Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Risperidone and 9-hydroxyrisperidone hapten, antigen and antibody and application thereof

A technology of hydroxyrisperidone and risperidone, which is applied in the field of immunology detection, can solve the problems of cumbersome operation, radioactive pollution, high blood drug concentration, etc., and achieve the effect of simple operation, high specificity and strong specificity

Active Publication Date: 2021-04-06
BEIJING DIAGREAT BIOTECH CO LTD
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, patients taking risperidone will also metabolize inactive metabolites 7-hydroxyrisperidone and N-dealkylated risperidone, and most patients will also take sedatives while taking risperidone , tricyclic antidepressants, selective pentamerin tryptamine reuptake inhibitors, etc., the above factors will affect the detection of risperidone and 9-hydroxyrisperidone
[0005] At present, radioimmunoassay and high-performance liquid chromatography (HPLC) are mostly used for blood concentration determination of risperidone and 9-hydroxyrisperidone. Liquid chromatography requires multiple repeated extractions, which has the disadvantages of cumbersome, complicated, time-consuming and labor-intensive operations, and low throughput, which is not conducive to clinical promotion
[0006] For example, the publication date of the application is July 1, 2015, and the patent document with the publication number CN104755479A discloses a hapten of risperidone and paliperidone, and the publication date of the application is June 24, 2015. The patent document No. CN104736565A discloses a risperidone hapten antibody and its application. The above two patent documents propose derivatization at the 9th hydroxyl position and the F atom position of the 9-hydroxy risperidone molecule, and the prepared antibody There is an obvious cross-reaction with the inactive metabolite 7-hydroxyrisperidone, and the detection reagent prepared by this antibody may cause the determination of the plasma concentration of risperidone and paliperidone in the blood sample to be too high
For example, the patent document with application publication date of August 21, 2018 and application publication number CN108431040A discloses the amino acid sequence of a risperidone antibody, but the antibody still has a serious crossover with the inactive metabolite 7-hydroxyrisperidone response, less specific

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Risperidone and 9-hydroxyrisperidone hapten, antigen and antibody and application thereof
  • Risperidone and 9-hydroxyrisperidone hapten, antigen and antibody and application thereof
  • Risperidone and 9-hydroxyrisperidone hapten, antigen and antibody and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] The structure of the hapten of risperidone and 9-hydroxyrisperidone is shown in formula I, and the specific synthetic route of the compound of formula I is as follows:

[0064]

[0065] Preparation of Compound 2: Add risperidone (4.1g, 0.01mol) into a 250mL one-necked bottle, add 150mL carbon tetrachloride, benzoyl peroxide (0.24g, 0.001mol) and NBS (3.9g, 0.022mol ), the system was refluxed in the dark for 6 hours, the TLC detection reaction was completed, and the system was down to room temperature. Pour the reaction solution into 200mL water for extraction, separate the organic phase, extract the aqueous phase three times with dichloromethane, each time the amount of dichloromethane is 50mL, combine the organic phases, dry over anhydrous sodium sulfate, filter, and evaporate to dryness to obtain a crude product . The crude product was purified by column chromatography to obtain 1.8 g of compound 2 (yield 32%).

[0066] Preparation of compound 3: Add compound 2 (...

Embodiment 2

[0074] Risperidone and 9-hydroxy risperidone antigen, the specific preparation method is as follows:

[0075] (i) dissolving the hapten of 10 mg risperidone and 9-hydroxy risperidone in 1 mL of dimethyl sulfoxide to obtain a dimethyl sulfoxide solution of the hapten;

[0076] (ii) Dissolve 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride in 100 uL of water to obtain 1-ethyl-(3-dimethylaminopropyl) Aqueous solution of carbodiimide hydrochloride;

[0077] (iii) adding an aqueous solution of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride to the dimethyl sulfoxide solution of the hapten, and reacting at room temperature for 1 hour to obtain a reaction solution;

[0078] (iv) the bovine serum albumin of 10mg is dissolved in the PBS damping fluid of 5mL to obtain bovine serum albumin solution;

[0079] (v) mixing the bovine serum albumin solution and the reaction solution, and stirring at room temperature for 2 hours to obtain a reaction mixture;

[...

Embodiment 3

[0083] An antibody capable of binding to risperidone and / or 9-hydroxyrisperidone, the specific preparation method is as follows:

[0084] (i) Selecting a host for antibody production: among them, the host can be mice, rabbits, goats, sheep, etc., and mice are used as hosts in this embodiment;

[0085] (ii) Inoculate the host with risperidone and 9-hydroxyrisperidone antigen: Dilute risperidone and 9-hydroxyrisperidone antigen to 1 mg / mL with physiological saline, add an equal volume of Freund's complete adjuvant, The emulsification was complete, and the mice were immunized for the first time according to the dose of 0.1mg / only; after an interval of four weeks, 1mg of risperidone and 9-hydroxyrisperidone antigen and 1mg of Freund's incomplete adjuvant were mixed and stirred at a speed of 2000rpm / min under the condition of stirring for 2 hours to complete the emulsification, and the mice immunized for the first time were boosted with a dose of 0.1 mg / mouse;

[0086] (iii) The ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to the technical field of immunological detection, and particularly discloses a risperidone and 9-hydroxyrisperidone hapten, antigen and antibody and application thereof. The structure of the hapten is shown as a formula I, the antigen is a conjugate formed by the hapten and carrier protein through a covalent coupling method, and the antibody is generated in response to the antigen. According to the invention, an immunological detection method with strong specificity and high sensitivity to risperidone and 9-hydroxyrisperidone is established.

Description

technical field [0001] This application relates to the technical field of immunological detection, more specifically, it relates to a hapten, antigen and antibody of risperidone and 9-hydroxy risperidone and the application thereof. Background technique [0002] Schizophrenia is a serious, disabling mental illness. As social competition intensifies, the pace of life accelerates, and family structures change, people are under increasing pressure, resulting in increasingly prominent mental health problems. Schizophrenia is the most common mental illness. [0003] Risperidone is a phenylpropisoxazole derivative with the chemical name 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl Base]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one is a new type of psychotropic drug. Risperidone targets 5-hydroxytryptamine (5-HT2) receptors and dopamine (D2) receptors, blocks their respective neurotransmitter absorption, thereby effectively improving psychotic symp...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D471/04C07K14/765C07K1/107C07K16/44G01N33/577G01N33/53
CPCC07D471/04C07K14/765C07K16/44G01N33/577G01N33/94
Inventor 周裕军周建平许秀丽吴鸣月
Owner BEIJING DIAGREAT BIOTECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com