Exploration of Spectrum-effect Relationship of Zhuriheng Dropping Pills Against Macrophage Foaming Based on UPLC-Q-Exactive Orbitrap MS / 中国实验方剂学杂志

ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Research progress in quality studies and antiviral effect of Qingyan Dropping Pills / 国际生物医学工程杂志

Qingyan Dropping Pills have the effects of relieving wind and heat, detoxifying, and promoting the pharynx. It is commonly used in traditional Chinese medicines to treat acute and chronic pharyngitis, as well as sore throats and dry throats caused by surgery. Recently, many studies have shown that Qingyan Dropping Pills have certain effects on bacteriostasis, anti-inflammatory, antioxidant, and antiviral activities. As the coronavirus disease 2019 (COVID-19) pandemic enters the post-epidemic era, the regular use of drugs for COVID-19 pandemic symptoms has become a new trend. Therefore, there is a good market prospect to explore and develop Chinese patent medicines with antiviral effects. A preliminary study on the herbal formula and material basis of Qingyan Dropping Pills revealed that they have potential for antiviral applications. In this paper, the research on the quality study and antiviral effect of Qingyan Dropping Pills was reviewed, and the research direction of its secondary development was discussed to provide ideas and references for the new use of old traditional Chinese medicines.

Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease / 药物分析学报

Parkinson's disease(PD)is the second most common neurodegenerative disease in the world;however,it lacks effective and safe treatments.Ginkgo biloba dropping pill(GBDP),a unique Chinese G.biloba leaf extract preparation,exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD.Thus,the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G.biloba extract EGb 761.Using liquid chromatography tandem-mass spectrometry,46 GBDP constitu-ents were identified.Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761.A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761,whereas EGb 761 had higher levels of organic acids.Moreover,we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice.Although similar effects were observed after EGb 761 treatment,the neuroprotective effects were greater after GBDP treatment on several endpoints.In addition,in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP.These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

Mechanism of Liangfu Dropping Pills in treatment of gastrointestinal diseases based on plasma pharmacochemistry and network pharmacology / 中国中药杂志

To study the active chemical components and mechanism of Liangfu Dropping Pills in treatment of gastrointestinal diseases. The UHPLC-Q-TOF-MS method was employed to analyze the components of Liangfu Dropping Pills in plasma. The protein targets of the absorbed compounds were predicted in the TCMSP database and the SwissTargetPrediction database. The targets associated with gastrointestinal diseases were collected from OMIM, CTD, GeneCards, and DrugBank. The common target genes between components and diseases were screened out for the building of protein-protein interaction(PPI) network in the STRING database. Metascape was used to carry out gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. Cytoscape was employed to construct the PPI network diagram and absorbed component-target network diagram. The molecular docking between the components absorbed in blood and potential key targets was performed by AutoDock vina 4.2.6 to screen and verify the main active components and targets. Twelve chemcial components were identified in Liangfu Dropping Pills, in which four components were absorbed in blood, including galangin, rhamnocitrin, galangin 3-methyl ether, and α-cyperone. These components acted on 189 common targets which were mainly involved in the cell responses to nitrogen compounds, organic cyclic compounds, and hormones, and enriched in the PI3 K-Akt signaling pathway, Foxo signaling pathway, and IL-17 signaling pathway. Molecular docking results showed that the four components had strong affinity with core targets. The material basis of Liangfu Dropping Pills treating gastrointestinal diseases may be galangin, rhamnocitrin, galangin 3-methyl ether, and α-cyperone. This study provides a theoretical basis for further development and application of Liangfu Dripping Pills.

Meta-analysis of efficacy and safety of Shexiang Tongxin Dripping Pills combined with conventional therapy of coronary heart disease / 中国中药杂志

