Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium / 中国中药杂志

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron / 中国天然药物

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 μmol·L-1.

Research progress of continuous manufacturing and process knowledge system of traditional Chinese medicine / 中国中药杂志

In the past few years, continuous manufacturing(CM) has been put forward by the FDA. Pharmaceutical enterprises are encouraged to promote the implementation of CM, which has become a hot research direction of pharmaceutical technology. In February 2019, the FDA issued a draft guideline for the implementation of CM, which greatly promoted the development of CM and provided reference for continuous manufacturing of traditional Chinese medicine(TCM). The production process of TCM is a complex system. With the innovation of production equipment and the promotion of automation and informatization of TCM production, the exis-ting policies, regulations and traditional production control capacity are difficult to meet the market demand for high-quality TCM pro-ducts. In this paper, we reviewed the new technologies and methods of quality control in accordance with the characteristics of TCM production by referring to modern manufacturing technology, information technology and quality control technology. Based on the "QbD" theory and "PAT" technology, process knowledge system(PKS), an advanced control strategy, was proposed to provide a reference for the implementation of CM in TCM production.

Rapid determination of active components in Ginkgo biloba leaves by near infrared spectroscopy combined with genetic algorithm joint extreme learning machine / 中国中药杂志

Near-infrared spectroscopy(NIRS) combined with band screening method and modeling algorithm can be used to achieve the rapid and non-destructive detection of the traditional Chinese medicine(TCM) production process. This paper focused on the ginkgo leaf macroporous resin purification process, which is the key technology of Yinshen Tongluo Capsules, in order to achieve the rapid determination of quercetin, kaempferol and isorhamnetin in effluent. The abnormal spectrum was eliminated by Mahalanobis distance algorithm, and the data set was divided by the sample set partitioning method based on joint X-Y distances(SPXY). The key information bands were selected by synergy interval partial least squares(siPLS); based on that, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA) and Monte Carlo uninformative variable(MC-UVE) were used to select wavelengths to obtain less but more critical variable data. With selected key variables as input, the quantitative analysis model was established by genetic algorithm joint extreme learning machine(GA-ELM) algorithm. The performance of the model was compared with that of partial least squares regression(PLSR). The results showed that the combination with siPLS-CARS-GA-ELM could achieve the optimal model performance with the minimum number of variables. The calibration set correlation coefficient R_c and the validation set correlation coefficient R_p of quercetin, kaempferol and isorhamnetin were all above 0.98. The root mean square error of calibration(RMSEC), the root mean square error of prediction(RMSEP) and the relative standard errors of prediction(RSEP) were 0.030 0, 0.029 2 and 8.88%, 0.041 4, 0.034 8 and 8.46%, 0.029 3, 0.027 1 and 10.10%, respectively. Compared with the PLSR me-thod, the performance of the GA-ELM model was greatly improved, which proved that NIRS combined with GA-ELM method has a great potential for rapid determination of effective components of TCM.

Simultaneous determination of five saponins in Yaobitong capsule by HPLC-CAD / 药学学报

A high performance liquid chromatography charged aerosol detector (HPLC-CAD) method was established for the simultaneous determination of five saponins (notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, Ginsenoside Rd) in Yaobitong capsule, providing a method for quality control. The sample was extracted with methanol and chromatographic separation was performed on a Waters Xbridge Phenol column (150 mm×4.6 mm, 3.5 μm) using acetonitrile-water as the mobile phase with gradient elution at a flow rate of 1.0 mL·min-1. The column temperature was 30 ℃ and the injection volume was 10 μL. The nebulizer temperature of CAD was 35 ℃ and the air pressure was 60.2 psi, the filtration was 3.6 s, and the collection frequency was 5 Hz. Notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd showed a good linear relationship in the range of 16.96-203.5 μg·mL-1 (R2 = 0.999 3), 54.46-653.5 μg·mL-1 (R2 = 0.999 3), 10.96-131.5 μg·mL-1 (R2 = 0.999 6), 51.50-618.0 μg·mL-1 (R2 = 0.999 0), 15.94-191.3 μg·mL-1 (R2 = 0.999 4), respectively. The average recoveries were 98.96%, 100.8%, 94.76%, 100.1%, 103.1%, and RSDs were 0.87%, 1.46%, 1.85%, 2.06%, 0.96% (n = 6), respectively. The proposed method is accurate, simple and reliable, and can be used for the determination of five saponins in Yaobitong capsule.

