2021 Vol. 39, No. 1
Display Method:
2021, 39(1): 1-3, 8.
doi: 10.12206/j.issn.1006-0111.202004038
Abstract:
Objective To review the research progress in new formulations of norcantharidin. Methods The foreign and domestic literature search in the new formulations of norcantharidin was conducted. The research and development of norcantharidin formulations were summarized and commented. Results The drug delivery systems, such as microspheres, nanoparticles, liposomes, and microemulsions, have great development potential as the new formulations for norcantharidin. Conclusion Norcantharidin is an excellent anti-tumor drug. The traditional injections and tablets have serious side effects in clinical application. The new formulations reduced the renal and urinary toxicity and side effects. Those formulations provided better therapeutic effects as target medication. Therefore, the new norcantharidin formulations have great development prospects.
2021, 39(1): 4-8.
doi: 10.12206/j.issn.1006-0111.202006024
Abstract:
Signal transducer and activator of transcription 3 (STAT3) is a signal transcription protein that exists in the cytoplasm. The abnormal activation of STAT3 is closely related to cell proliferation, differentiation, and canceration. It has abnormal expression in cancer stem cells such as breast cancer, pancreatic cancer, lymphoma, and lung cancer. Therefore, inhibiting the abnormal expression of STAT3 has become a new approach for antitumor therapy.
Signal transducer and activator of transcription 3 (STAT3) is a signal transcription protein that exists in the cytoplasm. The abnormal activation of STAT3 is closely related to cell proliferation, differentiation, and canceration. It has abnormal expression in cancer stem cells such as breast cancer, pancreatic cancer, lymphoma, and lung cancer. Therefore, inhibiting the abnormal expression of STAT3 has become a new approach for antitumor therapy.
2021, 39(1): 9-12, 43.
doi: 10.12206/j.issn.1006-0111.202004030
Abstract:
Baicalein (BE) is an active ingredient derived from the root of Scutellaria baicalensis Georgi. It is a polyhydroxyflavonoid in structure and has many biological activities. Among them, the antitumor effects of baicalein have received widespread attention. It exerts anti-tumor effects by inducing tumor cell apoptosis and invasion, inhibiting tumor angiogenesis, and eliminating free radicals. This article reviews the most recent research works of baicalein in its anti-tumor effects and mechanisms. It is aimed to provide a theoretical basis for the search and development of potential new anti-tumor drugs.
Baicalein (BE) is an active ingredient derived from the root of Scutellaria baicalensis Georgi. It is a polyhydroxyflavonoid in structure and has many biological activities. Among them, the antitumor effects of baicalein have received widespread attention. It exerts anti-tumor effects by inducing tumor cell apoptosis and invasion, inhibiting tumor angiogenesis, and eliminating free radicals. This article reviews the most recent research works of baicalein in its anti-tumor effects and mechanisms. It is aimed to provide a theoretical basis for the search and development of potential new anti-tumor drugs.
2021, 39(1): 13-16, 22.
doi: 10.12206/j.issn.1006-0111.202006077
Abstract:
Objective To investigate the effects of Nicotinamide mononucleotide (NMN) on ulcerative colitis induced by dextran sulfate sodium (DSS) in mice. Methods DSS-induced ulcerative colitis mice were used to evaluate the effects of NMN. After NMN administration, the survival time, weight, disease activity index (DAI), colon tissue length and pathological changes of colon tissue slices were observed. Results NMN did not cause significant changes in the survival time, weight, DAI, and intestinal morphology of ulcerative colitis mice. Conclusion NMN has no significant effect on DSS-induced ulcerative colitis mice.
