Study On Preparation Technology And Quality Standard Of Rhizoma Corydalis Decumbentis Dispensing Granules

Objective:In the light of the relevant technical documents issued by China Food and Drug Administration,the study on Rhizoma Corydalis Decumbentis dispensing granules is carried out.To determine preparation process,establish quality standards,prove the quality and efficacy of the dispensing granules and standard decoction are equal.Methods:（1）To investigate the resources of medicinal materials and make plant specimens,through medicine suppliers,field visits,and other ways.Detection and processing of medicinal materials according to the Pharmacopoeia,and compare the changes of the effective components during processing,establish the internal control standards.（2）To improve the preparation process of standard decoction,prepare 15 batches,determine dry extract rate,the content and transfer rate of Protopine and Palmatine chloride,establish HPLC characteristic spectrum and quality standard.（3）The dry extract rate,content and transfer rate of Protopine and Palmatine chloride as the evaluation index,design orthogonal test of the intermediate,including extraction time,frequency and volume.The drying method is determined by using the powder yield and the properties of the powder as the evaluation index.The quality comparison of intermediate and standard decoction was carried out.The study of granulation technology,screening of excipients,and taking molding rate,solubility and appearance as evaluation indicators,orthogonal test were carried out to study extrusion pressure,extrusion speed and feeding speed,confirm the process and verify it.To prepare dispensing granules,and complete the related examination.The TLC identification,content and HPLC characteristic spectrum methods were established,and the main characteristic peaks were qualitatively identified by LC-MS,the quality standard was established.（4）The standard decoction and dispensing granules prepared by the same batch of medicines were applied to the hot plate method and the acetic acid writhing method.To determine the PGE₂ andβ-EP of serum by enzyme linked immunosorbent assay,SPSS19.0 statistical analysis was used to compare the efficacy of standard decoction and dispensing granules.Result:（1）Preliminary understanding of the distribution,cultivation and resource growth of Jiangxi Rhizoma Corydalis Decumbentis medicinal materials,and made plant specimens.Multiple medicinal materials were purchased,tested and processing.The internal control standards were determined,and there was no significant difference during the processing.（2）Determine the standard decoction preparation process,decoct two times,first add9 times water to soak 30min,boil after decocting 30min,the medicine liquid through200 mesh sieve,second decoct add 7 times water boil,then decoct 20min.Combine two liquids,concentrate to a proper amount,and freeze drying.The quality standard of standard decoction was established.The identification of TLC was clear and specificit,the water was less than 5%.The measurement method of Protopine and Palmatine chloride was established,protopine was good in the ranges of 19.4～484.3μg,the regression equation s Y=13087.573X-19.719（R²=0.9999）,the average recoveries were 94.26%with RSD 1.56%（n=6）.Palmatine chloride was good in the ranges of 7.5～186.6μg,the regression equation Y=43,854.166X+16.933（R²=0.9999）,the average recoveries were 98.94%with RSD1.86%（n=6）.HPLC characteristic spectrum was established with 10 peaks.The limit range was determined by the average of 15 batches standard decoction.（3）Determine intermediate decoction preparation process,3 times each with 6 times water decoction,decoction 1 hour,the medicine liquid through 200 mesh sieve,concentrate to density of 1.05～1.10.For the spray drying,the air inlet temperature is120～140℃,the air outlet temperature 70～90℃,the speed is 30ml/min,and the frequency is 400Hz,respectively.The content,the transfer rate and the dry extract rate of intermediate are within the limits of the standard decoction.The dry granulating process of formula granule,speed 15r/min,pressure 20KN,speed18r/min.The quality standard of dispensing granules was established.The identification of TLC was clear and specificit.The measurement method of Protopine and Palmatine chloride was established,protopine was good in the ranges of 17.3～172.8μg,the regression equation Y=12,262.941X+2.628（R²=0.9999）,the average recoveries were 101.80%with RSD2.13%（n=6）.Palmatine chloride was good in the ranges of 10.7～266.3μg,the regression equation Y=41,342.595X+34.170（R²=0.9999）,the average recoveries were 96.16%with RSD 1.10%（n=6）.HPLC characteristic spectrum was established with 10 peaks,can correspond to the standard decoction,and completed the LC-MS characterization of four peaks.（4）The analysis of analgesic experimental data,can provide that the standard decoction and dispensing granules had analgesic effect,and there was no significant difference.Conclusion:（1）According to the management method of traditional Chinese medicine dispensing granules（draft 2015,No.283rd）,the study carried out.For the first time,we started from the source of medicinal materials,to control the quality of herbs,decoction pieces,standard decoction,intermediates and dispensing granules.（2）The preparation process of dispensing granules is determined by the limit range of the standard decoction.The quality standard of dispensing granules was established,including measurement,characteristic spectrum and so on.LC-MS was used for qualitative research of characteristic peaks.The method is highly exclusive,which is good for identifying.（3）The results of the analgesic experiment showed that the standard decoction and dispensing granules had the same effect.The dispensing granules can be used as a new type of dosage form,and it can be used in clinic accurately and reasonably.