Application of N-acetanilide cationic compound in preparation of local nerve blocking drug

A local nerve block and cationic compound technology, which is applied in the direction of active ingredients of heterocyclic compounds, drug combinations, nervous system diseases, etc., can solve the problems of unsatisfactory safety, damage, and safety problems of QX314, and achieve good development prospects Effect

Active Publication Date: 2015-03-04
WEST CHINA HOSPITAL SICHUAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the strong irritant of capsaicin makes it difficult for this composition to have application prospects
Although studies have shown that the combination of QX314 and clinically used local anesthetics such as bupivacaine and lidocaine can quickly produce long-lasting anesthesia and avoid the irritation of capsaicin, but the safety of QX314 itself is still unresolved. Avoidance, that is, the current research has found that the safety of QX314 itself is not ideal, mainly manifested as nerve damage, and intrathecal injection will cause the death of experimental animals, etc.
Therefore, whether QX314 is used alone or in combination with other active drugs, there are safety issues

Method used

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  • Application of N-acetanilide cationic compound in preparation of local nerve blocking drug
  • Application of N-acetanilide cationic compound in preparation of local nerve blocking drug
  • Application of N-acetanilide cationic compound in preparation of local nerve blocking drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Compounds I-Br and I-Cl, in which X in the compound of formula (I) are bromine and chlorine, respectively, were used to block the sciatic nerve of rats. Significantly prolonged.

[0017] experimental method

[0018] Select SD rats, half male and half male, and conduct behavioral adaptation one week before the experiment, and select 156 rats that are qualified for the baseline. They were randomly divided into 13 groups, with 12 rats in each group. They received the left sciatic nerve block as shown in Table 1, every 10 min, 30 min, 60 min, 120 min after injection, and then every 2 h to 12 h, and Afterwards, the sensory and motor functions of the limbs were measured by injection every 12 hours until the sensory and motor functions were fully recovered. The time point when the first sensory and motor block takes effect is the onset time of anesthesia; the time point when the first sensory and motor function recovers is the anesthesia failure time; the interval b...

Embodiment 2

[0023] Toxicity test of the above compounds I-Br and I-Cl on rat sciatic nerve.

[0024] experimental method

[0025] All rats in Example 1 were euthanized 7 days after administration. The sciatic nerve at the injection site of each rat was divided into two parts, one of which was stained with HE, and the histological changes of the sciatic nerve were observed under a light microscope; the other was observed under an electron microscope. Light microscope visual scoring standard: 0 points (slightly congested and dilated adventitial vessels, without inflammatory cell infiltration); 1 point (slightly congested and dilated adventitial vessels, with a small amount of inflammatory cell infiltration); 2 points (obvious congested adventitial vessels , expansion, with inflammatory cell infiltration); 3 points (adventitial vessel hyperemia, expansion, spinal cord parenchyma with inflammatory cell infiltration). Electron microscope visual score: 0 points (no obvious pathological chan...

Embodiment 3

[0030] Toxicity experiment of intrathecal administration of I-Br and I-Cl alone.

[0031] experimental method

[0032] As described in Example 1, 80 qualified SD male rats were selected and randomly divided into 8 groups, 10 rats in each group. Under isoflurane anesthesia, 10 ul of the drugs shown in Table 2 were injected intrathecally. Observe whether the rats have irritation symptoms after injection: such as writhing, hissing, convulsions, excitement, coma, or even death, etc. (7) .

[0033] Experimental results

[0034] The results are summarized in Table 3. Intrathecal administration, I-Br and I-Cl did not cause death, and the incidence of irritation symptoms was low; QX314 could cause death, and the incidence of irritation symptoms was high. It shows that the toxicity of I-Br and I-Cl is obviously less than that of QX-314.

[0035]

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Abstract

The invention discloses an application of an N-acetanilide cationic compound in preparation of a local nerve blocking drug. The cationic compound is a quaternary ammonium salt compound and has a structure as shown in a formula (I), wherein X is a halogen atom. When used alone, the compound has the characteristics of good safety performance, strong nerve blocking effect and the like, can take a reversible and durable local anaesthesia effect in vivo and can be used as a local anaesthesia drug or an analgesic drug which is long-acting and / or capable of realizing selective blocking. Particularly, a composition composed of the compound and other local anaesthesia drugs has the remarkable characteristics of high effect taking speed, strong effect, long acting time, little nerve injury and the like when used for nerve blocking.

Description

technical field [0001] The invention relates to the application of an N-acetanilide cationic compound in the preparation of local nerve block drugs. The compound can be used alone as a local anesthetic or analgesic at least with good safety, especially when used in combination with other clinically used local anesthetics, it can have a more durable local nerve block synergistic effect. Background technique [0002] Local anesthetics (local anesthetics) are a class of drugs that can reversibly block the generation and transmission of sensory nerve impulses in the local area while keeping the patient or animal awake, causing pain loss in local tissues. The effect of local anesthetics is related to the diameter of nerve cells or nerve fibers and the anatomical characteristics of nerve tissue. The general rule is that nerve fiber endings, ganglia and synaptic sites of the central nervous system are most sensitive to local anesthetics, and thin nerve fibers are more likely to b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/167A61P23/02A61P25/02A61P25/04A61K31/445A61K31/245
CPCA61K31/167A61K31/245A61K31/445A61K2300/00
Inventor 张文胜杨俊刘进唐磊柯博文尹芹芹
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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