaffe reaction and a test piece according to the present invention. Correlate these values 3
It is shown in the formula. Thus, both showed good correlation with actual urine.
【００４１】[0041]
【化３】ｒ＝０．９８４ ｙ＝０．０３３＋０．９６７ｘ （ｎ＝５０、ｘ＝自動分析装置用試薬、ｙ＝本発明によ
る試験片）Embedded image r = 0.984 y = 0.033 + 0.967x (n = 50, x = reagent for automatic analyzer, y = test piece according to the present invention)
【００４２】[0042]
【比較例１】比較対照として、３，４−ジニトロ安息香
酸の代わりに３，５−ジニトロ安息香酸を用い、３，５
−ジニトロ安息香酸の安定性を鑑みてアルカリ性物質量
が実施例１の試験片の１／５量である試験片を作製し、
実尿を試料として実施例２と同様に測定した。本発明の
試験片を用いた結果との相関を化４式に示す。Comparative Example 1 As a comparative control, 3,5-dinitrobenzoic acid was used in place of 3,4-dinitrobenzoic acid, and 3,5
In consideration of the stability of dinitrobenzoic acid, a test piece having an alkaline substance amount of ⅕ the amount of the test piece of Example 1 was prepared,
The actual urine was used as a sample and measured in the same manner as Example 2. The correlation with the result using the test piece of the present invention is shown in Formula 4.
【００４３】[0043]
【化４】ｒ＝０．７５０ ｙ＝０．４６０＋０．５６２ｘ （ｎ＝５０、ｘ＝自動分析装置用試薬、ｙ＝本発明によ
る試験片）Embedded image r = 0.750 y = 0.460 + 0.562x (n = 50, x = reagent for automatic analyzer, y = test piece according to the present invention)
【００４４】この結果から明らかなように、両者の相関
は低かった。これは、反応時のｐＨ（アルカリ性）が維
持されないような強い緩衝能を、尿が持つことが多いた
めに、比較例の試験片では正確な測定ができなかったた
めであると考えられる。As is clear from this result, the correlation between the two was low. It is considered that this is because urine often has a strong buffering capacity such that the pH (alkalineity) during the reaction is not maintained, and thus the test piece of the comparative example could not perform accurate measurement.
【００４５】[0045]
【発明の効果】本発明によれば、希釈されていない尿中
のクレアチニン濃度を精度よく測定できる安定な乾式の
試験片を提供することができる。According to the present invention, it is possible to provide a stable dry test piece capable of accurately measuring the creatinine concentration in undiluted urine.
【図１】 本発明の試験片の１実施例を示す側面図。FIG. 1 is a side view showing an embodiment of a test piece of the present invention.
【図２】 本発明による試験片によって得られたクレア
チニン測定用の検量線である。縦軸は１分間あたりのΔ
Ｋ／Ｓ値を、横軸はクレアチニン濃度（ｍｇ／ｄｌ）を
示す。FIG. 2 is a calibration curve for measuring creatinine obtained by the test piece according to the present invention. The vertical axis is Δ per minute
The K / S value is shown, and the horizontal axis shows the creatinine concentration (mg / dl).
１．展開層（水酸化リチウムを含浸させた化学合成繊維
生地） ２．３，４−ジニトロ安息香酸を含む試薬層 ３．支持層（白色ＰＥＴフィルム）1. Development layer (chemically synthetic fiber cloth impregnated with lithium hydroxide) 2. Reagent layer containing 3,4-dinitrobenzoic acid 3. Support layer (white PET film)
───────────────────────────────────────────────────── フロントページの続き (72)発明者 古田 仁志 京都府京都市南区東九条西明田町57株式会 社京都第一科学内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hitoshi Furuta 57 East Higashi Kujo Nishi-Ameracho, Minami-ku, Kyoto City, Kyoto Prefecture
Claims (6)
とも一部に接する３，４−ジニトロ安息香酸及び強アル
カリ性物質とを含む、体液中のクレアチニン測定用試験
片。1. A test piece for measuring creatinine in a body fluid, which comprises a spreading layer and 3,4-dinitrobenzoic acid and a strongly alkaline substance in contact with all or at least a part of the spreading layer.
有し、この支持体上に３，４−ジニトロ安息香酸を含む
試薬層が設けられ、この試薬層上に強アルカリ性物質を
含む展開層が設けられた請求項１記載の試験片。2. A support for supporting the spreading layer is further provided, a reagent layer containing 3,4-dinitrobenzoic acid is provided on the support, and a developing containing a strong alkaline substance is provided on the reagent layer. The test piece according to claim 1, wherein a layer is provided.
