Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method / 中国中药杂志

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

Optimization of the extraction technology of modified Tabusen- 2 and its inhibitory effects on osteoclast differen- tiation / 中国药房

OBJECTIVE To optimize the extraction technology of modified Tabusen- 2（MT-2），and to investigate inhibitory effects of the extract obtained by the optimal technology on osteoclast differentiation. METHODS The index components of MT- 2 process optimization were selected by using network pharmacology. Based on single factor tests ，the extraction technology of MT- 2 was optimized by Box-Behnken design-response surface methodology according to the comprehensive score of contents of above index components ，and then validated. RAW 264.7 cells were induced by receptor activator of nuclear factor-κB ligand（100 ng/mL） to prepare osteoclast differentiation model. Inhibitory effects of MT- 2 extract（18.6，37.2，74.4 ng/mL）obtained by the optimal technology on osteoclast differentiation were investigated. RESULTS The index components screened by network pharmacology included chlorogenic acid ，terpineol diglucoside ，isochlorogenic acid A ，1，5-dicaffeoylquinic acid ，hydroxysafflower yellow A ， ginsenoside Rg 1 and ginsenoside Rb 1. The optimal extraction technology of MT- 2 was ethanol volume fraction of 60％ ，the solid-liquid ratio of 1 ∶ 14（g/mL），extraction time of 94 min and extraction times of twice. The average comprehensive score obtained by the three validation experiments was 95.50，and the relative error with the predicted value （95.75）was －0.26％. Compared with osteoclastic differentiation model cells ，the cells treated with MT- 2 extract prepared by the optimal technology were mostly mononuclear round cells ，and the number of osteoclasts decreased significantly （P＜0.05），its inhibitory effects tended to strengthen with the increase of drug concentration. CONCLUSIONS The optimal extraction technology of MT- 2 is stable and feasible. Obtained extract can inhibit osteoclast differentiation.

Optimization of preparation technology of baicalin lipid nano foam aerosol / 中国药房

OBJECTIVE To optimize the pr eparation technology of the baicalin lipid nano foam aerosol （BC-LN-FA）. METHODS Baicalin lipid nanoparticle （BC-LN）and BC-LN-FA were prepared by the thin film dispersion method and homogeneous emulsification method ，respectively，using baicalin （BC） as the model drug. The preparation technology was optimized by Box-Behnken design-response surface methodology using particle size and encapsulation efficiency （EE）as indexes ，with dosage ， emulsifier dosage ，co-emulsifier dosage and homogenization time as factors. The morphology ，particle size ，polymerdispersity index（PDI），EE，the viscosity ，the foam dissolution rate and in vitro transdermal release of BC-LN-FA were characterized. RESULTS The optimal technology included 25 mg BC ，40 mg emulsifier （mass ratio of stearic acid-soybean lecithin-glycerol was 1∶1∶1），30 mg co-emulsifier （mass ratio of octadecanol-lactic acid was 1∶1），homogenization time of 20 min. Results of 3 times of validation tests showed that particle size of prepared BC-LN-FA was （151.70±2.40）nm，EE was （68.62±1.16）％；the deviation of them from the predicted value （particle size of 150.80 nm，EE of 67.02％）were 0.60％ and 2.39％ respectively. The BC-LN-FA prepared by the optimal process was light yellow opalescence ，uniform in particle size and round-like in shape. The viscosity，the foam dissolution rate ，the content of BC and PDI were （122.92±5.09）mPa·s，（65.32±3.22）％，（7.01±0.12）％ and（0.199±0.006），respectively. At 48 h，the cumulative release rates of BC-LN-FA in phosphate buffer saline （PBS）at pH 7.4， 6.8，5.0 were（54.12±2.69）％，（57.85±4.25）％ and（59.47±1.83）％，respectively；those of free BC in PBS at pH 7.4 was only （15.04±1.43）％. CONCLUSIONS The optimized technology is stable and feasible. Prepared BC-LN-FA has a uniform particle size，high digestion rate and certain viscosity.

