JPH04161854A - Method for measuring material in organism - Google Patents
Method for measuring material in organismInfo
- Publication number
- JPH04161854A JPH04161854A JP28965890A JP28965890A JPH04161854A JP H04161854 A JPH04161854 A JP H04161854A JP 28965890 A JP28965890 A JP 28965890A JP 28965890 A JP28965890 A JP 28965890A JP H04161854 A JPH04161854 A JP H04161854A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxycreatinine
- methylguanidine
- blood
- reagent
- 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
- 238000000034 method Methods 0.000 title claims abstract description 23
- SMQPRZPBBUJEGU-UHFFFAOYSA-N 2-amino-4-hydroxy-3-methyl-4h-imidazol-5-one Chemical compound CN1C(O)C(=O)N=C1N SMQPRZPBBUJEGU-UHFFFAOYSA-N 0.000 claims abstract description 80
- 238000011002 quantification Methods 0.000 claims 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N methylguanidine Chemical compound CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 abstract description 60
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 14
- 210000004369 blood Anatomy 0.000 abstract description 12
- 239000008280 blood Substances 0.000 abstract description 12
- 210000002700 urine Anatomy 0.000 abstract description 10
- 201000006370 kidney failure Diseases 0.000 abstract description 8
- 230000007062 hydrolysis Effects 0.000 abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 7
- 208000017169 kidney disease Diseases 0.000 abstract description 7
- 208000001647 Renal Insufficiency Diseases 0.000 abstract description 5
- 238000013399 early diagnosis Methods 0.000 abstract description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 abstract description 3
- 208000037157 Azotemia Diseases 0.000 abstract description 3
- 239000003729 cation exchange resin Substances 0.000 abstract description 3
- 208000009852 uremia Diseases 0.000 abstract description 3
- 239000011347 resin Substances 0.000 abstract description 2
- 229920005989 resin Polymers 0.000 abstract description 2
- 230000001131 transforming effect Effects 0.000 abstract 2
- 238000004811 liquid chromatography Methods 0.000 abstract 1
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 22
- 229940109239 creatinine Drugs 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 238000004445 quantitative analysis Methods 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000008085 renal dysfunction Effects 0.000 description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000033679 diabetic kidney disease Diseases 0.000 description 3
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000691 measurement method Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 206010018367 Glomerulonephritis chronic Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000012921 fluorescence analysis Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000004454 trace mineral analysis Methods 0.000 description 2
- 239000002441 uremic toxin Substances 0.000 description 2
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- -1 guanidino compound Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- 208000038001 non-diabetic kidney disease Diseases 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は５−ヒドロキシクレアチニンをメチルグアニジ
ンに変換して測定することを特徴とする５−ヒドロキシ
クレアチニンの定量法に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a method for quantifying 5-hydroxycreatinine, which is characterized by converting 5-hydroxycreatinine into methylguanidine.
（従来の技術）
メチルグアニジンは腎不全患者の血中に蓄積する゛
主要な尿毒素の一つとして知られており、クレアチニン
から活性酸素により生成するものと考えられている。(Prior art) Methylguanidine accumulates in the blood of patients with renal failure.
It is known as one of the major uremic toxins and is thought to be generated from creatinine by active oxygen.
本発明者らは腎障害におけるタレアチニン代謝に関して
研究した結果、腎障害患者の血中及び尿中から新規な化
合物、５−ヒドロキシクレアチニンを単離同定した。こ
の物質は健常人の血中にはなく、腎障害患者の血中に特
有にみられ、病態の進行に伴い産生昂進が認められるこ
と、また５−ヒドロキシクレアチニンは種々の実験結果
より、クレアチニンからメチルグアニジンが産生される
際のメチルグアニジンの前駆体であることを見出した０
本発明はこれらの事実に基づき、血中又は尿中における
５−ヒドロキシクレアチニンを測定することによって、
腎不全、尿毒症等各種腎ｍｕｍ害の早期診断を可能とし
たものである。As a result of our research on taleatinine metabolism in renal disorders, the present inventors isolated and identified a novel compound, 5-hydroxycreatinine, from the blood and urine of patients with renal disorders. This substance is not present in the blood of healthy people, but is uniquely found in the blood of patients with renal failure, and its production increases as the disease progresses, and various experimental results show that 5-hydroxycreatinine is derived from creatinine. It was discovered that methylguanidine is a precursor of methylguanidine when it is produced.
