Molecular interactions between the main components of Shuanghuanglian injection and ciprofloxacin injection based on self-assembly / 药学学报

The combination of Shuanghuanglian injection (SHLI) and ciprofloxacin injection (CIPI) is frequently prescribed in clinical practice, but the basis for the combination is weak. In this study, isothermal titration calorimetry and ultraviolet-visible absorption spectrometry were applied to identify the molecular interactions of SHLI and its main components, chlorogenic acid and neochlorogenic acid with CIPI. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and cold-spray ionization mass spectrometry were performed to confirm that this molecular interaction was related to the formation of self-assembled supramolecular systems induced by chlorogenic acid and neochlorogenic acid with CIPI through weak intermolecular bonds. The antibacterial activity toward Pseudomonas aeruginosa (P. aeruginosa) was evaluated via molecular interactions, and the inhibitory ability of SHLI, chlorogenic acid and neochlorogenic acid against P. aeruginosa was significantly reduced after interaction with CIPI. A molecular docking study demonstrated that the reduced antibacterial ability was closely related to the competitive binding of drug molecules to the same binding site of the DNA gyrase B (GyrB) subunit of P. aeruginosa. The present study uncovered the intermolecular interactions of SHLI and its main components chlorogenic acid and neochlorogenic acid with CIPI from the perspective of molecular self-assembly and contribute to the reduction of its antibacterial ability, providing a basis for the clinical combination of SHLI and CIPI.

Screening of Shuanghuanglian Injection allergenic ingredients based on immune fingerprint / 中国中药杂志

In this paper,immune fingerprint was used to screen the allergenic components of Shuanghuanglian Injection(SHLI) by enzyme-linked immuno sorbent assay(ELISA) combined with HPLC/MS method. ELISA-embedded anti-IgE antibody could successfully adsorb allergens in SHLI and its plasma samples containing drugs through different routes of administration,suggesting that SHLI can induce type I hypersensitivity in rats. HPLC fingerprints and MS map of SHLI and drug-containing plasma samples from different routes of administration before and after anti-IgE antibody adsorption were established. According to the similarity evaluation of HPLC fingerprints and analysis results MS map,the sensitization of traditional Chinese medicine injections can be changed by different administration methods. There were 22 kinds of components that can be adsorbed by specific anti-Ig E antibodies in Shuanghuanglian Injection and its drug-containing plasma,most of them were acids and nitrogen compounds. Based on supramolecular theory,it was inferred that these compounds came from SHLI or body,and may form supramolecular hapten,which results in immunotoxicity and allergic reaction when being used as injection instead of oral liquid. Immune fingerprint is not only used to screen out single component allergen,but also more comprehensive,sensitive and easy to operate. It can provide reference for the future research methods of allergic reaction of traditional Chinese medicine injections.

Determination of Specific Antibodies in Allergic Rabbits Induced by 1,3-Di-caffeoylquinic Acid in Shuanghuanglian Injection / 中国药师

Objective: To determine the antibody titer in the serum of allergic rabbits after the injection of 1, 3-di-caffeoylquinic acid contained in Shuanghuanglian injection.Methods: The complete antigen was prepared by incubating the suspected small molecular hapten 1, 3-di-caffeoylquinic acid contained in Shuanghuanglian injection with the serum from the normal rabbits.The specific antibody was obtained in the immunized rabbits.The antibody titers of antiserum were measured by ELISA kits.Indirect competitive ELISA was used to determine serological specificity, and the obtained data was used to plot the inhibition curves.The content of IgE antibody in the antiserum of rabbits was detected by rabbit immunoglobulin E (IgE) ELISA kits.Results: The antibody titer (A) of 1,3-di-caffeoylquinic acid was 2 times higher than that of the negative control, which indicated its potential allergenicity.The regression equation was I=0.170 6 lg C + 0.317 5 , which was with the correlation coefficient of r=0.985 4 , the detection limit of IC 10 =57.40 μg·ml-1 and the half inhibitory concentration of IC 50 =8.732 0 mg·ml-1.Furthermore, the exogenous IgE antibody was produced in the rabbits.Conclusion: The results indicated that the hapten substance 1,3-di-caffeoylquinic acid in Shuanghuanglian injection was allergenic under the present experimental conditions.

