The Research Of Huzhang Antidote Granules (Sugar-Free)

Objective:This topic develops Huzhang Antidote Granules(Sugar-free)based on Huzhang Antidote Granules,to substitute original granular necessity–sucrose and give full investigation to the quality standard,the fingerprint,the stability and the efficacy of these granules so as to release the limit of clinical applications and improve granule quality,finally develop a stable,controllable,safe and effective granules to provide theoretical basis and scientific guidance for the clinical applications of Huzhang Antidote Granules(Sugar-free).To lay the foundation and provide reference for the further development of hospital preparations.Method:1.This experiment used the technique of central composite design –response surface and overall desirability to filter the proportion of total necessities,mixed necessities and the volume fraction of ethanol as the wetter and obtain desired preparation conditions of Huzhang Antidote Granules(Sugar-free)and to validate reliability of the optimization results while the process of decoction,extraction and refining of the original Huzhang Antidote Granules remained unchanged.At the same time,the clinical dosage of the proposed preparation was determined based on the fluid extract and the yield of dry extract.The selected laboratory technique was put into production validation via three batches of the pilot scale-up experiment.2.For study on quality of Huzhang Antidote Granules(Sugar-free),the appearance,identification,inspection and content of the pilot samples of three batches were examined with reference to Chinese Pharmacopoeia 2015.The qualitative identification methods of Huzhang,Banlangen and Chuanshegan were determined with the technique of thin-layer chromatography.The approach to measure the content of polydatin and emodin was constructed by using HPLC,with which the content of polydatin and emodin was determined in the three batches of samples.3.The fingerprints of Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules were initially studied.Similarities of the fingerprints were calculated with median and correlation coefficient methods by using the evaluation software of TCM chromatogram fingerprint(Version 2004 A).Common patterns of Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules were constructed and compared.4.Thestability experiment subject high temperature and humidity,accelerated stability experiment,and long-term stability experiment were carried out on experiment samples from the three batches of Huzhang Antidote Granules(Sugar-free)to examine each indicator.The results were compared with the result of examination in month 0(or day 1)to determine stability of the drug.5.The animal model were constructed where xylene-induced mouse auricle swelling model was used to observe the anti-inflammatory effect of the drug.The dry yeast-induced rat fever model was used to observe the antipyretic effect of the drug.The maximum dosage of mouse was measured to evaluate acute toxicity of the drug.Considering the experimental study on pharmacodynamic action of anti-inflammationand antipyretic of Huzhang Antidote Granules(Sugar-free)and its acute toxicity,preliminary evaluation the efficacy and safety.Results:1.Upon validation,the formation technology of Huzhang Antidote Granules(Sugar-free)is determined as follows: six kinds of medicines including Huzhang,Chuanshegan,Banlangen,etc.were weighed based on the prescription for a total quantity of 2,650 g.Following thick paste obtained with the original process,dextrin,lactose and steviosin were added with a quantity of 625 g,225g and 1.6g,The acceptability of granules produced with the three batches on a pilot basis was 94.3%,94.8% and 96.1%,respectively,demonstrating that the scheme selected by the experiment was stable and feasible and might be applied tolarge-scale industrial production.2.Methods were developed to identify the properties of Huzhang,Chuanshegan and Banlangen,and results showed that the spots in the TLC were clear and the negative medicine was free of disturbance.These methods could identify presence of the medicine in granules in a sensitive and exclusive manner.Establish the HPLC method of measure the content of polydatin and emodin,the results demonstrated that the linearity,precision,repeatability,and the average recovery of HPLC were good.The temporary content of polydatin no less than8 mg per bag,the content of emodin no less than 5mg per bag.Upon examination and study,the appearance,identification,inspection and content of the pilot samples of the three batches conformed to the requirements.3.The chromatographic conditions of fingerprints of Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules were constructed with the high-performance liquid chromatography indicating that there were 19 common peaks in the fingerprints of both preparations.Compositions of polydatin,tectoridin and emodin in both preparations were identified.The similarities of fingerprints of Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules in 10 batches were greater than 0.9.The relative retention time of common peaks of both granules was substantially similar.4.It was shown in the study on stability of Huzhang Antidote Granules(Sugar-free)that during the experiment,obvious changes were not seen in the inspection indicators including product appearance,identification,inspection and content,which conformed t the provisions of the quality standards of pre-clinical drugs.5.The maximum dosages of Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules were 267 g crude drug/kg and 291.6g crude drug/kg,Both Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules showed some inhibitive effects on xylene-induced mouse auricle swelling.Moreover,both granules showed high inhibitive effects on swelling when they are orally taken with high(26.7g crude drug/kg)and medium(13.4g crude drug/kg)dosages.Both Huzhang Antidote Granules(Sugar-free)and Huzhang Antidote Granules could ease the dry yeast-induced rat fever action.The fever was greatly reduced in a period 4-8 hrs following rat fever when both granules were taken with high dosages(26.7g crude drug/kg).Conclusion:The proposed experiment managed to prepare Huzhang Antidote Granulse(Sugar-free),and the preparation technique is resonable and practicable,the standard is controllable,and the finished product is safe and effective as well as stable.Compare to Huzhang Antidote Granules,the clinical application of the patient population was enlarged,and the quality of the standard.was improved.