| Danhuang Gel was traditional Chinese medicines containing herbs:Rheum officinale Baill, Coptis chinensis Franch, Phellodendron chinense Schneid and so on, which had the effect of heat-clearing and detoxicating, cool the blood and stasis, eliminating wind and anthelminthic, detumescence and eliminating stagnation,was used for the Clinical treatment of acne. Under the guidance of TCM theory,the pharmaceutical researchs were performed in these aspects,including forrnulation,technology,the dissolvability of the extract,the release and transdermal penetration characteristics in vitro,quality tandard and stability using modern science and technology.1. Study on the quality of herbsRegarding the method of identifying of the Chinese Pharmacopoeia as reference, the selected herbs were identified, the content of five components in Rheum officinale Baill and berberine in Coptis chinensis Franch and Phellodendron chinense Schneid was determined, the results showed that the selected herbs meet the pharmacopoeia requirements.2. Study on the optimized extaction process of Danhuang GelAccording to the effectiveness of prescription indications, clinical drug characteristics and the nature of the active ingredients of drugs, We ground the sulfur and borneol to fine powder, the remaining six herbs were extracted.Based on the results of literature and pre-test,with the extraction rate of the active ingredients berberine and chrysophanol as the indicators and taking the yield of dry extract into account,single factor test was used to investigate the extraction temperature,and the uniform design method was used to investigate the ethanol concen tration,solvent usage,extraction time and extraction times,the results were optimized by multi variate statistical analysis and response surface analysis, the final result showed that the best conditions are adding 7 times the amount of 65%ethanol to extract prescription medicine for 3 times under 90℃,2 hours once,the verification test results showed that the extraction process is stable, reasonable and feasible. With the transfer rate of chrysophanol and berberine as the index,the method and temperature of concentration and drying were studied,the final and the best conditions was that the extract liquid was concentrated at a temperature of 45℃under vacuum, transferred to vacuum oven and dried into dry extract at 50℃when the extract liquid was concentrated to 10%of the original extract volume.3. Study on dissolvability of the extractThe dissolvability affeets the preparation,stallility and the pharmacodynamic action and the study of the dissolvability was important for performulation.We used the methods of precipi tation and dissolved load of the index components to investigate the dissolvability condition of the extract and the index components chrysophanol and berberine in some different reagents often used in the transdermal preparation,and the shake flask method was established to determine the apparent n-octanol/water partition cofficieent of the index components chrysop hanol and berberine.The research results showed that the extract had better solubility in the propylene glycol and water,while the index components had a good solubility in the propylene glycol, ethanol and isopropanol.The results of n-octanol/water partition cofficieent test showed that the liposolubility of chrysophanol and berberine in the extract is not good, and easily influenced by the pH value.4. Study on the proeessing technology of Danhuang GelAccording to the researh results of solubility of the extracts, the solvent used to dissolve the extract of gel was investigated,finding that the mixed solution composed by 30%propylene glycol,30%ethanol and 40%water was the best selection. Taking the transdermal penetration rate and release rate as the main index,we used the dialysis membrane diffusion method and transdermal penetration test in vitro to study the type and amount of gel matrix, penetration agents and the amount of penetration agents, drug loading of gel matrix,1.0%Carbomer-940 was selected as gel matrix,2%Azone was selected as transdermal penetration enhancers and the drug loading of gel matrix selected 4.5%by the use of related dynamic model analysis and the similarity factor analysis. On this basis, orthogonal design method was applied to investigate the amount of triethanolamine, propylene glycol dosage, the amount of ethanol and glycerol, the results of the amount were 1.5%,10.0%,10.0%,5.0%when the prescription had the best release. Then we determine the optimal Danhuang Gel formulation and preparation process,and three batches of sample gel were prepared.5. Study on the characteristics of release and transdermal penetration in vitroThe characteristics of release and transdermal penetration in vitro were investigated by using a variety of kinetic model equations to describe the law rules of release and transdermal penetration of the index components, and adopted the similar factor analysis to evaluate the differences of release and permeation between three batches of Danhuang Gel.The results showed that release of chrysophanol and berberine from the gel was the result of the synergy of diffusion and dissolution, release of chrysophanol can be described by zero-power kinetics model,while berberine by Ritger-Peppas model. The results of penetration test showed that penetration of chrysophanol and berberine in vitro skin was better fitted for the one-power kinetics model.The results of study on the correlation of release rate and penetration rate in vitro showed that the release and the transdermal penetration had a good linear correlation, taking the penetration datas for Y and the release datas for the X, the relevant linear equation of chrysophanol can be described as Y= 0.4687X+4.9722 (R= 0.9664), berberine as Y= 0.6669X +2.4874 (R= 0.9740), and the release rate was higher than the transdermal rate for two index components in Danhuang Gel,suggested that skin and other physiological factors may be he primary barrier for transdermal absorption of Danhuang Gel.6. Study on the quality standardWe checked on the appearance of Danhuang Gel and determined the pH value of Danhuang gel,the methods of TLC and high performance liquid chromatography (HPLC) were established for the qualitative identification, determination of preparation. Appearance inspection results showed that the Gel is yellowish brown semi-solid, gas micro fragrance,the results of pH value test showed that the pH value of Danhuang gel was 6.8±0.2; TLC method was established to identify the whole herbs in Danhuang gel, the results showed that the spots are clear on the TLC picture and the negative control was non-interference, so we could use it as the qualition identification; The determination methods of chrysophanol and berberine had been established using HPLC.As an important quality standard,the content of chrysophanol can not be less than 0.145mg in lg Danhuang gel,and berberine 0.907mg either.7. Study on the stability of Danhuang GelWith appearance, pH value, contents of Danhuang Gel as the indicators, influencing factors including centrifugalization,high temperature, low temperature,light radiation,high humidity on the stability of Danhuang Gel were investigated. The results showed that color of Gel deepened under high temperature and strong light radiation, the other indexs had no significant change, while the indicators had no significant changes at low temperatures and high humidity conditions, and no stratification and sedimentation, suggesting that the Gel should be stored under dark and low temperature. The stability study results of the effect of PH and salt on Gel showed that the viscosity of Danhuang Gel was influenced by pH and salts, salts has a strong role in the destruction of the features and viscosity of gel. Packaging Danhuang Gel in dark materials, the initial stability study of 3 months was carried out, the result showed that the nature of Danhuang Gel was stable. |
PDF Full Text Request