Study Of Preparation Technology And Quality Standard Of Xianxiong Gukang Granules

The Xian Xiong Gukang granules prescription in this project comes from Epimedium powder in "Tai Sheng Hui Fang",composed of epimedium,Rhizoma Chuanxiong,Radix Clematidis,Guangxi heart,Fructus Xanthii and other traditional Chinese Medicine,which has the efficacy of tonifing the kidney and strengthen bone、Promoting blood circulation to remove obstruction、wind-expelling and pain-alleviating.Clinical often to the party as the foundation with the card to add or subtract,Orthopedics in affiliated Hospital of the University has a clinical application of the treatment of Osteoarthritis significantly.Object Determine the best preparation process of Xian Xiong Gukang granules,establishing a quality standard of Xian Xiong Gukang granules and laying the foundation for the development of traditional Chinese medicine for the treatment of osteoarthritis.Method(1)Examined the the pieces in prescription by TLC and determination by HPLC,such asherba epimedii、Ligusticum wallichii、radix clematidis、cortex cinnamomi、cocklebur fruitand etc.To meet at the requirement of 2015 edition of"Chinese Pharmacopoeia" for qualified Pieces.And Study on Preparation Technology.(2)Take the transfer rate of Icariin,epimedin C,baohuoside I,ferulic acid,oleanolic acid,cinnamic aldehyde as evaluation indexes.To establish a HPLC content method of the 6 component in liquid.AHP to determine the weighting factor of each index component(Weighting coefficients were Icariin 0.35,epimedin C 0.14,baohuoside I 0.09,ferulic acid 0.2,oleanolic acid 0.13,cinnamic aldehyde 0.09).Design extraction method,soaking time,solvent extraction,extraction times,the amount of solvent and extraction time on the extraction process by single factor test and orthogonal.Integrated weighted scoring method to determine the optimum extraction technology of particle Xian Xiong Gukang,and test the best technology for 3 batches.Press optimum extraction prepared Xian Xiong GuKang liquid extract,Osteoarthritis rat model caused by Hulth method to give Xian Xiong Gukang liquid,Pharmacodynamic verification test to verify the reasonableness of the extraction process;Test the acute toxicity and the maximum dose,make a safety evaluation about Xian Xiong Gukang particles.According to the Obtained powder rate and the appearance of extract powder,comparison of different drying methods(vacuum drying,spray drying),determined Xian Xiong GuKang granule drying process.Regard forming rate,moisture absorption,angle of repose,solubility as evaluation indexes.Relatively dry granulation and wet granulation,determine the molding process of XianXiong GuKang granule.Single factor tests were used to investigate the proportion of different types of materials,mixing proportion of materials,accessories and extract powder,wetting agent concentration,optimized the molding process,3 batches of validation tests were carried out on the best molding process.According to the production process of sample of 3 batches of Xian Xiong Gukang granules,quality standard study.Setting up exclusive TLC method for the identification of Xian Xiong Gukang granules in Epimedium,Rhizoma Chuanxiong,Radix Clematidis,GUI Xin(cinnamon),Fructus Xanthii and other medicines.Take the icariin,epimedin C,content of baohuoside I,ferulic acid,oleanolic acid as the control index,Through the systematic study on methodology,to establish a HPLC-UVD method for determination of Xian Xiong particles of the 6 components of gukang;Take the test sample determination results of three batches as content limit;According to the requirements of the 2015 edition of Chinese Pharmacopoeia(four)appendix granules under the requirements of the relevant characters,grain size,moisture,melting and loading differences in the preparation of the general inspection,To establish a quality standard for Xian Xiong Gukang granules(Draft)and drafting instructions.Result(1)The pieces are qualified,which have reached the requirements of 2015 edition of "Chinese Pharmacopoeia"(one),and can be used to study the preparation process.