CN102305852A - Coloring agent for in vitro diagnostic device - Google Patents
Coloring agent for in vitro diagnostic device Download PDFInfo
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- CN102305852A CN102305852A CN201110127782A CN201110127782A CN102305852A CN 102305852 A CN102305852 A CN 102305852A CN 201110127782 A CN201110127782 A CN 201110127782A CN 201110127782 A CN201110127782 A CN 201110127782A CN 102305852 A CN102305852 A CN 102305852A
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Abstract
The invention relates to a coloring agent for an in vitro diagnostic device, in particular to a pigment generated through chemical oxidoreduction reaction, which can be used for quantitatively detecting biochemical substances in blood. A precursor of the coloring agent is easily combined with aromatic amines or aromatic alcohols, and the stable pigment is generated in hydrogen peroxide and oxygen environments, and cannot be interfered by protoheme in specific wavelength ranges.
Description
Technical field
The present invention relates to the used coloring agent of a kind of in-vitro diagnosis medical equipment (3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone) synthesis method (EMBH); A kind of pigment that particularly a kind of chemistry redox reaction back produces can be in order to the biochemical in the detection by quantitative blood.
Background technology
Different types of redox organic dyestuff has been applied in the clinical diagnosis of hospital.But the dyestuff great majority commonly used at hospital laboratory are not suitable for being used in small-sized or personal medical equipment.Have only the dyestuff of minority special formulation successfully to use in individual medical equipment.
Generally, the electron accepter mixing formula that the precursor of dyestuff or dyestuff and plysiochemical material to be measured match, for example blood glucose measurement uses glucose oxidase to be electron accepter.Blood sugar and glucose oxidase and oxygen produce hydrogen peroxide through after the electron exchange.The precursor of further oxidation dye of hydrogen peroxide and horseradish peroxidase or dyestuff.Consequent dye strength is directly proportional with plysiochemical material to be measured.
The most frequently used method of individual's diagnostic medical equipment is to use two kinds of dyestuffs.The advantage of this method is that the composition ratio fork-like farm tool used in ancient China that can adjust these two kinds of dyestuffs is regulated reinforcement chromatogenous weight of institute and stability; The most frequently used a kind of dyestuff is 3-methyl-2-[4-morpholinodithio quinoline ketone hydrazone hydrochloride hydrate (3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate at present; MBTH). this dyestuff has wide range of applications, and can produce dyes in different colors with various aromatic amines and alcohol coupling oxidation.
People such as Phillips.In United States Patent (USP) the 4734360th, 5059394 and 5304468, use MBTH to mix with DMAB dimethylaminobenzaldehyde (p-dimethylaminobenzaldehyde) and dredge the content of glucose in the liquid in order to measure blood.Because MBTH distils easily, at high temperature MBTH distils and reduces content, has changed initial dyestuff ratio.In neutrality or alkaline pH value, MBTH can be precipitated out in aqueous solution, so be not suitable for being applied in the solution of high pH value.For example, measure in the blood content of cholesterol and should about pH8, carry out, in this pH value, do not have dyestuff can with the shared chromogenesis of MBTH.
People such as Yu at U.S. Patent number 5453360, have delivered the synthesis method of a new MBTH derivant, and this MBTH derivant is more higher and comparatively stable in high temperature in the solubleness of acid and alkaline aqueous solution than MBTH.But this MBTH derivant to light sensitive, is easy to oxidized and degrades when solid-state powdery.In addition, the micromolecule organic solvent like acetone, can remain in the crystal, causes disturbing the coupling reaction of dyestuff.
Nikolyukin etc.No. the 5710012nd, United States Patent (USP).To have delivered the 6th of a phenyl ring and added a carboxylic group at the MBTH dyestuff. this derivant has good thermal stability.But its solubleness is very low 4 to 5 of pH values, is not suitable for blood glucose measurement.
People such as Douglas, at the sulfonic group derivant that United States Patent (USP) is delivered a MBTH No. 5776719, this derivant has good thermal stability and solubleness, but because sulfonic group has powerful electrophilic characteristics, the pigment of generation is shifted to red-light spectrum.Thereby by the protoheme interference measurement results in the blood. in addition, this derivant has too high water-soluble, has influence on the instability of measurement result.
The present invention provides a kind of fuel system, in any pH value good water-solubility is arranged all, has good thermal stability, and is blue to glaucous pigment with various aromatic amines and alcohol production easily, not disturbed by protoheme.
Summary of the invention
One know-why:
The main difficulty that extracorporeal blood detects is that protoheme disturbs; The stability of medicament and solubleness; Fuel system of the present invention adopts 3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH) and an oxidase and peroxidase; These three kinds of main agents are through special formulation, with cementing agent commonly used, sequestrant; Buffer becomes a kind of detection of drugs dyestuff of blood cause of disease; Have solubleness widely, high-temperature stability and not disturbed by protoheme.
Two synthesis methods:
1) 2-amino-3-ethanol-6-methylbenzothiazole.
Add 10 gram 2-amino-6-methylbenzothiazoles, 20 milliliters of methyl cellosolves and 5 milliliters of ethylene iodohydrins at 100 milliliters of round-bottomed flask.Slowly be heated to 85 degree, stirred simultaneously 6 hours, allow its cool to room temperature, filtration and air-dry back obtain about 5 grams of desirable product.
2) 3 ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH).
With 10 gram 2-amino-3-ethanol-6-methylbenzothiazoles, 20 milliliters distilled water, the mixture heated to 60 of 1 milliliter of hydrazine is spent 1 hour, obtains the yellow powder of 5 grams after the pale yellow solution cooling that is produced after filtering.
