Research On A New Analgesic Patch With Dual-target Compound BU08028

With the increase of people’s economic and life pressure,chronic pain symptoms appear commonly.Therefore,the development of new analgesics with good analgesic effect and reduced side effects has received extensive attention.As a dual-target compound,BU08028can simultaneously act on the nociceptin-orphanin FQ peptide（NOP）receptor and theμopioid peptide（MOP）receptor.NOP receptor activation can synergistically increase the analgesic effect of MOP receptors and reduce the side effects caused by MOP receptor activation.Experiments have shown that BU08028 has the same analgesic effect as gabapentin（GBP）and has no adverse reactions.So,BU08028 is considered as a potential novel analgesic.At the same time,the administration method of BU08028 was studied in this thesis.Different from the common oral and injection administration,a hydrogel analgesic patch was designed and prepared in this experiment,and the quality of the hydrogel patch was evaluated.In this experiment,the initial adhesion,holding force and peeling strength were used as evaluation indicators to comprehensively score the adhesion of the hydrogel patch,which was used to screen out the best conditions for preparing the hydrogel patch.The optimal mass ratio of each experimental factor was obtained by single factor experiment:Sodium polyacrylate NP-700（PAAS NP-700）was 8%,aluminum glycinate was 0.1%,polyvinylpyrrolidone K88-96（PVP K88-96）was 4%,and tartaric acid was 0.2%.According to the results of single factor experiments,orthogonal experiments were designed to screen the best ratio of hydrogel patch preparation.The result is that the hydrogel patch prepared by 9%PAAS NP-700,0.05%aluminum glycinate,5%PVP K88-96 and 0.2%tartaric acid has the highest score,and its adhesion Sex is the best.BU08028 was added to the hydrogel matrix to prepare the BU08028 hydrogel analgesic patch,and a transdermal absorption enhancer was added to increase the penetration of the drug.Under the action of different transdermal absorption enhancers,the cumulative permeation amount per unit area was calculated.The results were that the cumulative permeation amount per unit area of BU08028 in the blank patch for 24 hours was 148.23μg·cm^-2.When azone was used as the accelerator,the cumulative permeation amount per unit area of BU08028 in 24 hours was 513.42μg·cm^-2.When oleic acid was used as the accelerator,the cumulative permeation amount per unit area of BU08028 in 24h was 552.53μg·cm^-2.Therefore,oleic acid was selected as the transdermal absorption enhancer.At the same time,the optimal dosage of oleic acid was screened.When the proportion of oleic acid was 5%,the cumulative permeation amount per unit area of BU08028 in 24h was the highest,which was 659.38μg·cm^-2.As a new type of analgesic,BU08028 hydrogel analgesic patch not only exerts an effective analgesic effect but also reduces side effects such as addiction and damage to physiological functions compared with common analgesics.At the same time,it can play the role of slow-release drug,prolong the analgesic time of the drug,and reduce the number of administrations.This experiment is of great significance to the further study of analgesics in the field of medicine.