| Chronic Obstructive Pulmonary disease(COPD)is one of the common pulmonary disease in clinic.Its long course of disease and repeated attacks affect the quality of life of the patients seriously.The treatment of COPD is short of effective means in modern medicine,and insufficient attention is paid to the treatment of patients in stable period of disease,which often leads to poor therapeutic effect,which results in the recurrence and progressive aggravation of the condition,which affects the normal life of patients and the rehabilitation of diseases.Chinese medicine has certain advantages in the treatment of chronic lung diseases,especially the recurrent persistent diseases.Objectives of the study:Qizhi Yifei granule is an experiential prescription used in the treatment of COPD in Beijing Dongzhimen Hospital.The prescription is mainly composed of Astragalus membranaceus,Alcohol Rhizoma Polygonati,Leech,Pinellia ternate and so on.It has the effect of tonifying qi and nourishing lung,eliminating swelling and dispersing,eliminating Phlegm,relieving cough and asthma.The aim of this study was to develop this prescription into granules with the advantages of stable properties,convenient industrial production and convenient carrying and taking.Research methods:This subject mainly includes the extraction and purification technology of Qizhiyifei granule,the stability of Quercetin-3-O-β-D-glucose-7-O-β-D-gentiobiosid,the molding technology,the pilot-scale study and the quality standard study.The methods are as follows:1.Study on extraction and purification process:with the extraction rate of volatile oil as the index,the extraction process of the mixed volatile oil of Pummelo peel,Chinses Angelica and Forsythia suspensa Vahl was optimized;With the inclusion rate of volatile oil was taken as the index,the inclusion process of volatile oil was optimized;The inclusion complex was characterized by microimaging analysis and X-ray diffraction.In addition,the extraction,inclusion process and characterization of volatile oil from Pummelo peel were investigated separately.The extraction rate and retention rate of Astragaloside Ⅳ and Quercetin-3-O-β-D-glucose-7-O-β-D-gentiobiosid were used as indexes.The water extraction and alcohol precipitation of Astragalus membranaceus,Alcohol Rhizoma and semen Lepidii were studied by orthogonal experiment.2.Molding process:the fluidity of extract powder and granules was investigated by the method of angle of repose.The percentage of moisture absorption,the forming rate of particles,the state of soft material and the difficulty of granulation were used to determine the auxiliary materials,the ratio of medicament to auxiliary and the concentration of wetting agent.The solubility,density and critical relative humidity of the particles were measured respectively.3.Pilot-scale experimental study:according to the optimized technological route and operation steps,three batches of pilot-scale experiments were carried out to investigate the stability and feasibility of the pilot scale up to 600 prescriptions.4.Research on quality standards:Astragalus membranaceus,Alcohol Rhizoma Polygonati,Leech,Pinellia ternate,Fritillaria thunbergii Miq,Chinses Angelica and etc were qualitatively identified by TLC;The content of Astragaloside Ⅳ in Qizhi Yifei granules was determined by HPLC-ELSD method.It provides the basis for the quality evaluation of Qizhiyifei granules.5.Study on the Stability of Quercetin-3-O-β-D-glucose-7-O-β-D-gentiobiosid:The optimum extraction technology of semen Lepidii was determined by orthogonal design.The thermal stability of the constituents of semen Lepidii in aqueous solution was investigated by the classical isothermal method,and the validity period and half-life of the component were obtained at different temperatures.In addition,the stability of this component in different Ph,different solvents and different concentrations was investigated.Results of the study:1.Extraction and purification process:The optimum extraction process of volatile oil was no soaking,adding 12 times of water,and extracting for 10h.The optimum inclusion process was as follows:oil(mL):β-CD(g):water 1:10:100,inclusion temperature 40℃,inclusion time 3h.The optimum extraction process of volatile oil from Pummelo peel was no soaking,adding 10 times of water,and extracting for 10h.The optimum inclusion process was as follows:oil(mL):β-CD(g):water(mL)=1:8:80,inclusion temperature 50℃,inclusion time 3h.The volatile oil inclusion complex was characterized by microscope and X-ray diffraction.The results showed that the inclusion complex formed and the inclusion state was well.The process of extraction and alcohol precipitation from the remaining seven kinds of medicine is as follows:adding 10 times of water to the pieces,extracting 1.5h,and extracting 3 times.The optimum process of alcohol precipitation is to reduce the pressure to the relative density of 1.05-1.10(60℃),add ethanol to 60%alcohols,storage in refrigeration overnight,filtered,the filtrate recovery of ethanol and concentrated to the amount,dry extract with reduced pressure and finally the extract power was get.2.Molding process:It is determined that dextrin is the excipient,wet granlation and extract powder:dextrin is evenly mixed with 1:1,the wetting agent is 90%ethanol,the critical relative humidity is controlled below 82%,and the particle has good solubility and fluidity.3.pilot-scale experimental study:Three batches of pilot-scale production data show that the extraction and purification process and molding process are stable and feasible.4.Study on the quality standard:The TLC spots of all kinds of drugs in the prescription were separated well without negative interference.Astragaloside Ⅳ in 0.02502mg/mL～0.70056 mg/mL range showed a good linear relationship(R2=0.9994),the average recovery rate was 96.76%(n=6),RSD 0.52%.The conditions of astragaloside IV were:Agilent Zorbax SB-C18 column(4.6mm*250mm,5um),mobile Phase was acetonitrile(A)32%-water(B)68%;column temperature was 30 ℃,volume flow rate was 1 mL/min,injection volume was 20uL,time was 25min.The detector is an Agilent 380 evaporative light scattering detector(ELSD).The atomizer temperature of the detector is 85℃,the evaporator temperature is 85℃,the carrier gas is high purity nitrogen,and the gas flow rate is 1.00mL/min.5.Study on the stability of Quercetin-3-O-β-D-glucose-7-O-β-D-gentiobiosid:through linear fitting,it is found that the degradation law of the component is in accordance with the zero order reaction Y=-Kt+C0,and the regression equation is;1gK=-190.71/T-0.9203,The effective periods of 60,80 and 100℃ are 11.49h,1.15h,0.67h,respectively,and the half-life is 2814h,5.74h,3.35h,respectively.When PH=6,the composition is stable.When PH is less than 6,it is basically stable,and there is a small amount of degradation.When PH is greater than 6,a large number of degradation occurs,and with the extension of time,the degradation is more,indicating that the degradation of this component is alkali-catalyzed reaction.Under the condition of 30%methanol,the composition is relatively stable.Under the condition of 30%ethanol,it has great degradation in a relatively short time,and the content of this component gradually decreases in aqueous solution.Conclusion:The optimal extraction and purification process and molding technology of Qizhiyifei granules were determined in this paper.Three batches of pilot-scale experiments were carried out,and the criteria of TLC qualitative identification and content determination were established.The method was reasonable,stable and feasible.It can effectively control the quality of the preparation of Qizhiyifei granules. |
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