The present invention is based on these facts, and by measuring 5-hydroxycreatinine in blood or urine,
This enables early diagnosis of various renal mumps such as renal failure and uremia.
（発明が解決しようとする問題点）
本発明の目的は、腎臓障害の検査法として有用な５−ヒ
ドロキシクレアチニンの定量法を提供することにある。(Problems to be Solved by the Invention) An object of the present invention is to provide a method for quantifying 5-hydroxycreatinine that is useful as a method for testing kidney disorders.
（問題点を解決するための手段）
本発明は５−ヒドロキシクレアチニンをメチルグアニジ
ンに変換して測定することを特徴とする５−ヒドロキシ
クレアチニンの定量法である。(Means for Solving the Problems) The present invention is a method for quantifying 5-hydroxycreatinine, which is characterized by converting 5-hydroxycreatinine into methylguanidine.
グアニジノ化合物の測定法としては、９．１０−フェナ
ンスレンキノン（ＰＱ試薬）を用いる蛍光分析が繁用さ
れている。５−ヒドロキシクレアチニンは分子内にグア
ニジノ骨格を存しているが、これら蛍光分析用試薬との
反応性は極めて低く（低感度であるクレアチニンのさら
に５分の１に過ぎない）、微量分析が容易でない。As a method for measuring guanidino compounds, fluorescence analysis using 9,10-phenanthrenequinone (PQ reagent) is often used. Although 5-hydroxycreatinine has a guanidino skeleton in its molecule, its reactivity with these fluorescent analysis reagents is extremely low (only one-fifth of creatinine, which has low sensitivity), making trace analysis easy. Not.
そこで、５−ヒドロキシクレアチニンは加水分解によっ
てメチルグアニジンとなることから、５−ヒドロキシク
レアチニンをメチルグアニジンに変換して測定する本発
明定量法を見出した。Therefore, since 5-hydroxycreatinine becomes methylguanidine through hydrolysis, we have discovered the quantitative method of the present invention in which 5-hydroxycreatinine is converted into methylguanidine and then measured.
以下に本発明測定法について詳細に説明する。The measuring method of the present invention will be explained in detail below.
５−ヒドロキシクレアチニンをメチルグアニジンに変換
させる方法としては、一般に用いられている加水分解等
の方法が利用でき、例えば酸又はアルカリで処理する方
法や酸又はアルカリの存在下或いは非存在下にて加熱処
理する方法などが挙げられる。As a method for converting 5-hydroxycreatinine into methylguanidine, commonly used methods such as hydrolysis can be used, such as treatment with an acid or alkali, or heating in the presence or absence of an acid or alkali. Examples include processing methods.
また、酵素を用いて５−ヒドロキシクレアチニンをメチ
ルグアニジンに変換させる方法も利用できる。Alternatively, a method of converting 5-hydroxycreatinine into methylguanidine using an enzyme can also be used.
上記メチルグアニジンへの変換処理については、陽イオ
ン交換樹脂等による分画法や該樹脂を用いた高速液体ク
ロマトグラフィー（ＨＰＬＣ）などによって５−ヒドロ
キシクレアチニンを分離した後に加水分解処理する方法
が挙げられるＪまた、５−ヒドロキシクレアチニンを分
離する前に加水分解処理を行い、その試料中の全メチル
グアニジンを測定することも可能である。この場合、分
離前のメチルグアニジン量を別途に求め、全メチルグア
ニジン量よりこの量を引いて補正してもよいが、このよ
うな補正を行なわずとも、腎Ｉ！′障害の病態の進行番
二伴い産生昂進が認められる５−ヒドロキシクレアチニ
ン及びメチルグアニジンの両方を合わせて測定すること
も、腎臓障害の診断として有用である。加水分解の方法
や条件によっては、試料中に存在する５−ヒドロキシク
レアチニン以外の物質からメチルグアニジンが産生され
てくる場合を考慮に入れると、５−ヒドロキシクレアチ
ニンのみを選択的にメチルグアニジンに変換できるよう
な加水分解等の方法及び条件を適宜設定するのが好まし
い。Examples of the above-mentioned conversion treatment to methylguanidine include a method in which 5-hydroxycreatinine is separated by a fractionation method using a cation exchange resin or the like, or high performance liquid chromatography (HPLC) using the resin, and then subjected to a hydrolysis treatment. It is also possible to perform a hydrolysis treatment before separating 5-hydroxycreatinine and measure the total methylguanidine in the sample. In this case, the amount of methylguanidine before separation may be calculated separately and corrected by subtracting this amount from the total amount of methylguanidine, but even without such correction, the renal I! It is also useful for diagnosing kidney disorders to measure both 5-hydroxycreatinine and methylguanidine, whose production increases as the disease progresses. Depending on the hydrolysis method and conditions, it is possible to selectively convert only 5-hydroxycreatinine to methylguanidine, taking into account that methylguanidine may be produced from substances other than 5-hydroxycreatinine present in the sample. It is preferable to set the method and conditions for hydrolysis etc. as appropriate.