Optimization of the extraction technology of volatile components from Wuyao decoction / 中国药房

OBJECTIVE To optimize the extraction technology of volatile components from Wuyao decoction. METHODS On the basis of single factor investigation ，the extraction technology of volatile components from Wuyao decoction was optimized and validated by Box-Behnken design-response surface technology using the contents of bomyl acetate ，cyperotundone，α-cyperone， ligustilide and dehydrocostuslactone ， extraction rate of volatile oil as indexes ， with extraction time ， soaking time and liquid-material ratio as factors. On this basis ，the extraction state of the decoction was quantified. RESULTS The optimal extraction technology was as followed ：the ratio of liquid -material was 13∶1（mL/g），soaking time was 0.5 h，and the extraction time was 6 h in the boiling state. The comprehensive scores of the three validation experiments were 0.948 7，0.948 4 and 0.948 6 respectively （RSD＝0.02％，n＝3），and the deviation from the predicted value （0.947 9）was no more than 1％. The boiling state of the decoction in 180 ℃ oil bath was taken as the sudden boiling state. CONCLUSIONS The optimized extraction technology is stable and feasible.

Formulation Optimization and Characterization of Docetaxel PELGE Nanoparticles and Preliminarily Evaluation of Its Drug Release and Antitumor Activity in vitro / 中国药房

OBJECTIVE：To optimize the f ormulation of docetaxel （DTX）-mPEG-PLGA-mPEG （PELGE）-nanoparticles （NPs），and to characterize it and evaluate its in vitro drug release and antitumor activity. METHODS ：PELGE were synthesized by ring-opening polymerization. DTX-PELGE-NPs were prepared by using emulsion solvent evaporation method. The content of DTX in DTX-PELGE-NPs was determined by HPLC. Box-Behnken design-response surface methodology was applied to optimize the formulation of the nanoparticles using the amount of DTX ，PELGE and poloxamer 188 as independent variable ，using entrapped efficiency as dependent variable. The particle size and Zeta-potential of DTX-PELGE-NPs were characterized by laser particle size analyzer and transmission electron microscope. The in vitro release of the DTX-PELGE-NPs was investigated by ultra-filtered centrifugation，using DTX injection as reference. In vitro cytotoxicity of the DTX-PELGE-NPs was investigated by MTT assay ， using DTX and PELGE-NPs without DTX as reference . RESULTS ：The optimal formulation included 2.80 mg DTX ，20.60 mg PELGE and 6％ poloxamer 188. The entrapped efficiency of optimized DTX-PELGE-NPs was （86.79±1.32）％；drug-loading amount was （10.21±0.78）％，and average particle size was （78.4±2.9）nm；polydispersity coeffici ent was （0.187±0.018）and Zeta potential was （－20.6±1.5）mV. Furthermore ，DTX- PELGE-NPs showed a regular spherical and uniform distribution under scanning electron microscopy. Compared with DTXinjection（accumulative release rate of 92.3％ at 4 h），DTX- PELGE-NPs had a significant sustained-release effect （accumu-lative release rate of 78.6％ at 36 h）. 0.1-50 μg/mL PELGE-NPs had no obvious cytotoxicity to human breast cancer cells MCF-7（P＞0.05）. 0.5-10 μg/mL DTX-PELGE-NPs could significantly inhibit the growth of human breast cancer cells MCF-7， and its inhibitory effect （except for DTX-PELGE-NPs 10 μg/mL group）was significantly stronger than that of DTX injection （P＜ 0.05）. CONCLUSIONS ：The optimized formulation is stable and feasible. The obtained DTX-PELGE-NPs not only have uniform particle size ，high encapsulation rate obvious slow-release effect ，but also have stronger anti-tumor effect in vitro than DTX injection.

