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Application of combination of neuropeptide b23/w23 and morphine in the preparation of analgesic drugs

一种神经肽、吗啡的技术，应用在医药领域，能够解决限制阿片类药物应用范围、加大药物剂量、增加副作用的风险等问题，达到降低便秘和奖赏作用的效果

Active Publication Date: 2020-10-20
XUZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although opioids are widely used, a series of side effects during the application greatly limit the scope of opioids:
[0003] 1. Long-term opioid drug treatment causes hyperalgesia and tolerance. In this case, it is often clinically used to increase the drug dose to achieve the purpose of treating pain
[0004] 2. High doses of opioids increase the risk of side effects such as respiratory depression, nausea, constipation, rewarding effects, and dependence
[0007] 2. The combined use of these drugs can cause serious liver and kidney damage

Method used

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  • Application of combination of neuropeptide b23/w23 and morphine in the preparation of analgesic drugs
  • Application of combination of neuropeptide b23/w23 and morphine in the preparation of analgesic drugs
  • Application of combination of neuropeptide b23/w23 and morphine in the preparation of analgesic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 formalin experiment

[0034] After putting the rats into the grid for half an hour, intrathecally inject NPB23 (1, 5, 7, 10 μg), NPW23 (1, 5, 7, 10 μg), morphine (1, 5, 10, 15 μg), and morphine : NPB23 (1:1, 1.67, 3.34, 6.68, 13.36 μg), morphine: NPW23 (1:1, 1.64, 3.38, 6.56, 13.13 μg), immediately after plantar injection of 50 μl 5% formalin Put it into a transparent box, observe the number of times that the rats add and shake their feet in 1 minute at intervals of 5 minutes in 1 hour.

[0035] refer to figure 1 and figure 2 , in order to study the interaction of morphine-neuropeptide B23 and morphine-neuropeptide W23, a formalin experiment was carried out. It can be seen from the dose-dependent curve that the combined use of drugs has a significant left shift compared with the use of drugs alone, which means It is suggested that there may be a synergistic effect when drugs are used in combination. And through isoradiometric analysis, it can also be s...

Embodiment 2

[0038] Embodiment 2 neuropathic pain experiment

[0039] Rats were fed for 6 days after sciatic nerve ligation, and intrathecally injected with NPB23 (1, 5, 7, 10 μg), NPW23 (1, 5, 7, 10 μg), morphine (1, 3, 5, 7 μg), and morphine: NPB23 (1: 1, 1.075, 2.15, 4.3, 8.6 μg), morphine: NPW23 (1: 1, 1.2, 2.4, 4.8, 9.6 μg), Von Frey was used to record the 50% paw withdrawal threshold of rats.

[0040]Rats were fed for 6 days after sciatic nerve ligation, and after intrathecal injection of morphine: NPB23 (1:3, 2.3, 4.63, 9.25, 18.5 μg), morphine: NPW23 (1:3, 2.65, 5.3, 10.6, 21.2 μg), The rat's 50% paw withdrawal threshold was recorded using Von Frey.

[0041] Using the sciatic nerve ligation model, to study whether neuropeptide B23 or neuropeptide W23 will affect the inhibitory effect of morphine on mechanical allodynia, such as image 3 , also from the dose-dependent curve, it can be seen that the combined use of drugs has a significant left shift compared with the use of drugs a...

Embodiment 3

[0043] Experimental model device, operation process and experimental results of embodiment 3 conditional place preference experiment (CPP)

[0044] There are three grids in total. The left and right large grids (30×30×30 cm) are separated by the middle small room (5×20×20 cm). A 5×5 small door is opened at the bottom of the two large grids for the mice to enter and exit. The small door can be closed. Stay in the grid. Decorate the grid as follows to create visual and tactile differences: the walls and top of a large grid are pasted with black and white stripes (black 2mm, white 18mm), and the bottom is a rough barbed wire floor; the walls and top of another large grid Paste black spots (diameter 10mm, interval 10mm) on a white background, and the bottom is a smooth plexiglass floor.

[0045] Day 1: Measure the basic value. Rest for at least 3 days, and select rats with normal behavior, body posture and activity for embedding catheters in the lateral ventricle. The CPP app...

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PUM

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Abstract

The invention discloses the application of neuropeptide B23 / W23 combined with morphine in the preparation of analgesic drugs and the application of neuropeptide B23 / W23 in the preparation of drugs for inhibiting constipation / reward effects caused by morphine, wherein the neuropeptide B23 The dosage ratio of / W23 and morphine is 1:1. While the present invention achieves the same analgesic effect, the required dose of morphine or neuropeptide B23 / W23 is greatly reduced; and while the present invention achieves the analgesic effect, it effectively reduces the constipation and reward effects caused by morphine.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of neuropeptide B23 / W23 and morphine in the preparation of analgesic drugs and the application of neuropeptide B23 / W23 in the preparation of drugs for inhibiting constipation / reward effects caused by morphine. Background technique [0002] Although many novel strategies for the treatment of chronic pain have been invented, opioids are still the main drugs used in clinical pain management. Although opioids are widely used, a series of side effects during the application greatly limit the scope of opioids: [0003] 1. Long-term opioid drug treatment causes hyperalgesia and tolerance. In this case, increasing the drug dose is often used clinically to achieve the purpose of treating pain. [0004] 2. High doses of opioids increase the risk of side effects such as respiratory depression, nausea, constipation, rewarding effects, and dependence. [0005] T...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61K31/485A61P29/00A61P1/10A61P25/04
CPCA61K38/1709A61K31/485A61P29/00A61P1/10A61P25/04A61K2300/00
Inventor 邢燕红刘尧邓梦秋
Owner XUZHOU MEDICAL UNIV
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