Application of chemical genetics pharmaceutical composition in preparation of medicine for preventing and treating propofol addiction

A technology of composition and genetics, applied in the field of medicine, can solve the problems of unexplored mechanisms and treatment methods, and achieve the effects of safe and stable application, efficient expression and remarkable effect.

Active Publication Date: 2021-11-30
连庆泉 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, although the addictive behavior of propofol has been studied, its internal mechanism and treatment methods have not been explored in depth.

Method used

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  • Application of chemical genetics pharmaceutical composition in preparation of medicine for preventing and treating propofol addiction
  • Application of chemical genetics pharmaceutical composition in preparation of medicine for preventing and treating propofol addiction
  • Application of chemical genetics pharmaceutical composition in preparation of medicine for preventing and treating propofol addiction

Examples

Experimental program
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Effect test

Embodiment 1

[0015] Embodiment 1: Construct and verify chemical genetics pharmaceutical composition

[0016] The chemogenetic pharmaceutical composition mentioned in the present invention is composed of adeno-associated virus carrying chemical genetic genes and drug CNO that activates chemical genetic genes. The specific preparation and verification operations are as follows:

[0017] (1) Virus construction: the chemical genetic gene, green fluorescent gene and nerve cell-specific promoter were constructed on pAAV virus to obtain pAAV-hSyn-hM4Di-GFP.

[0018] (2) Transfect virus and verify its location: inject the adeno-associated virus obtained in step (1) into the mPFC area of ​​SD rats using a brain stereotaxic instrument, and the optimal amount of virus injection is 0.3ul on each side of the mPFC area. Adeno-associated virus will infect neurons in the relevant brain area at the injection site after injection. The optimal time for infection is 3-4 weeks, after 4 weeks to verify and mar...

Embodiment 2

[0020] Example 2: Effect of Chemogenetic Drug Composition in Propofol Behavioral Sensitization Model

[0021] The present invention first detects that long-term repeated injection of propofol can induce the formation of sensitization behavior, which is mainly related to the increased excitability of neurons in the mPFC area of ​​the cortex. Seventeen healthy male SD rats aged 7-8 weeks were selected and divided into two groups: propofol group and normal saline control group, and were given intraperitoneal injection of propofol or normal saline for 7 consecutive days. After injecting propofol or normal saline on the last day, they were placed in an open-field device to observe their sensitization behavior by detecting their movement distance per unit time, that is, their spontaneous activity. After the detection, anesthetize with isoflurane and perfuse the NMDG liquid mixed with ice water to take the brain, cut the rat brain into coronal slices with a thickness of 300um in a vi...

Embodiment 3

[0024] Example 3: Effect of Chemogenetics Drug Composition on Propofol Self-Administration Behavior

[0025]The present invention first detects that long-term repeated injection of propofol can successfully establish propofol self-administration behavior, which is mainly related to the increased excitability of neurons in the mPFC area of ​​the cortex. Select 16 healthy male SD rats aged 7-8 weeks and divide them into two groups: propofol group and normal saline control group. The external jugular vein catheterization operation was performed on them. Dosing training. During the training process, the computer automatically records the number of effective nasal touch pump injections of the rats, so as to observe its own drug administration training situation. After the training, anesthetize with isoflurane and perfuse the NMDG liquid mixed with ice water to take the brain, cut the rat brain into coronal slices with a thickness of 300um in a vibrating microtome, and collect the ...

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Abstract

The invention discloses the application of a chemical genetic drug composition in preparing a drug for preventing and treating propofol addiction. The propofol addiction mainly involves two classic addictive behaviors, behavioral sensitization and self-administration. The present invention fully proves that after long-term repeated use of propofol in rats, addictive behavior will be produced, which is mainly caused by the excitation of neurons in the medial prefrontal cortex (mPFC area) of the cortex; Inhibits the hyperexcitable state of mPFC region induced by propofol, thereby inhibiting propofol-addictive behavior in rats. The chemical genetic drug composition provided by the invention has the advantages of good effect, strong controllability and the like, and provides a new therapeutic drug for the treatment, research, development and prevention of propofol addiction.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the application of a chemical genetics drug composition in propofol addiction behavior, in particular to the application of the chemical genetics drug composition in the preparation of drugs for preventing and treating propofol addiction. Background technique [0002] Propofol is widely used in clinical anesthesia, painless outpatient clinics, and sedation of ICU patients due to its advantages of fast onset of action, fast elimination, and no accumulation. With the widespread use of propofol, some potential problems have gradually been paid attention to: some patients experience pleasure, excitement and euphoria after using it, which has potential spiritual dependence. Clinical investigation found that propofol has mental dependence, and there is a certain phenomenon of abuse, which is mainly related to its improper management. Therefore, in recent years, the U.S. Drug Enforcemen...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K35/761A61P25/30A61K31/5513
CPCA61K31/5513A61K35/761A61P25/30A61K2300/00
Inventor 连庆泉林函项赛琼
Owner 连庆泉
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