Objective: The reverse engineering technology was used to analyze the prescription and process of Good Sense Stay Awake®, the reference listed drug of caffeine tablets, in order to provide guidance for the development of generic caffeine tablets. Methods: Firstly, the prescription information of the reference listed drug was obtained by literature research. Then, quantitative analysis of the composition of the prescription was achieved by the high-performance liquid chromatography with a crystal refractive index detection and the gravimetric analysis method;the particle size of raw and auxiliary materials was analyzed by Raman imaging technology;the crystal habit and crystal form of active pharmaceutical ingredient(API)were characterized by the optical microscope and X-ray powder diffraction technology, respectively;the preparation process of reference listed drug was determined by disintegration method;and finally, the package material was identified by the morpholine reagent. Moreover, three batches of samples were pre-pared according to the determined prescription and process, and the quality was compared with the reference listed drug. Results: By the reverse engineering analysis of the reference listed drug, the prescription composition of the reference listed drug was determined to be composed of glucose, microcrystalline cellulose, pregelatinized starch, maltodextrin, magnesium stearate, colloidal silica and yellow lake, in which the glucose content was 32% and the microcrystalline cellulose content was <23%. The API crystal form of the reference listed drug was consistent with that of the self-made preparation. The average particle size of caffeine, microcrystalline cellulose, glucose, maltodextrin and pregelatinized starch was approximately 206, 112, 172 and 61 μm, respectively. The tablet preparation process was the direct compression method, and the packaging material was polyvinyl chloride aluminum foil. The quality of the three batches of home-made preparations was the same as that of the reference listed drug. Conclusion: Caffeine tablets with the same quality as Good Sense Stay Awake® were successfully prepared by reverse engineering of the reference listed drug, which provides a reference for the application of reverse engineering in the generic drug development and consistency evaluation.

There are two ways for marketing Over The Counter(OTC)drugs in the US: the OTC monographs and new drug application/simple application(NDA/ANDA) review procedures. New products that meet the final monograph can be marketed without FDA approval, but the reference preparations and standard preparations are not searchable in the FDA database, so the reference preparation cannot be determined for such products generally. For the convenience of finding out and confirming the US non-prescription generic reference preparation, this paper introduces the US OTC drug review procedure and inquiry method, taking the US OTC product caffeine tablet as an example to show how to determine the US OTC generic drug reference preparations, so as to provide a reference for the selection of reference preparations in the consistency evaluation of generic drugs in China.

Biopsy ; Histological Techniques ; instrumentation ; methods ; Humans ; Indicators and Reagents ; Paraffin Embedding ; Ultrasonics

Objective To study the prevalence rate and influential factors of diabetes among residents aged over 15 in Hubei province to provide evidences for diabetes control .Methods Through stratified cluster sampling ,20 cities and counties ,including 100 blocks and towns ,200 communities and villages were sampled .Household survey was carried out from October to November , 2013 .Data was analyzed with SPSS18 .0 .Results In total ,28 555 eligible residents were surveyed ,among which 823 (2 .88% ) self‐reported being diagnosed as diabetes .The prevalence rate for urban and rural residents were found as 4 .37% and 1 .83% respective‐ly ,that of male and female as 2 .61% and 3 .13% respectively .Residents aged 65 and above reported highest prevalence rate (6 .61% ) while those from 25 to 34 years old had the lowest (0 .06% ) .Multiple logistic regression analysis yielded results that ru‐ral‐urban residence ,age ,occupational status ,type of medical insurance ,alcohol drinking and obesity were influential factors of diabe‐tes .Conclusion Prevalence rate of diabetes among residents aged over 15 in Hubei province was at a relatively lower level and there were differences between population subgroups .

Objective To evaluate the effect of pulmonary function test on infants with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Forty-eight patients were divided into two groups based on physical examination. Pulmonary function were measured in 48 patients. Age-matched healthy infants were enrolled as controls. The parameters included ratio of volume to PEF to total expiratory volume(VPTEF/VE,tPTEF/tE),inspiratory time/expiratory time(TI/tE),inspiratory time/total respiratory time(TI/Ttot),ratio of 50% of the tital inspiratory flow to tital volume(TIF_ 50 /V_T),mean inspiratory flow(V_T/TI),function capacity(FRCp),resistance effective(Reff).Results TI/Ttot,ratio of 50% of the tital expiratory flow to 50% of the tital inspiratory flow(TEF_ 50 /TIF_ 50 ),FRCp,Reff were significantly higher in patients compared with controls(P

