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Application of anti-opioid peptide antagonist peptide

An anti-opioid peptide and antagonistic peptide technology, applied to the anti-opioid peptide antagonistic peptide and the application field of the antagonistic peptide, can solve the problem of tolerance to acupuncture, the limited effective rate of acupuncture analgesia, etc., and reduce the dosage of morphine. , easy to be degraded, high safety effect

Inactive Publication Date: 2012-10-03
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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  • Application of anti-opioid peptide antagonist peptide
  • Application of anti-opioid peptide antagonist peptide
  • Application of anti-opioid peptide antagonist peptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1. Obtainment and functional verification of anti-opioid peptide 21Kd and its active fragments

[0070] 1. Acquisition of pig brain anti-opioid peptide 21Kd

[0071] 1. Discovery of anti-opioid peptides

[0072] 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) (for dog brain extract The concentrated solution was successively filtered through Sephadex G-50 gel (purchased from pharmacia company), and after carboxymethyl-cellulose (CM-C, purchased from H.Reeve-Angel&.Co.Ltd company) cation exchange chromatography, the sample was obtained ), to observe the effect on the con...

Embodiment 2

[0087] Example 2, Detection of the relationship between anti-opioid peptide 21Kd and morphine tolerance and dependence

[0088] 1. Obtainment and functional detection of soluble single-chain variable region antibody fragment against opioid peptide 21Kd

[0089] Using phage display technology, using the human prophage antibody library constructed by Daniele Sblattero and Andrew Bradbury of the International School for Advanced Studies (SISSA) in Italy [For the construction method, see: Sblattero D, Lou J L, Marzari R, et al.In vivo recombination as atool 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 late...

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, Kalicki JM, Meyer ER, Cicero TJ (1993) Inhibition of the morphine withdrawal syndrome by nitric oxide synthase inhibitor, NG-Nitro -L-arginine methyl ester. Life Sci52: PL245-PL249; Cappendijk SL, Vries R, Dzoljic MR (1993) Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Neurosci7 Lett 162: -100; Herman BH, Vocci...

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Abstract

The invention discloses an anti-opioid peptide, antagonist peptide and application thereof. The anti-opioid peptide is polypeptide formed by the way that one of the following amino acid residue sequences: 1) SEQ ID NO: 1 in the sequence table; 2) SEQ ID NO: 3-5; 3) amino acid residue sequences of SEQ ID NO: 1, SEQ ID NO: 3-5 in the sequence table are subject to substitution, deletion or addition of one to ten amino acid residues to have antagonist morphine anti-harm effect. The antagonist peptide thereof is polypeptide formed by the way that one of the following amino acid residue sequences: 1) SEQ ID NO: 9-11 in the sequence table; 2) amino acid residue sequences of SEQ ID NO: 9-11 in the sequence table is subject to substitution, deletion or addition of one to ten amino acid residues to have effects of enhancing morphine analgesia, reversing morphine tolerance and / or reducing or eliminating abstinence symptom. The anti-opioid peptide and active segment thereof and antagonist peptide can play important role in the medicinal and rehabilitation medicine preparation field and has wide application prospect.

Description

[0001] This application is a divisional application with the application number 200710118104.2, the filing date is June 28, 2007, and the invention title is "an anti-opioid peptide, its antagonistic peptide and the application of the antagonistic peptide". technical field [0002] 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 [0003] 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...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08C12N15/11C12N15/63C12N1/15C12N1/19C12N1/21C12N5/10A61K38/10A61P25/00A61P25/04
Inventor 陈玉珍吴才宏曲红
Owner PEKING UNIV
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