Herbal Medicine Injection Research Articles

Physical compatibility of Xuebijing injection with 53 intravenous drugs during simulated Y-site administration.

Xuebijing injection (XBJ) is a commonly used herbal medicine injection in China. However, the physical compatibility of XBJ with other intravenous drugs remains unclear. The purpose of this research is to evaluate physical compatibility of Xuebijing injection (XBJ) with 53 intravenous drugs (including 31 Chinese medicine injections and 22 chemicals) during simulated Y-site administration. Y-site administration was simulated in vitro by admixing 0.33 ml/ml XBJ with an equal volume of other diluted 53 intravenous drugs, respectively. Physical compatibility including visual inspection, Tyndall beam, particle limits, turbidity, pH, chromacity value, spectroscopic absorption of 550 nm and 420 nm (A550 nm and A420 nm) were observed and assessed at 0, 1, 2, and 4 h. Physical compatibility was defined as all solutions with no color changes, no gas evolution, particulate formation and no Tyndall beam within 4 hours, turbidity changes <0.5 nephelometric turbidity unit (NTU) compared to 0 h, particle limits allowed by the Chinese Pharmacopoeia (Ch.P) 2020 edition, pH changes <10% compared to 0, chromacity value changes <200 compared to 0 h, or photometrical changes of A420 nm <0.0400 or A550 nm <0.0100 compared to 0 h. XBJ was physically incompatible with 27 of the 53 intravenous drugs tested, 26 were compatible with XBJ for 4 h. XBJ should not be simultaneously co-administered with 27 of the 53 intravenous drugs during simulated Y-site. If coadministration was inevitable, flushing tube with NS or D5W before and after infusion of XBJ was needed. Assessment included visual inspection, Tyndall beam, turbidity measurement, particle counts, pH measurement, chromacity value measurement and absorption of A550 nm were proved to be valid and robust for the quality control of infusion and compatibility of Chinese herbal injection.

Chinese herbal injection for cardio-cerebrovascular disease: Overview and challenges.

Cardio-cerebrovascular diseases are the leading cause of death worldwide and there is currently no optimal treatment plan. Chinese herbal medicine injection (CHI) is obtained by combining traditional Chinese medicine (TCM) theory and modern production technology. It retains some characteristics of TCM while adding injection characteristics. CHI has played an important role in the treatment of critical diseases, especially cardio-cerebrovascular diseases, and has shown unique therapeutic advantages. TCMs that promote blood circulation and remove blood stasis, such as Salvia miltiorrhiza, Carthami flos, Panax notoginseng, and Chuanxiong rhizoma, account for a large proportion of CHIs of cardio-cerebrovascular disease. CHI is used to treat cardio-cerebrovascular diseases and has potential pharmacological activities such as anti-platelet aggregation, anti-inflammatory, anti-fibrosis, and anti-apoptosis. However, CHIs have changed the traditional method of administering TCMs, and the drugs directly enter the bloodstream, which may produce new pharmacological effects or adverse reactions. This article summarizes the clinical application, pharmacological effects, and mechanism of action of different varieties of CHIs commonly used in the treatment of cardio-cerebrovascular diseases, analyzes the causes of adverse reactions, and proposes suggestions for rational drug use and pharmaceutical care methods to provide a reference for the rational application of CHIs for cardio-cerebrovascular diseases.

Chinese Herbal Medicine Used With or Without Conventional Western Therapy for COVID-19: an evidence review of clinical studies