５−ヒドロキシクレアチニンを変換して得られたメチル
グアニジンを測定する方法としては、ＰＱ試薬等の蛍光
試薬と反応させる蛍光分析法、メチルグアニジンアミジ
ノヒドラーゼを用いる酵素法など通常行われているメチ
ルグアニジンの測定法が利用できる。例えば、ＰＱ試薬
を用いる方法においては、ＰＱ試薬はアルカリ性でグア
ニジノ化合物と反応するため、アルカリの存在下にて５
−ヒドロキシクレアチニンを加水分解処理してメチルグ
アニジンに変換するのが、後のＰＱ試薬との反応におい
て有利であり手間を省くことができる。Methods for measuring methylguanidine obtained by converting 5-hydroxycreatinine include the fluorescence analysis method in which it is reacted with a fluorescent reagent such as PQ reagent, the enzymatic method using methylguanidine amidinohydrase, etc. measurement methods are available. For example, in the method using the PQ reagent, since the PQ reagent is alkaline and reacts with the guanidino compound, 5
- Hydrolyzing hydroxycreatinine to convert it into methylguanidine is advantageous and saves time and effort in the subsequent reaction with the PQ reagent.
（実施例）
（１）血清及び尿の調製法
血清は早朝空腹時に採血し、４℃で遠心分層した後、上
滑を凍結し測定時まで保存した。又、尿は２４時間尿を
採取し、尿量を記録後、凍結し測定時まで保存した。上
記検体をトリクロロ酢酸により除蛋白処理した後以下の
測定法を行った。(Example) (1) Preparation method of serum and urine Serum was collected early in the morning on an empty stomach, centrifuged at 4°C, and the supernatant was frozen and stored until the time of measurement. In addition, urine was collected for 24 hours, and after recording the amount of urine, it was frozen and stored until the time of measurement. After deproteinizing the above specimen with trichloroacetic acid, the following measurement method was performed.
（２）ＨＰＬＣによる分画
クレアチニン、メチルグアニジン等のグアニジノ化合物
の測定は、ＨＰＬＣで分離した後、ＰＱ試薬と反応させ
蛍光を測定する白木らの方法に準じて行った。（Ｊｏｕ
ｒｎａｌ ｏｆ Ｃｈｒｏｍａｔｏｇｒａｐｈｙ、 １
６２（１９７９）カラムハ陽イオン交換樹脂（ＴＯ３Ｏ
ＳＣＸ、 ＳＨＩＭＡＺＩＩＩＳＣ−０７／５１５０４
等）を用い、溶離液の組成は菜館らの方法に準じた。〔
分析化学、 ３３（１９８４） ３６６−３７０）（３
）蛍光反応試薬
ポストカラムにおける蛍光反応試薬としては、２Ｍ水酸
化ナトリウム水溶液及びＰＱ試薬溶液（Ｉｆｆｉのジメ
チルホルムアミドに５００■のＰＱを溶解して調製）を
用いた。(2) Fractionation by HPLC Guanidino compounds such as creatinine and methylguanidine were measured according to the method of Shiraki et al., which involves separating them by HPLC, reacting them with a PQ reagent, and measuring fluorescence. (Jou
RNA of Chromatography, 1
62 (1979) Column cation exchange resin (TO3O
SCX, SHIMAZIIISC-07/51504
etc.), and the composition of the eluent was according to the method of Saidate et al. [
Analytical Chemistry, 33 (1984) 366-370) (3
) Fluorescence Reaction Reagent As the fluorescence reaction reagent in the post-column, a 2M aqueous sodium hydroxide solution and a PQ reagent solution (prepared by dissolving 500 μm of PQ in Iffi's dimethylformamide) were used.