Optimization of the Formulation of Curcumin Transethosomes / 中国药房

OBJECTIVE：To optimize the formulation of Curcumin （CUR）transethosomes（CUR-TEs）. METHODS ：The contents of CUR in CUR-TEs were determined by HPLC. CUR-TEs were prepared by injection method. Using comprehensive score of encapsulation efficiency and drug loading as index ，based on signal factor test ，Box-Behnken design-response surface method was used to optimize and validate the formulation. The property of CUR-TEs prepared by the optimal formulation was investigated. RESULTS：The optimal formulation of CUR-TEs was as follows as lecithin of 4％，CUR of 0.13％，1，2-propylene glycol of 25％，tween-80 of 1％. Results of validation test of optimal formulation showed that comprehensive score of encapsulation efficiency and drug loading of CUR-TEs was 93.04±2.16，relative error of which to predicted value （91.19）was 2.03％. The encapsulation efficiency of CUR-TEs prepared by optimal formulation was （91.17±1.35）％，and its drug loading was （0.94± 0.02）％. The particle size was （190.64±15.97）nm with polydispersity index of 0.086±0.007，and Zeta potential was （－12.74± 1.60）mV. CONCLUSIONS ：The optimized formulation of CUR-TEs is stable ，feasible and repeatable ，with good stability.

Optimization of the Extraction Technology of Phenolic Acid from Amomum tsaoko / 中国药房

OBJECTIVE：To opt imize the extraction technology of phenolic acid from Amomum tsaoko . METHODS ：The extraction technology of phenolic acid from A. tsaoko was optimized by using Box-Behnken design-response surface methodology with ethanol volume fraction ，liquid-solid ratio and extraction time as factors ，using the total contents of protocatechuic acid and vanillic acid as response value. The optimizd extraction technology was vlidated. RESULTS ：The optimal extraction technology was as follows ：ethanol volume fraction 65％，liquid-solid ratio 4∶1（mL/g），extraction time 2.5 h. After 3 times of validation tests ， average total content of protocatechuic acid and vanillic acid were 12.32 mg/g（RSD＝0.26 ％，n＝3），average relative error of which with predicted value （12.63 mg/g）was 2.45％. CONCLUSIONS ：The optimal technology is stable and feasible .

Optimization of Extraction Process of Thymol and Carvacrol in Origanum vulgare by Box-Behnken Design-Response Surface Methodology / 中国药学杂志

OBJECTIVE: To optimize the extraction process of thymol and carvacrol in Origanum vulgare by Box-Behnken design-response surface methodology. METHODS: On the basis of single factor experiment, taking the sum of extraction rates of thymol and carvicol as the evaluation index, Box-Behnken design was used to investigate the effects of ethanol concentration, liquid-solid ratio and medicinal powder on the extraction rate. RESULTS: The optimal extraction parameters were as follows: ethanol concentration was 80%, liquid to solid ratio was 13∶1 (mL/g), medicinal powder passing through 40 meshes was used, and the highest extraction rate was 694.80 μg•g-1, with a small deviation from the predicted value. CONCLUSION: The optimal extraction method is simple, with low cost and good predictivity, and it can provide experimental basis for further large-scale production of thymol and carvacrol in Origanum vulgare.

Formulation Optimization and Cytotoxicity Study of GGPFV-modified Daunorubicin/dioscin Liposomes / 中国药房