Objective: To present the evidence of the effectiveness and safety of Chinese herbal medicine (CHM) used with or without conventional western therapy on COVID-19. Methods: Clinical studies on effectiveness and safety of CHM for COVID-19 were included. We summarized general characteristics of included studies, evaluated methodological quality of randomized controlled trials (RCTs), analyzed the use of CHM, estimated the effectiveness and safety of CHM. Results: A total of 58 clinical studies were identified including RCTs (17.24%, 10), non-randomized controlled trials (1.72%, 1), retrospective studies with a control group (18.97%, 11), case-series (20.69%, 12) and case-reports (41.38%, 24). No high methodological quality RCTs were identified. The most frequently tested Chinese patent medicine, Chinese herbal medicine injection or prescribed herbal decoction were: Lianhua Qingwen granule/capsule, Xuebijing injection and Maxing Shigan Tang. In terms of aggravation rate, pooled analyses showed that there had statistical differences between the intervention group and the comparator group (RR 0.42, 95% CI 0.21 to 0.82, 6 RCTs;RR 0.37, 95% CI 0.22 to 0.64, 4 retrospective studies with control group), that is, CHM plus conventional western therapy appeared better than conventional western therapy in reducing aggravation rate. In addition, compared with conventional western therapy, CHM plus conventional western therapy had potential advantages in increasing the resolution rate and shortening the duration of fever, cough and fatigue, improving the negative conversion rate of nucleic acid test, and increasing the number of patients with inflammatory disappearance or shortening the time from receiving treatment to beginning of inflammation disappearance. For adverse events, pooled data showed that there was no statistical difference between the CHM and the control groups. Conclusion: Current low certainty evidence suggests that there may be a tendency that CHM plus conventional western therapy is superior to conventional western therapy alone. The use of CHM did not increase the risk of adverse events.

Chinese Herbal Medicine Used With or Without Conventional Western Therapy for COVID-19: An Evidence Review of Clinical Studies.

Objective: To present the evidence of the therapeutic effects and safety of Chinese herbal medicine (CHM) used with or without conventional western therapy for COVID-19. Methods: Clinical studies on the therapeutic effects and safety of CHM for COVID-19 were included. We summarized the general characteristics of included studies, evaluated methodological quality of randomized controlled trials (RCTs) using the Cochrane risk of bias tool, analyzed the use of CHM, used Revman 5.4 software to present the risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) to estimate the therapeutic effects and safety of CHM. Results: A total of 58 clinical studies were identified including RCTs (17.24%, 10), non-randomized controlled trials (1.72%, 1), retrospective studies with a control group (18.97%, 11), case-series (20.69%, 12) and case-reports (41.38%, 24). No RCTs of high methodological quality were identified. The most frequently tested oral Chinese patent medicine, Chinese herbal medicine injection or prescribed herbal decoction were: Lianhua Qingwen granule/capsule, Xuebijing injection and Maxing Shigan Tang. In terms of aggravation rate, pooled analyses showed that there were statistical differences between the intervention group and the comparator group (RR 0.42, 95% CI 0.21 to 0.82, six RCTs; RR 0.38, 95% CI 0.23 to 0.64, five retrospective studies with a control group), that is, CHM plus conventional western therapy appeared better than conventional western therapy alone in reducing aggravation rate. In addition, compared with conventional western therapy, CHM plus conventional western therapy had potential advantages in increasing the recovery rate and shortening the duration of fever, cough and fatigue, improving the negative conversion rate of nucleic acid test, and increasing the improvement rate of chest CT manifestations and shortening the time from receiving the treatment to the beginning of chest CT manifestations improvement. For adverse events, pooled data showed that there were no statistical differences between the CHM and the control groups. Conclusion: Current low certainty evidence suggests that there maybe a tendency that CHM plus conventional western therapy is superior to conventional western therapy alone. The use of CHM did not increase the risk of adverse events.

Mitochondrial dynamics modulation as a critical contribution for Shenmai injection in attenuating hypoxia/reoxygenation injury

