Humans ; Estazolam ; Chromatography, High Pressure Liquid

Abstract: The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.

The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.
Cellulose ; chemistry ; Reproducibility of Results ; Technology, Pharmaceutical ; methods ; Water

This study was aimed to find out the correlation between chemical component contents and physical prop-erties of tanshinone extract powders. The contents of cryptotanshinone and tanshinone IIA from 50 batches of tanshi-none extract powders were determined by HPLC. And the physical properties were determined by classical methods. The correlation analysis between component contents and physical properties were also investigated. The results showed that two sets of variables had good intraclass correlation, especially for the contents of cryptotanshinone and tanshinone IIA, among D10, D50, D90, there were relatively strong correlation between the bulk density and tapped density, between the Hausner ratio and compressibility index. The angle of repose had a certain correlation with the uniformity, Hausner ratio and compressibility index, but with no strong correlation. The correlation coefficient be-tween two sets was below 0.400, suggesting there was a not so good inter-group correlation. After the canonical cor-relation analysis, three pairs of canonical variables had significant correlations with correlation coefficients being 0.851, 0.674 and 0.565, respectively. It was concluded that there was a good intraclass correlation for each of physi-cal and/or chemical quality set, but the correlation between the two sets was bad. Canonical variables performed bet-ter inter-group correlation compared with original variables, indicating there was a certain correlation between chem-ical and physical quality attributes of tanshinone extract powders.

Objective:To explore the relationship between vesicular monoamine transporter 2(VMAT2) density in the striatum and the non-motor symptoms(NMSs) in patients with Parkinson′s disease(PD).Methods:From December 2018 to December 2019, 29 normal controls (16 males, 13 females, age: (48.8±14.2) years), 31 patients with PD at the Hoehn-Yahr (mH-Y) Ⅱ stage (16 males, 15 females, age: (53.4±8.5) years) and 36 patients with PD at mH-Y Ⅲ stage (19 males, 17 females, age: (63.1±8.2) years) in the First Affiliated Hospital of Sun Yat-sen University were prospectively enrolled in this study. All subjects underwent 18F-fluoropropyl-(+ )-dihydrotetrabenazine( 18F-FP-(+ )-DTBZ, 18F-AV133) PET/CT imaging, then the specific uptake ratios (SURs) of striatal subregions were measured with the occipital cortex as the reference background region. The clinical data, laboratory data and imaging results were collected. The NMSs of each patient were evaluated with Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), Parkinson′s Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), Parkinson′s Disease Quality of Life Questionnaire (PDQL) and Non-Motor Symptoms Scale (NMSS). The independent-sample t test and one-way analysis of variance (the least significant difference t test) were used to compare data differences. Finally, the association of the striatal SURs with the clinical symptom scores were evaluated with Pearson correlation analysis and multivariable stepwise regression analysis. Results:Significant differences were found in depression (3.51±1.34 vs 11.36±3.87), anxiety (2.35±1.45 vs 6.00±3.32), sleep disorder (132.90±12.26 vs 110.34±19.69) and life quality (7.58±3.37 vs 24.01±10.15) scores between the mH-Y stage Ⅱ and the stage Ⅲ patients ( t values: from -10.573 to 5.439, all P<0.05), while cognitive scores did not differ significantly between the 2 PD groups ( t=1.067, P>0.05). Compared with healthy control group (1.28±0.22), the PD groups displayed a more marked decrease of SURs in the bilateral putamen and in the caudate nucleus (0.65±0.16 and 0.31±0.14; F=83.11, P<0.05), and the SURs of patients at stage Ⅱ were higher than those of the patients at stage Ⅲ ( t=9.116, P<0.05). NMSs scores of PD patients, with the exception of cognition scores, were correlated with striatal SURs ( r values: from -0.647 to -0.426, all P<0.05). Regression analysis showed that total striatum SURs was the best predictor of PDSS and NMSS scores ( R2 values: 0.234, 0.378, both P<0.001), while contralateral caudate nucleus SURs were best predictor of HAMD scores ( R2=0.402, P<0.001). The SURs of contralateral putamen were best variables for predicting HAMA scores ( R2=0.204, P<0.001). Conclusion:The correlation between the decreased striatal VMAT2 and a broad spectrum of NMSs in patients with PD is established, suggesting that the defect in dopamine supply may be an early abnormality promoting mechanisms leading to the development of NMSs in PD.

