The Study Of Gutong Plaster On Anti-inflammatory And Analgesia Mechanism And Preparation Security

ObjectiveThe aim of this study was to research the main pharmacodynamics of analgesia and anti-inflammatory by observing stimulation model in rats of Gutong plaster,to envaluate analgesic efficacy and explore its action mechanism,and study its preparation safety by skin irritation test,to provide theoretical basis for clinical application.MethodsExperiment 1:Using SD rats to prepare acute pain model of rats by formaldehyde stimulation,to envaluate analgesic efficacy of Gutong plaster,and the rats respectively(1)plasma beta-endorphin(β-EP)content determination;(2)plasma PGE2 content determination;(3)spinal cord c-fos gene detection;(4)the content of serum,local tissue NO;(5)serum,localtissue and cerebrospinal substance P content determination.Experiment 2:Using SD rats to prepare acute pain model of rats by trypsin stimulation,to envaluate analgesic efficacy of Gutong plaster,and the rats respectively(1)plasma beta-endorphin(β-EP)content determination;(2)plasma PGE2 content determination;(3)spinal cord c-fos gene detection;(4)the content of serum,local tissue NO;(5)serum,local tissue and cerebrospinal substance P content determination.Experiment 3:Using SD rats to prepare acute inflammation model of rats by formaldehyde stimulation,to envaluate anti-inflammatory efficacy of Gutong plaster,and the rats respectively(1)the content of tissue TNF-α;(2)the content of tissue IL-1;(3)the content of tissue IL-6;(4)the content of tissue PGE2;(5)the content of serum,tissue NO;(6)the content of serum,tissue 5-HT;(7)the content of serum,tissue HIS;(8)Histopathological observation of inflammation.Experiment 4:Using SD rats to prepare chronic granulomatous inflammation model of rats,to envaluate anti-inflammatory efficacy of Gutong plaster,and the rats respectively(1)the content of tissue TNF-α;(2)the content of tissue IL-1;(3)the content of tissue IL-6;(4)the content of tissue PGE2;(5)the content of serum,tissue NO;(6)the content of serum,tissue 5-HT;(7)the content of serum,tissue HIS;(8)Histopathological observation of inflammation.Experiment 5:Take New Zealand rabbits for a single drug skin irritation test by comparison with intra-individual left/right self comparison method after a single administration 6h,recording skin irritation,to evaluate the safety of Gutong plaster.Experiment 6:Take New Zealand rabbits for multiple dosing skin irritation test,Gutong plaster adminstration 24 h for 21 consecutive days,recording skin irritation,to evaluate the safety of Gutong plaster.ResultsExperiment 1: after dosing 1 h,2 h,3 h,4 h,6 h can raise the pain threshold.Gutong plaster can effectively reduce the PGE2 levels in plasma,increasebeta-endorphin content in plasma,reduce the NO content in serum and inflammatory tissue,reduce substance P content in inflammatory tissue and brain tissue,compared with model control group was statistically difference(P<0.05 orP<0.01).But there were no obvious effect on serum content of substance P and gene expression of rat spinal cord yuan c-fos(P>0.05)by Gutong plaster.Experiment 2: after dosing 1 h,1.5 h,24 h can raise the pain threshold.Gutong plaster can effectively reduce the PGE2 levels in plasma and improve beta-endorphin content in plasma,reduce substance P and NO content in serum and inflammatory tissue,and reduce the content of substance P of brain tissue,compared with model control group was statistically difference(P<0.05 or P <0.01).But there was no significant influence(P>0.05)to the spinal cord c-fos gene expression by the Gutong plaster.Experiment 3:The growth of foot plantar in mice was inhibited after the delivery.However,there was no statistical difference between 1h and 2h after administration(P>0.05).There was a statistically significant difference(P<0.05 or P<0.01)between the high-dose group and the control group from 3h after administration.There was a statistically significant difference(P<0.05 or P<0.01)compared the low-dose group,middle-dose group,high-dose group with the control group from 4h and 6h after administration.Gutong plaster can effectively reduce the NO,5-HTand HIS levels in serum and tissue,reduce the PGE2 levels in tissue,increase IL-6 in inflammatory tissue,significantly reduce the pathologic grading in rats,compared with model control group was statistically difference(P<0.05 or P<0.01).Gutong plaster can effectively reduce the TNF-α,however,without statistically difference(P>0.05).It had no significant effect on the content of IL-1β in inflammatory tissue.Experiment 4:Gutong plaster can effectively,reduce the NO,HIS and 5-HT levels in serum and tissue,reduce the granuloma tissue mass,reduce the PGE2 and IL-lβ evels in tissue,compared with model control group was statistically difference(P<0.05 or P<0.01).But no obvious pathology change of rat inflammatory tissue.Gutong plaster can effectively reduce the TNF-α,however,without statistically difference(P>0.05).It had no significant effect on the content of IL-6 in chronic inflammatory tissue.Experiment 5:the rabbits’ intact or damaged skin had no irritation response to low and medium-dose PIB Gutong plaster.High-dose PIB Gutong plaster caused no irritation response in the rabbits’ intact skin,but slight irritation in damaged skin 1 h after administration.The rabbits’ intact and damaged skin had slight irritation response to Gutong plaster of traditional dosage forms.Experiment 6:a high score of traditional formulations was early than PIB form,and traditional forms scored higher than PIB form in the same time period.Conclusion(1)Gutong plaster to formaldehyde causes pain in rats and trypsin cause pain in the rat all have certain analgesia effect,its mechanism may be by reducing plasma PGE2 levels in blood,increasing plasma β-EP content;Reduce the NO content in serum and inflammatory tissue,reduce inflammatory tissues and substance P content in brain tissue.(2)Gutong plaster to formaldehyde causes inflammation in rats have certain anti-inflammatory efficacy,its mechanism may be by reducing the NO,HIS and 5-HT levels in serum and tissue;reducing the PGE2 levels in tissue,increasing IL-6 in inflammatory tissue,improving subcutaneous edema and inflammatory cell infiltration of the local inlammation organization.(3)Gutong plaster to chronic granulomatous inflammation model of rats have certain anti-inflammatory efficacy and can reduce the weight of granulomatous tissue,its mechanism may be by reducing the NO,HIS and 5-HT levels in serum and tissue;reducing the PGE2 and IL-1β levels in tissue.(4)Gutong plaster(PIB)is safe for transdermal administration.