CN107703288A - Improve the bile acid detection reagent of reaction stability - Google Patents
Improve the bile acid detection reagent of reaction stability Download PDFInfo
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- CN107703288A CN107703288A CN201710502736.2A CN201710502736A CN107703288A CN 107703288 A CN107703288 A CN 107703288A CN 201710502736 A CN201710502736 A CN 201710502736A CN 107703288 A CN107703288 A CN 107703288A
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- Prior art keywords
- reagent
- bile acid
- detection reagent
- acid detection
- reaction stability
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/08—Hepato-biliairy disorders other than hepatitis
- G01N2800/085—Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
Abstract
The invention discloses a kind of bile acid detection reagent for improving reaction stability, by using circulation coenzyme Thio NAD, the circulation α HSD of enzyme 3, the cycle-index and circular response speed for the bile acid detection reagent for improving reaction stability can be improved, and the degree of accuracy of detection reagent is high, stability is good, high sensitivity, the range of linearity is wider, the dosage of key reaction material can be reduced simultaneously, reduce the cost of reagent.In addition, reaction rate can be stablized by optimizing Thio NAD and 3 α HSD ratio, reagent background reaction is reduced, strengthens detection sensitivity, testing result is accurately and reliably.The detection reagent of the present invention detects automation, speed is fast without sample preprocessing on automatic clinical chemistry analyzer.
Description
Technical field
The present invention relates to bile acid detection reagent field, more particularly to a kind of bile acid detection for improving reaction stability
Reagent.
Background technology
Human serum total bile acid (TBA) is to synthesize simultaneously catabolism by liver, so as to maintain the relative of human bile's acid
Stable, its regulation and control are a major functions of liver.Total bile acid be in liver by cholesterol biosynthesis, with glycine or
Taurine is combined into conjugated bile acidses, then enters bile by hepatocytes secrete, thin in enteron aisle after bile to enteron aisle
Sequestered bile acid is hydrolyzed under bacterium effect, more than 95% bile acid absorbs trans-portal vein blood by intestinal wall and returns to liver profit
With referred to as bile acid intestines-liver circulation.Therefore bile acid concentration is very low in normal person's blood.The generation and metabolism of bile acid and liver
There is very close relationship, once when lesion occurs for liver cell, serum bile acid is easy to raise, thus Serum And Bile sour water
Flat is an important indicator for reflecting liver parenchyma damage.
The TBA rises of all kinds of diseases in the liver and gallbladder：Oxyhepatitis and liver cancer are 100%, hepatic sclerosis 87.5%, Chronic Liver
Scorching, disease of biliary tract is also up to more than 65%.Illustrate that TBA measure is all quicker than traditional liver function index any one in disease in the liver and gallbladder
Sense.
The TBA of oxyhepatitis and chronic hepatitis is variant：Patients serum TBA and alanine glutamic-pyruvic transaminase during oxyhepatitis
(ALT) equally, in significantly increasing, it is normal 31 times averagely to increase amplitude, illustrates that TBA early diagnoses to oxyhepatitis and is worth
It is identical with ALT (positive rate 100%) measure, switch to quickly normally with the control of hepatocellular damage after active treatment, and TBA
Then gradually switch to normally with the recovery of liver function.During chronic hepatitis, TBA positive rates are 65.7%, and average elevation amplitude is normal
10 times.
When liver cancer, hepatic sclerosis, because liver declines to TBA metabolic functions, therefore serum T BA increases in different phase.When
During liver cancer, TBA positive rates are 100%, and hepatic sclerosis TBA positive rates are 88%, are also higher than other indexs.
The method of detection bile acid is mainly Enzymatic cycling at present.But the sample of this method various concentrations, cycle-index control
Make inconsistent, cause testing result poor repeatability, influence the degree of accuracy of measure.
The content of the invention
In view of this, it is an object of the invention to provide a kind of bile acid test agent, accuracy in detection are high.
