Research And Development Of Chinese Traditional Medicine Wenshenzhuanggu Granule For Treating Osteoporosis

Objective: In clinical curative effect and effective group is divided into basis for the treatment of osteoporosis.Studying the Wenshenzhuanggu granule,establishing a draft of quality standard to effectively control the quality of preparation and its preliminary stability had also been studied,which provided theoretical basis for the development of new preparations of traditional Chinese medicine for the treatment of primary osteoporosis.Methods:1.Study on the preparation process:(1)Water extraction process of radix rehmanniae praeparata and herba epimedii: The optimum extraction process was optimized by using orthogonal experimental design,with the comprehensive score of the content of icariin and paeoniflorin and the extracting rate as evaluation index.(2)Cnidii fructus alcohol extraction process: Alcohol extraction process was optimized by using orthogonal experimental design,with cnidium lactone content evaluation index.(3)Extraction process of volatile oil from aucklandia officinalis: The volatile oil from aucklandia officinalis was extracted by steam distillation,and the optimum extraction process was optimized by taking the yield of volatile oil as the evaluation index combined with orthogonal design.(4)Inclusion process: The optimum inclusion process was optimized by orthogonal design,taking the comprehensive score of inclusion rate and yield of volatile oil as evaluation index.(5)Concentration and drying process: The content of icariin,paeoniflorin and cnidium lactone and concentrated time were used as evaluation indexes to optimize the concentration conditions;the content of icariin,paeoniflorin and cnidium lactone and the solubility of dry cream powder were used as evaluation indexes to optimize the drying conditions.(6)Forming process: Dry granulation is selected to investigate the types and dosage of excipients based on the degree of difficulty,moisture absorption,forming rate and solubility of granulation.On the basis of single factor experiment,three factors which have great influence on the granulation process are selected as independent variables,and the primary forming rate(Y)of particles is taken as the response value.The experimental design of response surface is carried out.The relationship between each process parameter and response value is analyzed by regression equation,and the optimum process parameters are predicted accordingly.Process validation test was carried out.(7)The preparation technology of Wenshenzhuanggu Granule was summarized.2.Quality standard research:TLC was used to qualitatively study paeoniae radix alba,aucklandiae radix,cnidii rfuctus,epimedh folium,drynariae rhizoma,angelicae sinensis;HPLC was used to quantitatively study the effective active ingredients:icariin,paeoniflorin and cnidium lactone;and according to the method of granules(general rule 0401)on 2015 edition of the Chinese Pharmacopoeia(Four Part)to check the preparation below.3.Preliminary stability studies:According to the guideline of stability test of raw drug and preparation(General Principle 9001),the stability of preparation was investigated.Results:1.Study on the preparation process:(1)Water extraction process of radix rehmanniae praeparata and herba epimedii and so on: The best extraction process was to add 12 times of water for 3 times,2 hours each time.(2)Ethanol extraction process of fructus cnidii: The optimum extraction process is to add 10 times of 75% ethanol to extract three times,one hour each time.(3)Extraction technology of volatile oil from aucklandia officinalis: The optimum extraction technology was that aucklandia officinalis was crushed through 60 mesh sieve and added 8 times amount of water for 8 hours.(4)Inclusion process: The optimum conditions are inclusion time of 3 h,ratio of beta-CD to volatile oil of 8 g/mL and inclusion temperature of 50 C.(5)Concentration and drying process: 60℃vacuum concentration process,vacuum drying process for drying.(6)Forming process: The optimum ratio of dextrin and dry paste powder is 1:3,the optimum process of dry granulation is 9MPa for the rolling wheel,15 HZ for the rolling speed and 15 HZ feeding speed.(7)Preparation technology: The above eleven flavors were extracted from Aucklandia officinalis,and the volatile oil inclusion compound was obtained by inclusion of beta-CD.The Cnidium monnieri was extracted three times with 75% ethanol for 1 hour each time.The ethanol was recovered and concentrated to the dry extract for reserve.Drug residues of the above two herbs were decocted and extracted three times with 12-fold amount of water for 2 hours each time with cooked ground,Drynaria,Epimedium,Paeonia lactiflora,Lycium barbarum,Cuscuta,Eucommia ulmoides and Angelica sinensis.The decoction was filtered and concentrated to a relative density of 1.20-1.27(g/mL).The dry extract was obtained by vacuum drying.Mix with Cnidium monnieri dry extract,powder into fine powder,add antler gum powder and volatile oil inclusion complex of beta-CD,add dextrin and magnesium stearate,mix,granulate,whole grain,dry,make 1000 g,then get.2.Quality standard research:TLC identification:paeoniae radix alba,aucklandiae radix,cnidii rfuctus,epimedh folium,drynariae rhizoma and angelicae sinensis radix can be detected.Content determination: No less than 0.038% of icariin should be included in this product.Paeoniflorin should not be less than 0.132%;Cnidium lactone should not be less than 0.089%.Inspection: The granularity,water content,solubility and loading difference of Wenshen Zhuanggu Granules all conform to the relevant regulations.3.Preliminary stability study:From the results of the study,we can see that under the conditions of influencing factors test,accelerated test and long-term test,all the indexes of Wenshen Zhuanggu Granule conform to the relevant provisions.Conclusion:The preparation process of wenshenzhuanggu granules is reasonable,stable,scientific and quality controllable,which can achieve the expected research purpose.To provide effective test data for subsequent research and development of this preparation.