Study On Preparation Technology And Quality Standard Of Hospital Preparation “Fang-Xiang-Tong-Luo Decoction”

Objective:With the increasing aging of population and the change of diet structure,cardiovascular and cerebrovascular diseases have become the world’s first disease with high fatality rate,which seriously endangers human health and affects people’s quality of life.Research and development of effective drugs for the treatment of coronary heart disease is the trend of The Times.“Fang-Xiang-Tong-Luo”Decoction is a basic prescription condensed by Professor Yu Zuoying,a national famous old Chinese medicine doctor,according to his clinical experience for many years.It has good treatment and conditioning effect for a variety of chest arthralgia and heartache diseases.It has been widely used in clinic,especially in Jilin Academy of Chinese Medicine.Now TCM compound medical institution preparation has become a major feature of hospitals of traditional Chinese medicine.If“Fang-Xiang-Tong-Luo”Decoction can be further developed into a medical institution preparation,it will not only benefit the inheritance and development of the academic experience of famous traditional Chinese medicine compound and modern application,which can simplify the medical process,increase drug compliance,maintain the stability of curative effect and benefit the people.For the majority of chest arthralgia heartache patients bring good news.Methods:（1）Study on compound extraction technology:with the extraction rate of paste and the extraction amount of salvianolic acid B as indexes,orthogonal test was used to investigate and study the best extraction technology.（2）Study on preparation molding technology:According to the properties of pharmacodynamic substances and the theory of preparation process design,the formulation is granules.According to the process results and the economic principle of considering the production cost,the wet granulation and the appropriate auxiliary materials and their proportion are proposed.The formability,fluidity,solubility and hygroscopicity of particles were used as indexes to optimize the optimum preparation process.（3）Pilot study:three batches of pilot study were carried out on the prescription according to the optimized extraction process and preparation molding process to investigate the stability and feasibility of the process.（4）Quality standard research:Thin layer chromatography and high performance liquid chromatography were selected for qualitative identification and quantitative research of“Fang-Xiang-Tong-Luo”Decoction,and corresponding quality standards were established.（5）Component analysis of splitting square:By means of prescription splitting,the royal medicine Danshen was paired with other medicinal flavors in the compound.Finally,the main chemical markers of each medicinal herb included in the pharmacopoeia were taken as the investigation index,and the results of single decoction,mixed decoction and mixed decoction of the compound were compared,so as to investigate the content changes of core functional ingredients in different decoctions.To clarify the interaction mechanism of substance base formation in compound decoction.Results:（1）Results of compound extraction technology:The optimal extraction conditions were as follows:add7,6,6 times of water,decocting for 3 times（soak for 0.5h before the first decocting）,1h each time.（2）Results of preparation molding process:soluble starch and sucrose powder were used as excipients,dry paste powder:excipient powder（sucrose powder-soluble starch（1:2））1:1～1:1.5 is appropriate.In general preparations,sucrose powder is not more than 20%of the flavor-correcting agent added,that is,200g sucrose powder is added to 1000g preparation at most.Therefore,in this preparation,the amount of sucrose added is tentatively 200g,and soluble starch makes up the remaining prescription amount to 1000g.95%ethanol was used as wetting agent,the drying temperature was 70℃,and the relative humidity should be controlled below 43%.（3）Pilot study results:three batches of pilot production were carried out according to the standard prescription volume expanded by 10 times,the data of three batches of pilot production show that the extraction process and preparation molding process are stable and feasible.（4）Quality standard study results:A thin layer identification method was established for salvia miltiorrhiza,sandalwood,panax notoginseng,safflower and Radix glycyrrhiza.HPLC was used to determine the content of salvianolic acid B,kaempferol,ginsenoside Rg1,ginsenoside Rb1 and panax notoginseng saponin R1 in“Fang-Xiang-Tong-Luo”Decoction.Chromatographic conditions for salvianolic acid B were as follows:column Agilent Zorbax SB-C18（4.6X250nm,5μm）;Mobile phase:acetonitrile-0.1%phosphoric acid solution（22:78）iso-degree elution;Column temperature:20℃;Detection wavelength:286nm;Flow rate:1.2ml/min.The content standard is that salvianolic acid B(C₃₆H₃₀O₁₆)should be calculated in every1g of salvia miltiorrhiza,and not less than 7.95mg.Chromatographic conditions for kaempferol were as follows:column Agilent Zorbax SB-C18（4.6X250nm,5μm）;Mobile phase:methanol-0.4%phosphoric acid solution（52:48）isometric elution;Column temperature:20℃;Detection wavelength:367nm;Flow rate:1ml/min.The content standard is that every 1g of safflower contained in this product is measured by kaverol(C₁₅H₁₀O₆),not less than 0.30mg.Chromatographic conditions for the total contents of panax notoginseng saponin R1,ginsenoside Rg1 and ginsenoside Rb1 were as following:column Agilent Zorbax SB-C18（4.6X250nm,5μm）;Mobile phase:acetonitrile and water were used as mobile phases for gradient elution as follows;0～12min,19%acetonitrile,12～60min,19%～36%acetonitrile.Column temperature:20℃;Detection wavelength:203nm;Flow rate:1ml/min.The content standard is that the total amount of panax notoginseng R1(C₄₇H₈₀O₁₈),ginsenoside Rg1(C₄₂H₇₂O₁₄)and ginsenoside Rb1(C₅₄H₉₂O₂₃)in every 1g of this product shall not be less than 6.96mg.（5）The results of component analysis showed that the content of some pharmacopoeia index components decreased in the process of decocting,while the content of other components increased in different amplitude.This indicated that the change in the content of a single ingredient could not directly correlate with the overall synergistic effect of TCM compounds.However,for some traditional effective ingredients,the more the better is not in the process of decocting TCM compounds,and more attention is paid to the coordination changes between these ingredients and other ingredients.These are consistent with the“molecular effectorgroup”theoryandtheactionmechanismof“multi-component-multi-target-multi-pathway-multi-network”.Conclusion:In this paper,through the optimization of the extraction process of“Fang-Xiang-Tong-Luo”Decoction and the study of the preparation process,the feasibility and stability of the preparation process which is in line with the production economy and suitable for clinical large-scale production were established,and the pilot and pilot production were carried out.Trough the research of quality standard,the thin-layer qualitative identification method and content determination standard were established,which provided a strong basis for strict quality control agent.The interaction mechanism of substance base formation in water decoction was clarified through component analysis of the dissolving formula,which has important significance for clarifying the compatibility mechanism and synergistic principle of the compound.