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OBJECTIVE To provide a reference for the definition of the legal attributes of the provincial Chinese herbal pieces processing norms and the improvement of legal expression for the drug standards in Drug Administration Law. METHODS Based on the legal evolution of local drug standards in China， the composition of national drug standards for Chinese herbal pieces and the composition of current provincial Chinese herbal pieces processing norms were analyzed； at the same time， based on the method of legal interpretation， the legal connotation of the provincial Chinese herbal medicine processing norms in Drug Administration Law was investigated. RESULTS & CONCLUSIONS In the practice of drug supervision， the provincial Chinese herbal pieces processing norms are essentially local drug standards. The newly revised Drug Administration Law defines the drug standards specifically， but does not stipulate the legal attribute of drug standards for the provincial Chinese herbal pieces processing norms， and there are certain legislative technical defects. It is suggested that when amending the Drug Administration Law， the legal attributes of the drug standards of the provincial Chinese herbal medicine processing norms should be clarified.
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Objective To review Chinese medicine(CM)syndrome diagnostic criteria and analyze their diagnostic attributes for the confirmation of appropriate diagnostic modes for dampness syndrome.Methods We took well-accepted CM syndrome criteria and typical literature related to CM syndrome criteria as research objects,and analyzed their diagnostic attributes from the perspectives of syndrome criteria intension,diagnostic procedures,and diagnostic conditions.Accordingly,we analyzed the diagnosis attributes and modes of dampness syndrome based on syndrome differentiation combined with dampness characteristics.Results We summarized the CM syndrome diagnostic attributes as specificity,necessity,consistency and correspondence,and summed them up into the corresponding diagnostic modes.Besides,we gave an in-depth interpretation on each mode.We analyzed dampness syndrome characteristics,and found that the dampness syndrome had specific symptoms,which could reflect dampness characteristics of heaviness and stickiness,and the tongue dampness characteristic.We also found that dampness syndrome had some sensitive symptoms,and there were synergetic and supplement relationship among these symptoms.By combining these symptoms,the dampness syndrome could also be determined.As mentioned above,we inferred that the diagnostic attributes of dampness syndrome had the characteristics of specificity and consistency,and corresponding diagnostic modes were specificity and consistency modes.Conclusion This research focused on CM syndrome diagnostic attributes and modes to realize dampness syndrome scientific diagnosis,which was different from other researches of CM syndrome diagnostic criteria.We hope this research approach could provide reference for other researches of CM syndrome diagnostic criteria.
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This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.
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There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the KD of which reached to 8.722×10-10 g·mL-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.
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Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.
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To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.
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A simulating method for dripping process of Ginkgo biloba leaf dripping pills based on computational fluid dynamics was constructed. Ginkgo biloba leaf dripping pills was explored as the experimental subject to simulate the dripping process based on FLOW-3D software. The dripping process was simulated through the derivation of the governing equations, the selection of the models, and simulation parameters. Firstly, the droplet morphologies and drop speeds under different liquid viscosity were simulated. It was found that with the increase of the liquid viscosity, the drop speed decreased and the difficulty of droplet preparation gradually increased. The simulation results were consistent with the experiment results. Secondly, the droplet morphologies at different drop speeds were investigated and verified by experiments. It was found that the simulation results had a good correlation with the experiment results. The results shown that the viscosity of the liquid was the critical material attribute, and the drop speed was the critical process parameter, according to the droplet morphology. The establishment of the simulation method can deepen the understanding of the dripping process and provide a reference for the selection of raw materials and process parameters.