（４）５−ヒドロキシクレアチニンの測定系５−ヒドロ
キシクレアチニンをメチルグアニジンに変換して測定す
る定量分析システムの波路構成図を第１図に示す。第１
反応コイルには長さが５ｍ、内径が０．５１のステンレ
ス管を用い、反応器を１２５℃に設定することにより、
定量分析系における発色が最大となった。蛍光検出器の
励起波長は３４０ｎｓ＋に、蛍光波長は４９５ｒｖに設
定した。(4) Measuring system for 5-hydroxycreatinine FIG. 1 shows a wave path configuration diagram of a quantitative analysis system that converts and measures 5-hydroxycreatinine into methylguanidine. 1st
By using a stainless steel tube with a length of 5 m and an inner diameter of 0.51 as the reaction coil, and setting the reactor at 125 °C,
The color development in the quantitative analysis system was maximum. The excitation wavelength of the fluorescence detector was set to 340 ns+, and the fluorescence wavelength was set to 495 rv.
（作用）
５−ヒドロキシクレアチニンのＰＱ試薬に対する反応性
は極めて低いため、高感度で測定するのは困難であった
が、上記実施例の方法に従ってメチルグアニジンに変換
した後にＰＱ試薬と反応することにより、メチルグアニ
ジンの感度の約２分の１を確保できることが明らかにな
った。(Effect) Since the reactivity of 5-hydroxycreatinine with the PQ reagent is extremely low, it was difficult to measure it with high sensitivity. It has become clear that approximately one half of the sensitivity of methylguanidine can be secured.
この５−ヒドロキシクレアチニン定量分析系は再現性も
優れ、実際の生体試料の分析に十分適用可能であった。This 5-hydroxycreatinine quantitative analysis system had excellent reproducibility and was fully applicable to analysis of actual biological samples.
末法の定量性を検討した結果、１．５ｎ■ｏｌまで原点
を通る直線が得られることとを確認できた。As a result of examining the quantitative properties of the final method, it was confirmed that a straight line passing through the origin could be obtained up to 1.5 nol.
（効果）
糖尿病性腎症及び慢性腎炎、ループス腎炎、腎硬化症等
の非糖尿病性腎疾患の患者の血中及び尿中のクレアチニ
ン、メチルグアニジン並びに５−ヒドロキシクレアチニ
ンの各便を測定した。その結果、これら３物賞の血清中
の値は各々正の相関関係が見られた。(Efficacy) The levels of creatinine, methylguanidine, and 5-hydroxycreatinine in the blood and urine of patients with nondiabetic kidney diseases such as diabetic nephropathy, chronic nephritis, lupus nephritis, and nephrosclerosis were measured. As a result, a positive correlation was observed between the serum levels of these three substances.
一例として糖尿病性腎症における血清クレアチニン値と
血清５−ヒドロキシクレアチニン値との相関関係を第２
図に示す、血清５−ヒドロキシクレアチニン値は血清タ
レアチニン値と強い相関を示すことより、本発明５−ヒ
ドロキシクレアチニン定量法は腎機能障害の診断に有用
であることが示された。As an example, the correlation between serum creatinine level and serum 5-hydroxycreatinine level in diabetic nephropathy is
As shown in the figure, the serum 5-hydroxycreatinine value shows a strong correlation with the serum taleatinine value, indicating that the 5-hydroxycreatinine quantitative method of the present invention is useful for diagnosing renal dysfunction.
メチルグアニジンは血清中のクレアチニン値が約２■／
ｄ１以上でなければ検出されないのに対して、５−ヒド
ロキシクレアチニンはクレアチニン値が２■／ｄ１より
低い場合でも検出されるため、症状が軽い初期の腎疾患
の早期発見、早期治療への道を可能とするものである。Methylguanidine has a serum creatinine value of approximately 2■/
While 5-hydroxycreatinine is not detected unless the creatinine value is lower than d1, it can be detected even when the creatinine value is lower than 2■/d1, providing a path to early detection and early treatment of early stage kidney disease with mild symptoms. It is possible.
腎機能が正常であれば５−ヒドロキシクレアチニンは尿
に速やかに排泄されるため血中には蓄積せず、健常人血
中では検出されない、しかし、腎機能の低下とともに５
−ヒドロキシクレアチニンの血中での蓄積が増加する。If renal function is normal, 5-hydroxycreatinine is quickly excreted in the urine, so it does not accumulate in the blood and is not detected in the blood of healthy people.However, as renal function declines, 5-hydroxycreatinine increases.