Background Oxidative damage may cause the functional dysfunction and death of retinal vascular endothelial cells(RVECs),and further leads to the development of retinal vascular diseases.Fufang xueshuantong has a therapeutic effect on retinal vascular diseases,but little is known about its molecular mechanism.Objective The goal of this study was to investigate the protective effects and mechanism of fufang xueshuantong on injury of human RVECs induced by tert-butyl hydroperoxide(t-BHP).Methods Human RVECs were isolated from healthy donor eyes and primarily cultured and then identified by flow cytometry.The third to fifth generations of cells were used in this experiments.The fufang xueshuantong solution of 0.0625,0.1250,0.2500,0.5000 and 1.0000 g/L were added in the cuhure plate with 5 × 104/L cells respectively in the experimental groups,and t-BHP of 75,100,200 and 300 μ.mol/L were added in the model control groups.MTT was used to detect the A490and survival rate of RVECs.The apoptotic rate and death rate of the cells were evaluated by double staining of Annexin V-FITC/PI.Morphology of human RVECs were examined using invert microscopy and Hoechst33258 staining.The expressions of nitro tyrosine (a marker of oxidative damage of protein)and 8-OHdG(a marker of oxidative damage of DNA)in human RVECs were assessed by the immunofluorescence staining.Western blot was used to detect the expressions of nuclear factorkappa B(NF-KB),p53,bcl-2 and bax after 6,12,24 hours t-BHP action.This study was approved by the Ethic Committee of Zhongshan Ophthalmic Center.Results No significant difference was found in A490value among the normal control group,0.0625,0.1250,0.2500,0.5000 and 1.0000 g/L fufang xueshuantong groups(F =1.989,P＞0.05).The survival rates of the cells were lower in 75,100,200 and 300 μmol/L t-BHP groups compared with corresponding fufang xueshuantong groups(t =14.57,13.82,21.51,32.64,P＜ 0.01).The percentages of normal cells were evidently lower in 75,100,200 and 300 μmol/L t-BHP compared with corresponding fufang xueshuantong groups(t=14.908,5.495,17.165,26.330,P＜0.01).The numbers of deformation and death of the human RVECs increased as the elevated concentration of t-BHP,but those in fufang xueshuantong groups were less than the t-BHP groups under the invert microscopy.Compared with t-BHP groups,the expressions of nitro tyrosine,8-OHdG,NF-KB,p53 and bax were lower but the expression of bcl-2 was higher in human RVECs with the statistically significant differences(P＜0.05).Fufang xueshuantong at the concentration of 0.2500 g/L showed maximally protective effect on human RVECs.Conclusions Fufang xueshuantong protects human RVECs against the t-BHP-induced injury through downregulating the expression of NF-kB,p53,bax and up-regulating the express of the bcl-2 protein.

OBJECTIVETo construct a multiple-scale organized implant surface with super-hydrophilicity.

METHODSThe SiC paper polished titanium disc was sandblasted and treated with HF/HNO₃ and HCl/H₂SO₄, then acid-etched with H₂SO₄/H₂O₂. The physicochemical properties of the surfaces were characterized by scanning electron microscope, static state contact angle and X-ray diffraction. MC3T3-E1 cells were used to evaluate the effects of the surface on the cell adhesion, proliferation and differentiation.

RESULTSThe acid-etching process with a mixture of H₂SO₄/H₂O₂ superimposed the nano-scale structure on the micro-scale texture. The multiple-scale implant surface promoted its hydrophilicity and was more favorable to the responses of osteoprogenitor cells, characterized by increased DNA content, enhanced ALP activity and promoted OC production.

CONCLUSIONA multiple-scale implant surface with super-hydrophilicity has been constructed in this study, which facilitates cell proliferation and adhesion.

3T3 Cells ; Animals ; Cell Adhesion ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Dental Etching ; Dental Implants ; Hydrophobic and Hydrophilic Interactions ; Mice ; Surface Properties ; Titanium ; chemistry ; pharmacology

Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside.
Chemical Fractionation ; methods ; Chemistry, Pharmaceutical ; Chromatography, High Pressure Liquid ; Coumarins ; analysis ; isolation & purification ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; Glucosides ; analysis ; isolation & purification ; Phenols ; analysis ; isolation & purification ; Phenylethyl Alcohol ; analogs & derivatives ; analysis ; isolation & purification ; Rhodiola ; chemistry

This study preliminarily discussed the TCM syndrome types of myasthenia gravis (or flaccidity) and its treatments and prescriptions through consensus method,providing evidence and level revision of the recommended expert consensus of myasthenia gravis in TCM clinical practice guideline.Literatures over TCM syndrome types,symptoms,therapeutic regime,medication and acupuncture were involved in the syndrome analysis of myasthenia gravis through literature retrieval.The common clinical syndromes were outputted by mentioned rate.Ten first-rate hospitals were finally included,such as The Affiliated Hospital of Changchun University of Traditional Chinese Medicine,Dongfang Hospital of Beijing University of Chinese Medicine,Guangdong Province Traditional Chinese Medical Hospital and Affiliated Hospital of Anhui University of Traditional Chinese Medicine.Twelve experts in aggregate were confirmed to participate in the discussion for the identification of the TCM syndrome types,treatments and prescriptions of myasthenia gravis.As a result,five TCM syndrome types,such as syndrome of spleen and stomach qi deficiency,syndrome of spleen-kidney deficiency,deficiency syndrome of both qi and yin,syndrome of deficiency and sinking of qi,were confirmed;while five therapeutic regimes were approved,including reinforcement of qi,tonification of spleen and stomach,tonification of spleen and kidney qi,tonification of qi and yin,the supplement of qi and restoration of yang for ascending qi collapse.In addition,five prescriptions were supported by the experts,such as Bu Zhong Yi Qi (BZYQ) decoction,BZYQ decoction combined with You Gui pills,BZYQ decoction combined with Sheng Mai powders and Sheng Xian decoction.In conclusion,the expert consensus method for the screen of TCM syndrome types of myasthenia gravis embodied the conception of literature research based on the clinical practice combined with the scientific methods in conformity with the current research approaches to TCM syndrome types.

BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group (sepsis group) and simvastatin+sepsis serum intervention group (simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and flow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR. RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum;however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group. CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis.