It has been widely accepted in modern pharmaceutical industry that quality cannot be tested into products , instead quality should be built-in by design . However , the implementation of Quality by Design ( QbD ) in development , manufacture and supervision of traditional Chinese medicine ( TCM ) still remains to be a challenge . The program of safety re-evaluation of TCM injections provides an opportunity to practice QbD approach in TCM industry . This paper discussed some potential ways that improve the quality of TCM injec-tions base on QbD related tools , including identification of critical quality attributes , critical process parameters and critical material attributes, development of design space and control strategy.

Objective To isolate and purify high-purity neohesperidin from Fructus Aurantii extract.Methods Fructus Aurantii extract was treated by macroporous resin and extracted by n-butanol, then concentrated and some solid was precipitated.After crystallizing the precipitate three times, neohesperidin was obtained.The concentration of n-butanol extract was optimized, which was of great importance in the whole preparation.Results The yield of neohesperidin was 48.6% and purity of neohesperidin was up to 98.7% in Fructus Aurantii extract.Conclusion High-purity neohesperidin could be prepared feasibly and economically by proposed method.

Objective Near-infrared (NIR) spectroscopy was used as a fast analytical technique in the ethanol reflux-extraction process of red ginseng. Methods The NIR spectra of the extracting solution of red ginseng were obtained and the reference measurements of the active constituent in the extracting solution were performed by the colorimetric method. Firstly, the interference information in the spectra was detected by orthogonal signal correction (OSC) method. Then a calibration model between NIR spectra and reference measurements was established by partial least square regression. Results The results showed that the predictive accuracy of NIR calibration model used for the determination of ginsenoside in ethanol extracting process of red ginseng was good. Conclusion NIR Spectroscopy could be applied to the fast analysis for ethanol extracting processes of red ginseng.

Objective To develop recovery prediction models for danshensu,salvianolic acid B,and salvianolic acid D in danshen ethanol precipitation.Methods Recorded the operation parameters of 15 normal batches of danshen ethanol precipitation in one Chinese medicine plant and measured five active component contents in danshen concentrated liquid and danshen ethanol precipitated liquid,the Stepwise-MLR recovery prediction models of dashensu,salvianolic acid B,and salvianolic acid D were developed based on an approach which combined the process parameters and the active component contents in danshen concentrated liquid.The importance of variables in the prediction models was analyzed later.Results The coefficient correlations of dashensu,salvianolic acid B,and salvianolic acid D recovery prediction models were all above 0.95.Conclusion The models developed for active component recovery prediction show a good predictability.Models can be used to help manufacturers to understand the ethanol precipitation process and improve the quality control ability of danshen ethanol precipitation.

Objective Near-infrared (NIR) reflectance spectroscopy was used to develop a fast quality assessment method by simultaneous material identification and moisture quantification of Radix Ginseng Rubra (RGR). Methods The sample was identified by the comparison of its spectrum with a standard NIR spectral library. Similarity measurement was used as the discriminating parameter. The moisture content of sample was quantified by a partial least square (PLS) calibration model, correlative spectrum calculation was used for wavelength selection and multiplicative signal correction (MSC) was applied for pretreatment in the calibration model. Primary reference data were obtained using the traditional loss on drying (LOD) method. Results The NIR library can distinguish RGR from the counterfeit successfully. The optimized eight-factor PLS calibration model of NIR spectra has a high correlation coefficient (R=(0.999 7).) Conclusion The proposed method is rapid, accurate and can be used routinely in the traditional Chinese materia medica manufacturers for quality control of raw materials.

Objective To select the optimum conditions of the vacuum belt drying process of Radix Salvia Miltiorrhiza(RSM) extract.Methods The process was studied by using orthogonal test design and grading method for multi-index on the parameters of the water content of dried product and drying rate of RSM extract,the average quantity of vapour during unit time span,as the index.Results The optimum process determined by the grading method was listed as follows: water content of the extract before drying was 40%,the feeding speed was 1.5 mL/s,the belt speed was 5 cm/min.Conclusion This technology can increase the average quantity of vapour during unit time span and the drying product has high quality with lower water content and desirable drying rate.

