Determination of five saponins in Xuesaitong Dropping Pills by micellar electrokinetic chromatography and evaluation method of between-batch consistency / 中国中药杂志

The present study determined five saponins in Xuesaitong Dropping Pills(XDP) by micellar electrokinetic chromatography(MEKC), and evaluated between-batch consistency by MEKC fingerprints and similarity analysis. A background buffer was composed of 20 mmol·L~(-1) sodium tetraborate-20 mmol·L~(-1) boric acid solution(pH 8.5), 55 mmol·L~(-1) sodium dodecyl sulfate(SDS), 23 mmol·L~(-1) β-cyclodextrin, and 13% isopropyl alcohol. All separations were performed at 25 ℃,20 kV and the detection wavelength was set at 203 nm. The separation channel was a fused silica capillary with a dimension of 75 μm I.D. and a total length of 50.2 cm(effective length of 40.0 cm). The contents of notoginsenoside R_1, and ginsenosides Rg_1, Re, Rb_1, Rd were determined with their quality control ranges set. The fingerprints of XDP were established and the between-batch consistency was evaluated by similarity analysis. The contents of five saponins from the 19 batches of XDP were stable in the fixed ranges. Statistical analysis was carried out on the results of multiple batches of samples, and the specific quality control ranges were recommended as follows: notoginsenoside R_1 21.92-34.16 mg·g~(-1), ginsenosides Rg_1 83.54-131.78 mg·g~(-1), ginsenosides Re 13.58-19.82 mg·g~(-1), ginsenosides Rb_1 89.40-129.90 mg·g~(-1), and ginsenosides Rd 22.34-35.67 mg·g~(-1). Eleven characteristic peaks were identified in the fingerprints. Five peaks, notoginsenoside R_1 and ginsenosides Rg_1, Re, Rb_1, Rd, were identified with reference standards. The similarities of the 19 batches of samples were all above 0.988, indicating good between-batch consistency. This method is green and simple, and can be used for the quantitative determination and quality evaluation of XDP. It can also provide references for the quality control of other Chinese medicinal dripping pills.

Identification of critical influencing factors in dropping process of Xuesaitong Dropping Pills / 中国中药杂志

With the dropping process of Xuesaitong Dropping Pills(XDP) as the study object, critical factors affecting the quality indicators of pill pass rate, average weight of drop pills and roundness were screened out, so as to deepen the understanding of the dropping process. The critical process units, critical quality attributes and potential critical process influencing factors of XDP were determined by risk analysis and prior knowledge, and then the critical influencing factors were screened out by Plackett-Burman design. First, according to the risk assessment, the critical technique of XDP preparation process was dropping, and then the critical quality attributes of dropping process were pill pass rate, average weight of drop pills and roundness. Then, according to fishbone diagram and failure mode and effects analysis(FMEA), potential critical influencing factors were determined as flow rate, matrix ratio, solid-liquid ratio, feed-liquid temperature, top temperature of condensate, bottom temperature of condensate and dropping distance. Finally, among these seven potential factors, the critical influencing factors were determined as material liquid ratio, dropping distance, top temperature of condensate, bottom temperature of condensate. This study revealed the potential of Plackett-Burman design in screening and understanding the influence of selected factors on XDP dropping process, which could provide a reference for studying the dropping process.

Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

A numerical dynamic simulation study of licorice concentration process / 中草药

Objective Taking the concentration process of liquorice extract as the research object, the dynamic simulation process of concentration of Chinese materia medica (CMM) was constructed by combining experimental analysis with theoretical simulation, which provided the model support and theoretical analysis basis for the process research and equipment development of concentration process of CMM. Methods The corresponding relationship between boiling point and saturated vapor pressure of liquorice solution was determined by dynamic method. The experimental data were fitted by thermodynamic model to obtain relevant parameters. On this basis, the simulation process of liquorice water extract concentration was constructed by using ASPEN PLUS. According to the simulation of dynamic process, the effects of heating power, feed rate, and vacuum degree on liquorice solution concentration process in an external thermal concentrator were discussed. Finally, the equations about concentration time and heating power were obtained by simulation. Results The results of parameter fitting were Aij = 1.63, Aji = 2.32, Bij = 336.38, Bji = 792.00, and Cij = 0.5. Finally, the functional equation for the concentration time and heating power was t = 2 329 c1H/c0Q. Conclusion In this study, the effects of different process parameters on the concentration process of TCM were analyzed by simulation and related theories, and a simple prediction of the concentration process was realized. It also perfected and optimized the process simulation data, filled the relevant scientific research gap, and was of great significance to industrial guidance. Firstly, the relevant experimental data was obtained by fitting the thermodynamic model with the relevant experimental data. Then, under the ideal process conditions, the influencing factors of liquorice concentration process were analyzed and discussed by dynamic simulation. It was concluded that heating power was the key factor affecting the concentration process, and the concentration time gradually decreased with the increase of heating power. However, their functional relationship was non-linear. At the same time, the functional equation can be used to roughly predict the concentration time of CMM. To a certain extent, this fills in the gap between the related theoretical research and data of chemical thermodynamics, which provides theoretical support for the process research and equipment development of the concentration process of CMM.

Determination of saponins in Xuesaitong Drop Pills and study on batch consistency evaluation techniques / 中草药

Objective: To establish the fingerprint of Xuesaitong Dropping Pills (XDP) using ultra-high pressure liquid chromatography (UPLC), determine the content of its main components and propose a chemometrics method for the systemic, comprehensive and scientific quality evaluation. Methods: The Agilent 1290 UPLC and Acquity UPLC BEH C18 column were used for the establishment of the UPLC fingerprints of 14 batches of XDP with acetonitrile and water as mobile phase for gradient elution, and the content of five kinds of notoginsenosides wsa determined. Then, the further quality assessment of XDP was carried out with similarity evaluation, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Meanwhile, the Hotelling’s T2 and DModX control ranges were set for the different batches of samples. Results: Among the 14 batches, the content of five kinds of notoginsenosides was relatively stable, and the quality control ranges for notoginsenosides R, ginsenoside Rg1, Re, Rb1, Rd were set at 24.69-30.03 mg/g, 102.60-122.44 mg/g, 12.93-15.45 mg/g, 99.74-112.12 mg/g, and 23.35-31.75 mg/g, respectively. In this research, 15 chromatographic peaks were recognized as common peaks in the fingerprints, five peaks were identified with standard references compounds, which were notoginsenoside R1, ginsenoside Rg1, ginsenoside Re,ginsenoside Rb1 and ginsenoside Rd. The similarity values of the drugs were all above 0.998. In the PCA analysis, 14 batches of samples had no abnormal batch, indicating that the quality was relatively stable, however, the difference of the storage time was reflected in the fingerprint. According to the OPLS-DA result, the quantitative ginsenoside Rb1 and ginsenoside Rd had greater influence on the variables causing the gradual trend in 14 batches of samples. The upper limit of control for Hotelling’s T2 and DModX was 31.17 and 1.82, respectively. Conclusion: The established method was accurate, reliable, and simple. It can be used not only for the quality control of XDP, but also for the comprehensive evaluation of batch consistency. The study also provides a reference for solving the common problem of the consistency evaluation of Chinese materia medica.