OBJECTIVE：To prepare GGPFV-modified Daunorubicin/dioscin liposomes ，and to optimize their formulation and to preliminarily evaluate their cytotoxicity to breast cancer cells in vitro . METHODS ：Daunorubicin and diosgenin were wrapped by thin film dispersion method and ammonium sulfate hydration method ；the surface was modified with DSPE-PEG2000-GGPFV to prepare GGPFV-modified Daunorubicin/dioscin liposomes. Taking encapsulation rate as index ，Box-Behnken response surface methodology was used to optimize the film hydration volume ，cholesterol amount and daunorubicin amount in the formulation. The entrapment efficiency of 3 batches of liposomes prepared according to the optimal formulation was determined. The effects of Daunorubicin/dioscin liposomes ，GGPFV-modified Daunorubicin/dioscin liposomes and blank liposomes on the survival rate of human breast cancer MDA-MB- 435S cells were compared. RESULTS ：The optimal formulation was as film hydration volume of 5 mL，cholesterol of 4 mg，yolk lecithin of 22 mg，daunorubicin of 0.55 mg，dioscin of 0.85 mg，DSPE-PEG2000 of 3.5 mg， DSPE-PEG2000-GGPFV of 2 mg. The encapsulation rate of daunorubicin was （96.21±1.54）％ and that of dioscin was （95.39± 2.48）％ in the 3 batches of liposomes prepared. The in vitro cytotoxicity tests showed that the inhibition effect of GGPFV-modified Daunorubicin/dioscin liposome on MDA-MB-435S cells was significantly stronger than that of Daunorubicin/dioscin liposome （P＜ 0.05）. There was no cytotoxicity in the membrane. CONCLUSIONS ：GGPFV-modified Daunorubicin/dioscin liposomes are successfully prepared ，and its inhibitory effect on human breast cancer MDA-MB- 435S cells in vitro was significantly enhanced.

Optimization of Extraction Process for Active Ingredients in Seeds of Sophora alopecuroides by Plackett-Burman Design and Response Surface Analysis / 中国药学杂志

OBJECTIVE: To optimize extraction process for active ingredients in seeds of Sophora alopecuroides, to provide a reference for scale production. METHODS: Active ingredients from Sophora alopecuroides were extracted by ethanol, with average yield of oxysophocarpine and oxymatrine as index, some factors affecting index were firstly evaluated by Plackett-Burman design, then taking oxysophocarpine and oxymatrine as indexes respectively, extraction conditions were optimized by Box-Behnken design, experimental data was fitted by multiple linear regression and binomial formula fitting, extraction process was optimized by response surface method, and prediction was carried out through comparing the observed and predicted value. RESULTS: Extracting times, crushing degree and solvent times had significant effects on yields of oxysophocarpine and oxymatrine; binomial equation fitted well with good predictability. optimum extraction technology of Sophora alopecuroides was as following:crushed through 65 mesh sieve, extracted 4 times with 12-fold the amount of 60% ethanol for 2 h each time; yield of oxysophocarpine and oxymatrine was 92.3%, 78.6% respectively, both deviations were small by comparing with the predicted value. CONCLUSION: This extraction process is reasonable and feasible by Plackett-Burman design and response surface analysis with good predictability. This study can provide experimental basis for further scale production of Sophora alopecuroides.

Study on the Separation and Purification Technology of Total Flavonoids from Sparganium stoloni by Box-Behnken Design- response Surface Methodology / 中国药房

OBJECTIVE： To optimize the purification technology of total flavonoids from Sparganium stoloniferum. METHODS： Separation and purification by macroporus adsorption resin， using sample solution pH， flow rate and concentration of eluent， the purification rate of total flavonoids as evalution indexes， the purification technology of total flavonoids from S. stoloniferum were optimized by Box-Behnken design-response surface methodology based on single factor test. Validation test was conducted. RESULTS： The optimal purification technology was sample solution pH 4.8， flow rate of eluent 2.0 BV/h， concentration of eluent 72％. The purification rate of total flavonoids in 3 batches of samples was 72.34％ （RSD＝1.77％， n＝3） in validation test， relative errors of which to predicted value （73.99％） was 2.13％. CONCLUSIONS： The optimal purification technology is stable and feasible， and can be used for the purification of total flavonoids from S. stoloniferum.