OBJECTIVETo establish a method for monitoring the quality of intermediates generated in each working procedure during the production process of traditional Chinese medicine (TCM) , in order to ensure the batch-to-batch quality consistency of TCM products.

METHODThe multistage multivariate statistic quality control (MMSQC) was proposed to monitor production quality of TCMs based on multivariate data analysis technique. Hotelling T2 and SPE were adopted for monitoring the quality of intermediates generated in each working procedure. Danshen injection was taken as the example to introduce the application method of MMSQC.

RESULTMMSQC can monitor the quality of intermediates generated in multiple working procedures, which is simpler and more accurate compared with single-indicator monitoring method.

CONCLUSIONMMSQC can be popularized to monitor quality of multistage production of TCMs.

Drugs, Chinese Herbal ; chemistry ; standards ; Medicine, Chinese Traditional ; standards ; Phenanthrolines ; chemistry ; standards ; Quality Control ; Salvia miltiorrhiza ; chemistry

OBJECTIVEWater content in concentrated extract (WCCE), the concentration of ethanol used in precipitation (CEA) and the quantity of ethanol added( QEA) are three important variables in the first ethanol precipitation of Danshen injection. In this work, the relationships between the three variables and total solid removal, Danshensu (DSS)retention and DSS purity were investigated.

METHODExperiments according to central composite design were carried out and mathematical models were developed.

RESULTThe models were accurate and predictive. The relative deviations between prediction results and experimental results were less than 3%. The influences of the three variables were discussed with a response surface method. The decrease of WCCE and the increase of CEA both caused more precipitation and increase the purity of DSS. However, more loss of DSS was observed. The increase of QEA increased total solid removal. DSS retention and DSS purity increased first and then decreased when QEA increased.

CONCLUSIONThis result suggests the addition of ethanol should be optimized according to WCCE and CEA to obtain better supernatant

Chemical Precipitation ; Ethanol ; chemistry ; Models, Statistical ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry ; Water ; chemistry

OBJECTIVETo suggest a method for discriminating quality control indicators of concentrated solution before traditional Chinese medicine ethanol precipitation.

METHODThe second ethanol precipitation (SEP) of Guanxinning was taken as an example, with the concentrated supernatant of first ethanol precipitation (CSFEP) prepared with same dry matter content and the same amount of ethanol as raw materials, to conduct the ethanol precipitation test under the same conditions. The experimental data was analyzed by stepwise regression and partial least squares regression. Both of them selected the parameters which affect phenolic compounds retention ratios in SEP supernatant as the key indicators.

RESULTPhenolic compounds contents in SEP supernatant were mainly affected by the contents of danshensu, caffeic acid and salvianolic acid B in CSFEP.

CONCLUSIONThe discrimination method can be used to discover key quality control indicators of concentrated solution before ethanol precipitation.

Chemical Precipitation ; Ethanol ; chemistry ; Medicine, Chinese Traditional ; standards ; Quality Control ; Solutions

OBJECTIVEA component-knockout approach was established to discover active components from traditional Chinese medicine.

METHODAccording to the principle of gene knockout technique, an experiment workflow for component-knockout method was developed, which is distinct from the bio-guided screening method. The differences of therapeutic efficacies between different combinations of individual components were analyzed by some statistical methods including Analysis of Variance (ANOVA), whilst a set of criterias were established to assess active components. By comparing the difference of drug efficacy between the original formulae and the mixture being knockout certain component, the active components can be identified.

RESULTThe presented component-knockout method was applied to discover the active components of Shenmai formulae for the synergistic effects on the cyclophosphamide chemotherapy for S180 tumor-bearing mice. The results indicated that panoxadiol, a type of ginsenosides, were the effective components of Shenmai formulae.

CONCLUSIONA new method for identifying effective components from Chinese medicinal formulae was developed and successfully applied to discover the active components of Shenmai Formulae, which possesses the synergistic actions towards chemotherapy process.

Algorithms ; Analysis of Variance ; Animals ; Diagnosis, Differential ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Gene Knockout Techniques ; Ginsenosides ; chemistry ; therapeutic use ; Medicine, Chinese Traditional ; Mice ; Phytotherapy ; Spectrometry, Mass, Electrospray Ionization