The prediction of baicalin content in the extraction process of Scutellaria baicalensis by near-infrared spectroscopy combined with different variable selection methods / 药学学报

Near-infrared spectroscopy (NIRS) combined with chemometrics can achieve rapid detection in process analysis. After variable selection, the redundant information is effectively removed and the characteristic variables related to the response values are selected. Compared with global model, the complexity is significantly reduced and the prediction accuracy is also improved. In this study, near-infrared spectroscopy analysis combined with different variable selection methods was applied to achieve the rapid detection of baicalin in the extraction process of Scutellaria baicalensis. Data sets were divided based on sample set portioning based on joint x-y distance (SPXY) method. Competitive adaptive weighted resampling method (CARS), random frog (RF) and successive projections algorithm (SPA) were applied to variable selection. Partial least squares (PLS) models were constructed based on above three methods, and the prediction results were compared. After CARS, RF and SPA method, 92, 10 and 17 variables were screened out respectively. According to the performance of the models, CARS method is found to be more effective and suitable than RF and SPA. Furthermore, the characteristic variables selected by CARS method have a better correspondence with the chemical structure of baicalin. The root mean square error (RMSEC) of the calibration set and the root mean square error (RMSEP) of the prediction set are 0.528 2 and 0.720 2 respectively. Compared with the global PLS model, the correlation coefficient of the calibration set (Rc) is increased to 0.979 9 from 0.917 0, and the relative standard errors of prediction (RSEP) is reduced to 5.59% from 10.58%.

On-line detection of concentration process of Ganmaoling granules by near infrared spectroscopy combined with automatic control system / 药学学报

Our research was designed for on-line detection of multi-index in the concentration process of Ganmaoling granules by integration of near infrared spectroscopy and automatic control system. First, on-line detection system was set up in the concentration tank for Ganmaoling granules production. Spectra were scanned and values of chlorogenic acid, linarin, solid content and relative density were measured. Models of partial least squares regression were built and imported into near infrared workstation. By connecting the control system, real-time multi-index values were determined automatically in the concentration process. Results showed that correlation coefficients of chlorogenic acid, linarin, solid content and relative density models were 0.963, 0.989, 0.993 and 0.918, respectively. Relative standard errors of prediction were 3.71%, 4.28%, 4.17% and 0.24%, respectively, indicating a good performance and high accuracy of the models. Real-time data collection during the whole process was measured by the near infrared detecting system in the control system. In conclusion, the near infrared detection system is able to perform real-time automatic determination of multi-index in the concentration process of Ganmaoling granules with significant advantages.

On-line monitoring of extraction of coldrine by near-infrared spectrum / 中国中药杂志

Extraction of the four Chinese herbals is the beginning step of the production process of coldrine granules and influences on drug quality significantly. In this paper, the on-line near infrared spectrum was collected during the extraction process of coldrine and then pre-processed by the first derivative. Partial least square regression (PLSR) model was developed for the quantity indicators of linarin, chlorogenic acid and solid content, according to results of both HPLC and weight-loss as reference methods. The correlation coefficient, root mean square error of cross-validation (RMSECV), root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were used to optimize model parameters and confirm their performance. Correlation coefficients of three quality control indicator models reached more than 0.95.Values of RMSEC of linarin, chloroenic acid and solid content were 0.010 4, 0.009 34 and 0.055 5, respectively. And the values of RMSEP were 0.009 47, 0.142 and 0.008 42, respectively. The models, built on-line analyze data, revealed that the correlation coefficients of predicted values and measured values were greater than 0.97 and values of RSEP of linarin, chloroenic acid and solid content were 8.14%, 8.17% and 9.86%, respectively. The results showed that the NIR method could achieve the on-line detection and real-time monitoring of multi-indexes during the extraction process of coldrine. The technology could be used for drug quality control in the process of practical production, reducing the batch differences and ensuring pharmaceutical quality stability. In addition, it could provide real-time production data for subsequent product quality backtracking.