Meta-analysis on incidence of adverse drug reaction induced by Shuanghuanglian injection / 中国中药杂志

To conducted a systematic review on the safety of Shuanghuanglian injection in clinical use. In this paper, data from Pubmed, Embase, the Cochrane Library, CNKI, VIP and WanFang Data were retrieved. After extracting information and evaluating research methodological quality according to inclusion and exclusion criteria, Meta-analysis was conducted by using R3.2.3 software. A total of 56 individual studies were included, in which 585 cases showed adverse reactions in a total of 11 001 patients with Shuanghuanglian injections. Meta-analysis showed that the total incidence of adverse reactions was 6.5% (95%CI 0.051 to 0.082). Subgroup analysis showed that the incidence of adverse reactions was 4.8% (95%CI (0.032 to 0.067) and 8.1% (95%CI 0.054 to 0.112) respectively in children and adults; 7.2% (95%CI 0.049 to 0.095) and 6.6% (95%CI 0.036 to 0.104) respectively in 5%-10% glucose injection and 0.9% sodium chloride injection; 6.3% (95%CI 0.047 to 0.082) and 7.0% (95%CI 0.044 to 0.099) respectively in powder injection and liquid injection; 5.8% (95%CI 0.043 to 0.075) and 8.9% (95%CI 0.049 to 0.140) respectively in cases with duration of ≤7 d and >7 d; 4.2%(95%CI 0.027 to 0.059) and 8.4% (95%CI 0.059 to 0.113) respectively in single use and combined medication. Three most frequent types of adverse reaction symptoms reported were in skin and mucosa, digestive system, and body temperature center, with an incidence of 4% (95%CI 0.03 to 0.04), 3% (95%CI 0.02 to 0.03), and 1% (95%CI 0.00 to 0.01), respectively. The systemic evaluation demonstrated that the occurrence of adverse reaction of Shuanghuanglian injection was related to age, menstruum, duration of medication and combined medication. Incidence of adverse reactions differed considerably among different damage types. From the study demonstrated above, this paper concludes that we should follow the principles of evidence-based medication of traditional Chinese medicine; use Shuanghuanglian injection singly instead of combination with other drugs in clinical use; use Shuanghuanglian injection strictly in accordance to instructions, especially for children and the elderly, whose weight should be calculated and considered in medication; intensively monitor the drug adverse reaction after use; assess the risks of adverse effects for long-term usage, and take corresponding safety measures to ensure safety.

Clinical Observation of Shuanghuanglian Injection in the Treatment of Acute Exacerbation of Chronic Ob-structive Pulmonary Disease / 中国药房

OBJECTIVE:To evaluate the clinical efficacy of Shuanghuanglian injection in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD),and to observe its effects on the plasma levels of C-reactive protein (CRP),procalcitonin(PCT)and interleukin-6(IL-6). METHODS:A total of 100 AECOPD patients were randomly divided into observation group and control group,with 50 cases in each group. Control group received routine treatment,such as controlled oxygen therapy,intravenous dripping of moxifloxacin,bronchodilator for relieving asthma,mucolytic for eliminating phlegm,nu-tritional support. Observation group was additionally given Shuanghuanglian injection 1 ml/(kg·d)added into 5% Glucose injec-tion 250 ml intravenously,qd,on the basis of control group. Treatment course of 2 groups lasted for 10 d. Clinical efficacies of 2 groups were compared as well as the changes of serum levels of CRP,PCT and IL-6 before and after treatment and the occur-rence of ADR. RESULTS:After treatment,total effective rate of observation group was 96.0%,which was significantly higher than 82.0% of control group,with statistical significance(P0.05). After treatment,serum levels of CRP,PCT and IL-6 were de-creased significantly in 2 groups,and those of observation group were significantly lower than those of control group,with statis-tical significance (P0.05). CON-CLUSIONS:Shuanghuanglian injection can effectively improve serum inflammatory factors of AECOPD patients,and shows good clinical efficacy and safety.

Effect of Shuanghuanglian injection on CRP, PCT and IL-6 in pneumonia children / 中国生化药物杂志

Objective To study the effect of Shuanghuanglian injection on CRP, PCT and IL-6 in pneumonia children.Methods 68 cases of pneumonia children were selected and divided into the control group and the experiment group.33 case in the control group and 35 cases in the experiment group.The two groups were treated with conventional symptomatic treatment and anti infection treatment for the two groups were implemented routine symptomatic treatment and anti infection treatment.The control group were treated with cefotaxime sodium injection, the experiment group were treated on the base with Shuanghuanglian injection.CRP, PCT and IL-6 in serum were compared before and after the treatment.Results Compared with the control group, the level of CRP in serum was lower(P<0.05), the level of PCT in serum was lower(P<0.05), the level of IL-6 in serum was lower(P<0.05).Conclusion Shuanghuanglian injection has a good clinical effect on children’s pneumonia.It is speculated that the mechanism is related to the decrease of serum CRP and IL-6 level.

Study on Anaphylactoid Reaction Induced by Shuanghuanglian Injection / 中国中医药信息杂志

Objective To observe the anaphylactoid reactions of Shuanghuanglian injection, determine the serum histamine level of sensitized animal, and to investigate its correlation with anaphylactoid reactions.Methods The guinea pigs were randomly selected to observe the anaphylactoid reactions using Shuanghuanglian injections in the different injection speed or different doses, and the serum histamine and the serum IgE of sensitized animals were determined by ELISA. Results The anaphylactoid reactions were induced by Shuanghuanglian injections in the different conditions of injection speed and doses in guinea pigs. There were no obvious difference about the serum IgE level between Shuanghuanglian group and saline group were injected in injection speed and doses. The serum histamine level was significantly increased in Shuanghuanglian group both different conditions of injection speed and doses, and it related to doses and speed. Conclusion Shuanghuanglian injection can cause anaphylactoid reactions in guinea pigs, and the changes of serum histamine level are related to injection speed and doses of Shuanghuanglian injection.

In Vitro Inhibition of Cytochrome P450 in Rats Liver Microsomes by Shuanghuanglian Injection Powder and Its Active Components / 医药导报

Objective To evaluate the inhibition effects of shuanghuanglian injection powder and its active components on the activities of CYP1A,CYP 2D and CYP 3A in rats liver microsomes. Methods Three probe substrates including phenacetin for CYP1A,dextromethorphan for CYP2D and midazolam for CYP3A were incubated with shuanghuanglian injection powder and the active components (baicalin,phillyrin,forsythiaside A,lutin,chlorogenic acid,coffeic acid and lutiolin) in rat liver microsomes. Contents of three probe substrates were simultaneously determined by HPLC to evaluate the metabolic rates. Results Shuanghuanglian injection powder and baicalin inhibited the activities of CYP2D and CYP 3A, but didn 't affect CYP1A. The other active components showed no effect on CYP1A,CYP2D and CYP3A. Conclusion Drug-drug interactions may occur when combining shuanghuanglian powder injection with CYP2D and CYP 3A substrates and baicalin may be the effector substance responsible for the interactions.

Stability of Shuanghuanglian Injection Mixed with Cefazolin Sodium and Other Injections in Vitro / 中国中医药信息杂志

Objective To investigate the compatibility of Shuanghuanglian Injection mixed with Cefazolin Sodium for Injection, Dexamethasone Sodium Phosphate Injection and Ribavirin Injection. Methods Under room temperature, the changes of appearance were determined by pH meter and particle counter for Shuanghuanglian Injection mixed with Cefazolin Sodium for Injection, Dexamethasone Sodium Phosphate Injection and Ribavirin Injection. Results There were no evident changes in appearance and pH of Shuanghuanglian Injection mixed with Cefazolin Sodium for Injection, Dexamethasone Sodium Phosphate Injection and Ribavirin Injection. The number of particles (diameter≥25 μm) of Shuanghuanglian Injection mixed with Cefazolin Sodium for Injection and Dexamethasone Sodium Phosphate Injection was increased after 0.5 h. Conclusion Shuanghuanglian Injection can be mixed with Cefazolin Sodium for Injection, Dexamethasone Sodium Phosphate Injection and Ribavirin Injection for bigeminy, while should not for multitherapy.