Objective To analyze the impact of multiple factors on the incidence of pneumothorax associated with CT-guided transthoracic needle aspiration biopsy.Methods The sign of pneumothorax after 162 cases(lesion diameter from 1cm to 6cm)CT-guided transthoracic needle aspiration biopsy was observed and its relationship with multivariate factors were analyzed by multivariate logistic regression model.Results Thirty-two cases presented pneumothorax accounting for 19.8%.Single variate analysis showed that the sign of pneumothorax ralated to intercurrent COPD,distance from lesion and chest wall,needle dwelling time and lesion diameter.67 patients of intercurrent COPD with postoperative pneumothorax occurred in 22 cases (32.8%);With respect to those having lesions close to the chest wall(48 cases),and the cases with the distance between the chest wall and lesions less than 2cm(55 cases)and greater than 2cm(59 cases), the postoperative pneumothorax occurred in 0,14(25.5%),18(30.5%)cases respectively;For those patients with needle in the chest residence time of less than 10 minutes(82 cases),10—20 minutes (51 cases),more than 20 minutes(28 cases)after the occurrence of pneumothorax were 8(9.6%), 10(19.6%),14(50%)cases respectively;In contrast,those with lesion diameter less than 2 cm (65 cases),2—4cm(52 cases),more than 4cm(45 cases)were 19(29.2%),8(15.4%) and 5(11.1%)respectively.The multivariate logistic regression analysis showed that the prior three factors were risk factors of pneumothorax(OR=4.652,4.030,2.855 respectively).Conclusions To avoid the pneumothorax,caution must be taken with respect to CT-guided transthoracic needle aspiration biopsy, patients with intercurrent COPD,long distance between lesion and chest wall,and smaller lesion diameter. For operation the needle dwell time within thorax should be minimized.

Objective To study the changes and significance of serum beta 2-microglobulin(?2-MG),cytocine interleukin-2(IL-2) in the clinical progress of childhood idiopathic thrombocytopenic purpura(ITP).Methods One hundred and ten patients of childhood ITP were chosen for the test group(70 cases of primary ITP and 40 cases of recurrent ITP),and 110 normal children for the control group.Levels of serum ?2-MG and IL-2 were determined by radioimmunoassay kit and analysed with two sample t-test.Results Among the patients,the serum IL-2 levels were significantly lower and serum ?2-MG levels were significantly higher than those in control group(P0.05).Conclusion Determining serum IL-2 and ?2-MG levels has important significance to reflect the progress of disease and direct treatment.

α-Hederagenin (H), derived from Hedera nepalensis var.sinensis, is a pentacyclic oleane-type triterpenoid that exhibits clear cytotoxicity to different tumor cell lines.In this study,a series of novel C-28 derivatives of hederagenin (H) were designed and synthesized in attempt to develop potent tumor resistance reverse activities agents. Previous research showed that H6 displayed robust reverse activity for paclitaxel resistance in KBV cells. Importantly, Co-treatment of paclitaxel with H6 significantly reduced the tumor weight to 42%. Pleasingly, H6 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice.Mechanism studies had found that H6 activated permeability glycoprotein(P-gp)ATPase,reduced intracellular ATP levels and inhibited efflux of P-gp substrates,thus enhancing the antitumor activity of paclitaxel on KBV cells.Molecular docking analysis of homology P-gp and H6 then conducted using the Surflex-Dock module.H6 showed a high binding affinity docking score with a total score of 5.4148,much higher than that of H(0.1414).The nov-el C-28 derivatives of H was synthesized from H6 via three-step reaction. The reversal activity of all synthesized H derivatives were tested using the MTT assay.The results showed that the derivatives of nitrogen groups at C-28 displayed same even potent activity than parent compound H6.In addition,its underlying mechanism of action and in vivo activity are in explore.

The efficient and safe delivery of drugs to the therapeutic site through the biofilm has traditionally been a difficult and hot topic in the field of drug delivery. In recent years, alkyl polyglycoside (APG) have become ideal penetration enhancers for drug delivery systems because of their high permeability, good safety and biodegradability, which has attracted wide attention of domestic and foreign researchers. In this paper, the physical and chemical properties, characteristics, action mechanism and application of APG in drug delivery system are reviewed, and its application prospect in drug delivery system is prospected.

To explore the mechanism of the absorption enhancement of borneol, the effect of borneol on the intestinal absorption and the pharmacokinetics of tetramethylpyrazine phosphate after oral administration were investigated. In situ intestinal recirculation was performed to study the effect of various concentrations of borneol on the absorption of tetramethylpyrazine phosphate at duodenum, jejunum, ileum and colon. After oral administration of tetramethylpyrazine phosphate, the mixture of tetramethylpyrazine phosphate and borneol and the mixture of tetramethylpyrazine phosphate and verapamil in rats, the concentrations of tetramethylpyrazine phosphate in plasma were determined by RP-HPLC at predesigned time. The pharmacokinetic parameters were compared based on the results of the three animal experiments, and analyzed with software program 3p97. The result showed that tetramethylpyrazine phosphate could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: colon > duodenum > jejunum > ileum, but without saturation, which demonstrated that tetramethylpyrazine phosphate was absorbed via simple diffusion. Borneol could enhance the intestinal absorption of tetramethylpyrazine phosphate, however, not in proportion. There was no obvious difference between the test group and the control group when 10 microg x mL(-1) borneol was added (P > 0.05), while when the concentration comes to 25 microg x mL(-1) and 50 microg x mL(-1), significant differences were observed (P < 0.05). Borneol and verapamil did enhance the bioavailability of tetramethylpyrazine phosphate after oral administration in rats. The enhancing effect of borneol showed only when the concentration came to a certain level but with no specific sites existed in the intestine. One of the mechanisms of borneol on the enhancing effect on absorption of tetramethylpyrazine phosphate might be the inhibition of the metabolism of CYP 3A and exocytosis of P-gp.
Animals ; Biological Availability ; Bornanes ; pharmacokinetics ; Herb-Drug Interactions ; Intestinal Absorption ; drug effects ; Male ; Pyrazines ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley