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.

Comparative study on in vivo and in vitro permeability of Huoxue Zhitong gel patch and microemulsion gel / 中国中药杂志

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.

Textual Research of Classical Prescription Taohong Siwutang / 中国实验方剂学杂志

Taohong Siwutang， originating from Fuke Bingjian by CHAI Dehua in the Qing Dynasty， has been included in the first batch of the 100 classical prescriptions published by the National Administration of Traditional Chinese Medicine（TCM）. Taohong Siwutang is composed of six Chinese medicinals， namely the wine-washed Angelicae Sinensis Radix， wine-washed Rehmanniae Recens Radix， wine-washed Carthami Flos， wine-processed Paeoniae Alba Radix， Persicae Semen undergoing peel-off process in hot water， and Chuanxiong Rhizoma， possessing the effects of nourishing blood， promoting blood circulation， and removing blood stasis， and it is mainly applicable to patients with blood deficiency and stasis syndrome. The textual research on the key information of classical prescriptions and the summarization of their ancient and modern applications are conducive to learning about the research status and confirming the subsequent research direction， thus better guiding the preparation of substance benchmarks and the in-depth exploration of preparations. By exploring the sources and historic evolution of Taohong Siwutang and each Chinese medicinal， this paper uncovered the prescription composition， origin of each Chinese medicinal， processing method， and prescription dose. The review of its clinical applications showed that the application scope in modern times has been extended and expanded in contrast to that recorded in ancient books. As revealed by the clinical application literature， it has been mainly employed for treating gynecological diseases such as dysmenorrhea and irregular menstruation， orthopedic diseases like fracture， dermatological diseases such as chloasma， and internal diseases such as coronary heart disease， all of which were differentiated into the blood deficiency and stasis syndrome. It could be seen that Taohong Siwutang had great clinical application value. This review of the ancient and modern literature concerned with Taohong Siwutang and the analysis and determination of its key information are expected to provide a reference for the rational clinical application and further research of Taohong Siwutang.

Analysis on quality value transfer of substance benchmarks of Taohong Siwu Decoction / 中国中药杂志

By preparing 15 batches of substance benchmarks of Taohong Siwu Decoction, the methodology of the characteristic spectrums of substance benchmarks was established. The paste-forming rate range, the contents and the transfer rate range of the index components, hydroxy safflower yellow A, ferulic acid and paeoniflorin, the characteristic peaks and the similarity range of the characteristic spectrums of Taohong Siwu Decoction were determined to define key quality attributes of substance benchmarks of Taohong Siwu Decoction.In the 15 batches of substance benchmarks of Taohong Siwu Decoction, the similarity of characteristic spectrums was higher than 0.9. Furthermore, based on summarization of the characteristic peak information, there were 13 characteristic peaks in the whole decoction. Baishao had three characteristic peaks, Honghua had seven characteristic peaks, and Chuanxiong and Danggui had three characteristic peaks. The paste-forming rate of the 15 batches of substance benchmarks was controlled at 33.11%-40.62%. The content of hydroxy safflower yellow A was 0.129%-0.203%, with the average transfer rate of 16.596%±0.669%.The content of ferulic acid was 0.043%-0.055%, with the average transfer rate of 20.489%±1.772%.The content of paeoniflorin was 0.676%-0.943%, with the average transfer rate of 29.112%±3.273%.The quality value transfer of substance benchmarks of classical prescription Taohong Siwu Decoction was analyzed by the combination of characteristic spectrums, paste-forming rate and the content of index components. The established substance benchmark quality evaluation method was stable and feasible, and could provide a basis for quality control and subsequent development of relevant preparations of Taohong Siwu Decoction.

Analysis on quality value transfer of substance benchmarks of Qingwei San / 中国中药杂志

By preparing 10 batches of substance benchmarks freeze-drying powder( lyophilized powder),the methodology of the characteristic spectrum and the content of index component for substance benchmarks of Qingwei San was established. The characteristic peaks and the similarity range of the characteristic spectrum,the contents and the transfer rate range of isoferulic acid,palmatine and paeonol,and the paste-forming rate range were determined to define key quality attributes of substance benchmarks of Qingwei San. In the10 batches of substance benchmarks of Qingwei San,the similarity of characteristic spectrum was higher than 0. 90. In further comparison of the characteristic peak information,a total of 16 characteristic peaks were identified,including 5 characteristic peaks from Cimicifugae Rhizoma,5 characteristic peaks from Coptidis Rhizoma,2 characteristic peaks from Angelicae Sinensis Radix and 4 characteristic peaks from Moutan Cortex. The content of isoferulic acid was 0. 10%-0. 18%,with the average transfer rate of 49. 82%±4. 02%. The content of palmatine was 0. 17%-0. 31%,with the average transfer rate of 15. 84% ±2. 39%. The content of paeonol was 0. 41%-0. 75%,with the average transfer rate of 23. 41%±3. 23%. The paste-forming rate of the 10 batches of substance benchmarks were controlled at 27%-33%,with the transfer rate between the theoretical paste-forming rate and the actual paste-forming rate was 86. 59%±3. 39%. In this study,the quality value transfer of substance benchmarks of Qingwei San was analyzed by the combination of characteristic spectrum,the content of index component and the paste-forming rate. A scientific and stable evaluation method was preliminarily established,so as to provide the basis for subsequent development and quality control of relevant preparations of Qingwei San.

Effects of hypoxia on secretion of IL-1β, IL-6 and TNF-α in cerebral cortex cells of rats / 第二军医大学学报

Objective To investigate the effects of different hypoxia treatments on secretion of IL-1β, IL-6 and TNF-α in the cerebral cortex cells of rats. Methods Primary cultured cerebral cortex cells were subjected to hypoxia treatments (1% and 4% oxygen) for 3 h or 6 h. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IL-1β, IL-6 and TNF-α protein in cultural supernatants. Results (1) Compared with the corresponding normoxia (20% oxygen) controls, IL-6 level was significantly decreased after treatment with 1% oxygen for 3 h and 6 h (P0.05); the levels of IL-1β and IL-6 were significantly decreased in cells treated with 4% oxygen for 6 h (P0.05). Conclusion Oxygen at 1% has no influence on IL-1β or TNF-α secretion in cerebral cortex cells of rats, and it can inhibit the production of IL-6. Oxygen at 4% has inhibitory effect on IL-1β and IL-6 production, and it has no effect on TNF-α production.