Study on Optimization of the Extraction Technology of Total Vitamin E in Euryale ferox by Box-Behnken Design-response Surface Methodology / 中国药房

OBJECTIVE： To optimize the extraction technology of total vitamin E in Euryale ferox. METHODS： With the extraction amount of total vitamin E as reference index， using extraction time， extraction times， ultrasound power and comminution degree as reference factors， single fator test and Box-Behnken design-response surface methodology was used to optimize the extraction technology of total vitamin E from E. ferox. The validation tests were conducted for 3 times （the amounts of E. ferox were 2.0， 20.0， 40.0 g）. RESULTS： The optimal extraction technology of vitamin E included that extraction time of 80 min， extraction times of 3 times， ultrasound power of 240 W， comminution degree of 80 mesh. In validation test， extraction rates of total vitamin E were 2.063， 2.103， 2.085 mg/g （RSD＝2.6％， 1.5％， 1.3％， n＝3）， the relative errors of which to predicted value （2.092 mg/g） were 0.14％， 0.53％ and 0.33％， respectively. CONCLUSIONS： The optimal extraction technology is reasonable， stable and feasible， and can be used for the extraction of total vitamin E in E. ferox.

Optimization of Extraction Technology of Flavonoids in Glycyrrhiza uralensis by Single Factor Experiment Combined with Box-Behnken Design-response Surface Methodology / 中国药房

OBJECTIVE： To optimize the extraction technology of the flavonoids from Glycyrrhiza uralensis. METHODS： Using total contents of four flavonoids， liquiritinapioside， glycyrrhizin， isoliquiritin apioside and formononetin as indexes， types and volume fractions of extraction solvents （water， ethanol）， volume of addition and extraction time as factors， based on single factor experiment， Box-Behnken design-response surface method was used to optimize the extraction technology of flavonoids from G. uralensis. Validation test was also conducted. RESULTS： The optimal extraction technology was 50 mL 50％ ethanol as extraction solvent， 0.200 g G. uralensis， ultrasonic extraction for 50 min. In validation test， the extraction amounts of liquiritinapioside， glycyrrhizin， isoliquiritin apioside and formononetin were 10.733 0， 27.784 9， 3.441 9， 0.429 1 mg/g， respectively （all RSDs＜3.0％， n＝3）. The average total extraction amount of four flavonoids was obtained was 42.388 9 mg/g， the relative error of which to predicted value （42.173 2 mg/g） was 0.52％ （n＝3）. CONCLUSIONS： The optimized extraction technology is simple， rapid and stable， and can be used for the extraction of flavonoids from G. uralensis.

Optimization of processing technology of Momordicae Semen cream by Box- Behnken design-response surface methodology / 中草药

Objective To optimize the optimum processing technology of Momordicae Semen cream using Box-Behnken design-response surface method (BBD-RSM). Methods The overall desirability (OD) of indexes of the content of 3-O-β-D- glucuronic acid methyl ester, β-sitosterol, and oleanolic acid and the content of fatty oil in gypsogenin was comprehensively evaluated, and BBD-RSM with three factors and three levels was used to study the effect of baking temperature and time, and pressing time on the processing technology of Momordicae Semen cream. Results According to the experiment, the optimum processing conditions were optimized: the baking time 1.68 h, the baking temperature 80 ℃, the pressing time 30 min, and the OD value was 0.777. Considering the actual situation, the optimum processing technology of Momordicae Semen was obtained by fine-tuning the baking time (A). That was, the baking time was 1.7 h, the baking temperature was 80 ℃, and the pressing time was 30 min. Also, the calculated OD values were 0.779, 0.783, 0.766, and its RSD was 1.15% through the obtained conditions in parallel with three batches of samples. Conclusion The processing technology optimized by Box-Behnken design-response surface method has the advantages of stable, good model prediction effect and a new processing technology for Momordicae Semen cream production.

Study on rolling drying granulation of Rebiqing granules / 国际中医中药杂志

Objective@#Rebiqing granules were prepared and the rolling drying granulation process parameters were optimized.@*Methods@#According to the previous knowledge and experience, the feed rate, pressure and speed of rolling were used as the factors for investigation, and the primary forming rate and the solubility of the Rebiqing granule were taken as the evaluation indexes, and the Box-Behnken response surface method was used to optimize the rolling drying granulation parameters.@*Results@#The optimum rolling drying granulation parameters were as follows: feed rate was 8.5 Hz, rolling pressure was 6.0 Mpa and rolling speed was 8.5 Hz. After continuous production of 3 batches of validation, the Rebiqing granules had high molding rate and good solubility.@*Conclusions@#The rolling drying granulation processes were optimized by the experimental design, which could improve the robustness of the processes and control the stability of the product quality.