Study on concentrating process of Lvjiao Buxue Granule by near infrared spectroscopy / 中草药

Objective: To establish rapid quantitative analysis models of multiple indicators for quality control in the concentrating process of Lvjiao Buxue Granule (LBG) by means of near infrared spectroscopy(NIRS). Methods: Thesolid content (SC), totalpolysaccharides concentration (TPC), and ferulic acid concentration (FAC) were determined by weighing method, phenol-sulfuric acid method, and HPLC method, respectively. Calibration models of them were established with partial least squares regression (PLSR)method. The established models were applied to predicting the unknown samples for testing the performance of the models. Results: The correlation coefficients (r) of SC, TPC, and FAC were all above 0.9450.The root mean square error in calibration (RMSEC) and root mean square error in prediction (RMSEP) were very close, and the relative standard errors of predictions (RSEP) were all less than 10%, indicating that the models predicted and performed well. Conclusion: NIRS technique combined with chemo metrics can provide a novel efficient and environmental approach for the fast simultaneous determination of key quality indicatorsfriendly, and havethe potential application value in the concentration process of LBG.

Determination of 10 mycotoxin contaminants in Panax notoginseng by ultra performance liquid chromatography-tandem mass spectrometry / 药学学报

To ensure the quality and safety of Panax notoginseng, a method for the simultaneous determination of 10 mycotoxins in Panax notoginseng was developed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The sample was extracted with acetonitrile and purified by HLB multifunction cleanup column. The separation was performed on a Phenomenex Kinetex XB-C18 column by gradient elution using methanol and 5 mmol·L(-1) ammonium acetate as mobile phase. The targeted compounds were detected in MRM mode by mass spectrometry with electrospray ionization (ESI) source operated in both positive and negative ionization modes. The linear relationships of the 10 mycotoxins were good in their respective linear ranges. The correlation coefficients (r) ranged from 0.9981 to 1.0000. The LOQs of the 10 mycotoxins were between 0.15 and 8.6 μg·kg(-1). The average recoveries ranged from 73.8% to 107.0% with relative standard deviations (RSDs) of 0.10%-10.9%. The results demonstrated that the proposed method was sensitive and accurate, and suitable for the mycotoxins quantification in Panax notoginseng.

Application of near infrared spectroscopy combined with particle swarm optimization based least square support vactor machine to rapid quantitative analysis of Corni Fructus / 药学学报

A novel method was developed for the rapid determination of multi-indicators in corni fructus by means of near infrared (NIR) spectroscopy. Particle swarm optimization (PSO) based least squares support vector machine was investigated to increase the levels of quality control. The calibration models of moisture, extractum, morroniside and loganin were established using the PSO-LS-SVM algorithm. The performance of PSO-LS-SVM models was compared with partial least squares regression (PLSR) and back propagation artificial neural network (BP-ANN). The calibration and validation results of PSO-LS-SVM were superior to both PLS and BP-ANN. For PSO-LS-SVM models, the correlation coefficients (r) of calibrations were all above 0.942. The optimal prediction results were also achieved by PSO-LS-SVM models with the RMSEP (root mean square error of prediction) and RSEP (relative standard errors of prediction) less than 1.176 and 15.5% respectively. The results suggest that PSO-LS-SVM algorithm has a good model performance and high prediction accuracy. NIR has a potential value for rapid determination of multi-indicators in Corni Fructus.

Particle settling characteristics of alcohol precipitation mixture of Paeoniae Radix rubra extract and models establishment of settling velocity / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To understand the particle settling characteristics of alcohol precipitation mixture of Paeoniae Radix rubra extract and establish models of the sedimentation rate.</p><p><b>METHODS</b>Focusing on the particle settling characteristics such as particle settling curve, particle settling velocity (PSV), particle volume index (PVI), the particle settling process of alcohol precipitation was investigated. The effect of three key process factors on the settling process was discussed and mathematical models for describing the particle settling velocity were developed.</p><p><b>RESULTS</b>Controlling of higher final alcohol concentration, higher density of Paeoniae Radix rubra extract, or lower initial alcohol concentration, was conducive to settlement of alcohol precipitation particles. In the constant speed phase, an empirical calculation formula of v(0) was established, with both the variables PSV and PVI (v(0)=-0.236PSV+0.022PVI+7.521). Another developed model was applied to predict the settling velocity in decelerated phase and the simulation was very good [v=k(1-n(1)X)(4)exp(-n(2)X)/X].</p><p><b>CONCLUSION</b>The results of this work will contribute to a better control and optimization of alcohol precipitation process, and help to implementation of accuracy control in the manufacture of botanical medicines.</p>

Fast measurement method based on near infrared spectroscopy in purifying process of Carthamus tinctorius extracts / 中国中药杂志