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Objective To establish the detailed rules for the drug use evaluation(DUE)of prothrombin complex concentrate(PCC),and evaluate the use of PCC by weighted TOPSIS method to provide references for its clinical rational application.Methods Based on the instructions of PCC and referring to relevant data,the DUE standard rules were established,and weighted TOPSIS method was used to evaluate the rationality of medication in the cases of in patients who used PCC from January 2021 to December 2021 in the Affiliated Hospital of Xuzhou Medical University.Results A total of 121 cases were included,the relative weights of the three indicators were as follows:coagulation function,dosage,interval,course of treatment and,diagnosis,progress notes drug interaction,with the weights of 0.095 2,0.0913,0.091 3,0.091 3,0.089 7,0.084 1 and 0.081 7 respectively.There were 21 cases(17.36%)with reasonable medical records,39 cases(32.23%)with basically reasonable medical records,and 61 cases(50.41%)with unreasonable medical records.The main unreasonable problems were manifested in indications,usage and dosage,and drug interaction.Conclusion The DUE criteria of PCC established is more scientific,practical and feasible.The indications,usage,dosage,and drug interaction of PCC remain unreasonable criteria,and pharmaceutical intervention should be carried out to promote its rational use.
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Objective To establish drug use evaluation(DUE)standard of etamsylate and to evaluate the use of etamsylate by weighted superior and inferior solution distance(TOPSIS)method,so as to provide a basis for promoting its clinical rational use.Methods Based on the instructions of etamsylate for injection,the DUE criteria of etamsylate were established according to the relevant guidelines of hemostasis at home and abroad,evidence-based literature and expert consultation.The weighted TOPSIS method based on the attribute hierarchy model was used to evaluate the utilization of etamsylate in Beijing Beiya Orthopaedic Hospital.Results Among the 119 cases,2 cases(1.68%)were with the relative closeness degree between each case and the optimal regimen(Ci)no less than 0.8,which was evaluated as reasonable;70 cases(58.82%)were with the Ci ranging between 0.8 and 0.6,which was evaluated as basically reasonable;47 cases(39.50%)were with the Ci less than 60%,which was evaluated as unreasonable.The top three unreasonable rates were dose and frequency(66.39%),configuration method(49.58%),and drug interaction(24.37%).Conclusion The method of DUE of etamsylate based on weighted TOPSIS method can synthesize several evaluation indexes,and the evaluation method is simple and flexible.The rational rate of use of etamsylate in this hospital is low,especially there are problems in configuration method,administration dose and frequency,drug interaction,treatment course and so on,and the management still needs to be strengthened.
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ObjectiveA feedforward control model for dry granulation of polysaccharide components was established to guide the adjustment and optimization of critical process parameters （CPPs） in the design space， so as to reduce the impact of fluctuations in raw materials properties on the quality of medicines. MethodTaking Astragali Radix extract powder as the model drug， the design space of dry granulation CPPs was determined by Box-Behnken design. Astragali Radix mixed powder with different powder properties were prepared by mixture design， the variance inflation factor （VIF） was used to diagnose the multicollinearity of the powder properties， and principal component analysis （PCA） was used to extract the characteristic data of the model. Radial basis function neural network （RBFNN） was used to establish a feedforward control model for reflecting the relationship between the powder properties of polysaccharide components， dry granulation CPPs and one-time molding rate. ResultThe design space for dry granulation CPPs of polysaccharide components was 16-35 Hz for feeding speed， 10-23 Hz for roller speed， and 10-46 kg·cm-2 for roller pressure. The established RBFNN feedforward control model had a good predictive effect on the one-time molding rate of dry granulation of polysaccharide components， which could be used to guide the adjustment and optimization of CPPs in the design space， the relative error was 0.38%-6.73%， and the average relative error was 3.42%. ConclusionThe established feedforward control model can well reflect the relationship between the powder properties of the polysaccharide components， the dry granulation CPPs and the one-time molding rate of the granules， which can be used to guide the adjustment and optimization of CPPs in the design space， reduce the impact of material property fluctuation on product quality， and provide ideas for promoting the quality of traditional Chinese medicine from passive control to active control.
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The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.
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In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R2 = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f1 and similarity factor f2 were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.