The aim of the research was to evaluate the efficacy and safety associated with Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD). We searched 8 electronic databases up to November 2020, including PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP and SinoMed. Eligible studies were clinical trials of Shexiang Tongxin Dropping Pills combined with conventional therapy used in the treatment of coronary heart disease(CHD). The Meta-analysis was performed using STATA 15 software. A total of 21 RCTs(n=2 186) were shortlisted for the Meta-analysis. The results of efficacy evaluation showed that the total effective rate of Shexiang Tongxin Dropping Pills combined with conventional therapy was higher than that of conventional therapy of coronary heart disease(RR=1.20, 95%CI[1.15, 1.26], Z=8.63, P<0.001). Furthermore, Shexiang Tongxin Dripping Pills combined with conventional therapy had better effect on electrocardiogram efficacy(RR=1.24, 95%CI[1.16, 1.34], Z=5.98, P<0.001) and the number of angina attacks(SMD=-2.30, 95%CI[-3.47,-1.14], Z=3.88, P<0.001), the duration of angina attack(SMD=-2.31, 95%CI[-3.07,-1.55], Z=5.97, P<0.001), with lower levels of LDL-C(SMD=-0.73, 95%CI[-1.32,-0.14], Z=2.42, P=0.016), TC(SMD=-1.16, 95%CI[-1.35,-0.96], Z=11.56, P<0.001) and TG(SMD=-0.87, 95%CI[-1.06,-0.68], Z=8.97, P<0.001), and higher levels of HDL-C(SMD=0.87, 95%CI[0.02, 1.71], Z=2.00, P=0.045). The results of safety evaluation showed that the incidence of adverse reactions of Shexiang Tongxin Dropping Pills combined with conventional therapy was lower than that of conventional therapy of coronary heart disease(RR=0.45, 95%CI[0.22, 0.91], Z=2.23, P=0.026). There were significant differences in the above outcome indexes between the two groups. After the Harbord method test, the total effective rate outcome index has publication bias, but the sensitivity analysis of the cut-and-fill method suggested that the result was stable. In general, limited by the quantity and quality of included literature, more high-quality studies are needed to further verify the conclusions of this study.

Systematic evaluation on efficacy and safety of Gingko Ketone Ester Dropping Pills in treatment of angina pectoris and coronary heart disease / 中国中药杂志

To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.

Pharmacoeconomic evaluation of Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment for coronary heart disease by Markov model / 中国中药杂志

This research was to evaluate the economics of Shexiang Tongxin Dropping Pills combined with conventional therapy for patients with coronary heart disease(CHD) in Chinese medical environment. From the perspective of medical insurance, a Markov model was established in this study based on the results of Meta-analysis comparing the effectiveness and safety of Shexiang Tongxin Dripping Pills combined with conventional treatment and conventional treatment alone. The experimental group was treated with She-xiang Tongxin Dropping Pills combined with conventional Western medicine treatment, while the control group was treated with conventional Western medicine treatment alone. The cost-utility analysis and sensitivity analysis were performed for the two regimens using Treeage pro. After 30 cycles of model simulation, according to the results of Markov model, the total cost and health output were CNY 237 795.73 and 16.36 QALYs(the quality adjusted life years, QALYs), respectively for Shexiang Tongxin Dropping Pills combined with conventional Western medicine treatment, CNY 247 396.55 and 16.36 QALYs respectively for the conventional Western medicine treatment alone. Compared with the conventional treatment alone, the Shexiang Tongxin Dropping Pills combined with conventional treatment had lower long-term cost and higher health output, with advantages of cost-utility and pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is considered that compared with the conventional Western medicine alone, Shexiang Tongxin Dropping Pill combined with conventional Western medicine is a treatment regimen with pharmacoeconomic advantages for the treatment of CHD.

Meta-analysis of effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention / 中国中药杂志

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.

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.

Protective Effect of Huoxue Dingtong Prescription on Myocardial Ischemia Reperfusion Injury in Animal Model Based on NF-κB Signal Pathway / 中国实验方剂学杂志

Objective::To explore the protective effect of Huoxue Dingtong prescription on myocardial ischemia reperfusion injury in animal model based on nuclear transcription factor-κB(NF-κB) signal pathway. Method::In compound Danshen dropping pill group, SD rats were randomly divided into sham group, model group, compound salvia miltiorrhiza dropping pill group, high-dose Huoxue Dingtong group low-dose Huoxue Dingtong group, high-dose Huoxue Dingtong+ NF-κB inhibitor group. The rats in each group were administered continuously for 2 weeks. The rats in high-dose Huoxue Dingtong group+ pyrrolidine dithiocarbamate(PDTC) group were intraperitoneally administered the next day after modeling. Injection with PDTC and ligation of anterior descending branch of left coronary artery were performed to detect left ventricular function and Na+ -K+ -ATPase activity. Blood was collected from each animal abdominal aorta, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum creatine kinase isoenzyme (CK-MB), troponin T (cTnT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), superoxide gasification enzyme (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px). Western blot was used to detect the expressions of NF-κB, NF-κB inhibitor α (IκBα) and IκB kinase(IκκB) in myocardium. Result::Compared with model group, compound Danshen dropping pill group, high-dose Huoxue Dingtong group and low-dose Huoxue Dingtong group could reduce serum CK-MB, cTnT, TNF-α, IL-6, IL-1β, MDA, increase SOD and GSH-Px contents, increase the protein expressions of IκBα and IκB in myocardial tissue, and increase the activity of Na+ -K+ -ATPase in myocardial energy metabolism in myocardial ischemia-reperfusion model rats (P<0.05). However, high-dose Huoxue Dingtong group+ PDTC did not decrease serum CK-MB, cTnT, TNF-α, IL-6, IL-1β and MDA, increase SOD, GSH-Px, and increase the protein expression levels of IκBα and IκκB in myocardial tissue. There was no significant difference between high-dose Huoxue Dingtong group+ PDTC and model group. Conclusion::Huoxue Dingtang prescription can inhibit the activation of NF-κB signaling pathway, reduce the expression of inflammatory mediators and the production of free radicals, and increase the activity of Na+ -K+ -ATPase in the process of myocardial energy metabolism by up-regulating the expressions of IκBα and IκκB proteins in myocardial tissue of myocardial ischemia-reperfusion model.

Therapeutic effect of Toutongning Dropping Pills on migraine / 中草药

Objective: To evaluate the therapeutic effect of Toutongning Dropping Pills in the treatment of migraine in various experimental models. Methods: The experimental model of nitroglycerin-induced migraine in rats was used to observe the preventive effect of Toutongning Dropping Pills. The analgesic effect of Toutongning Dropping Pills was observed by chemical stimulation, thermal stimulation in mice, mechanical stimulation and formalin stimulation in rats. The sedative effect of Toutongning Dropping Pills was observed by using the mice convulsion model induced by strychnine nitrate and the model of spontaneous activity in normal mice. The blood-activating effects of Toutongning Dropping Pills were observed in rats with hyperviscosity and mice with microcirculation disorder. Results: Five days after Toutongning Dropping Pills were given, compared with the model group, 1 g/kg and 2 g/kg drug dose group significantly reduced the number of climbing cage and scratching head in migraine rats, and shortened the fading time of pink ears. Toutongning Dropping Pills 1.5 g/kg and 3 g/kg dose group significantly reduced the number of writhing induced by acetic acid in mice; While it had no obvious effect on the thermal stimulation model. Toutongning Dropping Pills 1 g/kg and 2 g/kg dose group could significantly improve pain threshold of the mechanical stimulation of rats, and shorten the phase II time of formalin pain in rats; 1.5 g/kg and 3 g/kg drug dose group could significantly prolong the incubation period of convulsion and reduce the number of spontaneous activities in mice; 0.5 g/kg and 1 g/kg and 2 g /kg drug dose group significantly inhibited the increase of whole blood viscosity in rats; 1.5 g/kg and 3 g/kg drug dose group significantly improved the blood flow pattern in mice, reduced erythrocyte aggregation, and increased the number of capillary intersection points. Conclusion: Toutongning Dropping Pills have obvious analgesic, sedative, blood-activating functions, and have therapeutic effects on experimental migraine.

Clinical pharmacokinetics of Ginkgolides Dropping Pills in healthy subjects / 中草药

Objective: In order to describe the pharmacokinetic profiles of two effective constituents ginkgolide A and ginkgolide B in healthy subjects, and to provide supports for setting out the clinical application of Ginkgolides Dropping Pills. Methods: Ten healthy subjects were enrolled in a randomized and open experimental design. Following a single oral administration of Ginkgolides Dropping Pills, blood samples which were anticoagulated by heparin sodium were collected at predetermined time, and then centrifuged to separate plasma samples. The total concentration of ginkgolide A and ginkgolide B in plasma samples and the lactone concentration of ginkgolide A and ginkgolide B were determined by a verified LC-MS/MS method, the pharmacokinetic parameters were calculated by WinNonlin 6.3 with non-compartment model. Results: After a single oral administration of Ginkgolides Dropping Pills, the tmax of lactone, total concentration of ginkgolide A respectively were (3.05 ± 1.40), (3.40 ± 1.22) h, the Cmax were (84.3 ± 32.8), (92.2 ± 35.0) ng/mL, respectively, and its Cmax ratio was 91.4%. The AUC0-t were (636 ± 183), (753 ± 205) ng∙h/mL, respectively, and its AUC0-t ratio was 84.5%, half-life time (t1/2) were (13.0 ± 10.3), (12.9 ± 8.49) h, respectively. The Tmax of lactone, total concentration of ginkgolide B were (3.15 ± 1.42), (3.35 ± 1.25) h, The Cmax were (74.1 ± 31.5), (148 ± 60.1) ng/mL, respectively, and its Cmax ratio was 50.1%.The AUC0-t were (627 ± 202), (1410 ± 431) ng∙h/mL, respectively, and its AUC0-t ratio was 44.5%, t1/2 were (13.2 ± 5.83), (13.7 ± 5.83) h, respectively. Conclusion: The results demonstrated that ginkgolide A and ginkgolide B were both at a moderate absorption and elimination rate, ginkgolide A mainly existed in human plasma upon lactone, while ginkgolide B presented as hydrolyzed forms with one or two lactone groups hydrolyzed and lactone, and the two forms of ginkgolide B were at equal exposure level after single oral administration of Ginkgolides Dropping Pills.

