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Application of norsinomenine in the preparation of analgesic drugs

A technology of norsinomenine and drugs, applied in the application field of norsinomenine in the preparation of analgesic drugs, can solve the problems of low effectiveness of pain drugs, large adverse reactions, and tolerance, and achieve no Effect of sedative side effect, pain relief, strong analgesic activity

Active Publication Date: 2019-12-20
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] In order to solve the problems of low effectiveness, large adverse reactions, or tolerance and addiction of current pain drugs, based on the analgesic activity of sinomenine, a sinomenine derivative with better pharmacodynamic characteristics is obtained. The object of the present invention is to provide the application of sinomenine derivative-norsinomenine in the preparation of pain medicine

Method used

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  • Application of norsinomenine in the preparation of analgesic drugs
  • Application of norsinomenine in the preparation of analgesic drugs
  • Application of norsinomenine in the preparation of analgesic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1: Comparison of the pharmacodynamic characteristics of norsinomenine and sinomenine on the analgesic effect of the mouse acetic acid writhing model

[0045] 1. The analgesic effect of norsinomenine and sinomenine (40mg / kg) over time

[0046] 1. Animal grouping and experimental design:

[0047] Eighty-eight ICR mice (provided by the Experimental Animal Center of Nantong University) were divided into 11 groups with 8 mice in each group. One group of i.p. normal saline (vehicle group), the other groups choose norsinomenine and sinomenine effective dose (40mg / kg), respectively, different pretreatment time before acetic acid treatment (5,30,60, 90, 180 min) intraperitoneal injection, and then i.p. 0.6% acetic acid, and observe the writhing times within 0-20 min after administration of acetic acid in each group. The writhing response was defined as contraction of the abdomen, extension of the body and hind limbs, tilting of the buttocks and creeping.

[0048] 2. E...

Embodiment 2

[0062] Example 2: The analgesic effect of norsinomenine on the rat CFA-induced inflammation model

[0063] 1. Preparation method of CFA-induced inflammation model:

[0064] After the rats were briefly anesthetized with isoflurane, the soles of the right feet were disinfected with alcohol disinfection tablets, and then 50 microliters of CFA were injected subcutaneously into the soles of the feet. Mechanical pain threshold (PWT) was measured 2 hours after injection and every 24 hours thereafter. The reference method for determining the mechanical pain threshold is as follows: use the Von-Frey fiber measurement kit (Stoelting Co., Ltd., the United States) to measure the paw withdrawal threshold of the operation side (right side) hind paw under a series of Von-Frey fiber stimulation as As for the mechanical pain threshold, the change of mechanical touch-evoked allodynia in rats in each group was observed at different time points. Von-Frey filaments of 7 strengths were used for t...

Embodiment 3

[0070] Embodiment 3: The analgesic effect of acute administration of norsinomenine on the pain model after incision in mice

[0071] 1. Establishment of mouse incision pain model:

[0072] The specific establishment method: using an anesthesia machine, the mice were induced anesthetized with 3% isoflurane, then maintained anesthetized with 1.5% isoflurane, fixed in supine position, and the right hind foot of the mouse was moved from 0.2cm close to the heel to the direction of the toe, with 11 Cut the skin with a scalpel blade, make a 0.5cm long longitudinal incision, pick out the fascia, and cut it longitudinally in the center of the fascia. After light pressure to stop the bleeding, a needle was sutured at the midpoint of the incision with a single No. 6 nylon thread, and then the animal was put back into the cage, and the mechanical pain threshold was measured after it woke up. References for the determination method of mechanical pain threshold (Pogatzki EM, Raja SN.A mous...

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Abstract

The invention relates to the technical field of medicines, in particular to an application of N-demethylsinomenine in preparation of an analgesic drug. An acetic acid writhing model, a complete Freund's adjuvant induced metapodium inflammation pain model and a postoperative incision pain model are prepared, N-demethylsinomenine is provided for treatment after molding and is utilized in an intraperitoneal injection mode, other administration methods can be adopted as well, the administration dosage is 10-40 mg / kg, and the operation proves that N-demethylsinomenine has a good analgesic effect on pain caused by chemical stimulation, inflammation pain and postoperative pain, is free of a sedative effect and has no adverse effects such as tolerance, addiction and the like after long-term administration; compared with sinomenine, N-demethylsinomenine is shorter in onset time and higher in analgesic activity; N-demethylsinomenine can be applied to drug therapy of various clinical pains, particularly the inflammation pain and the postoperative pain.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of norsinomenine in the preparation of analgesic drugs. Background technique [0002] Pain is the most common clinical symptom, and it is also one of the serious problems plaguing human health today. Chronic pain will bring persistent and unbearable pain to patients, and it is an important cause of disease, disability and death. Pain treatment is a very active research field at present, and analgesic drugs widely used in clinic are often accompanied by serious toxic side effects. For example, traditional non-steroidal anti-inflammatory drugs (NSAIDs) have adverse reactions such as gastrointestinal damage, liver and kidney damage. Long-term use of opioid analgesics such as morphine, methadone, and fentanyl can cause side effects such as respiratory depression, dependence, addiction, and tolerance. Although there are many pain medicines currently available clini...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/485A61P29/00
CPCA61K31/485
Inventor 李俊旭朱清欧云淘苏漫赵颖
Owner NANTONG UNIVERSITY
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