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Objective:To identify the essential quality, expected quality and charm quality of outpatient doctors based on Kano model.Methods:The Kano model quality attribute questionnaire for outpatient doctors was designed from 4 dimensions and 18 indicators of service, quality, safety and cost. 220 outpatients were investigated in a tertiary hospital. The reliability and validity of 212 valid questionnaires were tested and the questionnaire data were analyzed.Results:Both the Cronbach α coefficient and the KMO value were higher than 0.7, which indicated that the reliability and validity were good. Nine of the 18 survey indicators were essential quality, focusing on the quality dimension and service dimension; 4 items were expected quality; 4 items were charm quality, focusing on disease cognition, prevention and drug safety; 1 item was indifferent quality.Conclusions:The essential quality of outpatient doctors is to provide basic and standardized medical services to patients. Studying the quality attribute can provide behavior guidance for outpatient doctors, improve patient satisfaction and quality of outpatient medical services.
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Objectives The need to develop and produce human resources for global health is increasing. The objective of this study was to reveal through qualitative research as a first step of Discrete Choice Experiment, which job ‘attributes’ are considered important by Japanese medical and non-medical personnel in considering employment at health-related international organizations. We then sought to identify appropriate support measures that match the chosen attributes for those who wish to work for international organizations. Methods We requested a total of 20 subjects from 3 groups of Japanese medical and non-medical personnel; 1. those who wish to work for health-related international organizations (applicant group), 2. those who are currently working (working group) and, 3. those who resigned (resigned group). Subjects were asked to choose and rank in order of importance, 11 pre-defined attributes when considering employment at international organizations, followed by semi-structured interviews.Results All three groups chose job content, opportunity for self-realization and opportunity for capacity development as top three attributes. This was followed by duty station as second place tie for working group and fourth place for applicant and resigned groups. However, for applicant and working groups, emphasis on employee’s entitlements such as work-life-balance, salary, welfare, job security/long-term contract ranked mid- to lower-level between fifth to eighth places. Guaranteed job where one can return to when one leaves the current post, ranked ninth place and opportunity for children’s education and opportunity for spouse’s job ranked tenth equally. For the resigned group, work-life-balance and job security/long-term contract ranked fifth place equally but other attributes were not chosen.Conclusion The study findings suggested that Japanese medical and non-medical personnel who aim for employment at health-related international organizations have tendencies to opt for utilization of their experiences and expertise, and search for capacity development and self-realization, rather than better employee entitlements or working/living conditions. According to the attributes ranking, we consider implementation of career development seminars on expected job satisfaction at international organizations as the primary support measure to encourage and dispatch more personnel. However, publicity highlighting employee entitlements such as work-life-balance, working environment for women and welfare alongside salary may also provide better incentive. Insecure contract terms, a lack of national organizations and hospitals that value the experience gained in international organizations present a challenge. There is a need to work with these organizations in the mid- to long-term to inform them on the benefits of accepting those staff wishing to return after a period working within international organizations.
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The spatial distribution uniformity of valuable medicines is the critical quality attribute in the process control of Tongren Niuhuang Qingxin Pills. With the real world sample of the mixed end-point powder of Tongren Niuhuang Qingxin Pills as the research object, hyperspectral imaging technology was used to collect a total of 32 400 data points with a size of 180 pix×180 pix. Spectral angle matching(SAM), classical least squares and mixed tuned matched filtering(MTMF) were used to identify the spatial distribution of rare medicines. MTMF model showed higher identification accuracy, therefore the spatial distribution of the blended intermediates was identified based on the MTMF model. The histogram method was also used to evaluate the spatial distribution uniformity of rare medicines. The results showed that the standard deviation was 4.78, 6.5, 3.48, 1.96, and 3.00 respectively for artificial bezoar, artificial musk, Borneol, Antelope horn and Buffalo horn; the variance was 22.8, 42.3, 12.1, 3.82, and 9.00, and the skewness was 1.26, 1.71, 0.06,-0.86, and 1.04, respectively. The final results showed that the most even blending was achieved in concentrated powder of Borneol, Antelope horn and Buffalo horn, followed by artificial bezoar, and last artificial musk. A visualization method was established for quality attributes of distribution uniformity in blending process of Tongren Niuhuang Qingxin Pills. It could provide evidences of quality control methods in the mixing process of big brand traditional Chinese medicine.