Meta analysis on efficacy of Compound Danshen Dropping Pills in treating angina based on syndrome differentiation / 中草药

Objective: To evaluate the efficacy and safety of the combination therapy of Compound Danshen Dropping Pills and conventional chemical drugs in the treatment of the angina by Meta-analysis. Methods: Databases including CNKI, WanFang, CBM, VIP, PubMed, and Cochrane Library were searched to collect qualified researches, and the quality of articles was evaluated according to Cochrane Handbook. Meta-analysis including subgroup analysis was performed by using Stata 13.1 and RevMan 5.3 software. All these methods were used to systematically evaluate the safety and clinical efficacy of Compound Danshen Dropping Pills in the treatment of angina pectoris under two circumstances (with or without syndrome differentiation). Results: A total of 39 studies involving 3 941 patients were studied, including 1 991 patients in the experimental group and 1 950 in the control group. The results of Meta analysis showed that: the clinical efficacy [RR = 1.24, 95%CI (1.20, 1.28), P < 0.000 01], ECG efficacy [RR = 1.29, 95%CI (1.21, 1.37), P < 0.000 01], angina attack frequency [WMD = -1.82, 95%CI (-3.28, -0.36), P = 0.01], duration of angina attack [WMD = -2.09, 95%CI (-2.67, -1.50), P < 0.000 01], hs-CRP [WMD = -2.63, 95%CI (-4.39, -0.86), P = 0.003], ET [WMD = -16.22, 95%CI (-19.37, -13.06), P < 0.000 01], platelet aggregation [WMD=-7.46, 95%CI (-11.15, -3.78), P < 0.000 1], GMP-140 [WMD=-5.64, 95%CI (-6.88, -4.39), P < 0.000 01] and fibrinogen [WMD = -0.73, 95%CI (-1.00, -0.46), P < 0.000 01] of routine western medicine treatment combine with Compound Danshen Dripping Pills group had significant difference compared with the control group; In terms of clinical efficacy, the combination effect of dialectical medication group and non dialectical medication group had no significant difference (P = 0.55, I2 = 0). A total of 15 studies described adverse reactions, with 43 cases in the experimental group and 65 cases in the control group. There was no significant publication bias on funnel plot and Egger's test. Conclusion: It is safe and effective to use Compound Danshen Dropping Pills in patients with coronary heart disease and angina, which can further improve the clinical effect compared with the simple routine treatment. There is no significant difference between the therapeutic effect of Compound Danshen Dropping Pills and that of non-syndrome differentiation. However, these conclusions still need to be verified with more high-quality and large-sample literature.

Optimization of the Quality Control Method of Qingkailing Dropping Pills / 中国药学杂志

OBJECTIVE: To optimize and improve the quality standard of Qingkailing dropping pills. METHODS Lonicerae Japonicae Flos, geniposide in Gardeniae Fructus and baicalin in Scutellariae Radix of Qingkailing dropping pills were identified by TLC and HPLC respectively. Cholic acid and hydrodeoxycholic acid were determined by HPLC equipped with an ELSD and a column (4.6 mm×250 mm, 5 μm) packed with ODS bonded silica gel (5 μm particle size). The mobile phase was a mixture of methanol, acetonitrile and 0.1% formic acid (68∶17∶15, V/V/V) and the flow rate was 1.0 mL•min-1. Geniposide in Gardeniae Fructus of Qingkailing dropping pills was determined by HPLC equipped with a DAD (238 nm) and a column (4.6 mm×250 mm) packed with ODS bonded silica gel (5 μm particle size). The mobile phase was a mixture of acetonitrile and 0.05% phosphoric acid (10∶90, V/V) and the flow rate was 1.0 mL•min-1. Baicalin in Scutellariae Radix of Qingkailing dropping pills was determined by HPLC equipped with a DAD (275 nm) and a column (4.6 mm×150 mm) packed with ODS bonded silica gel (5 μm particle size), the mobile phase was a mixture of methnol, water and phosphoric acid (47∶53∶0.2, V/V/V), and the flow rate was 1.0 mL•min-1. RESULTS: The developed TLC spots were clear with good reproducibility. Hydrodeoxycholic acid, cholic acid, geniposide and baicalin showed good linear relationship in the ranges of 0.505 0-6.312 μg, 0.515-6.440 μg, 0.029 12-0.582 4 μg, and 0.109 2-1.092 μg, respectively. The average recoveries (n=6) were 101.5%, 101.6%, 98.61% and 99.77%, with RSDs of 1.7%, 1.5%, 1.42% and 0.79%, respectively. CONCLUSION: The method is simple, rapid, accurate, with low toxicity, and can be used to control the quality of Qingkailing dropping pills more effectively and comprehensively.

