Research progress in bioanalysis and pharmacokinetics of liposome nanomedicine / 药学学报

Liposome nanomedicine is a new drug preparation with nano scale, which is encapsulated by lipid bilayer vesicle structure. As a drug delivery carrier, liposome has many advantages such as good biocompatibility, biodegradation in vivo and strong targeting. The application of liposome nano drug delivery system can improve the pharmacokinetic behavior and efficacy of some drugs in vivo to a certain extent, and reduce toxic and side effects. After liposome nanomedicine enter into the body, free drugs will be released, so there will be loaded drugs and free drugs in the body. Loaded drugs are drug repositories, free drugs are related to their efficacy and adverse reactions. Therefore, the pharmacokinetics study of liposomes should focus on both loaded drugs and free drugs. Quantitative analysis of free drugs, liposome particles and their materials is a big challenge. The bioanalysis and pharmacokinetics of liposome nanomedicines will be introduced and discussed in this review. We hope this review will provide a reference for the development of liposome nanomedicine.

Development and performance test of the environment scale of unintentional injury in the home for children aged 0-6 years old in urban area of China / 中华预防医学杂志

To develop the environment scale of unintentional injury in the home for children aged 0-6 years living in urban area of China, and test its validity and reliability. The content of the environment scale was established through the literature review, expert consultation and pilot study. A total of 1 104 children aged 0-6 years in urban area of Changsha were enrolled in this study by using a multi-stage stratified cluster random sampling method. The questionnaire was used to collect the basic information of children, the incidence of unintentional injury and the status of home environment. The reliability of the scale was tested by using Cronbach's α coefficient and split-half reliability coefficient. The content validity and construct validity were tested by using Pearson correlation analysis and factor analysis. All children were divided into two groups according to the incidence of unintentional injury in the home and the discrimination validity of the scale was tested by using -test. The scale had 54 items in 6 dimensions. The number of eligible questionnaires was 1 074, including 554 (51.6%) from boys and 519 (48.3%) from children under 3 years old. The incidence rate of unintentional injury and in-home injury was 18.34% (197 children) and 10.71% (115 children). The internal consistency reliability (Cronbach's α) coefficient for the scale was 0.87 and the split-efficacy reliability coefficient was 0.82, both meeting the standard of reliability above 0.70. The Pearson correlation coefficient between each dimension and the whole scale ranged from 0.53 to 0.84 (all values <0.001). The common factor cumulative variance contribution rate of the scale was 58.34%. There were 54 items with factor loadings greater than 0.30. The root mean square error of approximation, comparative fit index and goodness-of-fit index were 0.07, 0.61 and 0.71, respectively. The score of scale in children with injury was significantly higher than that in children without injury (0.022). The validity and reliability of the environment scale for unintentional injury in the home for children aged 0-6 years old in the urban area of China are good.

Feasibility and safety of new simplified left bundle branch area pacing via nine-partition method / 中华心血管病杂志

Objective: To investigate the efficacy and safety of left bundle branch area pacing (LBBaP) with the new simplified approach (nine-partition method). Methods: A total of 118 patients with clinical indications and received pacemaker implantation from December 1, 2018 to December 31, 2019 in Beijing Anzhen Hospital were enrolled. LBBaP was performed with the nine-partition method (in the right anterior oblique 30° position, the ventriculogram was divided into nine partitions and the initial implant sites were located in the lower base 1/3 partitions). In X-ray image, the 3830 lead is located in the left bundle branch area, the unipolar pacing QRS wave is in the form of right bundle branch block, and the peak time from stimulation to left ventricular activation<90 ms is defined as successful operation. The clinical characters, such as the methods of venipuncture, electrode parameters, operation duration, fluoroscopy duration, the peak time from stimulation to left ventricular, pacemaker types, surgical success rate, complications, and immediate postoperative ECG parameters were collected. The patients were followed up after the operation, and the electrode parameters and postoperative complications were recorded. Results: This study is a retrospective study. There were 62 (52.5%) male patients in this cohort, the average age was (65.9±13.4) years old,and there were 49(41.5%) sick sinus syndrome, 6(5.1%) abnormal sinus node and atrioventricular node simultaneously, 63(53.4%) atrioventricular block, 26(22.0%) atrial fibrillation, 20(16.9%) cardiomyopathy; the baseline duration of QRS was (109.21±39.03) ms. Successful LBBaP was achieved in 109 patients with"nine-partition method"and the success rate was 92.4%; 104 patients (95.5%) were axillary vein puncture, 5 (4.6%) were subclavian vein puncture; the operation duration was (80.3±23.0) min, the fluoroscopy duration was (12.29±5.13) min; the QRS duration after LBBaP was (116.36±18.11) ms. The threshold of the left bundle branch (LBB) lead was (0.92±0.63) V, the R wave amplitude was (10.60±5.04) mV and the impedance was (798.71±194.90) Ω. In 1 V pacing, the peak time from stimulation to left ventricular activation was (67.91±12.15) ms, and in 5 V pacing was (67.52±12.45) ms; 1 case (0.9%) with a single-chamber pacemaker implanted, 106 cases (97.3%) with dual-chamber pacemaker and 2 cases (1.8%) with three-chamber pacemakers. There were no hematomas, pneumothorax, hemothorax, electrode dislocation, infection, and capsular hemorrhage and other serious surgery-related complications during the operation. A total of 97 patients (89.0%) were followed up for (6.21±2.90) months. The electrode parameters of all patients were stable and no complications observed. Conclusions: The LBBaP with nine-partition method is a simple, safe and effective physiological pacing approach. However, its long-term effect still needs to be further verified.