Mechanism of Sinomenii caulis in the treatment of rheumatoid arthritis based on network pharmacology
2021, 39(1): 17-22.
doi: 10.12206/j.issn.1006-0111.202004117
Abstract:
Objective To explore the molecular targets and associated potential pathways of Sinomenii caulis in the treatment of rheumatoid arthritis (RA) based on network pharmacology. Methods The constituents of Sinomenii caulis were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential active ingredients were screened based on oral bioavailability (OB) and drug like index (DL) in TCMSP database. The potential targets of active ingrediens were explored based on DRAR-CPI docking server. RA related gene targets were retrieved through GeneCards and OMIM database. Venn online software was used to obtain the common target of drugs and diseases. The "herbs-compound-target-disease" network diagram was constructed by using Cytoscape software. String database was used to draw the protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the intersection network were conducted by Bioconductor Database. Results 6 active ingredients and 176 targets were identified. 305 target genes directly related to RA were obtained from the GeneCards and OMIM databases. 15 genes were obtained from the intersection of component-target and disease-target. The GO function analysis found 500 items on biological process (BP), 18 items on cellular component (CC), and 28 items on molecular function (MF). KEGG pathway enrichment analysis revealed 77 pathways. Conclusion This study identified six active ingredients from Sinomenii caulis and revealed the key targets of the anti-RA treatment with Sinomenii caulis being IL10、IL4、INS、MAPK8、ELANE、MAPK1 and MAPK14. The important biological processes and signaling pathways including infection, inflammation and immunity were explored. It has laid the foundation for further molecular biology experiments.
2021, 39(1): 23-28.
doi: 10.12206/j.issn.1006-0111.202007128
Abstract:
Objective To establish an online quantitative analysis model for moisture content assay of hydroxychloroquine sulfate particles by near infrared (NIR) spectroscopy. Methods The NIR spectra were collected in real time when the material particles were dried in the fluidized bed. Meanwhile the water content of the particles was measured with the standard moisture tester. The multiplicative signal correction (MSC) and first derivative followed by Karl Norris smoothing were used for spectra pretreatment. Two spectral range (4 935−5 336 cm−1 and 6 911−7 297 cm−1) were selected for the quantitative model with the partial least squares (PLS) regression. Results The quantitative calibration model had good correlation coefficients with Rc value=0.952 9 and Rp value=0.936 6. The root mean square error of calibration (RMSEC) was 0.408 and the root mean square error of prediction error (RMSEP) was 0.435. The ratio of standard deviation of validation set to prediction standard deviation (RPD) was 5.18. There was no significant difference between the predicted value and the reference value by t test when the established model was applied in large-scale production. Conclusion The online model established for monitoring water content has high accuracy and stability, which can be applied in industrial scale process to monitor the particle moisture in real time.
2021, 39(1): 29-34.
doi: 10.12206/j.issn.1006-0111.202008109
Abstract:
Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.
2021, 39(1): 35-37, 57.
doi: 10.12206/j.issn.1006-0111.202007022
Abstract:
Objective To search for novel potent 3-ester derivatives of arenobufagin and test their antitumor activities in vitro. Methods Target compounds were synthesized by esterification of arenobufagin with acids. CellTiter method was used to assay the in vitro antitumor activities. Results 3-Ester derivatives exhibited excellent antitumor activities against all the cancer cells. Conclusion Among the 3-ester derivatives, compound 2a had the best activities with the IC50 of 4.0−91.7 nmol/L and appeared to be a valuable candidate for further study.
2021, 39(1): 38-43.
doi: 10.12206/j.issn.1006-0111.202003191
Abstract:
Objective To study the synergistic effects of aspirin and atorvastatin on cell proliferation of non-small cell lung cancer cell A549 and NCI-H460 and the mechanism of these actions. Methods The proliferation of A549 and NCI-H460 cells treated by aspirin or/and atorvastatin were determined by MTS assay. The migration of A549 and NCI-H460 cells were conducted by wound-healing assay. The expression of relevant protein in mTOR and NFκB signaling pathway were detected by western blotting. The mRNA expression of TNF-α and IL-1β were detected by quantitative real-time PCR. Results Aspirin or/and atorvastatin inhibited the proliferation and migration of A549 and NCI-H460 at concentration of 100 and 5 μmol/L or greater. The effect was enhanced by the combination of aspirin and atorvastatin. Aspirin or/and atorvastatin inhibited the protein expression of the phosphorylation of mTOR and NFκB, and down-regulated anti-apoptotic regulators Bcl-2 and Mcl-1 in NCI-H460 cells. The combination treatment of aspirin and atorvastatin was more efficacious than the single treatment. Atorvastatin decreased the mRNA expression of TNF-α. The combination of atorvastatin with aspirin decreased the mRNA expression of IL-1β by nearly 50 percent compared to the control (P<0.05). Conclusion Aspirin and atorvastatin have synergistic inhibitory effects on cell growth of non-small cell lung cancer cell A549 and NCI-H460 by suppressing mTOR and NFκB signaling pathway.
