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Preparation for inhibiting adverse reactions of opioid analgesic drugs and application of preparation

A technology of adverse reactions and opioids, applied in the field of medicine, can solve the problems of patient dependence, large dose, poor effect, etc., and achieve the effect of reducing treatment costs and opioid dependence

Active Publication Date: 2020-03-27
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] It is especially important to suppress the tolerance and dependence of opioid analgesics, because opioid analgesics are important drugs to relieve cancer pain in cancer patients, especially advanced cancer patients. With the extension of medication time, opioid analgesics The dose is getting bigger and bigger, the effect is getting worse and worse, and it leads to the patient's dependence, which is tantamount to worsening the situation for advanced cancer patients

Method used

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  • Preparation for inhibiting adverse reactions of opioid analgesic drugs and application of preparation
  • Preparation for inhibiting adverse reactions of opioid analgesic drugs and application of preparation
  • Preparation for inhibiting adverse reactions of opioid analgesic drugs and application of preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: Simultaneous administration of 17-AAG with morphine, experiment and results of acute administration

[0042] A total of 40 C57 / B6 mice were randomly divided into 4 groups. The basic pain range of the animals was measured on a hot plate (55°C) before administration, and then 5 microliters of 17-AAG (10nmol) and solvent (solvent) were administered intracerebroventricularly. ), 17-AAG (10nmol) and geldanamycin (10nmol), 15 minutes later, subcutaneous administration of normal saline (10ml / kg), morphine (Mor, 10mg / kg), morphine (Mor, 10mg / kg ), morphine (Mor, 10mg / kg), and the pain zone of the animals was measured on a hot plate 30 minutes after administration. Maximum analgesic percentage (%MPE)=(pain domain after administration-pain domain before administration) / (60-pain domain before administration)×100%. From Table 1 and figure 1 It can be seen that 17-AAG has no analgesic effect on mice, and morphine has obvious analgesic effect on mice. 17-AAG (10nmol) and...

Embodiment 2

[0047] Example 2 Simultaneous administration of 17-AAG with morphine, experiment and results of chronic administration

[0048] A total of 30 C57 / B6 mice were raised in the experimental environment for 2-3 days, randomly divided into 3 groups, administered twice a day, starting at 8:00 in the morning, and the animals were measured on a hot plate (55°C) before administration. For the basic pain zone, 5 microliters of solvent and 17-AAG (10nmol) were administered into the ventricle, and morphine (Mor, 100mg / kg) was administered subcutaneously 15 minutes later, and the pain zone was measured after 30 minutes of morphine administration. At 6:00 p.m., the animals in the three groups were only given morphine (100 mg / kg), continuously administered and measured for 7 days, and naloxone (10 mg / kg) was injected intraperitoneally 2 hours after the last administration, and immediately put Enter the withdrawal observation box, observe the withdrawal signs (withdrawl signs) such as jumping,...

Embodiment 3

[0056] Example 3 17-AAG co-administered with morphine, experiment and results of influence on mental dependence

[0057] The experimental timing design of chronic administration of 17-AAG on morphine conditioned place preference see Figure 5 A total of 50 C57 / B6 mice were used, and the animals were raised in the experimental environment for 2-3 days. The pre-adaptation period (d1-d3): 3 days, once a day, 15 minutes each time, and two times within 15 minutes after recording. Side residence time, the average value of d2 and d3 was used as the pre-test result, and unqualified animals were screened out.

[0058] Criteria for animal exclusion: the difference between the residence time of all animals in the two sides of the black box and the white box is more than 100s. It is considered that there is a natural bias, and the individuals with similar residence times in the two sides of the box are eliminated; The difference between the residence time in the box does not exceed 100s,...

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Abstract

The invention relates to a preparation for inhibiting adverse reaction of opioid analgesic drugs and application of the preparation. The preparation contains one or more of 17-N-allylamino-17-demethoxygeldanamycin or / and homologs thereof, and the opioid analgesic drug comprises one or a combination of more of a morphine hydrochloride tablet, a morphine sulfate sustained-release tablet, a codeine phosphate tablet, a morphine hydrochloride injection, a piperidine hydrochloride injection and a fentanyl injection. By the adoption of the technical scheme, 17-AAG can obviously inhibit the symptom ofprecipitation withdrawal reaction along with chronic administration of morphine, body tolerance and mental dependence of morphine can be obviously inhibited, 17-AAG and homologs thereof and opioid analgesic drugs are reasonably used. Meanwhile, the compound has dual effects of resisting tumors and inhibiting the tolerance and dependence of opioid analgesic drugs, so that the use of other drugs can be reduced.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation for inhibiting adverse reactions of opioid analgesics and its application. Background technique [0002] Cancer patients are tortured by pain. Clinically, opioid analgesics are generally used for analgesic treatment to relieve the pain of cancer patients, but opioids are prone to tolerance and dependence. [0003] Tolerance, the loss of analgesic potency, is one of the common complications of opioid therapy, leading to escalating dosage requirements and reduced effectiveness over time. [0004] Dependence, is the development of an altered physiological state revealed by opioid withdrawal syndrome involving autonomic and physical hyperactivity. [0005] Tolerance and dependence of opioids are well-known physiological phenomena. A large number of studies have found that the mechanism of adverse reactions of opioids, including tolerance and dependence, is quite complex, involv...

Claims

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Application Information

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IPC IPC(8): A61K31/395A61K31/36A61K31/365A61K31/7048A61P29/00
CPCA61K31/395A61K31/36A61K31/365A61K31/7048A61P29/00
Inventor 周培岚苏瑞斌张艺馨陈铭
Owner ACADEMY OF MILITARY MEDICAL SCI
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