Application of group of cobra neurotoxin molecules having high affinity with nicotinic acetylcholine receptors for rapid acting on pain easing

Abstract

The cobra neurotoxin is capable of binding to nicotinic acetylcholine receptors after nerve synapses to block neuronal caudal ion flow to realize analgesic effect, however, the product on the market takes 2 hours to be effective and the curative effect is unstable, which cannot meet clinical requirement. The neurotoxins need to pass a blood cerebral barrier in the brain to play an analgesic effect, and the product on the market has no clear components, including various molecular weight proteins, so the speed for permeating the blood cerebral barrier is slow; and at the same time, affinity with the nicotinic acetylcholine receptors is also inconsistent. The application screens a group of neurotoxin molecular monomers having high affinity with the nicotinic acetylcholine receptor, can quickly pass the blood cerebral barrier, and has analgesic effect and stable therapeutic effect in 30 minutes. The neurotoxin molecular monomer overcomes the defects that a mixture cannot specify which neurotoxin is present, the protein primary structure is not existed, the quality cannot be precisely controlled; according to the invention, the quality is controlled, clinical safety and effectiveness are better guaranteed.

Description

Background technique [0001] As early as the beginning of the 20th century, people began to use snake venom to relieve malignant tumor pain, neuralgia and joint pain. Since 1952, my country has carried out research on the analgesic effect of snake venom, and developed crude snake venom preparations and snake venom neurotoxin preparations for clinical treatment of pain. [0002] Cobra toxin is one of them, but there are many kinds of cobra toxins. The known components include neurotoxin, cytotoxin, cardiotoxin, nerve growth factor, hemolysin (DLP), CVA protein, membrane active polypeptide, cobra venom factor, etc. and other components , such as alkaline phosphomonoesterase, phosphodiesterase, acetylcholinesterase, L-amino acid oxidase, ribonuclease, proteolytic enzyme, etc. [0003] Among them, cobra neurotoxin is an antagonist of nicotinic acetylcholine receptor (nAChR), which is antagonistic and slowly reversible to muscle type and neuron type nicotinic acetylcholine receptor...

AI Technical Summary

Problems solved by technology

[0009] (2) 2 hours after the experimental animals were injected with cobra neurotoxin, the pain threshold of the rats increased significantly, and the best effect was achieved after 3 hours. The analgesic effect of NT was slow to take effect, but lasted for a long time

[0012] (1) This cobra neurotoxin molecule with high affinity to the nicotinic acetylcholine receptor (nAChR) cannot be optimally screened out;

[0013] (2) There is no guarantee that the protein will be denatured during the extraction process due to hydrolysis, temperature, chemical substances, and acetone or other reagents added to the cytotoxicity of the inactivated cobra neurotoxin;

[0016] (5) It is impossible to determine which neurotoxin is the real active ingredient in the extract

[0019] (2) Determine whether there is protein denaturation after the intervention of hydrolysis, temperature, and chemical substances in the extraction process. If the primary structure of the protein is not understood, it is impossible to know whether there is protein denaturation, and it is impossible to control the quality

[0023] As a kind of biopharmaceuticals, such as insulin, octreotide, calcitonin, goserelin, leuprolide, etc., all have clear primary protein structures, and the national new biopharmaceutical application also suggests that 15 N-terminal Amino acid sequence and C-terminal 1-2 amino acid sequence analysis, but cobra neurotoxin extracts currently on the market for pain treatment do not have a clear protein primary structure, that is, the amino acid sequence

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