"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Correlation between drug-induced liver injury in rats caused by Xianling Gubao oral preparation and extraction process / 中国中药杂志

In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P<0.05), a significant decrease in liver-to-brain ratio(P<0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P<0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P<0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.

Identification of taste critical quality attribute and formulation optimization of Xiaoer Qingrening Granules based on electronic tongue and human senses / 药学学报

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.

Meta analysis of efficacy of Compound Yuxingcao Oral Preparation in treatment of respiratory diseases in children / 中草药

Objective: To systematically evaluate the clinical efficacy of Compound Yuxingcao Oral Preparation in the treatment of respiratory diseases in children, and provide basis for its clinical application. Methods: The clinical controlled trial literatures of Compound Yuxingcao Oral Preparation in the treatment of respiratory diseases in children were searched from database to evaluate the effectiveness of Compound Yuxingcao Oral Preparation by evaluating the quality of literatures based on Meta-analysis. Results: A total of 17 literatures were included, of which 15 were RCT literatures. The average score of literatures was 4. A total of 1766 patients were included in the included literatures. The total effective rate and safety of Compound Yuxingcao Oral Preparation were higher than that of the control group, and the difference was statistically significant. Conclusion: Compound Yuxingcao Oral Preparation has good efficacy and safety in the treatment of children with respiratory tract infection.

Preparation Technology Study on Oridonin A Oral Liposomes Based on Supercritical Fluid Solution-enhanced Dispersion / 中国药房

OBJECTIVE： To optimize the preparation technology of Oridonin A oral liposomes （ORI-LIP） by using supercritical fluidsolution-enhanced dispersion （SEDS） technology， and to investigate its advantage with routine liposome preparation technologies. METHODS： Using particle size as evaluation index， orthogonal design was employed to investigate the influence of pressure， temperature and flow rate on the preparation technology of ORI-LIP by SEDS. At the same time， thin film dispersion and reverse evaporation method were used to prepare ORI liposomes. The particle size， encapsulation efficiency， drug loading amount and stability （accelerated test for 6 months） were compared among 3 methods. Moreover， the difference in dissolution behavior in vitro of ORI crude drug and 3 kinds of liposomes was evaluated. RESULTS： The optimized preparation condition of ORI liposomes by SEDS included temperature of 50 ℃， pressure of 18 MPa， flow rate of 1 mL/min. Compared with thin film dispersion and reverse evaporation method， the liposomes prepared by the SEDS method exhibited smaller particle size [（147.4±4.8）nm]， better encapsulation efficiency （67.8％）， drug-loading amount （7.8％） and stability （particle size increased slightly， encapsulation efficiency decreased only by 4.4％）. Results of in vitro dissolution test showed that compared with crude drug， release rate of each liposome was slow and persistent， and the cumulative release rate was higher. The accumulative release rate of ORI-LIP prepared by SEDS could achieve to 67.2％， and reached to dissolution equilibrium at 24 h. CONCLUSIONS： ORI-LIP prepared by SEDS has smaller particle size， higher encapsulation efficiency， drug loading amount and stability， which can improve the in vitro release of ORI. Compared with conventional methods， SEDS technology has certain advantages.

Research Progress of Granulation Technology for Taste Masking of Pharmaceutical Preparation / 中国实验方剂学杂志

In commonly used oral solid preparations, poor mouthfeel results in poor patient compliance with the drug, which in turn reduces the market competitiveness of the drug. The problem of taste masking of pharmaceutical preparations has always been one of the important problems faced by pharmaceutics. With the increasing demand for the taste of drugs, the methods of masking bad taste of drugs have gradually increased in recent years. By summarizing the relevant literature covering the bad taste of drugs, the commonly used taste masking techniques include the addition of taste masking agents, inclusion techniques, microsphere/microcapsule technology, solid dispersion technology, ion exchange technology and the like. However, in addition to the above taste masking techniques, in the manufacturing process of the solid preparation, the granulation technique also can achieve the shielding of the bad taste of the medicine, and the granulation technique is simple, and can well achieve the effect of masking the bad taste of the medicine. This paper systematically introduces the research progress of granulation technology in drug taste masking, in order to provide reference for the selection of drug taste masking technology. With the increasing demand for drug taste, drug masking technology has been paid more and more attention by the majority of preparation workers, however, there are still some problems, such as imperfect taste evaluation system and low specificity of methods. This series of problems need to be further studied and solved by relevant pharmaceutical researchers.

Advances in strategies of improving solubility and permeability of taxanes / 药学学报

As a new generation of anti-tumor drugs, taxanes has a good clinical efficacy in the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, head and neck cancer. However, low bioavailability of oral administration from low water solubility and low permeability significantly limited the development of their oral applications. Currently, the marketed preparations were non-oral drug preparations, and the injection contained a large number of surfactants (cremophor EL or Tween 80) and organic solvents (ethanol), which could result in fluid retention, hypersensitivity and other side effects, as well as poor compliance. Oral preparation will be an ideal form for development of taxanes medicines. According to the research by our and other groups in recent years, we investigate the technical strategies enhancing the water solubility and absorptive permeability to improve their oral bioavailability. Among them, we emphasize the application prospects of crystallography technology, and provide a theoretical basis to guide future research in the development of oral preparations for taxanes.

Application of information entropy theory in optimization of extraction technology for Lonicerae Flos and Gardeniae Fructus in Reduning Oral Preparation / 中草药

To optimize the extraction technology for Lonicerae Flos and Gardeniae Fructus in Reduning Oral Preparation by information entropy theory. With the contents of chlorogenic acid, gardenoside, luteoloside, and the yield of extract as comprehensive evaluation indexes, the extraction time, dosage of water, and extraction times were selected as factors, the weight of them was determined by information entropy theory, and the extraction technology was optimized by orthogonal test. Optimum extraction technology was: Reflux extraction for 3 times with 12 folds water, 1 h each time. The information entropy theory could be used in optimizing the extraction technology for Reduning Oral Preparation.

Renal Lesion Induced by Oral Preparations of Traditional Chinese Medicines:Analysis of 619 Cases / 中国药房

OBJECTIVE:To analyze the renal lesions induced by oral preparations of traditional Chinese medicines so as to provide theoretic basis for clinical rational drug use.METHODS:The CNKI full-text database between January 1991 and December 2008 were retrieved for clinical reports of renal lesions induced by oral preparations of traditional Chinese medicines.And the pertinent literature was sorted,analyzed and compared.RESULTS:176 reports(totaled 619 cases)were collected.Repeated long-term medication and overdosing etc were the major factors accountable for the renal lesion.CONCLUSION:Importance should be attached to the nephrotoxicity of oral preparations of traditional Chinese medicines,and which should be used rationally in the clinic and periodic examination of patients' renal function should be performed in taking oral preparations of traditional Chinese medicines.

Optimization of Preparation Technics for Liver-strengthening Cholagogue Oral Preparations by Orthogonal Test / 中国药房

OBJECTIVE:To optimize the extraction technics of liver-strengthening cholagogue oral preparation.METHODS:The effects of the four factors-the quantity of the added water,the decoction time,the decoction times and the alcohol precipitation concentration on the extraction results were determined with content of total flavonoids taken as index.RESULTS:The best extracting condition was the following,the amount of the added water was 10 times that of the medicinal materials,the decoction duration was 60min,the alcohol precipitation concentration was 50%and the decoction was carried out twice.CONCLUSION:The preparation under this technics is of high clarity and stable contents.