CN102305852B - Coloring agent for in vitro diagnostic device - Google Patents

Coloring agent for in vitro diagnostic device Download PDF

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Publication number
CN102305852B
CN102305852B CN201110127782.1A CN201110127782A CN102305852B CN 102305852 B CN102305852 B CN 102305852B CN 201110127782 A CN201110127782 A CN 201110127782A CN 102305852 B CN102305852 B CN 102305852B
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CN
China
Prior art keywords
coloring agent
mbth
dyestuff
diagnostic device
vitro diagnostic
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Expired - Fee Related
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CN201110127782.1A
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Chinese (zh)
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CN102305852A (en
Inventor
章新
陈伊卫
余少炀
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HUZHOU MAIDINUOHUA MEDICAL TECHNOLOGY CO LTD
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HUZHOU MAIDINUOHUA MEDICAL TECHNOLOGY CO LTD
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Publication of CN102305852A publication Critical patent/CN102305852A/en
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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

A kind of in-vitro diagnosis medical equipment coloring agent used
Technical field
The present invention relates to a kind of in-vitro diagnosis medical equipment coloring agent used (3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone) synthetic method (EMBH), a kind of pigment particularly producing after chemistry redox reaction, can be in order to the biochemical in quantitative detection blood.
Background technology
Different types of redox organic dyestuff has been applied in the clinical diagnosis of hospital.But be not suitable for being used in small-sized or personal medical equipment at the conventional dyestuff great majority of hospital laboratory.Only have the dyestuff of minority special formulation successfully to use in individual medical equipment.
Generally, the electron accepter mixing formula of the precursor of dyestuff or dyestuff and plysiochemical material pairing to be measured, for example to use glucose oxidase be electron accepter to blood glucose measurement.Blood sugar and glucose oxidase and oxygen, after electron exchange, produce hydrogen peroxide.The precursor of the further oxidation dye of hydrogen peroxide and horseradish peroxidase or dyestuff.Consequent dye strength is directly proportional to 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 of these two kinds of dyestuffs of capable of regulating regulates the reinforcement chromatogenous weight of institute and stability, the most frequently used a kind of dyestuff is 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate (3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate at present, MBTH). this application is in extensive range, can be oxidized the dyestuff that produces different colours with various aromatic amines and alcohol coupling.
The people such as Phillips.At United States Patent (USP) the 4734360th, use MBTH to mix to measure with DMAB dimethylaminobenzaldehyde (p-dimethylaminobenzaldehyde) content that blood is dredged glucose in liquid in 5059394 and 5304468.Because MBTH easily distils, 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, the content of measuring Blood Cholesterol should carry out in pH8 left and right, in this pH value, does not have dyestuff to share chromogenesis with MBTH.
The people such as Yu, at U.S. Patent number 5453360, have delivered the synthetic method of a new MBTH derivant, and this MBTH derivant is 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, little molecule organic solvent, as acetone, can remain in crystal, causes disturbing the coupling reaction of dyestuff.
Nikolyukin etc.No. 5710012nd, United States Patent (USP).To deliver the 6th of a phenyl ring at MBTH dyestuff and added a carboxylic group. 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.
The people such as Douglas, the sulfonic group derivant of delivering a MBTH No. 5776719 at United States Patent (USP), this derivant has good thermal stability and solubleness, but because sulfonic group has powerful electrophilic feature, the pigment of generation is shifted to red-light spectrum.Thereby by the protoheme interference measurement results in blood. in addition, this derivant has too high water-soluble, has influence on the unstable of measurement result.
The invention provides a kind of fuel system, in any pH value, have good water-solublely, there is good thermal stability, easily produce bluely to glaucous pigment with various aromatic amines and alcohol, 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 conventional cementing agent, sequestrant, buffering agent is mixed into a kind of detection of drugs dyestuff of blood cause of disease, there is solubleness widely, high-temperature stability, and not disturbed by protoheme.
Two synthetic methods:
1) 2-amino-3-ethanol-6-methylbenzothiazole.
At 100 milliliters of round-bottomed flasks, add 10 grams of 2-amino-6-methylbenzothiazoles, 20 milliliters of methyl cellosolves, and 5 milliliters of ethylene iodohydrins.Slowly be heated to 85 degree, stir 6 hours simultaneously, allow its cool to room temperature, filter and approximately 5 grams of products that air-dry rear acquisition is desirable.
2) 3 ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH).
By 10 grams of 2-amino-3-ethanol-6-methylbenzothiazoles, the distilled water of 20 milliliters, the potpourri of 1 milliliter of hydrazine is heated to 60 degree 1 hour, after the rear pale yellow solution producing of filtration is cooling, obtains the yellow powder of 5 grams.
The synthetic method of 3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH) is shown in accompanying drawing 1.
Accompanying drawing 2 is absorption spectrum comparisons that EMBH and MBTH produce, and the absorption peak of protoheme is in 550nm left and right, and with the absorption juxtaposition of MBTH generation, but the absorption spectrum producing with EMBH is separated far away.
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
Accompanying drawing explanation
The synthetic method of accompanying drawing 1:3-ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone (EMBH)
The absorption spectrum comparison that accompanying drawing 2:EMBH and MBTH and DMAB (dimethylaminobenzaldehyde) oxidation coupling produces.
Embodiment
Nylon membrane nearly 1.2 micro-not average pore sizes is evenly coated biology enzyme, is placed on 50 degrees Celsius of oven for drying 10 minutes, then coats dyestuff, according to above-mentioned same program, dries.Be cut into 0.5 square inch, be clipped in the mylar that two 0.005 inchs have 0.25 square inch of opening, a glucose solution is dropped on nylon membrane, then by catoptrics view, measure.The absorption peak of EMBH is at 607nm, and the absorption peak of MBTH is at 596nm.

Claims (2)

1. chemical reagent is used for measuring the purposes of physiological analytes of the biological fluids of human body or animal, described biological fluids comprises blood, serum and urine, described physiological analytes comprises blood sugar, cholesterol and triglyceride, and this chemical reagent comprises 3 ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone.
2. chemical reagent is used for measuring the purposes of physiological analytes of the biological fluids of human body or animal, described biological fluids comprises blood, serum and urine, described physiological analytes comprises blood sugar, cholesterol and triglyceride, this chemical reagent comprises 3 ethanol-6-methylbenzothiazole quinoline-(2)-hydrazone, the formula combination of oxidase and/or peroxidase.
CN201110127782.1A 2011-05-17 2011-05-17 Coloring agent for in vitro diagnostic device Expired - Fee Related CN102305852B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201110127782.1A CN102305852B (en) 2011-05-17 2011-05-17 Coloring agent for in vitro diagnostic device

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Application Number Priority Date Filing Date Title
CN201110127782.1A CN102305852B (en) 2011-05-17 2011-05-17 Coloring agent for in vitro diagnostic device

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CN102305852A CN102305852A (en) 2012-01-04
CN102305852B true CN102305852B (en) 2014-12-10

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Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0763396B2 (en) * 1991-10-30 1995-07-12 丸善石油化学株式会社 Reagent for detection of labeled peroxidase for immunoblot analysis
JP3342077B2 (en) * 1992-02-03 2002-11-05 ライフスキヤン・インコーポレーテツド Improved oxidative coupling dyes for spectrophotometric determination 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

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