Study On Preparation And Quality Standard Of Cheqing Nasal Spray Microemulsion

Cheqing nasal spray is a preparation of eight traditional Chinese medicines,Chuanxiong,Angelica sinensis,asarum,ligusticum,mint,vine,licorice and roasted licorice.It has the effect of clearing the head,dispelling wind and relieving pain.It is used for headache caused by external wind evils.Under the guidance of the theory of traditional Chinese medicine and through the characteristics of the preparation,our subject chooses the ancient prescription Cheqing ointment and develops it from the traditional Chinese Medicine Powder with slow effect,inconvenient carrying and large dosage to the modern nasal spray with convenient carrying,quick effect and outstanding curative effect by using modern preparation technology.It lays a foundation for the development of modern preparations of this prescription.This topic mainly includes the following four parts:1.Study on Extraction and purification process of prescriptionAccording to the index components and pharmacological effects of Chinese medicinal materials of prescription,the extraction rate of volatile oil and ligustilide content in volatile oil were selected as the index of volatile oil extraction process,and the content of ferulic acid,asaronin and Vitex flavin as the index of water decoction extraction and purification process.The process of extracting volatile oil from the whole prescription by steam distillation and decocting the distilled residue was studied.Through single factor investigation and orthogonal design experiment,the final technological parameters were as follows:crushing 10 mesh sieve,adding 8times of water,soaking 2 hours,extracting 10 hours by steam distillation,collecting volatile oil and distillate solution respectively;adding 8 times of water to distilled residue,decocting and extracting 1 time,extracting 40 minutes,collecting extract solution;combining extract and distillate solution,concentrating to 2.0 g/mL of crude drug and adding ethanol to contain.The amount of alcohol is 70%,and it is kept at room temperature for 12 hours.Ethanol is recovered by decompression and concentrated to the corresponding volume.The average yield of volatile oil was0.452%,and the average content of ligustilide in volatile oil was 276 mg/g.The average contents of ferulic acid,asarin and Vitexin in water decoction were 92.89 mg,16.94 mg and 8.98 mg,respectively.The average contents of ferulic acid,asarin and Vitexin in purified water decoction were 73.00 mg,12.26 mg and 7.18 mg,respectively.2.Preparation and physicochemical properties of microemulsionStudied to enhance the solubility and stability of volatile oil in the decoction.The microemulsion was chosen as the drug carrier,and the formulation of microemulsion was screened and optimized,and the physicochemical properties were characterized.In the process of microemulsion preparation,through the solubility test and the pseudo three phase diagram,the suitable oil phase,surfactant and cosurfactant were selected.the best prescription was optimized by using the Box-Behnken response surface method,taking the microemulsion size and the ligusticide loading as the index.The optimum preparation method was as follows:LM 1944 cs 8.17g,1.10g volatile oil,EL35 16.70g,T80 8.30g,PEG400 5.16g,and slowly adding 4.0g/mL of purified water decoction 56mL as water phase,stirring at 35?,and finally adding purified water to 100 mL,stirring to clarity and transparency.Finally,the laboratory amplification process was studied.The physical and chemical properties of microemulsion were characterized.The microemulsion was O/W microemulsion,with a pH value of 6.25,an average particle size of 46.06 nm,an average viscosity of2.70×10³Pa.s,and Zeta potential of-26.02 mV.Three batches of samples were prepared by laboratory enlargement.The results showed that the process was stable and reasonable.3.Study on the quality standard of Cheqing nasal sprayAccording to the requirements under the spray,routine inspection was carried out on the samples of Cheqing nasal spray enlarged in the laboratory,and the inspection was in accordance with the regulations.In the quality standard study,the general rules of spray preparation were checked,and TLC identification methods of Chuanxiong,Ligusticum,Mentha in Cheqing nasal spray were established.The results showed that the spots were clear,the negative was non-interference and the specificity was strong.The limit of aristolochic acid I was examined.The content of ligustilide,ferulic acid,asarin and Vitexin was determined by HPLC.The content limits of ligustilide,ferulic acid,asarin and Vitexin were established.The final formulation of this product contains ligustilide(C₁₂H₁₄O₂)no less than 2.30 mg per mL,ferulic acid(C₁₀H₁₀O₄)no less than 0.58 mg,asarin(C₂₀H₁₈O₆)no less than 0.095 mg,Vitexin(C₁₉H₁₈O₈)no less than 0.057 mg.4.The preliminary stability of Cheqing nasal sprayThe appearance and composition of Cheqing nasal spray were investigated under different temperatures and illumination conditions.The results showed that strong illumination and high temperature had significant effects on ligustilide and ferulic acid content of Cheqing nasal spray,and the stability of Cheqing nasal spray was good under low temperature and dark conditions.The preliminary stability of the samples was studied by accelerated and long-term tests.The results showed that the properties of the samples changed slightly during the accelerated test in June,and the contents of ligustilide and ferulic acid decreased slightly.The stability of three batches of samples in the long-term experiment was good within 6 months,and they all met the requirements of the draft quality standard.