２記載の試験片。3. The test piece according to claim 1, wherein the body fluid is undiluted urine.
釈尿を染み込ませたときに反応ｐＨを１２〜１３に維持
することができる請求項１〜３のいずれか一項に記載の
試験片。4. The test strip according to claim 1, wherein the strong alkaline substance can maintain a reaction pH of 12 to 13 when the test strip is impregnated with undiluted urine. .
である請求項１〜４のいずれか一項に記載の試験片。5. The test piece according to claim 1, wherein the strong alkaline substance is lithium hydroxide.
方法であって、試料液中に、試料液のｐＨが１２〜１３
となる量の強アルカリ性物質と、３，４−ジニトロ安息
香酸とを溶解させ、試料中に含まれるクレアチニンと
３，４−ジニトロ安息香酸との縮合反応による呈色を測
定することを特徴とするクレアチニンの測定法。6. A method for measuring the creatinine concentration in a sample solution, wherein the pH of the sample solution is 12 to 13 in the sample solution.
It is characterized in that the amount of strong alkaline substance and 3,4-dinitrobenzoic acid are dissolved, and the coloration due to the condensation reaction of creatinine and 3,4-dinitrobenzoic acid contained in the sample is measured. Method for measuring creatinine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22049695A JP3516002B2 (en) | 1995-08-29 | 1995-08-29 | Test piece for creatinine measurement |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22049695A JP3516002B2 (en) | 1995-08-29 | 1995-08-29 | Test piece for creatinine measurement |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0961430A true JPH0961430A (en) | 1997-03-07 |
| JP3516002B2 JP3516002B2 (en) | 2004-04-05 |
Family
ID=16751969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP22049695A Expired - Fee Related JP3516002B2 (en) | 1995-08-29 | 1995-08-29 | Test piece for creatinine measurement |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3516002B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008522641A (en) * | 2004-10-06 | 2008-07-03 | イー−ズィー−エム， インコーポレイテッド | Medical imaging system, dispensing system, method and computer program product for assessing a patient's renal function prior to dispensing a contrast agent as part of a medical imaging procedure |
| WO2009144881A1 (en) * | 2008-05-16 | 2009-12-03 | パナソニック株式会社 | Measurement method, measurement device, and measurement apparatus for creatinine concentration and measurement method, measurement device, and measurement apparatus for amount of salinity using the same |
| EP2518501A2 (en) | 2011-04-28 | 2012-10-31 | ARKRAY, Inc. | Dry test strip and method for measuring creatinine |
| JP2018185335A (en) * | 2014-02-28 | 2018-11-22 | 日東電工株式会社 | Urine analysis apparatus and dry reagent for quantitative urine analysis |
-
1995
- 1995-08-29 JP JP22049695A patent/JP3516002B2/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008522641A (en) * | 2004-10-06 | 2008-07-03 | イー−ズィー−エム， インコーポレイテッド | Medical imaging system, dispensing system, method and computer program product for assessing a patient's renal function prior to dispensing a contrast agent as part of a medical imaging procedure |
| WO2009144881A1 (en) * | 2008-05-16 | 2009-12-03 | パナソニック株式会社 | Measurement method, measurement device, and measurement apparatus for creatinine concentration and measurement method, measurement device, and measurement apparatus for amount of salinity using the same |
| JP4486702B2 (en) * | 2008-05-16 | 2010-06-23 | パナソニック株式会社 | Creatinine concentration measuring method, measuring device and measuring apparatus, and salinity measuring method, measuring device and measuring apparatus using them |
| JP2010151826A (en) * | 2008-05-16 | 2010-07-08 | Panasonic Corp | Measurement method for amount of salinity |
| US7816145B2 (en) | 2008-05-16 | 2010-10-19 | Panasonic Corporation | Method, device and apparatus for measuring the concentration of creatinine, and method, device and apparatus for measuring the amount of salt using the same |
| JPWO2009144881A1 (en) * | 2008-05-16 | 2011-10-06 | パナソニック株式会社 | Creatinine concentration measuring method, measuring device and measuring apparatus, and salinity measuring method, measuring device and measuring apparatus using them |
| EP2518501A2 (en) | 2011-04-28 | 2012-10-31 | ARKRAY, Inc. | Dry test strip and method for measuring creatinine |
| US8815531B2 (en) | 2011-04-28 | 2014-08-26 | Arkray, Inc. | Dry test strip and method for measuring creatinine |
| JP2018185335A (en) * | 2014-02-28 | 2018-11-22 | 日東電工株式会社 | Urine analysis apparatus and dry reagent for quantitative urine analysis |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3516002B2 (en) | 2004-04-05 |
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