To achieve these goals, the present invention provides following technical scheme：
A kind of bile acid detection reagent for improving reaction stability, including reagent R1 and reagent R2；
Reagent R1 component is described in every liter of bile acid detection reagent：
Reagent R2 component is described in every liter of bile acid detection reagent：
Preferably, in the reagent R1, the buffer solution is Hepes, Tris-HCL, triethanolamine or MOPS；It is described slow
The pH value of fliud flushing is 3.0~5.5.
Preferably, in the reagent R1, the enzyme stabilizers are bovine serum albumin(BSA), glycerine, mannitol, sorbierite
Or ethylene glycol.
Preferably, in the reagent R1, the surfactant be Triton450, Triton100, Tween20 or
Tween80。
Preferably, in the reagent R1, the preservative is Sodium azide or PC300.
Preferably, in the reagent R2, the buffer solution is Hepes, Tris-HCL, triethanolamine or MOPS；It is described slow
The pH value of fliud flushing is 8.0~9.5.
Preferably, in the reagent R2, the enzyme stabilizers are bovine serum albumin(BSA), glycerine, mannitol, sorbierite
Or ethylene glycol.
Preferably, in the reagent R2, the surfactant be Triton450, Triton100, Tween20,
Tween80 or PEG2000.
Preferably, in the reagent R2, the preservative is Sodium azide or PC300.
A kind of bile acid detection reagent for improving reaction stability provided by the invention, by using circulation coenzyme
α-the HSD of enzyme 3 are used in Thio-NAD, circulation, it is possible to increase are improved the cycle-index of the bile acid detection reagent of reaction stability and followed
Ring reaction speed, and the degree of accuracy of detection reagent is high, stability is good, high sensitivity, the range of linearity is wider, while can reduce
The dosage of key reaction material, reduce the cost of reagent.In addition, can be with by the ratio for optimizing Thio-NAD and 3 α-HSD
Stable reaction rate, the reaction of reagent background is reduced, strengthens detection sensitivity, testing result is accurately and reliably.The detection examination of the present invention
Agent detects automation, speed is fast without sample preprocessing on automatic clinical chemistry analyzer.
Brief description of the drawings
Fig. 1 is the phase of the bile acid detection reagent for the raising reaction stability that Hitachi 7100 and AU400 detects embodiment 5
Guan Tu；
Fig. 2 is the phase of the bile acid detection reagent for the raising reaction stability that Hitachi 7100 detects embodiment 5 with Toshiba 40
Guan Tu；
Fig. 3 is the related of the bile acid detection reagent for the raising reaction stability that AU400 detects embodiment 5 to Toshiba 40
Figure；
Fig. 4 is the schematic diagram for the bile acid detection reagent detection bile acid for improving reaction stability.
Embodiment
In order to further appreciate that the present invention, the preferred embodiments of the invention are described with reference to embodiment, but
It is it should be appreciated that these descriptions are simply for further explanation the features and advantages of the present invention rather than to patent requirements of the present invention
Limitation.
The invention provides a kind of bile acid detection reagent for improving reaction stability, including reagent R1 and reagent R2；
Reagent R1 component is described in every liter of bile acid detection reagent：
Reagent R2 component is described in every liter of bile acid detection reagent：
In above-mentioned technical proposal, by using circulation coenzyme Thio-NAD, the circulation α-HSD of enzyme 3, it is possible to increase carry
The cycle-index and circular response speed of the bile acid detection reagent of high reaction stability, and the degree of accuracy of detection reagent is high, steady
Qualitative good, high sensitivity, the range of linearity is wider, while can reduce the dosage of key reaction material, reduce reagent into
This.In addition, reaction rate can be stablized by optimizing Thio-NAD and 3 α-HSD ratio, reagent background reaction, enhancing are reduced
Detection sensitivity, testing result is accurately and reliably.The detection reagent of the present invention is analyzed without sample preprocessing in full-automatic biochemical
Automation is detected on instrument, speed is fast.
