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Aripiprazole key group derivative, immunogen, anti-aripiprazole specific antibody and preparation method and application thereof

A technology of aripiprazole and its derivatives, applied in the field of biomedical detection, can solve the problems of difficult popularization in grassroots medical institutions, complex structure, high maintenance cost, etc., and achieve the effects of facilitating clinical promotion and use, high sensitivity, and reducing detection costs

Pending Publication Date: 2022-07-01
长沙博源医疗科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

High-performance liquid phase tandem mass spectrometry (LC-MS / MS) has high detection sensitivity and speed, but its structure is complex and maintenance costs are high. It requires specially trained technicians to operate, and it is not easy to popularize in primary medical institutions.

Method used

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  • Aripiprazole key group derivative, immunogen, anti-aripiprazole specific antibody and preparation method and application thereof
  • Aripiprazole key group derivative, immunogen, anti-aripiprazole specific antibody and preparation method and application thereof
  • Aripiprazole key group derivative, immunogen, anti-aripiprazole specific antibody and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Example 1: Synthesis of Aripiprazole Key Group Derivatives

[0082] Aripiprazole key group derivatives were synthesized by the following synthetic routes:

[0083] ;

[0084] The specific synthesis steps are as follows:

[0085] (1) Synthesis of compound 2:

[0086]

[0087] Compound 1 (5 g, 22 mmol) was co-dissolved with methyl 5-bromovalerate (4.3 g, 22 mmol) in a solution containing K 2 CO 3 (3g, 22 mmol) in dimethylformamide (50 ml) to make a mixed solution, and the mixed solution was stirred at 80 ° C for 20 hours; the mixed solution after the reaction was diluted with ethyl acetate, and then with hydrogen carbonate Washed with sodium solution and concentrated brine, and dried over sodium sulfate. After evaporation of the solvent, 4 g of compound 2 was obtained as a white foam.

[0088] (2) Synthesis of aripiprazole key group derivatives:

[0089]

[0090] Compound 2 (4 g, 12 mmol) was dissolved in methanol (50 ml), and then LiOH (0.6 g, 15 mmol) wa...

Embodiment 2

[0091] Example 2: Preparation of Aripiprazole Immunogen

[0092] The specific steps of the preparation method of aripiprazole immunogen are as follows:

[0093] (1) Preparation of carrier protein solution: Dissolve recombinant human serum albumin in 0.35mol / L potassium phosphate buffer (pH=8.5), the final concentration of recombinant human serum albumin is 5.0mg / mL, to obtain carrier protein solution;

[0094] (2) Preparation of aripiprazole key group derivative solution: 250.0 mg of the above-mentioned aripiprazole key group derivative, 7.5 mL of dimethylformamide, 7.5 mL of ethanol, and 15.0 mL of potassium phosphate buffer (10.0mmol / L, pH=8.0), 150.0mg 1-ethyl-3-(-3-dimethylaminopropyl)carbodiimide, and 90.0mg N-hydroxythiosuccinimide were mixed and dissolved by stirring React for 3 hours to obtain aripiprazole key group derivative solution;

[0095] (3) Synthesis of aripiprazole immunogen: add the aripiprazole key group derivative solution obtained in step (2) dropwise ...

Embodiment 3

[0096] Example 3: Preparation of anti-aripiprazole-specific antibodies

[0097] The specific steps of the preparation method of anti-aripiprazole-specific antibody are as follows:

[0098] (1) Dilute the above-mentioned aripiprazole immunogen with 0.15mol / L sodium phosphate buffer (pH=7.0) to a final concentration of 3.5mg / mL to obtain an artificial antigen solution, and then mix 3.0mL of the artificial antigen solution with Etc. Amount of Freund's complete adjuvant was mixed, and the experimental animals were injected into rabbits at multiple points;

[0099] (2) After 4 weeks, 3.0 mL of the same artificial antigen solution and the same amount of incomplete Freund's adjuvant were injected into the above-mentioned experimental animal rabbits at multiple points, and then once every 5 weeks, for a total of 6 injections;

[0100] (3) Blood is collected from the experimental animal rabbits injected in step (2), separated and purified to obtain an anti-aripiprazole specific antibo...

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Abstract

The invention discloses an aripiprazole key group derivative, an immunogen, an anti-aripiprazole specific antibody and a preparation method and application thereof. Firstly, a novel aripiprazole key group derivative and recombinant human serum albumin obtained through genetic engineering modification are coupled to prepare an aripiprazole artificial antigen, then the aripiprazole artificial antigen is used for immunizing an experimental animal to obtain an anti-aripiprazole specific antibody, and ELISA detection shows that the specific antibody is high in specificity and sensitivity and can be used for preparing the aripiprazole specific antibody. An interference experiment shows that the specific antibody does not have any cross reaction with 100 common drugs; the anti-aripiprazole specific antibody is applied to preparation of aripiprazole detection reagents, the aripiprazole detection reagents comprise an aripiprazole homogeneous enzyme immunoassay reagent and an aripiprazole latex enhanced immunoturbidimetry detection reagent, and the detection reagents can realize high-flux and rapid detection of aripiprazole on a full-automatic biochemical analyzer.

Description

technical field [0001] The invention relates to an aripiprazole key group derivative, an immunogen, an anti-aripiprazole specific antibody, a preparation method and application thereof, and belongs to the technical field of biomedical detection. Background technique [0002] Aripiprazole, a dihydroquinolinone compound, is an atypical antipsychotic drug that partially agonizes dopamine (D2) receptors and serotonin (5-HT1A) receptors, antagonizes pentamine - Action of serotonin (5-HT2A) receptors. Clinically, it is mainly used for the treatment of schizophrenia, bipolar disorder and epilepsy. Its molecular formula is: C23H27N3O2Cl2, and the relative molecular weight is: 448.39. [0003] Aripiprazole is well absorbed after oral administration and reaches the peak plasma concentration within 3-5 hours. The average elimination half-lives of its active metabolite dehydroaripiprazole are 75 hours and 94 hours, respectively, and both reach steady-state concentrations within 14 day...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/15C07K14/765C07K16/44C07K16/06G01N33/546G01N33/543G01N33/535
CPCC07D295/15C07K14/765C07K16/44C07K16/065G01N33/94G01N33/54313G01N33/535
Inventor 张小可周涛余琳周伟峰
Owner 长沙博源医疗科技有限公司
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