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Lamotrigine derivative, preparation method thereof and application of lamotrigine derivative in homogeneous enzyme immunoassay reagent

A technology of lamotrigine enzyme and lamotrigine, which is applied in the direction of measuring devices, instruments, scientific instruments, etc., can solve the problems that are not suitable for the inspection of large batches of samples, the test results cannot be provided quickly, and the pretreatment of samples is cumbersome, etc. To achieve the effect of facilitating clinical promotion and use, rapid determination, and improvement of detection accuracy

Active Publication Date: 2020-04-07
长沙博源医疗科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, the commonly used methods for detecting lamotrigine mainly include: gas chromatography, gas chromatography-mass spectrometry, liquid chromatography, high-performance liquid chromatography, etc. Although these instrumental analysis methods have high sensitivity, the detection results are high in precision and accuracy. Good, but there are defects such as cumbersome sample pretreatment, long measurement time, special equipment, complex operation process, long detection time for a single sample, and inability to quickly provide test results. It is not suitable for large batches in clinical practice. Sample inspection

Method used

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  • Lamotrigine derivative, preparation method thereof and application of lamotrigine derivative in homogeneous enzyme immunoassay reagent
  • Lamotrigine derivative, preparation method thereof and application of lamotrigine derivative in homogeneous enzyme immunoassay reagent
  • Lamotrigine derivative, preparation method thereof and application of lamotrigine derivative in homogeneous enzyme immunoassay reagent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1. Synthesis of Lamotrigine Derivatives

[0052] The chemical structure of lamotrigine derivative is shown in formula (I):

[0053]

[0054] The preparation method of above-mentioned lamotrigine derivative, its synthetic route is as follows:

[0055]

[0056] Concrete preparation steps are as follows:

[0057] a. Synthesis of lamotrigine-acid derivatives

[0058]

[0059] Weigh 5g of compound 1 and 3.35g of compound 2 and dissolve them in 50mL of THF to make a reaction solution, then heat the reaction solution to reflux for 72 hours, remove the solvent after the reaction, and then purify the residue through a silica gel column to obtain 3.1g Lamotrigine-acid derivative as white solid.

[0060] b. Synthesis of lamotrigine derivatives

[0061]

[0062] Weigh 2g of lamotrigine-acid derivative and dissolve it in 40mL of DCM, then add 1.25g of compound 3, 1g of TEA and 3.1g of HATu to prepare a reaction mixture, then stir the reaction mixture at room ...

Embodiment 2

[0064] Example 2. Synthesis of Lamotrigine Immunogen

[0065] The lamotrigine immunogen in this example is formed by linking the lamotrigine derivative shown in formula (I) with human fibrinogen, and its structural formula is shown in the following formula (II):

[0066]

[0067] The concrete steps of the synthetic method of this lamotrigine immunogen are as follows:

[0068] a. Weigh 3.2g of potassium dihydrogen phosphate, 4.5g of disodium hydrogen phosphate, 11.8g of sodium chloride, and 1.8g of magnesium chloride, dissolve them in 1.8L of deionized water, adjust the pH to 8.0, and make buffer solution A;

[0069] b. Weigh 5.0 mg of human fibrinogen and dissolve it in 5.0 ml of the above-mentioned buffer solution A at 3°C ​​to make a carrier solution;

[0070] c. Weigh 5.0 mg of the lamotrigine derivative represented by the above formula (I), and dissolve it in 500 μl of the above buffer solution A at 3° C. to prepare a lamotrigine derivative solution;

[0071] d. When ...

Embodiment 3

[0073] Example 3. Preparation of anti-lamotrigine specific antibody

[0074] The lamotrigine immunogen prepared in Example 2 was used to inoculate experimental animal rabbits with Freund's adjuvant immunization method, and the antiserum was taken after booster immunization. The specific steps were as follows:

[0075] a. the lamotrigine immunogen shown in above-mentioned formula (II) is diluted to 4.0mg / ml with PBS damping fluid, obtains antigen solution, then 4.0ml described antigen solution is mixed with equivalent amount of Freund's complete adjuvant, Inject the experimental animal rabbit;

[0076] b. After 3 weeks, mix 4.0ml of the same antigen solution with the same amount of Freund's incomplete adjuvant, inject once into the above-mentioned experimental animal rabbit, and then inject once every 3 weeks, a total of 5 injections;

[0077] c. Taking blood from the immunized experimental animal rabbit, separating and purifying the antiserum, and obtaining the specific antib...

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Abstract

The invention belongs to the technical field of biological detection, and particularly relates to a lamotrigine derivative, a preparation method thereof and application of the lamotrigine derivative in homogeneous enzyme immunoassay reagents. The structural formula of the lamotrigine derivative is shown as the following formula (I). The lamotrigine immunogen with high immunogenicity, a corresponding antibody, a lamotrigine enzyme-labeled conjugate and a lamotrigine homogeneous enzyme immunoassay reagent are obtained by using the compound shown as the formula (I). The lamotrigine immunogen is strong in specificity and high in immunogenicity; the prepared anti-lamotrigine antibody is strong in specificity and high in titer; the prepared homogeneous enzyme immunoassay reagent can rapidly andaccurately determine the content of lamotrigine in a biological sample, can simultaneously determine a plurality of samples on a full-automatic biochemical analyzer, realizes high-flux and rapid determination of lamotrigine, has high accuracy and strong specificity, and has greatly improved precision and detection efficiency compared with the prior art.

Description

technical field [0001] The invention belongs to the technical field of biological detection, in particular to a lamotrigine derivative, its preparation method and its application in homogeneous enzyme immunoassay reagents. Background technique [0002] The chemical structural formula of lamotrigine (Lamotrigine) is shown in the following formula (IV): [0003] [0004] Lamotrigine is a voltage-sensitive sodium ion channel blocker that is mainly used for antiepileptic therapy and can also be used for the treatment of seizures associated with Lennox-Gastaut syndrome. Pharmacokinetic studies show that: lamotrigine is rapidly and completely absorbed in the intestinal tract, and reaches the peak plasma concentration in 2.5 hours after oral administration. When the single highest dose reaches 450 mg, the pharmacokinetic curve remains It is linear, and the highest steady-state plasma concentration varies greatly among individuals, but the difference in concentration in the same...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/535
CPCG01N33/535Y02A50/30
Inventor 林观样胡卢丰周子晔虞留明
Owner 长沙博源医疗科技有限公司
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