Optimization of Meloxicam Nanosuspensions Fast Dissolving Sublingual Films (MLX-NS-Fdsfs) by Box-Behnken Response Surface Methodology / 中国药学杂志

OBJECTIVE: To prepare and optimize meloxicam nanosuspensions fast dissolving sublingual films (MLX-NS-FDSFs) and to evaluate its in vitro dissolution characteristics. METHODS: Meloxicam nanosuspensions (MLX-NS) were prepared by pH-dependent dissolving-precipitating/high speed shearing method and then transformed into fast dissolving sublingual films (FDSFs). The formulations of MLX-NS-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amount of HPMC-E30, PEG-400 and MLX-NS as investigation factors, and particle size of reconstituted nanoparticles from MLX-NS-FDSFs, disintegration time and stretch length as indexes. The morphology, content uniformity and in vitro dissolution of the optimal formulation were also evaluated. RESULTS: The MLX-NS-FDSFs prepared by optimized formulation (35 mg·mL-1 HPMC-E30, 40 mg·mL-1 PEG-400, 10 mL MLX-NS) could fast disintegrate in (26.08±1.76) s, the tensile length was (1.51±0.13) mm, and the particle size of reconstituted nanoparticles from MLX-NS-FDSFs was (186.4±6.3) nm. There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. Morphological analysis showed that well-dispersed MLX nanoparticles embedded in MLX-NS-FDSFs. The conformity of drug content was up to standard. MLX could be released in vitro as much as (91.75±8.05)% within five minutes. CONCLUSION: Using Box-Behnken design and response surface method to optimize MLX-NS-FDSFs is effective and feasible. MLX-NS-FDSFs can significantly increase the cumulative dissolution of MLX.

Optimization of Phencynonate Hydrochloride Transdermal Patch Formulation by Box-Behnken Design-response Surface Methodology / 中国药房

OBJECTIVE:To optimize the formulation of Phencynonate hydrochloride transdermal patch. METHODS:Phencynonate hydrochloride transdermal patch was prepared by solvent evaporation method. Using 48 h accumulative transdermal volume as index,single factor test and Box-Behnken design-response surface methodology were used to optimize drug dosage,the amount of transdermal enhancers azone and pressure-sensitive adhesive,and evaluate the appearance,adhesion of the formulation prepared by the best prescription. RESULTS:The optimized formulation was as follows as 263 mg drug dosage,165 mg azone, 1.94 g pressure-sensitive adhesive and 1.6 g methanol. 48 h accumulative transdermal volume of prepared patch was(119.48 ± 2.95)μ g/cm2(n=5),related error of which to predicted value was 2.48%. The prepared patch showed smooth surface and incision,good adhesiveness. CONCLUSIONS:Phencynonate hydrochloride transdermal patch is prepared successfully,its accumulative transdermal volume is in agreement with predicted standard.

Optimization of Extraction Technology of Total Flavonoids Psidium guajava Leaves by Box-Behnken Design-Response Surface Method and the Effects of Total Flavonoids on Glucose Tolerance in Diabetic Model Mice / 中国药房

