Study On Preparation Process And Quality Standard For Compound Yanhusuo Tablet

Primary dysmenorrheal is the most common disease in women. It made patientsSuffering and deeply affected their living, learning and working. Besides that, it hadbecome a burden and greatly decreased the level of living. Modern therapy mainlyadopts anodynes and hormones, and has many side effects. However, Chinesemedicine diagnosis and treatment are based on overall analysis of symptoms andsigns, the cause, nature and location of the illness and the patients physical condition,so it has showed unique curative effect. According to the principle of activating blood,transforming stasis and breaking gas occlusion, famous Chinese gynecologists hadformulated a recipe that had definite effect during clinical application. The recipeconsisted of some herbs such as Rhizoma corydalis, Pollen Typhae, Rhizomasparganii, Rhizoma curcumae Aeruginosae, Ruxiang and Myrrha. After beinganalyzed each herb' compounds and pharmacologic effects, it was believed that therecipe was adapted to develop a Chinese compound formulation which would affordpatients suffering primary dysmenorrheal more convenient, effective, credible andsafe medicine.The contents of thesis include the study on extraction and purification processfor the active ingredients of each herb, the study on preparation process and the study on the quality standard of products.The paper includes six aspects, wherein its method and result as follow.1. Study on alcohol extraction of Rhizoma corydalis and Pollen TyphaeMethods: (1) First, the evaluation index of alcohol extraction for Rhizomacorydalis and Pollen Typhae was established, including the overall amount ofextracted dl-trtrahydropalmatine and the yield of solid substance. (2) HPLC methodwas established to determine the overall amount of extracted dl-trtrahydropalmatine.(3) We had compared the extraction efficiency of different extraction times andexamined the influence of ethanol concentration, ethanol amount and time on byL₉(3⁴) orthogonal design experiment. (4) Analysis of variance on experiments' resultswas carried out and the best extraction condition was optimized. (5) Finally, the bestextraction condition was validated.Results: The alcohol extraction condition had been established, that was, firstlygrinding Rhizoma corydalis intocoarse into coarse powder and combining with PollenTyphae; then extracted two times by 70% ethanol (4 double amount and 1.0 h for thefist time, 3 double amount and 0.5 h for the second time).2. Study on extraction process for Rhizoma sparganii, Rhizoma curcumaeAeruginosae, Myrrha and Radix Cynanchi PaniculatiMethods: (1) The extraction conditions of the total Volatile oil of Rhizomasparganii, Rhizoma curcumae, Aeruginosae and Myrrha were examined by theevaluation index of extracted volatile oil amount. (2) The extraction condition ofpaeonol in Radix Cynanchi Paniculati was examined by the evaluation index ofextracted paeonol yield. (3) The extraction conditions of the water-soluble ingredientsin the above five herbs was examined by the evaluation indexes of solid substancesyield and n-propanol extracts content.Results: (1) It had established the extraction conditions of total volatile oil in Rhizoma sparganii, Rhizoma curcumae, Aeruginosae and Myrrha, that was, firstlyadding 8 times water to the above four herbs and soaking for 1h, then extractingvolatile oil by steam distillation for 7h. (2) The extraction condition of paeonol inRadix Cynanchi Paniculati had been established, that was, firstly adding 10 timeswater and soaking for 1h, then heating,. distilling and collecting distillates 8 timesamount (V/W), finally under 4℃placing all the distillates for 24h, filtrating andcollecting the paeonol crystal. (3) It has established the extraction condition ofwater-soluble ingredients in Rhizoma sparganii, Rhizoma curcumae Aeruginosae,Ruxiang, Myrrha and Radix Cynanclii Paniculati, that was, after extracting thevolatile ingredients in the above five herbs, separating solution from residues, thencombining the residues of two parts and extracting by water(4 double amount and 1.5h), finally combining all the solution.3. Study on the separation and purification processMethods: (1) The method of removing the solid particles from distillates andthe method of removing the water-soluble macromolecules impurities from thewater-extracted solution by alcohol depositing method had been established, (2)Using the n-butanol extract retained rate in the