Study on postprandial bioequivalence of Diacerein capsules in healthy volunteers / 中国药房

OBJECTIVE To evaluate the postprandial bioequivalence of two kinds of Diacerein capsules in healthy volunteers with oral administration . METHODS A total of 24 adult healthy subjects were included and randomly divided into two groups ， with 12 subjects in each group . A randomized ，open，double-cycle cross -over trial design was adopted . Both groups took 50 mg of the test preparation （domestic Diacerein capsules ）or the reference preparation （Ambridine®）respectively at 30 min after eating the standard meal in the morning of the first day of each cycle of the trial . The cleaning period was one week . Blood samples were collected at different time points before and after taking the medicine and the protein was precipitated with methanol for sample pretreatment. The concentration of active metabolite rhein was determined by LC -MS/MS using emodin as internal standard . The pharmacokinetic parameters were calculated with DAS 3.2.9 software，and the bioequivalence of test and reference preparation were evaluated. RESULTS After the subjects took the test preparation and the reference preparation after meal ， the main pharmacokinetic parameters of rhein were as follows ：cmax were（3 517±1 121）and（3 225±755）ng/mL；AUC0－24h were （25 764±6 134）and（24 316±5 856）ng·h/mL；AUC0－∞ were（26 679±6 409）and（25 170±6 415）ng·h/mL；tmaxwere 3.50 （0.67，12.00）and 4.00（1.50，7.00）h；t1/2 were（4.26±1.12）and（4.19±1.05）h，respectively. The 90% confidence intervals of the geometric mean ratios of cmax，AUC0－24h and AUC 0－∞ were 100.8%-113.9%，103.1%-109.4% and 103.2%-109.9%，respectively. CONCLUSIONS The test preparation and reference preparation are bioequivalent in the postprandial state of healthy subjects .

A retrospective analysis of the efficacy and safety of dicycloplatin in the treatment of malignant tumor / 药学实践杂志

Objective To observe the short-term efficacy and adverse reactions of dicycloplatin in the treatment of malignant tumors. Methods A retrospective analysis was performed in our hospital from January 2017 to August 2018 using dicycloplatin to treat patients with malignant tumors. The efficacy and adverse reactions were evaluated after at least 2 cycles of chemotherapy. Results Among the 20 patients with an average of 4 cycles of chemotherapy, 1 had complete remission (CR), 4 had partial remission (PR), 7 had stable diseases (SD), 8 had progression (PD). The total efficacy was 25%. The control rate was 60%. The KPS scores for quality of life was higher than that before treatment (P<0.05). The main adverse effects during chemotherapy were bone marrow suppression, gastro-intestinal reactions. The incidence of leukopenia, thrombocytopenia, reduced hemoglobin, nausea vomiting and liver damage was 45%, 35%, 50%, 20%, and 5%, respectively. Conclusion Dicycloplatin-based chemotherapy has a good curative effect on malignant tumors, and the adverse reactions are mild and tolerable, which deserves further clinical observation and application.

Clinical characteristics of gastrointestinal symptoms and liver function injury in patients with coronavirus disease 2019 / 中华消化杂志

Objective:To analyze the clinical characteristics of gastrointestinal symptoms and liver function injury in patients with coronavirus disease 2019 (COVID-19).Methods:From January 23, 2020 to February 29, 2020, the medical records of 251 patients with COVID-19 admitted to the West Campus of the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, were collected. The proportion of the patients with gastrointestinal symptoms including anorexia, nausea and vomiting, diarrhea and abdominal pain were analyzed respectively. The patients were divided into common type (76 cases), severe type (65 cases) and critical type (110 cases). The incidence of liver function injury and the changes of liver function parameters such as total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), albumin and globulin of the patients with different clinical types and with or without gastrointestinal symptoms were analyzed. Mann-Whitney U test, Chi square test and Fisher′s exact test were used for statistical analysis. Results:The main gastrointestinal symptoms of patients with COVID-19 were anorexia (33.9%, 85/251), diarrhea (12.0%, 30/251), nausea and vomiting (7.6%, 19/251) and abdominal pain (1.2%, 3/251). 143 patients (57.0%) had liver function injury, the rate of liver function injury in critical type patients was 75.5% (83/110), which was higher than that of common type patients (40.8%, 31/76) and severe type patients (44.6%, 29/65), and the differences were statistically significant ( χ2=22.765 and 16.865, both P<0.01). There was no significant difference in the proportion of patients with liver function injury between common type and severe type patients ( P>0.05). There was no statistically significant difference in the proportion of liver function injury between patients with gastrointestinal symptoms and those without gastrointestinal symptoms (57.8%(67/116) vs. 56.3%(76/135), P>0.05). The median values of TBil, DBil, ALT, AST, ALP, GGT, LDH and globulin level of critical type patients were 13.5 μmol/L, 4.9 μmol/L, 44.5 U/L, 50.0 U/L, 64.0 U/L, 41.0 U/L, 527.0 U/L and 33.6 g/L respectively. The proportions of critical type patients with TBil level >34.2 μmol/L, DBil level>13.6 μmol/L, ALT level>80 U/L and AST level>80 U/L were 7.3% (8/110), 7.3% (8/110), 17.3% (19/110) and 17.3% (19/110), respectively. These results were all higher than those of common type patients (9.5 μmol/L, 2.9 μmol/L, 28.5 U/L, 28.5 U/L, 54.0 U/L, 25.5 U/L, 225.5 U/L, 30.1 g/L, 0, 0, 6.6% (5/76) and 2.6% (2/76) ) and severe type patients (10.4 μmol/L, 3.4 μmol/L, 30.0 U/L, 31.0 U/L, 49.0 U/L, 25.0 U/L, 284.0 U/L, 30.7 g/L, 0, 0, 6.2% (4/65) and 1.5% (1/65)), and the differences were statistically significant ( Z=-4.264, -5.507, -4.000, -6.558, -3.112, -4.333, -4.858, -3.873, Fisher′s exact test, Fisher′s exact test, χ2=4.574, 9.620; Z=-3.060, -3.850, -3.923, -5.005, -9.495, -7.651, -3.853, -2.725, Fisher′s exact test, Fisher′s exact test, χ2=4.425, 10.169; all P<0.01). The median values of pre-albumin level, albumin level and the albumin to globulin ratio of critical type patients were 85.3 g/L, 28.2 g/L and 0.8, which were all lower than those of common type patients (157.3 g/L, 32.3 g/L and 1.1, respectively) and severe type patients (133.6 g/L, 31.6 g/L and 1.1, respectively), and the differences were statistically significant ( Z=-6.631, -3.647, -4.924, -4.503, -5.283 and -3.903, all P<0.01). The median albumin level of patients with diarrhea was lower than that of patients without diarrhea (28.2 g/L vs. 30.5 g/L), the proportion of diarrhea patients whose TBil level >20.0 to 34.2 μmol/L was higher than that of patients without diarrhea (70.0%, 21/30 vs. 10.9%, 24/221), and the differences were statistically significant ( Z=-2.182, χ2 =62.788; both P<0.05). Conclusions:Anorexia is the most common digestive symptom in COVID-19 patients, and the incidences of abdominal pain is low. The incidence of liver function injury of critical type patients is high. There is no significant correlation between gastrointestinal symptoms and liver function injury, and patients with diarrhea have lower albumin levels.

Progress and ideas of irritable bowel syndrome animal model construction based on combination of disease and syndrome / 中国药理学通报

Establishment of combination of disease and syndrome animal model is an ideal technology platform in TCM research. Currently, many scholars have prepared matching IBS animal models combined typical animal models with etiology, which em-bodies the advantages of syndrome differentiation and promotes the development of combination disease and syndrome animal model. Even though, there still exists some problems about sub-jective evaluation on syndromes, paying more attention on dis-ease and less on syndromes. Therefore, we should deepen the pathogenesis of diseases and TCM syndromes research on animal model replication and improve the method of construction of combination of disease and syndrome animal model through the biological research of combination of disease and syndrome sys-tem. By this way, the idea of preparation animal models will be more mature and the scientific connotation of TCM will be pres-ented more exactly.

Study of optimization for the cream base of benzhydramine hydroehloride / 药学实践杂志

Objective To optimize the cream base of benzhydramine hydroehloride .Methods Five nonionic surfactants as an emulsifier were used to prepare benzhydramine hydroehloride creams .The five sorts of cream were evaluated from the ap-pearance ,preliminary stability ,accelerated test stability and room temperature stability .Results Benzhydramine hydroehloride cream could be prepared using five nonionic surfactants .On appearance of smoothness ,gloss and spread ,formula E was best but formula A was worst ,while formulas B and D were close and worse than formula E only .In the stability tests ,all of creams had no obvious change after the centrifugal experiment and the low temperature experiment .In the high temperature ex-periment ,the formula E was stable ,formulas A ,B and D showed a little appearance change ,and the formula C became layered bleeding .In room temperature ,the formula C became bleeding after five days ,which happened to the formula A after one month ,and formula B after two months .The formulas D and E had no obvious change until six months in room temperature . Conclusion The formulas D and E were stable ,which had clinical application value .