2021, 39(1): 44-48, 76.
doi: 10.12206/j.issn.1006-0111.202005030
Abstract:
Objective To prepare an ultra-porous hydrogel capable of controlled release and investigate the drug loading, releasing, administration route and efficacy with insulin as a model drug. Methods The polymer interpenetrating network method was used to prepare ultra-porous hydrogels (SPH-IPN). Insulin was selected as a model drug to study the drug loading and efficacy. Fourier transform infrared spectroscopy and nuclear magnetic resonance carbon spectroscopy were used to investigate the structure of the gel. The swelling ratio and porosity were measured to evaluate the gel performance. Results The drug loading capacity of insulin ultra-porous hydrogel was 3.19%. The insulin-loaded freeze-dried gel exhibited good hypoglycemic effect on diabetic rats in 1−24 hours from the experimental results on rats with subcutaneous implantation. Conclusion The subcutaneously embedded lyophilized insulin ultra-porous hydrogel provided good controlled release efficacy. It maintained stable blood glucose levels within 24 hours.
2021, 39(1): 49-52.
doi: 10.12206/j.issn.1006-0111.202006043
Abstract:
Objective To study the pharmacokinetic differences of pure salidroside and Kunfukang pills in rats and explore the pharmacokinetic changes of salidroside as a pure form or in the mixture. Methods The rats were divided into two groups. One group received pure salidroside and the other was administrated with kunfukang pills. Concentrations of salidroside in both groups were determined by LC/MS/MS method. The main pharmacokinetic parameters were calculated. Results AUC0−t of salidroside was (587.11±35.02) in pure salidroside group and (956.35±47.65)ng·h/ml in Kunfukang group. cmax was (85.81±15.66) and (143.86±46.91)ng/ml separately, with significant difference. Conclusion The results indicated that other components in kunfukang pills had influence on the absorption, distribution and elimination of salidroside.
2021, 39(1): 53-57.
doi: 10.12206/j.issn.1006-0111.202005038
Abstract:
Objective To establish an assay method for monohydroxy carbamazepine, the active metabolite of oxcarbazepine, in human plasma. Methods Ornidazole was used as the internal standard. Plasma samples were processed with methanol and analyzed by HPLC. The column was ZORBAX Eclipse XDB-C18(150 mm×4.6 mm, 5 μm) with the mobile phase of water-acetonitrile (80∶20, V/V) at a flow rate of 1.0 ml/min. Dual wavelength detection is applied. The detection wavelength of monohydroxy carbamazepine was set at 192 nm and ornidazole at 318 nm. Results There was an excellent liner relationship for monohydroxy carbamazepine from 2 to 50 μg/ml(r= 0.998 6). The limit of quantification was 2 μg/ml with the range of accuracy between 95.57% and 100.59%. The RSD of intra-day and inter-day precisions were less than 15%. The average extraction recovery rate of MHC and internal standard were in the range of 89.62% to 98.76%. The RSD of stability was less than 6%. Conclusion This method is specific, sensitive, and easy to operate. It is suitable for the clinical assay of monohydroxy carbamazepine in human plasma.
2021, 39(1): 58-61, 72.
doi: 10.12206/j.issn.1006-0111.202008062
Abstract:
Objective To screen and identify the penetration enhancer in pharmacy prepared compound terbinafine ointment. Methods In vitro percutaneous penetration test was conducted with vertical Franz diffusion pool. The SD rat's abdomen skin was used for permeable membrane and 60% polyethylene glycol 400-40% saline for receiving liquid to analyze different osmotic promoters. Results The permeability of compound terbinafine ointment was significantly higher with 10% propylene glycol than 15% propylene glycol. The compound terbinafine ointment with 10% propylene glycol was also better than 3% azone in permeability. Conclusion 10% propylene glycol was selected to be the penetration promoter for pharmacy prepared compound terbinafine ointment, which improved the solubility of the drug in the skin.
