| Parkinson’s disease is a nervous system disease.Its pathogenesis and causes are many,mainly due to the damage of dopaminergic neurons,resulting in the decrease of dopamine secretion.Its clinical manifestations are:muscle tremor and rigidity,slow motor response,unstable standing,etc.Another feature of Parkinson’s disease is the formation of Lewy bodies in the substantia nigra.The Pathogenesis of Parkinson’s disease is ambiguous,and its pathogenic factors are complex,which are related to environment,toxic substance contact,genetic factors,external trauma and mitochondrial dysfunction.At present,the treatment of PD is few and has little effect,mainly taking levodopa.However,the long-term effect of the treatment would be greatly reduced,and the side effects will be greater.In 2017,Mittal and other researchers found that β2 receptor agonists can regulate α-Synuclein to inhibite the production of Lewy body.Our team initially explored the possibility of salbutamol euenantiomer(R)-salbutamol intranasal administration in the treatment of Parkinson’s disease.1.Related substances and content detection methods,establish the liquid phase method of related substances and content detection,and verify its related indicators(exclusive,quantitative detection limit,durability,linearity,recovery rate,etc.)to ensure the reliability of the method.Then,the related substances and content of salbutamol nasal drops were detected.The results showed that the two methods could accurately measure the related substances and contents of(R)-salbutamol nose drops.Three batches of prescriptions were reconstituted and the related substances and contents were tested to be in conformity with the regulations2.The spatial distribution of(R)-salbutamol in the brain of rats delivered by intranasal and intravenous administration was studied by using a DESI-MS.The brain targeting rate of 1-salbutamol was significantly higher in the nasal delivery group than in the intravenous injection group.In addition,The results show that DESI-MS can be used to analyze the delivery efficiency of drug delivery routes.3.Rotenone induced Parkinson’s model was feasible in this study.There are obvious behavioral differences between the model and the non model,and the successful model basically mimics the clinical characteristics of Parkinson’s disease.Several behavioral experiments were conducted to detect the improvement of motor function in rats.The therapeutic effect of(R)-salbutamol on the model rats was successful,and its motor ability was improved.In addition,the nasal administration of 1-salbutamol is better than atomization.4.The pathological analysis of each group was made by immunohistochemistry.The results of pathological analysis can basically confirm that(R)-salbutamol has therapeutic effect on rotenone induced Parkinson’s model in rats.In addition to confirming that salbutamol can affect the expression of α-synuclein to treat Parkinson’s disease,we also found that(R)-salbutamol can inhibit and promote GFAP and TH.5.Through the experiments of cytotoxicity,toad mucosal toxicity and heart rate,it was found that(R)-salbutamol has not toxic in three experiments,while(S)-salbutamol was toxic in the cytotoxic experiments,but not in toad mucosal experiments.In conclusion,compared with intravenous and Nebulizer,(R)-salbutamol has better brain targeting efficiency and better therapeutic effect.The behavioral and pathological results showed that(R)-salbutamol nose drops had therapeutic effect on rotenone induced Parkinson’s disease in rats.At the same time,the toxicity test showed that the safety of(R)-salbutamol nose drops was initially guaranteed. |