Screening of the Base Formula of Compound Titanium Dioxide Cream / 中国药师

Objective:To screen the optimal base of compound titanium dioxide cream. Methods:Phenyl salicylate and titanium dioxide were respectively combined with 5 kinds of matrices to prepare compound titanium dioxide cream. The properties and stability of compound titanium dioxide cream were studied. Results:The 5 kinds of anionic emulsifiers all could be used to prepare compound titanium dioxide cream. The cream prepared with formula A was thick,and the cream prepared with formula B, C,D and E were delicate,luster and easy to smear. After the centrifugal test and low temperature test,the cream had no obvious changes. After the high temperature test,the cream prepared with formula A and B was dry and rough,the cream prepared with formula D had no significant changes when compared with that stored under room temperature,and the cream prepared with C and E was attenuated and changed into solution. Stored under the room temperature for 12 months,the cream prepared with formula D had no changes in the content and properties. Conclusion:Compound titanium dioxide cream prepared formula D is delicate and easy to smear with good stability,which shows good clinical application value.

Effects of Baoyuan Anticancer Oral Solution on Scavenging of O-2 and DPPH Free Radi-cals / 医药导报

Objective To investigate the scavenging effect of Baoyuan anticancer oral solution on superoxide anion (O-2 ) and 1,1-diphenyl-2-picrylhydrazyl hydrate(DPPH) free radicals. Methods O-2 and DPPH were examined with the ESR (electron spin resonance) spin trapping method. Results The scavenging effect of Baoyuan anticancer oral solution diluted to 50 fold, on O-2 and DPPH free radicals was 81. 32% and 98. 47% , respectively. Conclusion Baoyuan anticancer oral solu-tion has a dose-related effect on free radical elimination.

Determination of Phenyl Salicylate in Compound Titanium Dioxide Cream by HPLC / 中国药师

Objective:To establish a method for the determination of phenyl salicylate in compound titanium dioxide cream. Meth-ods:The HPLC assay was carried out on an Agilent Zorbax SB C18 (250 mm × 4. 6 mm, 5 μm) column with methanol -water (78∶22) as the mobile phase. The sample was detected at 308 nm with a UV detector. The column temperature was set at 25 ℃ and the flow rate was 1. 0 ml·min-1 . Results:Phenyl salicylate could isolate from the other materials by HPLC. The linear range of phenyl salicylate was 59.460-198.200 μg·ml-1(r=0.999 5). The recovery was 101.84% with RSD of 0.64%(n=9). The content of phenyl salicylate in 3 batches of compound titanium dioxide cream was 107. 7%, 107. 5% and 109. 8%, respectively. Conclusion:The method is simple, rapid, exclusive, accurate and sensitive, which is suitable for the determination of phenyl salicylate in com-pound titanium dioxide cream.

EMP3 Overexpression in Primary Breast Carcinomas is not Associated with Epigenetic Aberrations

Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule with important roles in the regulation of apoptosis, differentiation and invasion of cancer cells, but the detailed is largely still unknown. We analyzed the mRNA levels and methylation statuses of EMP3 in 63 primary breast carcinomas and assessed their correlations with clinicopathologic variables. The expression of EMP3 mRNA in primary breast carcinomas was significantly higher than the expression of 20 normal breast tissues (p<10(-7)). EMP3 overexpression in breast carcinomas was significantly related to histological grade III (p=3.9X10(-7)), lymph node metastasis (p= 0.003), and strong Her-2 expression (p=3.3X10(-6)). Hypermethylation frequencies of EMP3 were detected in 36.5% of breast carcinomas by methylation-specific polymerase chain reaction. However, no significant correlations were found between methylation status of EMP3 and mRNA expression levels as well as other clinical parameters. In conclusion, EMP3 may be a novel marker of tumor aggressiveness. Overexpression of EMP3 in primary breast carcinoma is not associated with DNA methylation.

Recent advances in the preparation progress of protein/peptide drug loaded PLA/PLGA microspheres / 药学学报

Sustained release drug delivery from microparticles is an excellent alternative for daily protein/peptide drug administration protocol. Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are the most commonly used polymer carriers in the development of protein/peptide microspheres. Basically there are three preparation methods for PLA/PLGA microspheres: the solvent extraction/evaporation based multiple emulsion (W/O/W emulsion) method, the phase separation method and the spray drying method. The stability of the protein/pipetide loaded, encapsulation efficiency, and the burst effect of the microspheres are key problems usually met in the preparation of microspheres. In this review the preparation techniques and progress in the development of protein/pipetide microspheres which aimed to stabilize protein/peptide structural integrity, keep the bioactivity of drugs, increase the encapsulation efficiency and improve the release profile were summarized and evaluated.