2021, 39(1): 62-67, 96.
doi: 10.12206/j.issn.1006-0111.202012001
Abstract:
Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs. Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP18 column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside. Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, cmax was (9 680±3725) and (9 310±1 645) ng/ml; tmax was (1.25±0.67) and (0.011±0.017) h, AUC0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t1/2 was (1.31±0.63) and (0.98±0.13) h, respectively. Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%.
2021, 39(1): 68-72.
doi: 10.12206/j.issn.1006-0111.202003189
Abstract:
Objective To improve the quality control of Dilong Shenmai oral liquid. Methods TLC was used for the qualitative identification of Astragali Radix, Ophiopogonis Radix and Schisandrae Chinensis Fructus in Dilong Shenmai oral liquid. HPLC was used to determine the contents of schisandrin and ethylparaben in the preparation. Wondasil C18 column (250 mm×4.6 mm, 5 μm) was used with acetonitrile-water as the mobile phase at the flow rate of 1.0 ml/min for gradient elution. The detection wavelength was set at 254 nm, and column temperature was 30 ℃. Results TLC spots were clear and well-separated without negative interference. The linear ranges of schisandrin and ethylparaben were 5.81−58.06 μg/ml (r=0.999 9) and 25.29−252.94 μg/ml (r=0.999 9). The average recoveries were 99.35% (RSD=1.02%) and 99.72% (RSD=0.76%). Conclusion This method is simple, quick and accurate. It can be used for effective quality control of Dilong Shenmai oral liquid.
2021, 39(1): 73-76.
doi: 10.12206/j.issn.1006-0111.202003085
Abstract:
Objective To establish a UPLC-MS/MS method for the determination of dexmedetomidine in human plasma and investigate the effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo. Methods Samples were obtained by liquid-liquid extraction. Agilent Eclipse Plus C18 column was used for chromatograph with methanol and 0.1% formic acid-water solution as mobile phase. Flow rate was 0.2 ml/min. The column temperature was 35 ℃, and the MS detection was selected in MRM mode. Results The calibration curves of dexmedetomidine showed good linearity in the ranges of 0.01−10.00 ng/ml. The results of intra and inter-day precisions were both within 15%. The recovery rate was 85.5%−93.1%. Matrix effect was 91.2%−95.6%. Samples remained stable during analysis. Compared with the control group, cmax、AUC(0−t)、AUC(0−∞) and Vz of dexmedetomidine in the patients with obstructive jaundice were increased by 63.4%, 78.9, 66.4%, 82.5%, respectively (P<0.01). CLz was decreased by 42.1%. Conclusion This method is accurate, sensitive and reproducible. It is suitable for dexmedetomidine assay in human plasma. The elimination rate of dexmedetomidine is slower in obstructive jaundice.
2021, 39(1): 77-81.
doi: 10.12206/j.issn.1006-0111.202005041
Abstract:
Objective To screen the macroporous adsorption resin suitable for the separation and purification of total polyphenols from purple tea and establish the purification process parameters to prepare high-purity total polyphenols from purple tea. Methods The static adsorption-elution test was used to screen macroporous adsorption resin for the purification of total polyphenols from purple tea. Based on the single factor test, the comprehensive score of adsorption rate was used as the index to investigate the effects of different factors on the purification process and identify the optimal parameters for the purification process. Those factors included sample concentration, the pH value of the sample solution, the ratio of column diameter to height, sample size, ethanol percentage in the eluent, eluent volume and elution flow rate. Results The best process parameters for purification of total polyphenols from purple tea by AB-8 macroporous adsorption resin were as following. The sample concentration was 375 μg/ml with flow rate 2 ml/min. The sample volume was 3 BV. The sample solution pH was 2. The ratio of colume diameter to height was 1∶6. The impurities were removed first by water 3 BV. 50% ethanol 4 BV was used for elution with flow rate 2 ml/min. Conclusion AB-8 macroporous resin was selected for the purification of polyphenols from purple tea under the optimized technological conditions. The mass fraction of total polyphenols increased from 40.2% to an average of 69.8%. The solid content decreased from 56.0 mg to 29.9 mg. The established purification process has good stability and feasibility. It can be used as a purification process for total polyphenols from purple tea.
