Pre-clinical Pharmaceutical Study On Zhujie Hewei Granules

Zhujie Hewei Fang is a clinical experience prescription used in Shanghai Traditional Chinese Medicine Hospital to treat gastroesophageal reflux disease.In the long-term clinical application process,notable curative effect.According to the requirements of the Provisions for Drug Registration by CFDA,the prescription was developed into Zhujie Hewei Granules by pharmaceutics method.Systematic pre-clinical pharmacy research was carried out in the aspects of formulation technology,quality standard,stability and pharmacodynamics,which laid a foundation for the later application of new drugs.In the preparation study,taking gardenoside,atractylode III and total saponins as indexes,the preparation process and parameters of extraction,concentration and drying were optimized by orthogonal design.The optimum extraction process was determined as follows: extracting three times with 10 times volumes of boiled water,1 h for each extraction.The effects of concentration temperature and time on the index components in the extract were investigated.The vacuum concentration process temperature was determined to be 75?,and the relative concentration density ranged from 1.14 to 1.16.The boiling granulation was optimized by comparing the different drying and shaping processes with the feasibility of preparation,the yield of granules and the transfer rate of index components,and the formulation and process were investigated.The formulation process was determined as follows: using dextrin as base material,concentrated liquid as binder,and boiling granulation.The feasibility of the preparation process was verified by pilot scale-up,and three batches of pilot-scale particles were prepared.In the study of quality standard,a method for determination of Geniposide and atractylolide III by HPLC and TLC qualitative identification of loquat leaves were established,and methodological investigation was carried out.The results show that the method is specific,stable and reliable,and can be used for the quality control of granules.The stability of 20151218,20151221 and 20151224 batches of pilot-scale particles was investigated.The room temperature and accelerated stability were in accordance with the requirements.In pharmacodynamics,a rat model of reflux esophagitis model was established with the steps of hemiplegia ligation,cardiotomy and hydrochloric acid perfusion.The levels of GAS,MTL and VIP in serum were detected by ELISA;the p H value of supernatant of gastric contents and total bilirubin level were measured;Esophageal mucosal injury was assessed by macroscopic observation integral,mucosal injury index scores and esophageal inflammation scores.The results showed that Zhujie Hewei Granules could increase the p H value of gastric contents,ameliorate mucosal and inflammatory lesions of reflux esophagitis,regulate the increase of serum GAS,MTL and VIP,but had no effect on the total bilirubin level of gastric contents.Pharmacodynamic studies on gastric motility,intestinal motility,anti-inflammation and analgesia were carried out.The results showed that Zhujie Hewei Granules could effectively promote absorption of gastric emptying and accelerate intestinal peristalsis,and had certain anti-inflammatory and analgesic effects.Preliminary safety evaluation was carried out by observing the toxic reaction and death of mice after oral administration of drugs.The results showed that Zhujie Hewei Granule was safe to some extent.