Experimental studies and evaluation on safety of compound aluminum sulfate injection / 中国临床药理学与治疗学

AIM: To study the in situ stimulation effect of compound aluminum sulfate injection after i.m. in rabbit quadriceps and dog bladder. The absorption of aluminum and the healing of the bladder wall were also studied to give an evaluation on the safety of the compound injection. METHODS: Compound aluminum sulfate injection was i.m. injected into quadriceps of the rabbits. The in situ stimulation effect was observed macrographically. Blood samples were collected at different time after i.m. injection. Aluminum concentrations were determined by ICP-MS assay and simulated with DAS software. Tissue necrosis as well as the healing of the bladder wall were observed macrographically or pathologically after the injection was given into dog bladder. RESULTS:Severe stimulation was observed after intra quadriceps injection, however, there was no obvious elevation of blood aluminum concentration. The average AUC0-24 was 2.93±1.82 mg·h·L-1 (n=5), corresponding to a relative bioavailability of about 2.77%. Injecting in bladder muscle necrotized the bladder wall in situ, but fibroblast generated and took place of the necrotized membrane and muscle four weeks after injection. There was no bleeding or perforation on the bladder wall. CONCLUSION:Caused compound aluminum sulfate injection in situ necrosis which healed up in 4 weeks. Aluminum absorption is very low after injection, giving a further explanation to the safety of the compound injection.

Changes of the Function of Platelet and Anticoagulation in Patients with Acute Pancreatitis / 天津医药

Objective:To investigate the clinical value of changes of platelet and anticoagulation function in patients with acute pancreatitis. Methods:β-TG, PF4 ,TXB2 ,GMP-140,antithrombin-Ⅲ,and protein C were measured in all patients. Results:There was no significant difference in all parameters between acute edema pancreatitis group and normal group(P＞0.05).Compared with the control group, parameters of platelet significantly increased in acute necrosis pancreatitis group(P＜0.01),and parameters of anticoagulation significantly decreased(P＜0.01). Conclusion: The platelet system was activated and the level of anticoagulation system decreased in acute necrosis pancreatitis. Parameters are important in understanding and preventing this disease.

Preparation of carboplatin-loaded albumin microsphere and its properties in vitro / 中国药学杂志

To prepare bio-degradable albumin microspheres containing carboplatin. METHODS: Bovin serum albumin microspheres containing carboplatin were prepared by using emulsion-direct heat cross linking techniques. RESULTS: The microsphere was yellow, powdery, with a mean diameter of 58.2 μm. The microphere loaded (11.26±0.48)% carboplatin. The trapping efficiency was (84.5±3.6)%. The pattern of drug releasing from the microspheres in vitro fitted to zero order release plot, with an initial burst in the first 2 hours. The releasing rate can be expressed by the follow equation: Q=21.90+8.50 t (d), r=0.995 8. t50=3 d. Stored at 4 ℃ and 37 ℃ respectively for 3 months, the microspheres did not alter much in shape, size and drug content. CONCLUSIONS: This method is simple, reproducible, having high drug trapping efficiency. The microsphere obtained is stable and release drug at a consistant rate in vitro, leading to a prosperity in clinical use.

Content Determination of Aspirin: Comparison among 3 Calculation Methods / 中国药房

OBJECTIVE: To compare 3 different calculation methods in the determination of aspirin in the bicomponent (aspirin and salicylic acid) system. METHODS: Different concentrations of mixed standard solution of aspirin and salicylic acid were prepared and scanned under a wavelength ranged from 230nm to 350nm. The absorbabilities of the 2 constituents were recorded at 265nm, 295nm and 320.5nm, and the data were treated with Iso-absorption diplo-wavelength method, proximal multiplying factor coefficient method and SA concentration fractional approximate calculation method. The recoveries of aspirin were calculated. RESULTS:The recoveries of aspirin determined by 3 different methods were (99.11?1.68)%, (98.82?1.17) % and (96.23?4.10)%, respectively. CONCLUSION: The proximal multiplying factor coefficient method is stable with little fluctuation in determination results, which proved to be simple while effective for the determination of sample at a great quantity.