OBJECTIVE:To optimize the extraction technology of total flavonoids from Psidium guajava leaves and investigate the effects of total flavonoids from P guajava leaves on glucose tolerance in diabetic model mice.METHODS:Based on single factor test,using extraction time,solid-liquid ratio and the amount of ethanol as independent variables,comprehensive scores of the yield of hyperin,quercetin-3-O-β-D-arabinopyranoside,quercetin-3-O-α-L-furanarabino side ethyl acetate and extract as dependent variable,Box-Behnken design-response surface method was used to optimize the reflux extraction process of total flavonoids from P guajava leaves,and validation test was also conducted.Sixty mice were randomly divided into blank group,model group,metformin group (170 mg/kg),P.guajava leaves total flavonoids low-dose,medium-dose and high-dose groups (23.41,46.81,93.62 mg/kg,by the content of total flavonoids),with 10 mice in each group.Except for blank group,diabetic model was induced in those groups,and then model mice were given relevant medicine intragastrically once a day for consecutive 21 d,6 h after last medication given glucose 2.0 g/kg intragastrically.The levels of blood glucose were determined 0,0.5,1.0,2.0 h after intragastric administration of glucose,and the area under the curve (AUC) of blood glucose was calculated.RESULTS:The optimal technology of P guajava leaves total flavonoids was as follows as extracting twice,lasting for 1.0 h each time,solid-liquid ratio of 1 ∶ 17,ethanol volume fraction of 56％.In validation test,the contents of hyperin,quercetin-3-O-β-D-arabinopyranoside and quercetin-3-O-α-L-furanarabino side ethyl acetate were 2.57,3.38,2.26 mg/g(RSD＜2％,n=3);the yield of extract was 25.71％ (RSD=1.19％,n=3);average comprehensive score was 96.41 (RSD=l.34％,n=3);relative error was 3.57％ with the predicted value of 99.98.Compared with blank group,AUC of mice were increased significantly in each group;compared with model group,AUC of metformin group,P.guajava leaves total flavonoids medium-dose and high-dose groups were all decreased significantly,with statistical significance (P＜0.05 or P＜0.01).CONCLUSIONS:The optimal extraction technology is stable,feasible and controllable in quality.Total flavonoids from P.guajava leaves can promote the recovery to normal level of blood glucose.

Optimization of Dry Granulation Technology of Typha Pollen Granules by Box-Behnken Design and Response Surface Method / 中国中医药信息杂志

Objective To optimize the dry granules process of Typha Pollen. Methods The particle size and particle friability were selected as evaluation indexes. The inspect factors were water content, compression frequency, and granulation frequency. Influence of inspect factors on evaluation indexes was investigated by single factor test, the influence of inspect factors on OD value was investigated by Box-Behnken design, and response surface method was adopted to predict, analyze and choose optimal process. Results The optimal dry granulation technology was as follows: the water content was 35.0%; the frequency of tabletting was 27 Hz; the granulating frequency was 15 Hz. Conclusion The selected process is stable, feasible and reproducible, which can be used for granulation of Typha Pollen granules.

Optimization of processing technology of stir-frying with vinegar of Curcuma Longa Radix by orthogonal design and Box-Behnken design-response surface based on entropy method / 中草药

Objective To optimize the processing technology of stir-frying with vinegar of Curcuma Longa Radix (CLR) by orthogonal design and Box-Behnken design-respanse surface method (BBD-RSM) based on entropy method. Methods As comprehensive evaluation indexes, the contents of curcumin, demethoxycurcumin, and bisdemethoxycurcumin in CLR processed by traditional method were determined by HPLC. The orthogonal test was adapted to examine the influence of the amount of vinegar, the moistening time, parching time, and parching temperature on processing technology of stir-frying with vinegar. Based on the results above, BBD-RSM was adopted to optimize the processing technology further using the moistening time, parching time and parching temperature as factors. Results The optimum processing technology of the orthogonal test was covered the amount of vinegar of 15%, moistening time of 10 min, parching temperature of 130 ℃, and parching time of 10 min. The optimum processing technology by BBD-RSM was covered moistening time of 12 min, parching temperature of 150 ℃, and parching time of 8 min. The verification esting indicates that the process conditions are reasonable and feasible with good reproducibility. Conclusion The method and data are precise and reliable. Besides, it established the processing technology of vinegar CLR and provided a theoretical basis for the processing technology of stir-frying with vinegar of CLR.