Illustrate the detection raw material of the bile acid detection reagent of the raising reaction stability of the present invention with reference to Fig. 4：
Bile acid is by 3 α-hydroxysteroid dehydrogenase (3 α-HSD) and oxidized form β-Thionicotinamide urea purine dinucleotides
(Thio-NAD) specific oxidation, 3- ketosteroids and reduced form β-Thionicotinamide urea purine dinucleotides are generated
(Thio-NADH).The 3- ketosteroids of generation are in 3 α-hydroxysteroid dehydrogenase and reduced form β-niacinamide urea purine dinucleotides
(NADH) in the presence of, bile acid and oxidized form β-niacinamide urea purine dinucleotides (Thio-NAD) are regenerated.
Illustrate the present invention, examination is detected to the bile acid of raising reaction stability provided by the invention with reference to embodiment
Agent is described in detail, but they can not be interpreted as into limiting the scope of the present invention.
Embodiment 1~5
The present embodiment 1~5 is related to a kind of bile acid detection kit of total raising reaction stability of stabilization, kit
Including reagent R1 and reagent R2, reagent R1, R2 each component and content are shown in Table 1：
Reagent R1, R2 each component and content in the embodiment 1~5 of table 1
By taking the bile acid detection reagent of the raising reaction stability of embodiment 5 as an example, test accuracy, sensitivity, stably
Property and uniformity.
First, the test of the degree of accuracy
Two varying level quality-control products are detected with the bile detection reagent of embodiment 5, testing result is shown in Table 2.
The testing result of table 2
As known from Table 2, average is compared with target value, and deviation is respectively less than 5%, therefore the raising reaction stability of embodiment 5
The degree of accuracy of bile acid detection reagent is high.
2nd, the test of sensitivity
According to U.S. clinical and laboratory standards institute EP17-A files, enter line blank detection limit LOB, detection limit LOD,
Quantitative detection limit LOQ detection.
According to EP17-A, repeat to detect water blank 60 throughout 10 low concentration samples 60 times, obtain the raising of embodiment 5
The blank test limit LOB of the bile acid detection reagent of reaction stability is 0.06 μm of ol, and detection limit LOD is 0.11 μm of ol, quantitative
Detection limit LOQ is 0.50 μm of ol.It follows that the bile acid detection reagent high sensitivity of the raising reaction stability of embodiment 5
3rd, the test of stability
The absorbance of the bile acid detection reagent for the raising reaction stability that detection embodiment 5 obtains before refrigeration, then will be real
The bile acid detection reagent for applying the raising reaction stability of example 5 is placed in 4 DEG C of refrigerating chamber and refrigerated 18 months, detection refrigeration
The absorbance of the bile acid detection reagent of reaction stability is improved afterwards, the results are shown in Table 3.
The testing result of table 3
As shown in Table 3, the absorbance drop-out value of the front and rear bile acid detection reagent for improving reaction stability of refrigeration exists
Less than 5.24%, therefore the bile acid detection reagent stability of the raising reaction stability of the present invention is high.
The bile acid detection reagent of the raising reaction stability of embodiment 5 is put in atmosphere, daily detection, continuous inspection
Survey 1 month, deviation is not more than 5%.
4th, the test of uniformity
Choose the representational 3 producer's automatic clinical chemistry analyzers of in the market：Hitachi 7100, AU400, Toshiba 40, makes
With bile acid detection reagent, calibration and the Quality Control of the raising reaction stability of embodiment 5,40 parts of clinical serum samples are detected, are entered
Capable correlation ratio two-by-two is compared with the system of Hitachi 7100 is 09954 with AU400 systematic comparisons correlation coefficient r, sees Fig. 1.System of Hitachi 7100
System is 0.9970 with the systematic comparison correlation coefficient r of Toshiba 40, sees Fig. 2.AU400 systems and the systematic comparison correlation coefficient r of Toshiba 40
For 0.9990, Fig. 3 is seen.Good correlation is respectively provided between three systems.It follows that the raising reaction stability of embodiment 5
Bile acid detection reagent it is good in different instrument system result uniformity, it is applied widely.
