| AIS is one of the three serious treaten human healthy diseases,lacks of ideal therapeutic tool,the case fatality ratio and mutilation ratio is very high,and becomes a puzzle of medicine in the world.The main component of Nao-Qing Nasal Spray Microemulsion is Moschus,Notoginseng,Ligustici,Rhizoma,Borneol,et al..The feature is multiplicity compositions and multiplicity constitution.This topic uses the neo-technique in the world,to combine the microemulsion and nasal cavity dosage,to make the drug in Nao-Qing Nasal Spray Microemulsion keeping close-up and persistence with membrana mucosa nasi,elevating bioavailability,raising patient compliance,especially to utilize the feature of dosage form -nasal spray,to strengthen the target to pars encephalica,refer to stringency deal with the metabolic effect cercbral vessels inadequacy acute stage.It is none report about microemulsion binding Chinese crude drug nasal spray.Microemulsion makes up with oil phase,aqueous phase,surfactant and cosurfactant.According to the character of active component in Nao-Qing Nasal Spray Microemulsion,to make the Rhizoma oil and peponida as oil phase,the extration of Notoginseng and Ligustici as aqueous phase,through the Pseudo-ternary phase diagrams sieved the composition of microemulsion.Of the total,the method of extracting Notoginseng and Ligustici was using 10 times 60% ethanol to extract 3 times,and 45min every times,recovered the extract to no ethanol flavor,centrifuged,adjusted the concentration to 0.33g/ml medical material,passed the D101 macroporous resin,used water to wash to the effluent colorless,and than used 2 times resin volume 70% ethanol to elute,collected the eluant,re-enrich to mastic,when applied,used water dilute to 1g/ml medical material,as aqueous phase.On the basis of the amount of oil phase in prescription,on the principle of the very limit surfactant and cosurfactant,through the Pseudo-ternary phase diagrams sieve the composition of Nao-Qing Nasal Spray Microemulsion,and through the mono-factor investigation to determin the preparation technology.The optimization was peponidium-rhizoma: Cremophor EL:ethanol:the extration of notoginseng-ligustici(3:10:10:77).Apply the method of phase inversion emulsification,in 25℃,first to take surfactant ,cosurfactant and oil to mix,agitated uniformity,and than dorpwised the aqueous phase torpidity, agitated and balance 30min,added sodium chloride q.s. to ajust the osmotic pressure,filtered by 0.22μm filter membrane,to get the Nao-Qing Nasal Spray Microemulsion which the grain size was mormal distribution and fairly narrow.Then to study the physical chemistry property and investigate the rudiment stability of Nao-Qing Nasal Spray Microemulsion.The finding of physical chemistry property was,viscosity 3.056×10-3Pa.s,surface tension 11.8×10-3N·m-1,reractive index 1.3685,pH value 6.1,mean diameter 19.9±5.07nm,Zate electric -1.39±3.06mv.The result of stability was,to place microemulsion the in room temperature(25℃) for 4 months,centrifuged in 10000r/min for 5min,non-demix,no sediment educed,the microemulsion was still brown clear solution;the content of muscone was Nao-Qing Nasal Spray Microemulsion content target, change from 54.3μg/ml to 54.1μg/ml,no obviously depress;grain size change from 21.0±8.49nm to 42.9±18.2nm,according to the tendency of grain size change,prediction the grain size of Nao-Qing Nasal Spray Microemulsion was still to fit the request of microemulsion.This thesis used blood serum pharmacology to study the action of Nao-Qing Nasal Spray Microemulsion, PC12 cells were treated with glumatic acid and physico-hypoxia to induce models of hypoxia,compared the microemulsion and traditional water extration,and the different adminstration routes,through the nasal and intragastric adminstration.The protective effects of the serum contained drug on two kinds models were evaluated by the activity of lactate dehydrogenate(LDH) and staining with MTT assay.The experiment proved, the serum contained drug can protect PC12 cells from injury induced by glumatic acid and physico-hypoxia,and presented dose dependent, microemulsion was better than traditional water extration, the nasal and intragastric adminstration was no significant difference.To certificate Nao-Qing Nasal Spray Microemulsion can through nasal mucosa absorption and educed therapeutical effect,to get out of the way first pass effect,targeted to pars encephalica,straight to reach the focus of infection, educed therapeutical effect.Meanwhile,according to related rule,studied the acute toxicity and mucosa stimulus of Nao-Qing Nasal Spray Microemulsion.Experimental result confirmed was no conspicuous tox-adverse reaction,local application was safety and reliability.This investigation establishes foundation for developing the Nao-Qing Nasal Spray Microemulsion,for providing the future clinical application reference.
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