Analysis of adverse drug reaction/adverse event and early warning signal mining of Ginkgo biloba Dropping Pills based on SRS data / 中国中药杂志

In order to understand the characteristics of adverse drug reaction/adverse event(ADR/AE) of Ginkgo biloba Dropping Pills and evaluate the safety of clinical use after marketing, 407 ADR/AE case report data of Ginkgo biloba Dropping Pills collected by National Center for ADR Monitoring System during 2009-2018 was systematically analyzed, and its general characteristics were analyzed using descriptive statistical methods. The results showed that among the 407 cases of spontaneous reporting system(SRS) data, 401 cases were general ADR/AE, accounting for 98.5%, and 6 cases were severe ADR/AE, accounting for 1.5%; there were more females than males(171/150) in ADR/AE, and they were mainly middle-aged and elderly people aged 45-64 years(152 cases, accounting for 37.35%); gastrointestinal system(23.89%) was mostly involved in ADR/AE. The top ten clinical symptoms were nausea(15.49%), dizziness(9.88%), vomiting(8.11%), rash(5.60%), chest tightness(5.46%), palpitations(5.31%), pruritus(4.72%), headache(4.57%), abdominal distension(3.83%), gastric dysfunction(3.54%); proportional reporting ratio(PRR) and Bayesian confidence progressive neural network method(BCPNN) were adopted to mine ADR/AE warning signals. Due to the small sample size, there were only 0-2 ADR/AE cases with various symptoms in many quarters, with no warning signal by PRR and BCPNN methods. The findings suggest that ADR/AE of Ginkgo biloba Dropping Pills based on SRS system was not recorded in the package insert, and further active monitoring studies shall be conducted to improve relevant ADR/AE information and pay attention to its clinical drug safety issues.

Optimization of the Preparation Technology of Syzygium aromaticum Oil Dropping Pills / 中国药房

OBJECTIVE： To establish the method for content determination of eugenol in Syzygium aromaticum oil dropping pills， and to optimize the preparation technology. METHODS： The content of eugenol in S. aromaticum oil dropping pills was determined by UV spectrophotometry. Based on single factor test， using the percentage of drugs in total amount， liquid temperature， falling distance of condensate， liquid drop distance as factors， taking the roundness， weight and hardness difference and comprehensive score as factors， L9（34） orthogonal design test was adopted to optimize the preparation process. RESULTS： The linear range of eugenol was 15.15-45.45 μg/mL（r＝0.999 6）； RSDs of precision， stability and reproducibility tests were all lower than 1％； the recoveries were 97.41％-100.59％（RSD＝1.35％， n＝6）. The optimal preparation technology included that the percentage of drugs in total amount was 5％； liquid temperature was 80 ℃； falling distance of condensate was 13 cm； liquid drop distance was 6 cm. The dropping pills had smooth appearance， good roundness and moderate hardness； the average content of engenol was 4.073％（RSD＝0.35％，n＝6）. CONCLUSIONS： The established method is simple， and can be used for the content determination of eugenol in S. aromaticum oil dropping pills. The optimal preparation technology is stable and feasible.