Detailed Jie has been carried out to a kind of bile acid detection reagent for improving reaction stability provided by the invention above
Continue, specific case used herein is set forth to the principle and embodiment of the present invention, and the explanation of above example is only
It is the method and its core concept for being used to help understand the present invention, it is noted that for those skilled in the art
For, under the premise without departing from the principles of the invention, some improvement and modification can also be carried out to the present invention, these improve and
Modification is also fallen into the protection domain of the claims in the present invention.
Claims (9)
1. a kind of bile acid detection reagent for improving reaction stability, it is characterised in that including reagent R1 and reagent R2；
Reagent R1 component is described in every liter of bile acid detection reagent：
Reagent R2 component is described in every liter of bile acid detection reagent：
2. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R1
In, the buffer solution is Hepes, Tris-HCL, triethanolamine or MOPS；The pH value of the buffer solution is 3.0~5.5.
3. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R1
In, the enzyme stabilizers are bovine serum albumin(BSA), glycerine, mannitol, sorbierite or ethylene glycol.
4. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R1
In, the surfactant is Triton450, Triton100, Tween20 or Tween80.
5. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R1
In, the preservative is Sodium azide or PC300.
6. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R2
In, the buffer solution is Hepes, Tris-HCL, triethanolamine or MOPS；The pH value of the buffer solution is 8.0~9.5.
7. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R2
In, the enzyme stabilizers are bovine serum albumin(BSA), glycerine, mannitol, sorbierite or ethylene glycol.
8. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R2
In, the surfactant is Triton450, Triton100, Tween20, Tween80 or PEG2000.
9. the bile acid detection reagent of reaction stability is improved as claimed in claim 1, it is characterised in that the reagent R2
In, the preservative is Sodium azide or PC300.
Priority Applications (1)
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|---|---|---|---|
| CN201710502736.2A CN107703288A (en) | 2017-06-27 | 2017-06-27 | Improve the bile acid detection reagent of reaction stability |
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| CN201710502736.2A CN107703288A (en) | 2017-06-27 | 2017-06-27 | Improve the bile acid detection reagent of reaction stability |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108220387A (en) * | 2018-03-28 | 2018-06-29 | 潍坊市康华生物技术有限公司 | A kind of total bile acid detection kit |
| CN110261337A (en) * | 2019-07-15 | 2019-09-20 | 三诺生物传感股份有限公司 | A kind of total bile acid detection reagent |
| CN112903671A (en) * | 2021-02-02 | 2021-06-04 | 广东云曌医疗科技有限公司 | Determination kit using cyclic enzyme method and determination method thereof |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776779A (en) * | 1994-09-13 | 1998-07-07 | Kyoto Daiichi Kagaku Co., Ltd. | Integral multi-layer element for analyzing bile acid sulfate |
| CN1378077A (en) * | 2002-05-10 | 2002-11-06 | 肖洪武 | Method for detecting total bile acid and detecting reagent |
| CN1632578A (en) * | 2004-12-24 | 2005-06-29 | 上海复星长征医学科学有限公司 | Bile acid determination reagent |
| CN101003831A (en) * | 2007-01-17 | 2007-07-25 | 王贤理 | Kit for diagnosing diseases in system of liver and gall |
| CN102539791A (en) * | 2012-01-09 | 2012-07-04 | 宁波天康生物科技有限公司 | Total bile acid quantitative determination method and determination reagent kit |
