Pharmaceutical Research On Xiaosheng Granule

Dry eye(DED)or dry keratoconjunctivitis(KCS)refers to ocular surface disorders that cause tear quality,quantity and kinetics abnormalities due to any cause,resulting in tear film instability and(or)ocular surface integrity.The causes of the Dry eye disease is unknown,generally believed that it associated with inflammation,hormone secretion,living environment,psychological and other factors.Western medicine in the treatment of dry eye,just has the little effect of their exact drug or means.Mostly it focus on relieving the symptoms,and it is difficult to cure.Chinese medicine in the treatment of this disease,not only have a long history,but also emerges a large number of effective prescription and treatment,to achieve the purpose of both sides of the symptoms.Therefore,Chinese medicine treatment of dry eye is of great significance.Objective:Xiaoshengsan Prescription is the clinical experience of the Chinese Academy of Traditional Chinese Medicine Eye Hospital,the form of granules in the clinical application for many years.The treatment of Yin deficiency type dry eye,the effect is significant.Xiaoshengsan party by the habitat,angelica,white peony root,Codonopsis and other eight herbs composition,with Shugan Yangyin eyesight effect.This subject is based on the original drug efficacy,combined with modern formulation technology,and ultimately developed it into granules.The extraction process was screened from the efficacy index and the extraction rate of the index component(quantity),then the three batches of the pilot test were enriched and the quality standard of Xiaosheng particles was established.Methods:In this study,the research and development of purification process,concentrated drying process,molding process,pilot production and quality standard were carried out for Xiaosheng particles used for dry eye treatment.The specific processes are as follows:1.The study on extraction and purification process:①Tear secretion Schirmer I test(SIT),tear film rupture time test(BUT)and corneal fluorescence staining test under different extraction process to screen out the optimal group.②Taking the extraction of volatile oil as an index,extract volatile oil from Angelica sinensis and Volatile Oil by steam distillation.By this way the extraction time and water times were determined.Study the inclusion volatile oil by aqueous solution of β-cyclodextrin saturated.③Taking the extraction rate of paeoniflorin,the extraction amount of saikosaponin D and the extraction of n-butanol as the index,the orthogonal design was used to investigate the parameters of water extraction.2.The study on the molding process:The wetting granulation method was used to study the wetting agent,auxiliary materials and drug-supporting ratio.The determination of the moisture content and the critical relative humidity of the finished granules were carried out.3.The study on the pilot-scale process:The optimized extraction process is used in the three batches pilot-scale study.Adjust the concentration of the wetting agent ethanol in the grain production to ensure a higher grain yield.4.The study on the quality of the standard:The six herbs of Xiaoshengsan with granules,angelica,white peony root,Bupleurum and others were identified by thin layer chromatography,and the content of paeoniflorin was determined by high performance liquid chromatography.Finally,the corresponding quality standards were developed.Results:1.extraction and purification,concentrated drying process to determine:① Angelica and mint mixed volatile oil extraction and inclusion part:add 8 times water extracted by steam distillation for 6 hours,collecting volatile oil,water filtration filter collection.The mixed volatile oil was mixed at a temperature of 30℃ for 3 hours,and the ratio of volatile oil(ml):β-CD(g):water(ml)was 1:6:60.Meanwhile the inclusion compound was dried at 40℃.②Water extraction process part:the remaining drug taste,add 8 folds the amount of extraction 3 times,2 hours for each time.Filterd the liquid when it is hot.③Alcohol precipitation purification process:The two parts filtrate was combined,concentrated to a relative density of 1.15～1.20(60℃),add ethanol to ethanol concentration of 50%,standing for 16 hours in refrigeration,centrifugation supernatant.Vacuum recovery Ethanol(60℃～80℃ can be),vacuum drying chamber below 80℃ under reduced pressure,crushed to get the extract powder.2.The molding process to determine:Xiaosheng granule final selection of the excipient dextrin,drug ratio of 2:1,wetting agent for 90%ethanol for wet granulation.According to the critical relative humidity of the particles,it is recommended that the relative humidity of the environment be controlled below 87%.Then the granules are prepared,dried and packaged.3.The establishment of quality standards:The six herbs of Xiaoshengsan,such as raw places,white peony root,angelica,mint,Schisandra and Bupleurum was established the TLC identification method;established paeoniflorin HPLC method which can be used in Xiaosheng particles content determination.By methodological verification,the method is stable and feasible.The final determination of Xiaoshengsan scattered particles per 1g of white peony root to paeoniflorin(C23 H28 O11)dollars,not less than 3.32 mg.Conclusion:In this paper,the extraction process was optimized by using the combination of pharmacodynamics and index components,and the parameters of concentrated drying were also investigated.Carried out the study of Xiaosheng granule molding process,through three batches of pilot-scale production,finally get a stable and feasible process route.Obtained a qualified finished particles.The qualitative identification method of six herbs in Xiaosheng granules and the HPLC method of paeoniflorin were determined by the related research.The method was stable and reliable.By this way we could achieve the purpose of quality control for Xiaosheng particles.