- Increased accumulation of hydroxycreatinine in the blood.
また、腎機能障害が重症になるにつれて尿毒素でありメ
チルグアニジンの前駆体である５−ヒドロキシクレアチ
ニンの総量は増加し、それに伴い体液中並びに尿中の５
−ヒドロキシクレアチニン量が増加する。従って、血液
等の体液中や尿中の５−ヒドロキシクレアチニン値の測
定は、腎機能障害を診断するうえで非常に重要である。Additionally, as renal dysfunction becomes more severe, the total amount of 5-hydroxycreatinine, which is a uremic toxin and a precursor of methylguanidine, increases, and as a result, the amount of 5-hydroxycreatinine in body fluids and urine increases.
-The amount of hydroxycreatinine increases. Therefore, measurement of 5-hydroxycreatinine levels in body fluids such as blood and urine is very important in diagnosing renal dysfunction.
以上の述べたように、５−ヒドロキシクレアチニンをメ
チルグアニジンに変換して測定する本発明定量法は、蛍
光反応試薬との反応性が極めて低い５−ヒドロキシクレ
アチニンの微量分析を可能としたものである。特に血中
の５−ヒドロキシクレアチニン値を測定することは腎機
能障害の早期診断に有用であり、本発明測定法は腎不全
、尿毒症、慢性腎炎、尿路閉塞等の各種腎臓障害の早期
診断可能な検査法として有用性が高い。As stated above, the quantitative method of the present invention, in which 5-hydroxycreatinine is converted to methylguanidine and measured, enables trace analysis of 5-hydroxycreatinine, which has extremely low reactivity with fluorescent reaction reagents. . In particular, measuring the 5-hydroxycreatinine level in blood is useful for early diagnosis of renal dysfunction, and the measurement method of the present invention can be used for early diagnosis of various renal disorders such as renal failure, uremia, chronic nephritis, and urinary tract obstruction. It is highly useful as a possible testing method.
（１）１１図は５−ヒドロキシクレアチニンの定量分析
システムの波路構成図である。
（２）第２図は糖尿病性腎症における血清クレアチニン
値と血清５−ヒドロキシクレアチニン値を測定し、その
相関関係を調べた結果である。
代理人 （６Ｂ９１） 弁理士 村山佐武部第１図
第２図
血清クレアチニン値（ｍｇ／ｄｌ）(1) Figure 11 is a wave path configuration diagram of a quantitative analysis system for 5-hydroxycreatinine. (2) Figure 2 shows the results of measuring serum creatinine and serum 5-hydroxycreatinine values in diabetic nephropathy and investigating the correlation between them. Agent (6B91) Patent Attorney Sababe Murayama Figure 1 Figure 2 Serum creatinine level (mg/dl)
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28965890A JP2948649B2 (en) | 1990-10-26 | 1990-10-26 | Biological substance measurement method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28965890A JP2948649B2 (en) | 1990-10-26 | 1990-10-26 | Biological substance measurement method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04161854A true JPH04161854A (en) | 1992-06-05 |
| JP2948649B2 JP2948649B2 (en) | 1999-09-13 |
Family
ID=17746080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28965890A Expired - Fee Related JP2948649B2 (en) | 1990-10-26 | 1990-10-26 | Biological substance measurement method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2948649B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6696301B2 (en) | 2000-10-03 | 2004-02-24 | Nippon Zoki Pharmaceutical Co., Ltd. | Method for determination of 5-hydroxycreatinine |
| JP2009517677A (en) * | 2005-11-30 | 2009-04-30 | モザイク・ダイアグノステイツクス・アンド・テラピユーテイツクス・アー・ゲー | Polypeptide markers for diagnosis and evaluation of renal pelvic and ureteral junctions |
-
1990
- 1990-10-26 JP JP28965890A patent/JP2948649B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6696301B2 (en) | 2000-10-03 | 2004-02-24 | Nippon Zoki Pharmaceutical Co., Ltd. | Method for determination of 5-hydroxycreatinine |
| JP2009517677A (en) * | 2005-11-30 | 2009-04-30 | モザイク・ダイアグノステイツクス・アンド・テラピユーテイツクス・アー・ゲー | Polypeptide markers for diagnosis and evaluation of renal pelvic and ureteral junctions |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2948649B2 (en) | 1999-09-13 |
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