| CN104155438A (en) * | 2014-09-09 | 2014-11-19 | 湖北科技学院 | Determination reagent of total bile acid |
| CN104198420A (en) * | 2014-08-14 | 2014-12-10 | 上海睿康生物科技有限公司 | Stable detection kit of total bile acid |
| CN104359906A (en) * | 2014-11-28 | 2015-02-18 | 山东博科生物产业有限公司 | Serum total bile acid detection reagent with stable and strong anti-interference capability |
| CN105002264A (en) * | 2015-07-28 | 2015-10-28 | 中生北控生物科技股份有限公司 | Total bile acid measuring kit |
| CN105039495A (en) * | 2015-07-28 | 2015-11-11 | 中生北控生物科技股份有限公司 | 3-alpha-HSD reagent as well as preparation method and application thereof |
| CN105067541A (en) * | 2015-07-28 | 2015-11-18 | 中生北控生物科技股份有限公司 | Thionicotinamide adenine dinucleotide reagent and application thereof |
| CN106092923A (en) * | 2016-05-31 | 2016-11-09 | 安徽伊普诺康生物技术股份有限公司 | A kind of test kit measuring TOTAL BILE ACID TBA and preparation method thereof |
-
2017
- 2017-06-27 CN CN201710502736.2A patent/CN107703288A/en active Pending
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776779A (en) * | 1994-09-13 | 1998-07-07 | Kyoto Daiichi Kagaku Co., Ltd. | Integral multi-layer element for analyzing bile acid sulfate |
| CN1378077A (en) * | 2002-05-10 | 2002-11-06 | 肖洪武 | Method for detecting total bile acid and detecting reagent |
| CN1632578A (en) * | 2004-12-24 | 2005-06-29 | 上海复星长征医学科学有限公司 | Bile acid determination reagent |
| CN101003831A (en) * | 2007-01-17 | 2007-07-25 | 王贤理 | Kit for diagnosing diseases in system of liver and gall |
| CN102539791A (en) * | 2012-01-09 | 2012-07-04 | 宁波天康生物科技有限公司 | Total bile acid quantitative determination method and determination reagent kit |
| CN104198420A (en) * | 2014-08-14 | 2014-12-10 | 上海睿康生物科技有限公司 | Stable detection kit of total bile acid |
| CN104155438A (en) * | 2014-09-09 | 2014-11-19 | 湖北科技学院 | Determination reagent of total bile acid |
| CN104359906A (en) * | 2014-11-28 | 2015-02-18 | 山东博科生物产业有限公司 | Serum total bile acid detection reagent with stable and strong anti-interference capability |
| CN105002264A (en) * | 2015-07-28 | 2015-10-28 | 中生北控生物科技股份有限公司 | Total bile acid measuring kit |
| CN105039495A (en) * | 2015-07-28 | 2015-11-11 | 中生北控生物科技股份有限公司 | 3-alpha-HSD reagent as well as preparation method and application thereof |
| CN105067541A (en) * | 2015-07-28 | 2015-11-18 | 中生北控生物科技股份有限公司 | Thionicotinamide adenine dinucleotide reagent and application thereof |
| CN106092923A (en) * | 2016-05-31 | 2016-11-09 | 安徽伊普诺康生物技术股份有限公司 | A kind of test kit measuring TOTAL BILE ACID TBA and preparation method thereof |
Non-Patent Citations (5)
| Title |
|---|
| FUMIKO MASHIGE等: "A simple and sensitive assay of total serum bile acids", 《CLINICA CHIMICA ACTA》 * |
| STEPHEN D. TURLEY等: "Re-evaluation of the 3 alpha-hydroxysteroid dehydrogenase assay for total bile acids in bile", 《JOURNAL OF LIPID RESEARCH》 * |
| XIAOQING ZHANG等: "A highly sensitive electrically driven electrochemiluminescent assay for quantification of bile acids in human serum", 《ANALYST》 * |
| 侯玥等: "3α羟类固醇脱氢酶在血清总胆汁酸测定中的应用", 《中国实验诊断学》 * |
| 李顺康等: "酶循环法检测血清总胆汁酸的方法学评价", 《检验医学与临床》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108220387A (en) * | 2018-03-28 | 2018-06-29 | 潍坊市康华生物技术有限公司 | A kind of total bile acid detection kit |
| CN108220387B (en) * | 2018-03-28 | 2022-06-21 | 山东康华生物医疗科技股份有限公司 | Total bile acid detection kit |
| CN110261337A (en) * | 2019-07-15 | 2019-09-20 | 三诺生物传感股份有限公司 | A kind of total bile acid detection reagent |
| CN112903671A (en) * | 2021-02-02 | 2021-06-04 | 广东云曌医疗科技有限公司 | Determination kit using cyclic enzyme method and determination method thereof |
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Application publication date: 20180216 |