Clinic observation on retention enema of Shuanghuanglian Injection in treating 162 Cases of infant hand-foot-mouth disease / 国际中医中药杂志

Objective To observe the effects of retention enema of Shuanghuanglian injection in treating infantile hand-foot-and-mouth disease. Methods A total of 162 patients of hand-foot-mouth disease were recruited into a control group and treatment group randomly, with 81 cases in each group. The treatment group was treated with retention enema of Shuanghuanglian injection, and the control group was treated with ribavirin granules. Clinical effects were observed in both groups. Results The total effective rate of the treatment group and the control group was 97.53% and 88.89% respectively, showing statistical significance(P<0.05). The time of clinical symptom relief and course of treatment were shorter in the treatment group than those in the control group (P<0.05). Conclusion Retention enema of Shuanghuanglian injection is effective in treating infantile hand-foot-mouth disease.

Clinical Study on Shuanghuanglian Injection in Treating Uterine Tube Obstruct / 中国中医药信息杂志

Objective To investigate the effect of Shuanghuanglian injection parafornix-injecting in treating uterine tube obstruct (UTO) and explore its mechanism. Methods Clinic study included 386 uterine tubes of 200 patients, which were randomly divided into treatment group (50 cases, treated with Shuanghuanglian injection parafornix-injecting) and three control groups - group one (50 cases, treated with Lincocin vial parafornix-injecting), group two (50 cases, treated with hydrotubation) and group three (50 cases, treated with transvaginal catheter dilation). The changes of UTO condition and blood rheology, IL-2, IgA, IgG and IgM were observed before and after treatment. Results The total effective rate of Shuanghuanglian injection in treating UTO was 97.76%. It was characterized by regulating the blood stasis and hyperviscosity, improving the immune function of human body. Conclusions Shuanghuanglian injection parafornix-injecting has obvious therapeutic effect on UTO. The effect may be related with rectifying the body pyrotoxin and blood stasis, improving pelvic blood circulation and immune function.

Analysis on ADR/ADE Reports Induced by Shuanghuanglian Injection in Guangxi of 2009 / 中国药房

OBJECTIVE:To understand ADR and ADE reports induced by Shuanghuanglian injection in Guangxi Zhuang Na- tionality Autonomous Region of 2009 to provide reference for clinical application of Shuanghuanglian injection and ADR monitoring. METHODS:818 ADR and ADE cases induced by Shuanghuanglian injection from Jan. 1 and Dec. 31 of 2009 collected from Guangxi Center for ADR Monitoring were analyzed statistically. RESULTS:Male(n=437)involved in 818 ADR cases was more than female(n=381).Ratio of male to female was equal to 1.15∶1.The ADR incidence of patients aged from 0 to 9 was higher than other age groups,accounting for 43.77%.88.39%of primary disease in ADR patients was respiratory diseases.27.25%of cassound prognosis. Occurrence time of ADR cases were short,777 cases were collected from primary hospitals,accounting for 94.99%. CONCLUSION:Great importance should be attached to the application of Shuanghuanglian injection,ADR monitoring and rational use of drugs.

Adverse Drug Reactions Induced by Shuanghuanglian Injections:Analysis of 78 Cases / 中国药房

OBJECTIVE:To discuss the regular patter of the occurrence of adverse drug reactions(ADR)induced by Shuangjhuanglian Injection and to improve the knowledge on the safe and rational use of this kind of drug in the clinic.METHODS:A total of 78 ADR cases induced by Shuanghuanglian Injections in the database of Tianjin ADR monitoring center were analyzed statistically in respect of patients' general data,systems or organs involved and the clinical manifestations and medication etc.RESULTS:The main adverse drug reactions caused by Shuanghuanglian Injections presented as lesions of skin and its appendants.And the ADR were chiefly resulted from the drugs(Shuanghuanglian Injections)themselves or the incompatibility etc.CONCLUSION:It is necessary to standardize the preparation technology of Shuanghuanglian Injections and attach great importance to the dosage of Shuanghuanglian Injections for children and aged patients and the imcompatibility when used in combination with other drugs.

