Research On Preparation Technology And Quality Control Of Broken Panax Quinquefolium Pieces

Objective:1.Adopt low-temperature air jet pulverization technology is used to determine the best cell-breaken process parameters;the granulation technology of non-reinforced excipients is optimized to produce a new type of Chinese medicine pieces with 30-100mesh particles and easy dissolution and absorption.2.In terms of effectiveness and controllability,the quality evaluation system of Panax quinquefolium broken wall pieces was initially established.3.The in vitro dissolution of saponins in broken pieces,coarse powder and fine powder of Panax quinquefolium were compared,and the influence of powder particle size and shape on the dissolution of effective components of Panax quinquefolium was studied.4.Panax quinquefolium broken pieces,coarse powder and fine powder are based on the comparison of the absorption of saponin components in the body after intragastric administration of rats.Methods:1.Through cooperation with enterprises,explore the low-temperature air current collision breaking and crushing technology of Panax quinquefolium pieces and the granulation technology of non-reinforced excipients.The cell wall-breaking micronizer was used to prepare the wall-broken powder with a particle size of D₉₀<45μm.Using the cumulative distribution rate of D₉₀particle size and the content of active ingredients as indicators,the orthogonal design method was used to investigate the interaction between different influencing factors;combined with single factor,the effects of different material ratio,wetting agent（ethanol）concentration,drying temperature and drying time on granulation process were investigated,and the preparation process parameters of Panax quinquefolium broken pieces were optimized;the cell limit of broken pieces was verified and the sterilization method was investigated.2.Establish a quality evaluation system of broken pieces:1)Optimize the identification method of Panax quinquefolium in the Chinese Pharmacopoeia by thin-layer chromatography;2)Use HPLC-CAD（high performance liquid chromatography and electrospray detection combined）to establish the fingerprints of Panax quinquefolium broken pieces and the similarity of the fingerprints of traditional pieces of Panax quinquefolium from the same batch were evaluated and analyzed to explore the correlation between the two.Use DRS Origin software to perform liner calibration with two reference substances correction to predict the retention time of characteristic peaks,and assist in qualitative analysis of chromatographic peaks;3)Use HPLC-DAD for quantitative analysis,and use DRS Origin software to perform liner calibration with two reference substances correction to predict the retention time of characteristic peaks.The index components were qualitatively combined with the relative correction factor method to quantify the index components,and a two reference substances for determination of multiple components was established to simultaneously determine the contents of ginsenosides Rg₁,Re,Rb₁,Rc,Ro,Rb₂,Rb₃,and Rd in broken pieces of Panax quinquefolium.3.Using water,artificial gastric juice and artificial intestinal juice as media,investigate the accumulation of 6 saponin（Rg₁,Re,Rb₁,Rc,Rb₃,Rd）components in broken pieces,coarse powder and fine powder of Panax quinquefolium at different sampling time points Dissolution,draw the dissolution curve,compare the dissolution rules of different forms of Panax quinquefolium ginsenosides.4.Through intragastric administration of rats,the blood concentration of ginsenosides in the drug-containing plasma was determined by HPLC-CAD method,The pharmacokinetic parameters were obtained by processing and analyzing with DAS 2.0pharmacokinetic software,and the absorption differences of Panax quinquefolium broken pieces,coarse powder and fine powder in animals were compared.Results:1.Optimizing the best breaking and crushing process for Panax quinquefolium:the water content of the medicinal material is about 6.0%,the crushing time is 50 min,and the crushing temperature is-10～-15℃;the best granulation process of unconsolidated excipient:wet granulation with wetting agent（85%ethanol）and material 0.7:1,drying temperature 70℃,drying time 45～60 min.2.Thin-layer chromatography identification test found that the spreading distance has a greater influence on the separation effect of spots and the clarity of spot color.When the unfolding distance is 18 cm,Panax quinquefolium and Panax ginseng can be simultaneously identified under the same chromatographic conditions.3.After preliminary analysis of the similarity evaluation system,the fingerprints of the selected 10 batches of Panax quinquefolium broken pieces and traditional pieces were all above 0.951.A total of 17 common peaks were identified,and 8 characteristic peaks of ginsenoside Rg₁,Re,Rb₁,Rc,Rb₂,Rb₃,Rd and pseudo-ginsenoside F₁₁are identified.4.The test compound predicted by the standard curve fitted by the DRS Origin software has high accuracy,and the content calculated by combining the correction factor is compared with the content determined by the external standard method,and the relative error（RE）is less than 3.0%.5.In terms of dissolution rate and cumulative dissolution,Panax quinquefolium broken pieces are better than coarse powder and fine powder;in terms of dissolution medium,the overall dissolution rate of the six ginsenosides in artificial gastric juice is less than that of water and artificial intestinal juice,which is due to saponins.The ingredients are easily degraded in an acidic environment.6.Compared with coarse powder and fine powder,Panax quinquefolium has the largest release amount and the slowest elimination rate in animals,which greatly improves the bioavailability of Panax quinquefolium.The overall order is:broken pieces>coarse powder>fine powder.Conclusion:1.Systematically study the key technologies for the preparation of broken pieces of Panax quinquefolium,and optimize the preparation process of broken pieces of American ginseng.2.Established a thin-layer chromatography identification method,with large amount of information on thin-layer chromatography spots,clear and good resolution.And it is better than the method of identifying the Panax quinquefolium and Panax ginseng under two chromatographic conditions under the"Panax quinquefolium"identification item in the Chinese Pharmacopoeia.3.Using DRS Origin software to predict the retention time accuracy of the liner calibration with two reference substances correction is better than the relative retention time method,and this method not only selects a wide range of chromatographic columns,but also saves the cost of reference materials,providing multi-component quality analysis of Panax quinquefolium broken pieces new ideas.4.Studies have shown that the dissolution rate and cumulative dissolution rate of the 6saponin components in the broken pieces of Panax quinquefolium are better than those of coarse powder and fine powder.It shows that the broken pieces not only retains the advantage of the smaller the particle size,the faster the dissolution rate,but also effectively avoids the shortcomings of powder agglomeration and incomplete dissolution.5.At the same dose,there is a significant difference in the absorption degree of Panax quinquefolium broken pieces,coarse powder and fine powder in rats.Among them,broken pieces have the highest bioavailability,coarse powder second,and fine powder the lowest.For the phenomenon that coarse powder is better than fine powder,it can be seen that the dissolution and absorption in the body may not be large in the small particle size,which may be related to the characteristics and surface morphology of traditional Chinese medicine powder.