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Anti-opium peptide and antagonistic peptide and its application

An anti-opioid peptide and antagonistic peptide technology, applied in application, medical preparations containing active ingredients, peptide sources, etc., can solve the problems of limited efficacy of acupuncture analgesia, tolerance problems of acupuncture, etc. Efficacy of degradation, reduction of morphine consumption, and reversal of morphine tolerance

Inactive Publication Date: 2011-07-20
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Professor Han Jisheng used an acupuncture treatment device to treat withdrawal symptoms, trying to stimulate the synthesis of endogenous opioids in the body through specific frequency electrical pulse stimulation to relieve symptoms, but its biggest defect is that the effectiveness of acupuncture analgesia in the population is limited and continues Acupuncture also has tolerance issues

Method used

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  • Anti-opium peptide and antagonistic peptide and its application
  • Anti-opium peptide and antagonistic peptide and its application
  • Anti-opium peptide and antagonistic peptide and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Example 1. Obtainment and functional verification of anti-opioid peptide 21Kd and its active fragments

[0069] 1. Acquisition of pig brain anti-opioid peptide 21Kd

[0070] 1. Discovery of anti-opioid peptides

[0071] In the isolated mouse vas deferens specimens, stimulation with a square wave pulse (0.1MS width, 1 time / second) can cause contraction (see the literature for the specific method: J. Hughes et al (1975) Effect of morphine on adrenergic transmission in the Mouse Vas deferens.Assessment of agonist and antagonistpotencies of Narcotic analgesics 53,371-381), then, successively add morphine hydrochloride (3.2nM) or dog brain extract (AOS, 200μg / mL) to the perfusate (concentrated dog brain extract Successively filtered through SephadexG-50 gel (purchased from pharmacia company), after carboxymethyl-cellulose (CM-C, purchased from H.Reeve-Angel&.Co.Ltd company) cation exchange chromatography, obtain the sample), observe Influence on contractile effect induced ...

Embodiment 2

[0086] Example 2, Detection of the relationship between anti-opioid peptide 21Kd and morphine tolerance and dependence

[0087] 1. Obtainment and functional detection of soluble single-chain variable region antibody fragment against opioid peptide 21Kd

[0088] Using phage display technology, using the human prophage antibody library constructed by Italian International School for Advanced Studies (SISSA) Daniele Sblattero and Andrew Bradbury, etc. [For construction methods, see: Sblattero D, Lou J L, Marzari R, et al.In vivo recombination asa tool to generate molecular diversity in phage antibody libraries. Reviews in Molecular Biotechnology. 2001, 74: 303-315], a soluble single-chain variable region antibody fragment with a molecular weight of about 20,000 Daltons of anti-opioid peptide 21Kd was screened out from the phage antibody library, Abbreviated as ScFv. Intraperitoneal injection of morphine (M 10 , 10 mg / kg) 10 minutes later, the ScFv was injected into the lateral ...

Embodiment 3

[0096] Example 3. Detection of the role of NMDA receptors and NOS in antagonizing the antinociceptive effect of morphine on the anti-opioid peptide 21Kd and its active fragments

[0097] Studies have shown that excitatory amino acid NMDA receptors and nitric oxide synthase system (NOS) play a crucial role in the process of morphine tolerance and dependence in adult mice, and mice were treated with NMDA receptor antagonists or NOS inhibitors After pretreatment, it can inhibit the formation of morphine tolerance and dependence, and prevent the appearance of withdrawal symptoms [Adams ML, KalickiJM, Meyer ER, Cicero TJ (1993) Inhibition of the morphine withdrawal syndrome by nitric oxide synthase inhibitor, NG-Nitro- L-arginine methyl ester. Life Sci 52: PL245-PL249; Cappendijk SL, Vries R, Dzoljic MR (1993) Inhibitory effect of nitric oxide (N0) synthase inhibitors onnaloxone-precipitated withdrawal syndrome in morphine-dependent mice. Neurosci Lett 162 97-100; Herman BH, Vocci ...

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Abstract

The invention discloses an anti-opioid peptide, and antagonistic peptide and the application thereof. The anti-opioid peptide is one of the amino acid residue sequences: 1) SEQ ID No.1 in the sequence list; 2) SEQ ID NO.3-5; 3) the peptides derive from the amino acid residue sequences of SEQ ID NO.1 and SEQ ID NO.3-5 in the sequence list that are substituted by, lost by or added with one to ten amino acid residue sequences, with antagonistic morphia effects and harm resistance. The antagonistic peptide is one of the amino acid residue sequences: 1) SEQ ID NO.9-11 in the sequence list; 2) the amino acid residue sequences of the SEQ ID NO.9-11 in the sequence list are substituted or lost by one to ten amino acid residue sequences, or opypeptide provided with functions of intensified analgesia, reversing morphia resistance and / or releasing or removing withdrawal symptoms is added. The anti-opioid peptide and the active segments thereof and antagonistic peptide of the invention play important roles in the preparation fields of medical science and anti-additive drugs, and have a promising prospect.

Description

technical field [0001] The present invention relates to peptides and their coding genes and applications, in particular to an anti-opioid peptide and its antagonistic peptide which can antagonize the antinociceptive effect of morphine, and the antagonistic peptide can enhance morphine analgesia, reverse morphine tolerance and / or or in drugs that reduce or eliminate the effects of withdrawal symptoms. Background technique [0002] As we all know, rampant drug trafficking and drug use around the world has become a cancer that endangers society, seriously interfering with orderly economic construction and social stability. In addition, intravenous drug use has also caused a rise in the infection rate of AIDS populations. At present, although the governments of various countries have stepped up efforts to jointly crack down on drug smuggling, drug abuse and drug trafficking activities are still repeatedly banned. One of the important reasons is that the principles of morphine to...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/63A61K38/16C12N15/12A61P25/36C07K14/47
Inventor 陈玉珍吴才宏曲红
Owner PEKING UNIV
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