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Drugs, Chinese Herbal , Medicine, Chinese Traditional , Powders , Quality ControlABSTRACT
For the field detection problems of critical quality attribute(CQA) of moisture content in traditional Chinese medicine(TCM) manufacturing process, big brand TCM Tongren Niuhuang Qingxin Pills were used as the carrier, to establish a moisture content NIR field detection model with or without cellophane in real world production with use of near infrared(NIR) spectroscopy combined with stoichiometry. With the moisture content determined by drying method as reference value, the partial least square method(PLS) was used to analyze the correlation between the spectrum and the moisture reference value. Then the spectral pretreatment methods were screened and optimized to further improve the accuracy and stability of the model. The results showed that the best quantitative model was developed by the spectral data pretreatment of standard normal variate(SNV) with the latent variable factor number of 2 and 7 of Tongren Niuhuang Qingxin Pills with or without cellophane samples. The prediction coefficient of determination(R_(pre)~2) and standard deviation of prediction(RMSEP) of the model with cellophane samples were 0.765 7 and 0.157 2%; R_(pre)~2 and RMSEP of the model without cellophane samples were 0.772 2 and 0.207 8%. The NIR quantitative models of moisture content of Tongren Niuhuang Qingxin Pills with and without cellophane both showed good predictive performance to realize the rapid, accurate and non-destructive quantitative analysis of moisture content in such pills, and provide a method for the field quality control of the critical chemical attributes of moisture in the manufacturing of big brand TCM.
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Drugs, Chinese Herbal , Least-Squares Analysis , Medicine, Chinese Traditional , Spectroscopy, Near-InfraredABSTRACT
Identification of critical quality attribute(CQA) is crucial in quality control of Tongren Niuhuang Qingxin Pills(TRNHQXP). In this study, 661 active components in TRNHQXP were selected by liquid chromatography-mass spectrometry(LC-MS) and network pharmacology based on reported data and TCMSP, BATMAN-TCM, and TCMID databases, as well as mass spectrometry data, and 1 413 targets of the active components were obtained through SwissTargetPrediction. The 152 potential targets obtained from the intersection of predicted targets with 456 stroke targets underwent functional enrichment analysis by Metascape. The 27 Chinese medicinals in TRNHQXP were divided into four sets according to efficacies. Thirty-seven key targets in the blood-activating and stasis-resolving set and 41 in the tonifying set were screened out. On the basis of these potential key targets, 137 potential key CQA of TRNHQXP for stroke were reversely predicted. This study revealed the possible mechanism of TRNHQXP in treating stroke and established a modular identification method for the potential CQA of big brand traditional Chinese medicine(TCM) based on efficacies and chemical properties. Consequently, the CQA of TRNHQXP were identified by this method, which has provided a reference for the following experimental studies of CQA.
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Chromatography, Liquid , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Quality ControlABSTRACT
Spatial distribution uniformity is the critical quality attribute(CQA) of Ginkgo Leaves Tablets, a variety of big brand traditional Chinese medicine. The evaluation of the spatial distribution uniformity of active pharmaceutical ingredients(APIs) in Ginkgo Leaves Tablets is important in ensuring their stable and controllable quality. In this study, hyperspectral imaging technology was used to construct the spatial distribution map of API concentration based on three prediction models, further to realize the visualization research on the spatial distribution uniformity of Ginkgo Leaves Tablets. The region of interest(ROI) was selected from each Ginkgo Leaves Tablet, with length and width of 50 pixels, and a total of 2 500 pixels. Each pixel had 288 spectral channels, and the number of content prediction data could reach 1×10~5 for a single sample. The results of the three models showed that the Partial Least Squares(PLS) model had the highest prediction accuracy, with calibration set determination coefficient R_(pre)~2 of 0.987, prediction set determination coefficient R_(pre)~2 of 0.942, root mean square error of calibration(RMSEC) of 0.160%, and root mean square error of prediction(RMSEP) of 0.588%. The classical least-squares(CLS) model had a greater prediction error, with the RMSEP of 0.867%. Multivariate Curve Resolution-Alternating Least Square(MCR-ALS) model showed the worst predictive ability among the three models, and it couldn't realize content prediction. Based on the prediction results of PLS and CLS models, the spatial distribution map of APIs concentration was obtained through three-dimensional data reconstruction. Furthermore, histogram method was used to evaluate the spatial distribution uniformity of API. The data showed that the spatial distribution of APIs in Ginkgo Leaves Tablets was relatively uniform. The study explored the feasibility of visualization of spatial distribution of Ginkgo Leaves Tablets based on three models. The results showed that PLS model had the highest prediction accuracy, and MCR-ALS model had the lowest prediction accuracy. The research results could provide a new strategy for the visualization method of quality control of Ginkgo Leaves Tablets.