<p><b>OBJECTIVE</b>To really realize quality control of Chinese herb purifying process, near-infrared spectroscopy (NIRS) was used not only for fast monitoring quality-control index of the process, but also for fast judgment of absorption endpoint.</p><p><b>METHOD</b>The purification process of Carthamus tinctorius extracts with nonionic macroreticular resin was selected as an example. HPLC was used as the reference method to determine the content of HSYA. Quantitative and qualitative detection modes of purification were developed by NIRS combined with partial least squares (PLS) and moving block of standard deviation (MBSD).</p><p><b>RESULT</b>The correlation coefficient of the calibration model was 0.999, and the RPD for calibration and validation were above 5, of 5.54 and 5.22, respectively. Based on acquisition spectra, absorption endpoint calculated by MBSD was close to that by HPLC, Only 1 min deviation.</p><p><b>CONCLUSION</b>The method mentioned above is proved to be convenient, rapid and nondestructive, and is applicable for fast monitoring the content of HSYA and fast judgment of absorption endpoint in purifying process of C. tinctorius extracts.</p>

Optimization of alcohol precipitation process for extract of Carthamus tinctorius by multiple guidelines grading method / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the optimal alcohol precipitation parameters for extract of Carthamus tinctorius.</p><p><b>METHODS</b>The effects of different factors on the transfer rate of hydroxy safflower yellow A (HSYA) was studied via single factor experiments, including the final alcohol concentration of the liquor, the speed of stirring, the initial density of the extract, the temperature and the pH of the liquor. Based on the results of single factor experiments, the final alcohol concentration of the liquor, the speed of stirring, the initial density of the extract and the pH of the liquor were studied by an orthogonal test and a multiple guidelines grading method, and the transfer rate of HSYA, the yield and the purity of extract in the supernatant were used as comprehensive evaluation index.</p><p><b>RESULT</b>The optimal alcohol precipitation process of Carthamus tinctorius extract was as follows: the final alcohol concentration of the liquor 50%, the speed of stirring 500 r/min, the initial density of the extract 1.15 g/ml and the pH of the liquor 5.0.</p><p><b>CONCLUSION</b>The proposed alcohol precipitation process is convenient and steady with high transfer rate of HSYA, high yield and purity of extract in the supernatant.</p>

Effect of transurethral resection of prostate on quality of life in aged patients with benign prostatic hyperplasia / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of transurethral resection of prostate (TURP) on the quality of life in aged patients with benign prostatic hyperplasia(BPH).@*METHODS@#Altogether 358 BPH patients were evaluated by International Prostate Symptom Score (IPSS), the 5-Item Version of the International Index of Erectile Function (IIEF-5),Quality of Life Scale (QOLS) questionnaires, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS),residual urine volume (RUV), and maximum flow rate(Qmax) before and at 3 months after they underwent TURP.@*RESULTS@#The mean scores of IPSS, QOLS, SAS, and SDS, and mean RUV decreased, and mean Qmax increased significantly at 3 months after receiving operation compared with those before the treatment in aged patients with BPH. But no significant difference was found in the scores of IIEF-5 between post-operation and pre-operation.@*CONCLUSION@#TURP may alleviate BPH clinical symptoms and improve quality of life, but may not be helpful to the recovery of sexual function in aged patients with BPH.

Optimization for vacuum belt drying process of Panax notoginseng extract / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize the conditions of the vacuum belt drying process (VBD) for drying Panax notoginseng extract and compare with methods of vacuum freezing drying and spray drying.</p><p><b>METHOD</b>The optimum conditions of VBD were obtained by orthogonal design and validated by determinations of moisture content of the dried product and recovery of active ingredients. Experiments on different drying methods were also conducted.</p><p><b>RESULT AND CONCLUSION</b>The optimum conditions are as follows, the feeding speed was 15 mL x min(-1), the belt speed was 4 mm x min(-1), and the heating temperature was (105, 100 degrees C). Comparing with the drying methods of vacuum freezing drying and spray drying, vacuum belt drying possesses some advantages, such as higher recovery of active ingredients, less moisture content of dried product and better overall yield.</p>

Advances in studies on multi-stage countercurrent extraction technology in traditional Chinese medicine / 中国中药杂志

Multi-stage countercurrent extraction technology, integrating solvent extraction, repercolation with dynamic and countercurrent extraction, is a novel extraction technology for the traditional Chinese medicine. This solvent-saving, energy-saving and high-extraction-efficiency technology can at the most drive active compounds to diffuse from the herbal materials into the solvent stage by stage by creating concentration differences between the herbal materials and the solvents. This paper reviewed the basic principle, the influence factors and the research progress and trends of the equipments and the application of the multi-stage countercurrent extraction.