Research of the Immunotoxicity of Shuanghuanglian Injection / 中药新药与临床药理

Objective To investigate the allergic reaction of Shuanghuanglian Injection(SI)and chlorogenic acid.Meth- ods The sensitization of SI was evaluated by observed the systemic active allergic reaction on guinea pigs.The homogeneous and heterogenic passive skin allergic reactions in rats,mice and guinea pigs were observed to compare the sensitationz of SI and chlorogenic acid.Results The possibility of SI causing allergic reaction was higher than that of chlorogenic acid.Con- clusion It is suggested that the possibility of SI as a compound arising adverse reactions be higher than that of chlorogenic acid.

Determination of Baicalin in Shuanghuanglian Injection by UV Spectrophotometry / 中成药

Objective: To determine the content of baicalin in Shuanghuanglian Injection. Methods: Baicalin was separated from injection by the precipitation separation with chlorhydric acid and determinel by UV spectrophotometry. Results: The average content was 6～9mg/ml, RSD was 0.34%. This result was similar to the results obtained by HPLC. Conclusion: This method is simple, highly sensitive, reproducible with stable results. It can be used as a quickly quantitative method for the quality control of this injection.

Analysis of Shuanghuanglian Injection Powder by HPLC-ESI-mass/mass spectrometry / 中成药

AIM: To analyse the main chemical constituents of Shuanghuanglian Injection Power(Flos lonicerae japanicae,Radix scutellariae and Fructus forsythiae) by high performance liquid chromatography-electrospray ionization-mass/mass spectrometry. METHODS: The sample solution was analysed by a Zorbax C_18 column with a gradient mobile phase comprised of acetonitrile and water.Electrospray ionization mass spectrometry detector was used,full-scan detection mode was evaluated for the identification of the liquid chromatography peaks. RESULTS: To analyse the mass spectrum of every liquid chromatography peaks,we identified 18 molecular mass from the ion chromatogram of Shuanghuanglian Injection Powder,9 compounds were identified,including quinic acid,caffeic acid,three monocaffeoylquinic acids,dicaffeoylquinic acid,forsythin,forsythoside and baicalin. CONCLUSION: Quinic acid is identified from Shuanghuanglian Injection Power for the first time.High performance liquid chromatography-mass/mass spectrometry is emerging as an important tool in traditional Chinese medicine.

Content Determination of Scutellarin in Radix Scutellariae and Shuanghuanglian Injection(Flos Lonicerae,Radix Scutellariae and Fructus Forsythiae / 中成药

The content of scutellarin in Radix Scutellariae and Shuanghuanglian Injection was determined with dual wavelength TLC scanner. This method can be used as a rapid quantitation one in quality verification because of its simplicity involving hign sensitivity, good reproducibility and stable result.

Epidemiological characteristic of anaphylactic shock caused by Shuanghuanglian Injection / 中成药

AIM: To investigate the epidemiological characteristic and causative factors of anaphylactic shock caused by Shuanghuanglian Injection(Flos Lonicerae Japonicae,Radix Scutellariae,Fructus forsythiae). METHODS: Domestic medicine periodicals were searched between 1978 and 2005,and 72 cases with anaphylactic shock caused by Shuanghuanglian Injection were analysed by literature metrologic method. RESULTS: There were large proportion of young sufferers from age 18 to 44 in the case reports,and male 52.11%,female 47.89%,the primary affections were mainly upper respiratory tract infection,the occurrence of ADRs was commonly within 30 mins after injection,seven patients died of the terrible anaphylactic shock. CONCLUSION: Shuanghuanglian Injection may induce dangerous,even fatal anaphylactic shock,its mechanism includes many factors,such as patient's physical constitution.

Flavonoids in Shuanghuanglian Injection / 中成药

AIM: To investigate the chemical constituents of Shuanghuanglian Injection(Flos lonicerae japonicae, Radix scutellariae, Fructus forsythiae). METHODS: Chromatography and spectral analysis were used respectively to isolate and identify the constituents. RESULTS: Six compounds were isolated from Shuanghuanglian Injection which included baicalin(Ⅰ)、quercitrin(Ⅱ)、hyperoside(Ⅲ)、rutin(Ⅳ)、quercetin(Ⅴ) and luteolin(Ⅵ). CONCLUSION: The other five compounds were first isolated and identified in Shuanghuanglian Injection except baicalin(Ⅰ).