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Application of heat shock protein 70 inhibitor to preparation of opioid drug analgesia reinforcing agent

A technology for heat shock proteins and opioids, applied in antipyretics, drug combinations, anti-inflammatory agents, etc., can solve problems that limit the application of opioid analgesic effects, improve analgesic effects, and strengthen application space , the effect of reducing adverse reactions

Inactive Publication Date: 2017-11-24
CHINA JAPAN FRIENDSHIP HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Similarly, clinically there is no way to cope with the change in the analgesic effect of opioids, even if it is a therapeutic means to alleviate or delay this change, which is an urgent clinical problem that seriously limits the powerful analgesic effect of opioids Applications

Method used

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  • Application of heat shock protein 70 inhibitor to preparation of opioid drug analgesia reinforcing agent
  • Application of heat shock protein 70 inhibitor to preparation of opioid drug analgesia reinforcing agent
  • Application of heat shock protein 70 inhibitor to preparation of opioid drug analgesia reinforcing agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1: Decreased analgesic ability and increased expression of Hsp70 caused by continuous administration of morphine

[0040] Male Sprague-Dawley rats (SD rats, body weight 250-270 g), purchased from Victoria Lihua Company, clean grade. Animals were reared in the same cage after purchase (4-6 per cage). The animal room is kept at constant temperature and humidity (temperature 22±1°C, humidity 50±10%), controlled by 12-hour circadian rhythm (8:00-20:00). The animals were randomly divided into groups. Before the start of the experiment, they were acclimatized in the animal room for at least 5 days, with unlimited food and water, and the rats were grasped, placed and stroked regularly every day, and allowed to adapt to the thermal tail flick instrument. The rats were randomly divided into two groups. Except the control group was given normal saline, the other groups were given 10 mg / kg (s.c.) morphine hydrochloride, and the analgesic ability of morphine was measured b...

Embodiment 2

[0043] Example 2: Administering Hsp70-specific expression inhibitor KNK437 and morphine to improve the total analgesic ability of chronic administration of morphine

[0044] After SD rats were adaptively fed for at least 5 days in the animal room, they were randomly divided into 4 groups, and the administration arrangements of each group were: olive oil (0.1ml / 100mg, i.p.) and normal saline (0.1ml / 100mg, s.c. ), olive oil (0.1ml / 100mg, i.p.) and morphine (10mg / kg, s.c.), KNK437 (100mg / kg, i.p.) and saline (0.1ml / 100mg, s.c.), KNK437 and morphine (10mg / kg, s.c.), the dosing interval of the two drugs was 6 hours. The analgesic effect of morphine was measured by heat flick method before and 30 minutes after administration of morphine or normal saline on the 1st, 4th, 7th and 10th day respectively, and the brain tissue was collected 4 hours later to determine the expression level of Hsp70.

[0045] 6 hours before each morphine administration, the Hsp70-specific expression inhibit...

Embodiment 3

[0047] Example 3: Administering Hsp70-specific expression inhibitor PES and morphine to improve the total analgesic ability of chronic administration of morphine

[0048] After SD rats were adaptively fed for at least 5 days in the animal room, they were randomly divided into 4 groups, and the administration arrangements of each group were: olive oil (0.1ml / 100mg, i.p.) and normal saline (0.1ml / 100mg, s.c. ), olive oil (0.1ml / 100mg, i.p.) and morphine (10mg / kg, s.c.), PES (20mg / kg, i.p.) and normal saline (0.1ml / 100mg, s.c.), PES (20mg / kg, i.p.) and morphine (10mg / kg, s.c.), the administration interval of the two drugs was 6 hours. The analgesic ability of morphine was measured by heat flick method before and 30 minutes after administration of morphine or normal saline on day 1, 4, 7 and 10, respectively.

[0049] Before each administration of morphine, administration of Hsp70-specific functional inhibitor PES (Tocris Bioscience, UK) can significantly improve the total analge...

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Abstract

The invention discloses application of a heat shock protein inhibitor to preparation of an opioid drug analgesia reinforcing agent and belongs to the field of pharmacy. The invention provides application of a the heat shock protein 70 inhibitor to the preparation of the opioid drug analgesia reinforcing agent. The application disclosed by the invention has the beneficial effects that the invention discloses the application of the heat shock protein 70 inhibitor to enhancement of an analgesia effect of opioid drugs after chronic utilization for the first time. The heat shock protein 70 inhibitor can be used for enhancing the analgesia effect in a chronic opioid application process, alleviating adverse effects and sufficiently expressinggiving full play to the strong analgesia effect of the opioid drugs and provides more options for pain treatment.

Description

technical field [0001] The present invention relates to the use of heat shock protein 70 inhibitors in the preparation of opioid analgesic enhancers, providing methods and reagents for enhancing the analgesic effect of opioid analgesics after chronic use; providing heat shock protein 70 inhibitors The new application is used for preparing preparations for enhancing the analgesic effect of opioid analgesics after chronic use, and belongs to the technical field of pharmacy. Background technique [0002] Opioid analgesics mainly include morphine, fentanyl, codeine, hydromorphone, oxycodone, methadone, pethidine, and tramadol. Opioids have a strong analgesic effect and are widely used in the treatment of pain, such as acute postoperative pain, neuropathic pain, and cancer pain. The analgesic effect of opioids has a common mechanism of action, that is, it mainly acts on specific opioid receptors in the nervous system to reduce the excitability of pain-transmitting neurons to exe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/4025A61K31/18A61P29/00
CPCA61K45/06A61K31/18A61K31/4025
Inventor 覃旺军张镭王燕婷刘莹邓昂梁建辉张相林
Owner CHINA JAPAN FRIENDSHIP HOSPITAL
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