Research and development thought on biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.

Study on biopharmaceutics classification system of Chinese materia medica for Gegen Qinlians Tablets based on anti-inflammatory activity / 中国中药杂志

The research on biopharmaceutics classification system of Chinese materia medica( CMMBCS) should be finally implemented to the holistic research level of traditional Chinese medicine compounds,while the overall biopharmaceutical properties of traditional Chinese medicine compounds are not only the sum of solubility and permeability of each component. In this study,Gegen Qinlian Tablets was used as the research object,and the contents of 12 representative components,i.e. puerarin,daidzin,baicalin,daidzein,wogonoside,baicalein,wogonin,glycyrrhizic acid,coptisine hydrochloride,epiberberine,berberine hydrochloride and palmatine hydrochloride,were simultaneously determined by HPLC to obtain the mass weight of each component. The in vitro lipopolysaccharide( LPS)-induced RAW264. 7 cells inflammation model was established to investigate the anti-inflammatory effects of 12 representative components and obtain the efficacy weight of each component. In order to obtain the number of doses and effective permeability coefficient which can represent the overall biopharmaceutical properties of Gegen Qinlian Tablets,mass weight was combined with efficacy weight to integrate the solubility and permeability data of each component determined by typical shake flask method and in situ single pass intestinal perfusion model respectively. The results indicated that Gegen Qinlian Tablets should be categorized Ⅳ drug of the CMMBCS with low solubility and low permeability.

Impacts of multicomponent environment on intrinsic dissolution rate of berberine in biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

To illustrate the intrinsic dissolution rate(IDR) involved in biopharmaceutics classification system of Chinese materia medica(CMMBCS), investigate the effect of artificial multicomponent environment on IDR of berberine, by using a non-disintegrating disk, and summarize related rules by using the obtained data. Progressive levels design was used to investigate the effects of single component environment (puerarin, baicalin, and glycyrrhizic acid); double-component environment(puerarin+baicalin, puerarin+ glycyrrhizic acid, baicalin+glycyrrhizic acid); and triple-component environment(puerarin+baicalin+glycyrrhizic acid) on IDR of berberine, laying a foundation for further researches on the absorption mechanism of multiple components.

Discussion on research thinking of traditional Chinese medicine standardization system based on whole process quality control / 中国中药杂志

The concept of "Quality by design" indicates that good design for the whole life cycle of pharmaceutical production enables the drug to meet the expected quality requirements. Aiming at the existing problems of the traditional Chinese medicine (TCM) industry, the TCM standardization system was put forward in this paper from the national strategic level, under the guidance by the idea of quality control in international manufacturing industry and with considerations of TCM industry's own characteristics and development status. The connotation of this strategy was to establish five interrelated systems: multi-indicators system based on tri-indicators system, quality standard and specification system of TCM herbal materials and decoction pieces, quality traceability system, data monitoring system based on whole-process quality control, and whole-process quality management system of TCM, and achieve the whole process systematic and scientific study in TCM industry through "top-level design-implement in steps-system integration" workflow. This article analyzed the correlation between the quality standards of all links, established standard operating procedures of each link and whole process, and constructed a high standard overall quality management system for TCM industry chains, in order to provide a demonstration for the establishment of TCM whole-process quality control system and provide systematic reference and basis for standardization strategy in TCM industry.

Study on biopharmaceutics classification system for Chinese materia medica of extract of Huanglian / 中国中药杂志

One of the advantages of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is expanding the classification research level from single ingredient to multi-components of Chinese herb, and from multi-components research to holistic research of the Chinese materia medica. In present paper, the alkaloids of extract of huanglian were chosen as the main research object to explore their change rules in solubility and intestinal permeability of single-component and multi-components, and to determine the biopharmaceutical classification of extract of Huanglian from holistic level. The typical shake-flask method and HPLC were used to detect the solubility of single ingredient of alkaloids from extract of huanglian. The quantitative research of alkaloids in intestinal absorption was measured in single-pass intestinal perfusion experiment while permeability coefficient of extract of huanglian was calculated by self-defined weight coefficient method.