Ethnopharmacological relevanceShenmai injection (SMI) is a CFDA-approved and widely prescribed herbal medicine injection in China for treating cardiac dysfunction, especially myocardial ischemia and reperfusion (I/R) injury. However, despite of its known clinical efficacy, the cardioprotective mechanisms of SMI remain to be established. Aim of studyThe present study aimed to investigate the role of SMI on mitophagy and mitochondrial dynamics in cardiomyocytes with a hypoxia/reperfusion (H/R) injury setting. Materials and methodsH9c2 cardiomyocytes were subjected to 12 h of hypoxia followed by 2 h of reoxygenation to induce cellular injury. Multi-parameter imaging analysis was performed using Operetta High Content Imaging System to detect changes in mitochondrial function and morphological texture. The mPTP opening was directly assessed by analyzing mitochondrial calcein release in H9c2 and by Ca2+-induced swelling of isolated cardiac mitochondria. Mitochondrial respiration was measured by XF 24 analyzer of Seahorse Bioscience. RT-PCR and Western blotting analyses were used to detect mitophagy, mitochondrial fusion and fission biomarkers at the gene and protein levels. ResultsPretreatment of SMI significantly improved myocardial cell survival and protected against H/R-induced deterioration of mitochondrial structure and function, as evidenced by decreased mitochondrial mass and cytosolic Ca2+, increased mitochondrial membrane potential (ΔΨm) and mitochondrial morphology by SER Texture analysis, inhibited mPTP opening in H9c2 cells and isolated cardiac mitochondria, and alleviated severely impaired mitochondrial respiration. Mechanistically, SMI attenuated H/R injury by inducing mitophagy and then modulated mitochondrial dynamics as indicated by a significantly increased expression of LC3, Beclin 1, Parkin and Pink, and the inhibition of excessive mitochondria fission and increased mitochondrial fusion. Finally, the cardioprotective effect of SMI was confirmed in a LAD-induced cardiac dysfunction model in vivo. ConclusionWe found that alleviation of H/R injury by pretreatment with SMI may be attributable to inducing mitophagy and modulating mitochondrial dynamics in cardiomyocytes, thereby providing a rationale for future clinical applications and potential mitoprotective therapy for MI/R injury.

Analysis of Diemailing Kudiezi injection use in real world in 7 189 patients with cerebral infarction

This is a study based on hospital intensive monitoring to explore medication use of Diemailing Kudiezi injection(one Chinese herbal medicine injection) in real word in the patients with cerebral infarction. The active monitoring model was adopted and hospital intensive monitoring on safety of 7 189 cases of patients with cerebral infarction was conducted to obtain the drug use information of Diemailing injection. The results were analyzed by using statistical description and association rule method. The statistical description and association rule analysis were conducted based on patients' basic demographic characteristics, use of Diemailing injection and combined use of drugs. Sixty-two percent(4 437/7 189) of the patients were from traditional Chinese medicine hospitals as compared with 39%(2 752/7 189) from western medicine hospitals; 84%(6 003/7 189) of the patients were from tertiary hospitals as compared with 16%(1 186/7 189) from second-class hospitals. The hospitals were mostly located in north China. Drug related indicators such as a single dripping speed, stash time after allocating transfusion, duration of injection, and injecting room temperature were not noted in instruction manual. It was also found that there were off label use in the practice, for instance, non-intravenous infusion, >14 d treatment course, use of non-designated solvent, and a single dose>40 mL or<10 mL. Analysis of association rules showed that only Edaravone among the most frequent combined drugs was listed in the current guideline in China, and the other three most frequent combined drugs deproteinized calf blood extractive injection, Cinepazide Maleate injection and Alprostadil injection were used with little evidence. Diemailing＋Aspirin＋Alprostadil was the most common combined use in our study, but the recommended clopidogrel＋Aspirin was not found in this study. The drug use situation of Diemailing injection in the real world was obtained by data analysis on large size samples, providing basic reference information for clinicians and researchers. However, efficacy was not concerned in this study, so efficacy-related information could not be explained.

Hemolytic assay for Huangqi Injection

ObjectiveHuangqi Injection is a preparation with an extract of Astragali Radix which has a long history of being used as a tonic to strengthen the body's immunity. Anaphylaxis and hemolysis are two main adverse drug reaction (ADR) of injections. Our study was aimed to establish an approach for the (ADR) prediagnosis of Huangqi Injection. MethodsAn in vitro model for anaphylactoid assay of Huangqi Injection based on the release rate of histamine and β-hexosaminidase of RBL-2H3 cells induced by injections and a colorimetric method based on the detection of hemoglobin resulted in the erythrocyte hemolysis for prediagnostic assaying the hemolytic ADR of injections were established. ResultsBoth histamine and β-hexosaminidase are the anaphylactiod mediators, but β-hexosaminidase release induced by Huangqi Injection could not be determined by spectrophotometry due to the interference of the injection itself. In addition, normal hemolysis and abnormal hemolysis were discovered during the experiment. The fingerprints and tannins in different batches of injections showed obvious differences, indicating that the content of tannins was related to abnormal hemolysis and higher histamine-secreting from RBL-2H3 cells. ConclusionThe results indicate that the hemolytic assaying method is not only suitable for prediagnostic assaying of hemolytic ADR of herbal medicine injection, but also partly reflects the anaphylaxis of herbal injections, and tannins may be the major factors causing abnormal hemolysis.

Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection

Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein–kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction.

An improved method for the determination of 5-hydroxymethylfurfural in Shenfu injection by direct analysis in real time-quadrupole time-of-flight mass spectrometry.

The emergence of direct analysis in real time (DART) ion source provides the great possibility for rapid analysis of hazardous substance in drugs. DART mass spectrometry (DART-MS) enabled the conducting of a fast and non-contact analysis of various samples, including solid or liquid ones, without complex sample preparation or chromatographic separation. In this study, a modified DART-quadrupole time-of-flight mass spectrometry (DART-QTOF-MS) method was developed for identification and determination of 5-hydroxymethylfurfural (5-HMF) in Shenfu (SF) injection. The quantitative transfer of sample solution was introduced to the glass tips of DIP-it sampler at a fixed volume, which significantly increases the repeatability and accuracy of analytical results. The protonated ion of dibutyl phthalate in the atmosphere was used as the reference mass for TOF-MS recalibration during the data acquisition for constant high accuracy mass measurements. Finally, the developed DART-MS method was used to determine 5-HMF in seven batches of SF injection, and the contents of 5-HMF were not higher than 100 µg/mL. The results obtained were further confirmed by an ultra-high performance liquid chromatography combined with triple quadrupole mass spectrometer (UHPLC-QQQ-MS). The overall results demonstrated that the DART-QTOF-MS method could be applied as an alternative technique for rapid monitoring 5-HMF in herbal medicine injection. Copyright © 2015 John Wiley & Sons, Ltd.

Pathway as a pharmacological target for herbal medicines: an investigation from reduning injection.

As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.

A novel systems pharmacology model for herbal medicine injection: a case using reduning injection

BackgroundCompared with the traditional oral administration form, injection administration is basically superior in terms of both biological availability and therapeutic effects. However, few researches have focused on the traditional Chinese medicinal injection due to the complicated constituents and the intricate mechanism of action.MethodsIn the present work, a novel systems pharmacology model, integrating ADME (absorption, distribution, metabolism, and excretion) filtering such as half-life evaluation, network targeting, pathway and systems analyses, is specifically developed for the identification of active compounds and the study of the mechanism of action of TCM injection, which is exemplified by Reduning injection confronting the influenza.ResultsThe ADME filter successfully identifies 35 bioactive compounds (31 molecules and 4 metabolites) from the Reduning injection. The systems analysis and experimental validation further reveal a new way of confronting influenza disease of this injection: 1) stimulating the immunomodulatory agents for immune response activation, and 2) regulating the inflammatory agents for anti-inflammation.ConclusionsThe novel systems pharmacology method used in this study has the potential to advance the understanding of the molecular mechanisms of action of multicomponent herbal injections, and provide clues to discovering more effective drugs against complex diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-430) contains supplementary material, which is available to authorized users.