Optimizing process of four-effect countercurrent extraction of danshensu from Salvia miltiorrhiza / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the process factors and characteristic of four-effect countercurrent extracting process of Danshensu from Salvia miltiorrhiza. Optimizing the parameters by using regression analysis and principal components analysis (PCA).</p><p><b>METHOD</b>Applying the orthogonal design method to optimize the extracting process. The factors of extraction time, solvent volume, extraction temperature and the degree of grinding were considered. And also, the new process was compared with the refluence process.</p><p><b>RESULT</b>The optimal condition of four-effect countercurrent extraction of Danshensu from S. miltiorrhiza was 1 h extraction time, solvent to sample ratio of 12 mL x g(-1), 80 degrees C , 20 - 40 mesh of particle size. Compared with the refluence process, the countercurrent extracting process has the advantages of higher recovery, less solvent consumption and shorter extraction time.</p><p><b>CONCLUSION</b>The four-effect countercurrent extraction process has great advantages and is good for Chinese medicinal materials.</p>

Clinical applications of devitalized autogenous calvarial bone flaps fixed with titanium clamps (CranioFix) for cranioplasty / 中华整形外科杂志

<p><b>OBJECTIVE</b>To evaluate reimplantation of devitalized autogenous calvarial bone flaps and the fixation of titanium clamps (CranioFix) for cranioplasty.</p><p><b>METHODS</b>From March 2000 to December 2003, 21 patients underwent (1) delayed reimplantation of preserved autogenous bone flaps, which were removed during the initial operations for increased intracranial pressure and stored in a freezer and autoclaved before use, or (2) immediate reimplantation of tumor invaded bone flaps that were devitalized by boiling. All of these flaps were fixed with titanium clamps (CranioFix). Resorption of the bone flaps was monitored by skull roentgenograms and computed tomography (CT). The clinical and aesthetic results were evaluated.</p><p><b>RESULTS</b>During the follow-up period of 6 to 30 months, no complications were found. There was slight resorption of the bone flaps in all cases, but the edge of the bone flaps was within the range of the titanium clamps according to skull roentgenograms and CT. Clinical and aesthetic results were highly satisfactory.</p><p><b>CONCLUSIONS</b>It is simple and practical using devitalized autogenous calvarial bone flaps for cranioplasty. The firmness decreasing of the reimplanted bone flap due to resorption can be prevented greatly by titanium clamps (CranioFix).</p>

CD226 monoclonal antibody induces variation of intracytosolic free calcium level in human umbilical vein endothelial cells / 生理学报

In order to study the possible mechanism of CD226 monoclonal antibody (mAb)-mediated intracellular message transduction in human umbilical vein endothelial cells (HUVECs), the influence of CD226 mAb and its cross-linking by secondary antibody (II Ab) on the concentration changes in [Ca(2+)](i) in the HUVECs under different conditions were determined by confocal laser scanning microscopy. The main results are as follows. (1) When the culture medium was balanced by Hanks Buffer, [Ca(2+)](i) in HUVECs increased slowly after stimulation by CD226 mAb, whereas [Ca(2+)](i) increase was accompanied by [Ca(2+)](o) decrease after the mAb was cross-linked by goat anti-mouse IgG. Then [Ca(2+)](i) and [Ca(2+)](o) all returned to the normal level. (2) When the culture medium was balanced by D-Hanks buffer, [Ca(2+)](i) in HUVECs showed little variation when the cells were stimulated by CD226 mAb, but [Ca(2+)](i) decreased markedly after cross-linking. (3) When HUVECs were pretreated with EGTA, there was no variation in [Ca(2+)](i) of HUVECs after CD226 mAb stimulation alone or cross-linking of the mAb. Our results suggest that stimulation by CD226 mAb and cross-linking by goat anti-mouse IgG induce the variation of [Ca(2+)](i) in HUVECs under different conditions and the variation of [Ca(2+)](i) in HUVECs may play an important role in many physiological and pathological processes.