supernatant fluid after alcoholdepositing as evaluation index, the influence of relative cencentration before alcoholdepositing, alcohol amount during alcohol depositing, and depositing time on alcoholdepositing effects was examined by L₉(3⁴) orthogonal design. (3) The analysis ofvariance on the results was carried out and the best alcohol depositing condition wasoptimized. (4) The rationality of alcohol depositing removing impurities wasvalidated by the common experimental identification of chemical compounds.Results: (1) It had established that we should adopt filtration to remove the solidparticles from the alcohol extract and adopt filtration and high-speed centrifugation toremove the solid particles from the water extract. (2) It had established the alcohol depositing condition of water extract, that was, concentrating the water extract toproportion 1.05(under 80℃), and adding 95% ethanol to solution to 60% alcohol anddepositing 4 h. (3) It had confirmed that the method of alcohol depositing removingimpurities was reasonable.4. Study on the process of volatile ingredients inclusion withβ-cyclodextrinMethods: (1) The method of determining the inclusion rate of paeonol andvolatile oil had been established. (2)Influence of agitation speed on the inclusioneffect had been examined by Using the inclusion yield and inclusion rate as evaluationindex. (3) Using the above evaluation index, the influence of feed proportion,inclusion temperature, and agitation time on the inclusion effect had been examinedby L₉(3⁴) orthogonal design. (4) The analysis of variance on the results was carriedout and the best inclusion process condition was optimized.Results: (1) It had established the method of examining volatile oil inclusionamount by volatile oil measurement and the method of examining paeonol inclusionamount by UV absorb coefficient. Furthermore, it had established the calculationmethod of the paeonol and volatile oil inclusion rate. (2) It had established theinclusion process condition, that was, agitation speed was 1500 rpm, feed proportionwas 1:10, inclusion temperature was 40℃, and stiring for 2 hours.5. Study on the process of preparing dosage formMethods: (1) Themoisture absorption percentage of the mixture of extracteddry powder and inclusion compounds had been examined. (2) The appropriatediluents was determined and optimized by moisture absorption curve. (3) Using theproperties and sifted condition of flexible material, granule yield; particle distributionand mucosity, rigidity and disintegration of tablets during preforming as evaluationindexes, the amount of diluents and the concentration of wetter was optimized. (4)The influence of different wetter amount on granulating effect was examined. (5) The influence of different disintegrating agent and lubricant amount on tabletting effectwas examined. (6) The critical relative humidity(CRH) of dry granule was examinedto afford reference to control the ambient condition during tabletting. (7) The filmcoating condition on plain film had been established, (8) The intact tablet formulationand preparation process had been established.Results: (1) Starch and dextrin were used as diluents. (2)It had establishedwetter was 95% ethanol and its amount was 20～24%. (3) It had established thatdisintegrating agent, was carboxymethylstarch sodium and its amount was 3%. (4) Ithad established that lubricant was magnesium stearate and its amount was 0.3%. (5)Critical relative humidity(CRH) of dry granule was about 74%, thus it had establishedthat it should control ambient relative humidity under 70% during tabletting. (6) Ithad established that coating film is gastric-soluble GAIXY14B film coat powder (ironoxide red) and its amount was 4% (wt.) of tablet.6.Study on the quality standard of productsMethods: (1) Rhizoma corydalis, Resina draconis, Pollen Typhae, Ruxiang,Myrrha, Radix Cynanchi Paniculati were identified by TLC; (2) HPLC wasdeveloped to determine the dl-trtrahydropalmatine in the main drugs of theformulation; (3) The general inspection to this formulation was carried out.Results: (1) In the identification test there was the same color speck in theformulation chromatograms as that in the reference and the blank test showed nointerference. (2) The dl-trtrahydropalmatine showed a good linear relationship in theconcentration range of 1.05～6.30μg (r=0.9999). The average recovery rate was up to99.04%, RSD was 1.43%. The content of the dl-trtrahydropalmatine in each tabletwas not required lower than 0.1 mg.