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Calibration , Ginkgo biloba , Least-Squares Analysis , Medicine, Chinese Traditional , Plant Leaves , Quality Control , Spectroscopy, Near-Infrared , TabletsABSTRACT
The physical properties of ginkgo leaves extract(GLE) are the critical quality attributes for the control of the manufacturing process of ginkgo leaves preparations. In this study, 53 batches of GLE with different sources from the real world were used as the objects to carry out the research from 3 levels. First, based on micromeritics evaluation method, a total of 29 physical attribute quality parameters in five dimensions were comprehensively characterized, with a total of 1 537 data points. Further, with use of physical fingerprinting technology combined with similarity evaluation, the powder physical properties of 53 batches of GLE showed obvious differences from an overall perspective, and the similarity of the physical fingerprints was 0.876 to 1.000. Secondly, hierarchical clustering analysis(HCA) and principal component analysis(PCA) models were constructed to realize the reliable identification and differentiation of real-world materials produced by GLE from different sources. Multivariate statistical process control(MSPC) model was used to create GLE material Hotelling T~2 and squared prediction error(SPE) control charts. It was found that the SPE score of B_(21) powder exceeded the 99% confidence control limit by 22.495 9, and the SPE scores of A_1 and C_(10) powder exceeded the 95% confidence control limit by 16.099 2, realizing the determination of abnormal samples in the materials of GLE from the production in real world. Finally, the physical quality control method of GLE in the production process of ginkgo leaves preparations was established in this study, providing a reference for the quality control methods of ginkgo leaves preparations in their manufacturing process.
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Drugs, Chinese Herbal , Ginkgo biloba , Medicine, Chinese Traditional , Plant Extracts , Plant Leaves , Powders , Quality ControlABSTRACT
The chemical properties of characteristic components are significant to the manufacturing quality control of big brand traditional Chinese medicine. In this study, the Huangjing Zanyu Capsules were used as the research carrier to determine the content of five characteristic components including icraiin, emodin, schisandrin A, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, and osthole simultaneously by high-performance liquid chromatography(HPLC). The results showed that the chemical properties of five cha-racteristic components had a good linear relationship(r>0.999 9) within the quantitative range; the relative standard deviations(RSD) was 0.11%-2.0% and 0.25%-2.8% respectively for intra-day and inter-day precision; the RSD of repeatability was 1.8%-2.6%; the RSD of stability within 48 hours was 0.19%-2.8%, and the average recovery rate was 95.52%-100.1%, all meeting the requirements of pharmaceutical quantitative analysis. Additionally, the interval estimation method was used to directly reflect the distribution of samples with abnormal chemical properties of characteristic components, and the results showed ten samples were detected beyound the 95% control line of confidence level. Multivariate statistical process control(MSPC) method was used to monitor the abnormal samples of Huangjing Zanyu Capsules collectively, and the results showed that two samples were beyond the 95% control line of Hotelling's T~2 and three samples beyond the 95% control line of squared prediction error(SPE), indicating consistent quality control of Huangjing Zanyu Capsules. In conclusion, the proposed method is not only accurate and efficient but also a compensation for the traditional single-component quality control method, providing a scientific basis for the quality control in manufacturing process of Huangjing Zanyu Capsules. Furthermore, it could also serve as a reference method for the quality control in manufacturing big brand traditional Chinese medicine.