Medical dispute cases involving traditional Korean medical doctors: A survey

IntroductionMedical dispute cases have increased worldwide as patients become more aware and able to access medical information. The aim of this survey was assessing the frequency and resolution of medical dispute cases involving traditional Korean medicine (TKM). MethodsA total of 501 TKM clinics were randomly selected from throughout South Korea, and stratified by region and contacted by mail. The clinics were asked about the frequency and resolution of any medical dispute cases between June 1 and December 9, 2008. ResultsResponse rates were 4.0% for TKM private clinics and 40.1% for TKM hospitals. Out of a total of 501 clinics, 64 (12.7%) reported having at least one medical dispute case. The rates of medical disputes for each TKM therapy in proportion to the 112 respondents were as follows: acupuncture, 38 (34%); herbal medicine, 31 (28%); moxibustion, 13 (17%); physical therapy, 11 (10%); herbal medicine injection, 7 (6%); chiropractic, 7 (6%); and misdiagnosis, 5 (4%). Of the 97 disputes, 71 (73%) were resolved by mutual agreement, 15 (15%) were resolved by insurance claims, 3 (3%) went to civil suits, and 8 cases (8%) were resolved using other methods. ConclusionsA method to record medical disputes would be necessary to further clarify this process if accurate information on frequency and resolution is to be achieved. The standardisation of TKM and the establishment of evidence-based medicine should continue to improve this situation. Furthermore, legal guidelines and regulations of TKM should be established for the resolution of medical disputes.This article belongs to the Special Issue: Ensuring and Improving Patients’ Safety in Integrative Health Care.

Prediagnostic methods for the hemolysis of herbal medicine injection

Ethnopharmacological relevanceThe Xue-Sai-Tong injection, a traditional Chinese medicine injection with total saponins extracted from Sanchi Ginseng, has been used for more than half a hundred years to treat coronary artery disease. The study is to establish a prediagnostic method for the hemolytic adverse effect of herbal medicine injection by taking Xue-Sai-Tong injection as an example. Materials and methodsA new method named “fuzzy dissemination” was established to identify the hemolytic ginsenosides in Xue-Sai-Tong injection on the basis of fuzzy changes of individual ginsenosides in the injections altered by re-adding the fractions prepared from the total saponins and statistic analysis between hemolytic degrees and individual ginsenosides. Related substances test, safety tests and fingerprints of the injections in different batches were tested. ResultsHD50, P50 and interactions on hemolysis of individual ginsenosides were examined. Experiment indicated that the content of Rg1, Rg2, M51 (an unknown ingredient with retention time at 51min in HPLC) and M70 in Xue-Sai-Tong injection showed a significant positive correlation with hemolytic degree, and the content of R1, Re, Rb1 and Rd showed a significant negative correlation with hemolytic activity. Furthermore HD50 of injection exhibits superiority to other tests for the hemolysis of injections. Abnormal hemolysis in some batches of injections was observed, but there were no significant differences among injections of different batches in related substances test, safety test and fingerprints. ConclusionsThis is an original method to analyze active ingredients of a complicated integrity instead of studying on individual ingredients, it showed that the interactions of some individual ginsenosides and some unknown micro-ingredients in Xue-Sai-Tong injection were the major factors causing hemolysis, and this method could also be utilized in research of corresponding aspects. HD50 of injection can reflect the changes of hemolytic property of injections caused by not only the change of active constituents of injection, but also the auxiliary materials. Thus it was recommended as an index for the hemolytic prediagnosis of the injections in practice.

Analysis of marker compounds with anti‐platelet aggregation effects in mailuoning injection using platelet binding assay combined with HPLC‐DAD‐ESI‐MS and solid‐phase extraction technique

Mailuoning is prepared from a traditional formula of Chinese medicines and widely used as an antithrombotic agent. In this study, the platelet binding assay was used as a novel biospecific separation and analysis method to explore its active constituents, which could be considered as marker compounds for quality control. To establish a rapid and simple method to predict marker compounds in herbal medicine injection and evaluate the effects of those compounds. Platelets were used to bind and separate constituents. Binding constituents were analysed and taken as potential active compounds for further evaluation. Solid-phase-extraction was adopted to improve sensitivity. HPLC-DAD and ESI-MS were used to determine the binding constituents. Five compounds were extracted through the platelet binding process and identified as neochlorogenic acid, caffeic acid, isochlorogenic acid and their isomers. Caffeic acid was selected for the flow cytometric assay to test its effect on platelets activation, which was determined by CD62P (P-selectin) expression. The results indicated that caffeic acid could significantly inhibit platelet activation while chlorogenic acid did not. Caffeic acid could be considered as a marker compound of Mailuoning injection due to its anti-platelet effect. The study also suggested that platelet binding assay combined with some preconcentration technique could be efficiently used to predict anti-platelet compounds in complicated herbal medicines.