Overall intestinal permeability of multiple components in lotus leaf by in situ single pass intestinal perfusion models / 中国中药杂志

To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻⁴ cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻⁴ cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.

Validation of in situ single pass perfusion model based on P-gp / 中国中药杂志

To validate in situ rats intestinal single pass perfusion model based on P-glycoprotein (P-gp). Firstly, phenol red perfusion was carried out to verify the close connection structure of intestinal epithelial cells, and the integrity of the intestinal epithelium, with a gravimetric method for correcting water flux. The level of phenol red was determined by high performance liquid chromatography (HPLC) both before and after perfusion. Secondly, the positive drug digoxin specified by FDA was used to validate the model. After different mass concentrations of verapamil were given in the rats, the absorption parameters of digoxin in ileum of rats were observed and compared. The results showed that the phenol red was absorbed in rats ileum segment, with an effective permeability coefficient of (1.09±0.62)×10 ⁻⁶ cm•s ⁻¹. The experiment results indicated that the close connection structure of intestinal epithelial cells was normal, and the integrity of the intestinal epithelium was maintained well. In digoxin perfusion experiment, in case no verapamil was given, digoxin showed certain degree of absorption in rat ileum, with an effective permeability coefficient (Peff) of (1.07±0.59)×10 ⁻⁵ cm•s ⁻¹; after mass concentrations of 0.01,0.1 mmol•L ⁻¹ verapamil were given, the absorption of digoxin was on the rise in rat ileum, with an effective permeability coefficient Peff of (1.58±0.69)×10 ⁻⁵, (3.28±0.95)×10 ⁻⁵ cm•s ⁻¹ respectively (P<0.05). Digoxin perfusion experiment verified that P-gp expression in small intestine epithelium was intact and can be used in the research of P-gp efflux transporter.

Biopharmaceutics classification system of Chinese materia medica of berberine in Gegen Qinlian decoction / 中国中药杂志

One of the top-level researches of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is the study on single component in compound Chinese medicine. The medicines shall be classified according to its solubility and intestinal permeability, as well as the ascending degree in multicomponent environment. Based on above, we chose berberine as the main object to explore the change rules of its solubility and intestinal permeability in Gegen Qinlian decoction. Shaking flask-HPLC was used to detect the solubility changes of berberine in compounds. The qualitative investigation of berberine in intestinal absorption was measured by everted gut sac, and the quantitative research of berberine in intestinal absorption was measured by single-pass intestinal perfusion experiment, while the qualitative and quantitative research of berberine absorption into blood was measured by in intestinal perfusion with venous sampling experiment.

In vitro and in vivo intestinal absorption of Huanglian decoction in multi-component environment / 中国中药杂志

The effect of drugs in the body is always inseparable with the dynamic processes of absorption, distribution, metabolism and excretion. For oral drug, absorption, as the first link to enter the body, is particularly valued. Traditional Chinese medicine has multiple components and multiple targets, and the nature of its single composition is different from that in the multicomponent environment. Alkaloids in Huanglian extract was used as the main object in this study to establish an analytical method for determining the content of alkaloids in Huanglian. In addition, the compositions of the Huanglian aqueous extract solution which can be absorbed through intestinal wall into blood, were initially determined by the means of everted gut sac and in intestinal perfusion with venous sampling experiment. This paper can provide data reference and support for the further study on the absorption and metabolism of Huanglian.

Experimental study on effect of arsenic trioxide on vascular smooth muscle cells / 中华放射学杂志

Objective To investigate the effect of arsenic trioxide(As_2 O_3)nanoparticles on rabbit vascular smooth muscle cells in vitro in comparison with normal form As_2 03.Methods The rabbit vascular smooth muscle cells were cultured in vitro.Nano and normal forms of As_2O_3 with drug concentrations of 3?mol/L were added into the cells.Cell proliferation curve was drawn according to the light absorption values of MTT test.Flow cytometry was applied to observe the apoptosis.DNA was extracted and underwent electrophoresis.Results Cell proliferation treated with the 3?mol/L concentration of As_2O_3 was inhibited. Cell growth was inhibited markedly with increased treatment time,and the inhibition effect of nano drug form seemed stronger than that of normal form.MTT light absorption values of cells treated at 24,48 and 72 h showed statistically significant difference(H=10.934,15.039,15.539,P