2021, 39(1): 82-85, 93.
doi: 10.12206/j.issn.1006-0111.202003107
Abstract:
Objective To study the clinical effects of Yinlian Qufeng decoction in the treatment of chronic urticaria (CU) and the effects on the changes of serum IgE and T cell subsets (CD4+, CD8+). Methods 96 patients were randomly divided into two groups, treatment group and control group, with 48 cases in each group. The treatment group was treated with Yinlian Qufeng decoction, while the control group was treated with desloratadine dispersible tablets for 8 weeks. The clinical symptom score, TCM syndrome score and quality of life [skin disease quality of life index (DLQI)] of the two groups were evaluated before and after treatment. The serum levels of IgE and CD4+ and CD8+ were measured by ELISA and flow cytometry. Clinical effect was observed and the rate of adverse reactions was counted. Results There was no statistically difference between two groups in clinical symptom scores, TCM syndrome scores, DLQI, the levels of IgE, CD4+, CD8+, and the ratio of CD4+/CD8+ before treatment (P>0.05). After treatment, the clinical symptoms, TCM syndromes and DLQI were reduced in both groups. The treatment group had lower scores than that in control group with statistical significance（P < 0.05). CD4+ level and ratio of CD4+/CD8+ were increased, while IgE and CD8+ levels were decreased in both groups after treatment with statistical significance (P < 0.01). The changes of above indexes in the treatment group were better than those in the control group with statistical significance (P < 0.01). The effective rates of the two groups were 91.67% and 77.08% and rates of adverse reactions were 6.25% and 20.83% separately with statistical difference (P < 0.05). Conclusion Yinlian Qufeng decoction can effectively regulate the cellular immune function, alleviate the disease symptoms and improve life quality with few adverse reactions. This decoction deserves the promotion for clinical application.
2021, 39(1): 86-89.
doi: 10.12206/j.issn.1006-0111.202004025
Abstract:
Objective To explore the treatment of pancytopenia and liver injury induced by methimazole and provide medication therapy reference for clinical pharmacists in clinical practice. Methods The clinical pharmacists provided clinical interventions by the evaluation of adverse drug reactions, assessment of the therapeutic effects, adjustment of therapeutic regime based on the patient′s disease condition. Results The physician adopted the recommendations from the clinical pharmacists. The patient with pancytopenia and liver injury induced by methimazole gradually recovered with biochemical indices back to normal levels. Conclusion The therapeutic outcome was improved with clinical pharmacist’s knowledge on medication, optimization of therapeutic regime and implement of pharmaceutical care.
2021, 39(1): 90-93.
doi: 10.12206/j.issn.1006-0111.202004087
Abstract:
Objective To analyze the characteristics and trends of adverse drug reactions (ADR) induced by anti-infective drugs in Shanghai Prison General Hospital and provide a guideline of rational drug use and pharmacovigilance for detainees. Methods The anti-infective drug induced ADR cases reported to the national ADR monitoring center in our hospital from January 2011 to October 2018 were collected. The primary and secondary factors of types, organs and (or) systems affected by anti-infective drugs that lead to ADR were studied with Pareto diagram. Results 158 ADR cases caused by anti-infective drugs were collected. 143 cases (90.51%) were male in 20-59 years old. Pareto diagram analysis showed that ADRs mainly involved eight kinds of anti-infective drugs (antituberculosis drugs, cephalosporins, sulfonamides, antiviral drugs, penicillin, aminoglycosides, fluoroquinolones and nitroimidazoles). ADRs mainly involved in hepatobiliary and blood system. Both topical and systemic reactions were reported. Abnormal liver function, liver injury, rash and allergic reaction were the most common. Conclusion Pareto diagram method reflected the "critical minority and minor majority" analysis on detainees with ADRs caused by anti-infective drug. It was recommended to focus on anti-tuberculosis drugs and cephalosporin drugs to reduce or avoid the occurrence of ADR.
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