Pharmaceutical Study Of QH Granules

The QH granule originated from clinical effective prescription which is composed of Fructus Corni,Radix Puerariae lobatae,Radix Rehmanniae Praeparata,Herba Plantaginis,and Rhizoma Curcumae Longae.It has been used in the treatment of early renal lesions in type 2 diabetes caused by yin deficiency and dampnessheat,venae discord,which has the effect of nourishing yin and the kidney,clearing and promoting blood circulation.Diabetic nephropathy is the glomerular microangiopathy caused by diabetes,which expressed as abnormalities of protein excretion and filtration.It is a common and serious chronic microvascular complication of diabetes,which is the leading cause of end-stage renal failure,which is also the main cause of death in patients with diabetes.We need to remove inactive ingredients and retain the active ingredients to the greatest extent,reflect the comprehensive efficacy of compound preparation,but also need to make the finished products safe,effective,stable and controllable,to meet the clinical requirements.So,according to the requirements of Drug Registration of SFDA,we studied its raw materials,preparation process,quality standard and stability.The study details are as the following:Study on material:According to the relevant provisions of the Chinese Pharmacopoeia(edition 2010,part I),the raw materials of preparation were identified.The results are in line with the requirements and can be used in pharmaceutical research of QH granules.Study on preparation process:According to the theory of Traditional Chinese Medicine and the physicochemical property of the active ingredients,preparation process has been designed.?.The extraction rate of volatile oil in Rhizoma Curcumae Longae was used as index to optimize the extraction process of volatile oil by L9(34)orthogonal experiment.The optimized conditions are immersing with 8-fold volume of water for I hour and distilling for 6 hours.And the optimum extraction process of volatile oil was verified.2.Using the inclusion rate of volatile oil,the recovery rate of inclusion compound,and the oil-bearing rate of inclusion compound as indexes to optimize the inclusion process of volatile oil by L9(34)orthogonal experiment.The optimized conditions are using colloidal mill method to incluse the volatile oil with 8 times of?-cyclodextrin,with 4 times of water for 30 minutes.And the optimum inclusion process of volatile oil was verified.3.The contents of loganin and puerarin and the yield of alcohol extract were used as indexes to optimize the alcohol extraction process of Fructus Corni and Radix Puerariae lobatae by L9(34)orthogonal experiment.The optimized conditions are extracting 3 times with 12-fold total volume of 60%ethanol for 1.5 hours each time.And the optimum alcohol extraction process was verified.4.The content of polysaccharide and the yield of water extract were used as indexes to optimize the water extraction process of Radix Rehmanniae Praeparata and Herba Plantaginis by L9(34)orthogonal experiment.The optimized conditions are immersing 0.5 hour and extracting 2 times with 15-fold total volume of water for 2 hours each time.And the optimum water extraction process was verified.5.The alcohol precipitation of the water extract has been studied.The result is:the relative density of the water extract is 1.08?1.11(determined under 60 ?),adding ethanol to the extraction and making it a 50%alcohol solution,then letting it stand for 48 hours.6.Using the contents of loganin,puerarin and polysaccharide as indexes to optimize the enrichment and drying process.The optimized enrichment conditions are:the water-alcohol liquid was recycled ethanol and merged with the concentrated liquid of alcohol extract,then decompressive concentrated to the relative density for 1.05?1.08(60 ?)under 0.08Mpa and 60 ?.The optimized spray drying conditions are:the feed speed is 3000?3600 ml/h,the inlet air temperature is 165?175 ?,and the outlet air temperature is 85?90 ?.7.Preparation proeess for the granule has been optimized.The molding process conditions are:the proportion of extract powder,dextrin and microcrystalline cellulose is 1:1.2:0.05,wet granulation with 90%ethanol,and drying at 50?.8.Pilot-scale experiments have been carried out.The results showed that the transfer rate of loganin and puerarin were both greater than 60%,the process was stable and feasible.Study on quality standard:1.Identifications of Fructus Corni,Radix Puerariae lobatae,Radix Rehmanniae Praeparata and Rhizoma Curcumae Longae were carried out by TLC.The results showed that the TLC spots were clear and specific,and the negative control was non-interference.So the qualitative identification method was established.2.According to the corresponding inspection items of the Chinese Pharmacopoeia(Edition 2010,Part ?,Appendix I C),the pilot scale samples were examined,including granularity,moisture,solubility,content uniformity,microbial limits and so on.The results were all consistent with the requirements.3.HPLC method was used for the simultaneous determination of loganin and puerarin in QH Granules.The results of methodological study showed that the linear relationships of loganin and puerarin were good within 0.041?0.412,0.420?4.200 pg,respectively,the average recoveries were 98.38%and 97.29%,respectively,and the RSD were 2.17%and 1.64%,respectively.According to the determination results of the three batch of samples,the limitations of loganin and puerarin were made.It was determined for the moment that each bag should contain no less than 6 mg of loganin and 40 mg of puerarin.The determination method of loganin and puerarin was established and the quality standard of the end products was established.Study on stability:The long-term stability test of 12 months and the accelerated stability test of 6 months were carried out,including inspection items of sample characters,identification,granularity,moisture,solubility,content uniformity,microbial limits and the contents of loganin and puerarin.The results showed that the quality of preparation was stable.In order to determine its actual validity period,this job is going on.The study results show that the preparation process is reasonable and practicable,the quality standard is controllable,and the quality of products is stable.Under the guidance of the theory of Traditional Chinese Medicine,basing on the character of active ingredients,clinical demand and the practice of industrial production and utilizing the latest achievements in preparation technology and quality control technology fully and flexibly,we successfully completed the pharmaceutical study of QH granules,and grounded a solid foundation for developing a new drug.