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
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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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