Preparation and simulation effect evaluation of placebos for Ginkgo Folium Dropping Pills / 中草药

Objective: To explore the placebo-preparation method of Ginkgo Folium Dropping Pills (GFDP) and evaluate its simulation effect objectively, which could provide production and evaluation reference for Chinese materia medica (CMM) placebo. Methods: Taking the placebo-preparation of GFDP as an example, the simulation effect was evaluated from aspects of appearance, color, smell, and taste. It employed three different approaches as possibility of experimental drug, similarity evaluation between placebo and experimental drug and the similarity analysis among the drugs. Results: The two placebo-preparation prescriptions of GFDP have high similarity with the original drug in terms of appearance, color, smell, and taste. The simulation effect of No. 2 placebo-prescription (0.6 g of sucrose octaacetate as bitter agent, 2.1 g of caramel as colorant, 13.3 g of PVP K30 as fillerz and 44.0 g of PEG 4000 as water-soluble bases to prepare 1 000 pills) is better than No. 1 placebo-prescription (1.2 g of sucrose octaacetate as bitter agent, 2.1 g of caramel as colorant, 12.7 g of PVP K30 as filler, and 44.0 g of PEG 4000 as water-soluble bases to prepare 1 000 pills). Conclusion: The placebo-preparation of GFDP conform to placebo requirements of randomized controlled trials. It fills the vacancy of dropping pills form placebo-preparation in CMM and provides method and idea for placebo-preparation and simulation-effect evaluation of CMM.

Effect of Shexiang Tongxin Dropping Pills () on the Immediate Blood Flow of Patients with Coronary Slow Flow / 中国结合医学杂志

OBJECTIVE@#To observe the immediate effect and safety of Shexiang Tongxin dropping pills (, STDP) on patients with coronary slow flow (CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain.@*METHODS@#Coronary angiography (CAG) with corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) was applied (collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary flow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood flow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments.@*RESULTS@#There was a significant difference in CTFC between groups (P0.05).@*CONCLUSIONS@#The immediate effect of STDP in treating CSF patients was apparent. This medication could significantly improve coronary flow without affecting blood pressure or heart rate. Our findings support the potential of Chinese medicine to treat ischemic chest pain.

Study on preparation of volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills and its protective effect on acute myocardial ischemia injury / 中国中药杂志

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of β-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.

Myocardial Protection Effect of Qishen Yiqi Dropping Pills on Patients After PCI and Control Effect and Mechanism on Cardiac Adverse Events / 中国实验方剂学杂志

Objective: To discuss the myocardial protection effect of Qishen Yiqi dropping pills on patients with Qi deficiency and blood stasis syndrome after PCI and the control effect and mechanism on cardiac adverse events. Method: One hundred and twenty-five patients were randomly divided into control group (61 cases) and observation group (64 cases) by random number table after PCI. Patients in control group got Tigrillo tablets, 90 mg/time, 2 times/days, aspirin enteric-coated tablets, 100 mg/time, 1 time/day, and bisoprolol fumarate tablets, 5 mg/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given Qishen Yiqi dropping pills, 0.5 g/time, 3 times/days, 3 days before operation. A course of treatment was 6 months, and follow-up were carried out for 6 months. Before treatment, and at the 24th, 72th hour after treatment, cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) were detected. During the first week after operation, and at the 6th month after operation, left ventricular ejection fraction (LVEF), settling velocity (SV), wall motion score index (WMSI), percentage of normal myocardium and myocardial perfusion score index (PS) were recorded. After 12 months of the operation, recurrence of angina pectoris, severe arrhythmia, heart failure, revascularization, non-fatal myocardial infarction, cardiogenic death and in-stent restenosis (ISR) were all recorded. During the first week after the operation, and at the 6th month after operation, six-minute walking test (6 MWT), Seattle angina scale (SAQ) and Qi deficiency and blood stasis syndrome were all scored. Before the operation, and at 48 hours and 6 months after operation, levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), plasma soluble intercellular adhesion molecule-1 (sICAM-1), high-sensitivity C-reactive protein (hs-CRP), superoxide dismutase (SOD), malondialdehyde (MDA) and endothelin-1 (ET-1) were all detected. Result: At the 24th, 72th hour after treatment, levels of cTnI and CK-MB in control group were lower than those in observation group (Pth hour after operation and the 6th month after operation, levels of TNF-α, IL-6, s ICAM-1 hs-CRP, MDA and ET-1 were lower than those in control group (PPth months after operation, LVEF, SV and percentage of normal myocardium were higher than those in control group (PPPPth month after operation, score of six-minute walking test was higher than that in control group (PPPConclusion: Qishen Yiqi dropping pills has anti-inflammatory and antioxidant effects, and can ameliorate intradermal function, prevent and treat myocardial injury, reduce rate of MACE, relieve symptoms, and improve activity ability and quality of life of patients.