(2)The optimum preparation of Xian Xiong Gukang granules was determined as:the slices were extracted twice by 50%ethanol,the amount was 10 times,1h per time.Then recycled the alcohol till the extract without alcohol flavor,and the liquid relative density was in the range of 1.25～1.30 by vacuum concentration.The liquid was decompression dried with the environment of 0.1MPa,50℃ for 36h,Smashed and Sieved to dry extract powder.The powder was granulated by dry granulator without accessories,with the pressure of 25 MPa and rotating speed of 15 rpm,then the granules were through 10 mesh sieve.Validation test showed that compared to OA model group,the MMP-13,IL-1β of rats’blood was significantly reduced in Xian Xiong Gu Kang administration group,the pathology results showed that rats’ knee cartilage has obviously improved,which means the efficacy of Xian Xiong Gu Kang liquid was exact by optimum extraction.The drug maximum tolerance of mice was about 70 times with adults,and the solution had no effect on the organs of mice,proving the security.Established the quality standard of Xian Xiong Gukang granules,TLC identify spots clear,negative control without interference,reproducible and specific.General inspection melt indexes preparation,particle size,moisture,etc.,are in line with 2015 version of "Chinese Pharmacopoeia" under the relevant provisions of(four)granules item.Established the HPLC determination method for Icariin,epimedin C,Bao beans glycosides-I,ferulic acid,oleanolic acid of Xian Xiong Gukang granules.Icariin showed a good linear relationship within the range of 0.6028～12.056 μg,the regression equation was Y=888.13X+117.05(r=0.9998),the average recovery rate was 99.6%,RSD was 2.3%(n=6).Epimedin C showed a good linear relationship within the range of 0.7792～15.584 μg,the regression equation was Y=651.19X-12.435(r=0.9998),the average recovery was 101.3%,RSD was 2.0%(n=6).Bao beans glycosides-I showed a good linear relationship within the range of 0.0834～1.668 μg,the regression equation was Y=151.81X+30.14(r=0.9999),the average recovery was 99.4%,RSD was 1.8%(n=6).Ferulic acid showed a good linear relationship in the range of 0.2130～4.259 μg,the regression equation was Y=810.99X-221.6(r=0.9998),the average recovery was 100.6%,RSD was 1.9%(n=6).Oleanolic acid in showed a good linear relationship the range of 0.1951～3.902μg,the regression equation was Y=107.72X+28.761(r=0.9997),the average recovery was 100.9%,RSD was 2.6%(n=6).3 batches of 80%in the average content of the test sample to develop content limit Xian Xiong GUKANG particles of each component,Icariin were not less than 3.852 mg/g,epimedin C shall not be less than 3.919 mg/,not less than Bao beans glycosides I 0.3553mg/g,not less than ferulic acid 0.9358mg/g,Qi oleanolic acid not less than 1.363 mg/g,respectively.Conclusion(1)According to "Chinese Drug Research technical requirements",the project was to study the preparation and Quality Standard of new Chinese drug Xian Xiong Gu Kang granules,and completed the corresponding pharmacy experimental(stability studies are in progress),advanced technology,stable and controllable quality,and laid the foundation for the development of new drugs.(2)Pharmacodynamic verification and acute toxicity tests showed that bone Kang Xiong Xian liquid osteoarthritis Curative effect and no significant side effects,drug development in line with the principle of safe and effective.The study fist established an analysis method,HPLC-UVD multi wavelength switching gradient elution method to Simultaneously determinate the multi-component content of Xian Xiong Gu Kang granules.According to the peak order of each component,set the detection wavelength respectively to ensure that all components were detected at its maximum absorption wavelength with high sensitivity and lowl interfering.The results show that the determined optimum preparation can more fully extract the medicinal ingredient,stable,suitable for industrial production;simple established qualitative and quantitative methods,accurate,reliable,reproducible and can be used quality control and quality assessment particles.In the process and quality standard of preparation,the establishment of quality evaluation system for multi-component of multi Chinese medicine,more in line with the overall effect of Chinese medicine characteristics,contribute to a comprehensive quality control of Xian Xiong Gu Kang granules formulation.