The synthesis method of 3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH) is seen accompanying drawing 1.
Accompanying drawing 2 is that the absorption spectrum that EMBH and MBTH produce compares, and the absorption peak of protoheme with the absorption juxtaposition of MBTH generation, but separates far away with the absorption spectrum of EMBH generation about 550nm.
Three, technical indicator:
The spectral absorption peak of EMBH between 600-620nm,
The mass spectrophotometry molecular weight of EMBH is between 206-208
The ultimate analysis of EMBH is C10H13N3S
Description of drawings
The synthesis method of accompanying drawing 1:3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH)
The absorption spectrum that accompanying drawing 2:EMBH and MBTH and DMAB (dimethylaminobenzaldehyde) oxidation coupling produces is relatively.
Embodiment
Nylon membrane one nearly 1.2 little not average pore size is evenly coated biology enzyme, is placed on 50 degrees centigrade of oven for drying 10 minutes, coats dyestuff then, according to above-mentioned same program oven dry.Be cut into 0.5 square inch, be clipped in the two 0.005 inch thick mylar with 0.25 square inch of opening, a glucose solution is dropped on the nylon membrane, measure with the catoptrics view then.The absorption peak of EMBH is at 607nm, and the absorption peak of MBTH is at 596nm.
Claims (5)
1. a chemical reagent is used for measuring the biological fluids of human body or animal, includes but not limited to blood, serum and urine, and the physiological analytes that is contained includes but not limited to blood sugar, cholesterol and triglyceride.This chemical reagent comprises the synthesis method and the application of 2-amino-3-ethanol-6-methylbenzothiazole (2-amino-3-ethanol-6-methylbenzothiazole)
2. a chemical reagent is used for measuring the biological fluids of human body or animal, includes but not limited to blood, serum and urine, and the physiological analytes that is contained includes but not limited to blood sugar, cholesterol and triglyceride.This chemical reagent comprises synthesis method and the application of 3 ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (3-ethanol-6-methyl benzothiazolinone-(2)-hydrazone (EMBH)).
3. a chemical reagent is used for measuring the biological fluids of human body or animal, includes but not limited to blood, serum and urine, and the physiological analytes that is contained includes but not limited to blood sugar, cholesterol and triglyceride.This chemical reagent comprises 3 ethanol-6-methylbenzothiazole-2-hydrazone, the formula combination of oxidase and/or peroxidase.
4. a chemical reagent is used for measuring the biological fluids of human body or animal, includes but not limited to blood, serum and urine, and the physiological analytes that is contained includes but not limited to blood sugar, cholesterol and triglyceride.This chemical reagent comprises 8 aniline-1-naphthalene.
5. a chemical reagent is used for measuring the biological fluids of human body or animal, includes but not limited to blood, serum and urine, and the physiological analytes that is contained includes but not limited to blood sugar, cholesterol and triglyceride.This chemical reagent comprises trimethylbenzene boric acid.
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CN201110127782.1A CN102305852B (en) | 2011-05-17 | 2011-05-17 | Coloring agent for in vitro diagnostic device |
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CN201110127782.1A CN102305852B (en) | 2011-05-17 | 2011-05-17 | Coloring agent for in vitro diagnostic device |
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CN102305852A true CN102305852A (en) | 2012-01-04 |
CN102305852B CN102305852B (en) | 2014-12-10 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108181470A (en) * | 2017-09-09 | 2018-06-19 | 广东医科大学 | It is a kind of to detect endotoxin and the kit and detection method of (1-3)-callose content in jaundice blood sample |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05123190A (en) * | 1991-10-30 | 1993-05-21 | Maruzen Petrochem Co Ltd | Reagent for detecting labeled peroxidase for immunoblotting analysis |
US5453360A (en) * | 1992-02-03 | 1995-09-26 | Lifescan, Inc. | Oxidative coupling dye for spectrophotometric quantitive analysis of analytes |
US5710012A (en) * | 1993-08-25 | 1998-01-20 | Actimed Laboratories, Inc. | Salt of 6-carboxy-3-methylbenzothiazolone hydrazone hydrate in colorimetric determination of hydrogen peroxide |
US5776719A (en) * | 1997-07-07 | 1998-07-07 | Mercury Diagnostics, Inc. | Diagnostic compositions and devices utilizing same |
-
2011
- 2011-05-17 CN CN201110127782.1A patent/CN102305852B/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05123190A (en) * | 1991-10-30 | 1993-05-21 | Maruzen Petrochem Co Ltd | Reagent for detecting labeled peroxidase for immunoblotting analysis |
US5453360A (en) * | 1992-02-03 | 1995-09-26 | Lifescan, Inc. | Oxidative coupling dye for spectrophotometric quantitive analysis of analytes |
US5710012A (en) * | 1993-08-25 | 1998-01-20 | Actimed Laboratories, Inc. | Salt of 6-carboxy-3-methylbenzothiazolone hydrazone hydrate in colorimetric determination of hydrogen peroxide |
US5776719A (en) * | 1997-07-07 | 1998-07-07 | Mercury Diagnostics, Inc. | Diagnostic compositions and devices utilizing same |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108181470A (en) * | 2017-09-09 | 2018-06-19 | 广东医科大学 | It is a kind of to detect endotoxin and the kit and detection method of (1-3)-callose content in jaundice blood sample |
CN108181470B (en) * | 2017-09-09 | 2020-05-26 | 广东医科大学 | Kit and method for detecting contents of endotoxin and (1-3) - β -D-glucan in jaundice blood sample |
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