In order to get fast approval and market access, innovator pharmaceutical companies usually adopt the most mature and relatively simple formulations for their first generation new drug products. This leaves the opportunities for these products to improve their clinical performance, safety profiles and/or patient adherenceby switching to more sophisticated new formulations, which usually happen around the time when the patents for the new drugs expire. This approach may also work for older drugs. On the other hand, the task of new formulation and process development are more challenging forhigh-technology drug products based on, for examples, various controlled release formulations. In this article, the authors give a discussion regarding the thinking behind initiating the endeavor of new-formulation based development project. Based on the principles of Quality-by-Design, the authors also give a review regarding the trend of using experimental design, statistical and chemometric data analysis and multivariate modeling in formulation and process development. By analyzing examples in the literature, the authors try to demonstrate the advantages of designed studies vs. the traditional univariate methods.

Animals ; Hypertension, Pulmonary ; chemically induced ; physiopathology ; Monocrotaline ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Thrombomodulin ; metabolism

Objective:To combine the detection of serum levels of adenosine deaminase (ADA) and T-cell spot test (T-spot.TB),and to explore their significances in diagnosis of pulmonary tuberculosis.Methods:159 patients suspected with pulmonary tuberculosis were selected and divided into pulmonary tuberculosis group and non-tuberculosis group (n=68);80 healthy people were randonly selected as healthy control group.The serum ADA levels and number of T-spot of the subjects in three groups were detected.Ther serum ADA levels and the positive rates of T-spot.TB in various groups and their sensitivities and specifities were compared. Results:The serum ADA level of the patients in pulmonary tuberculosis gruop was (22.10±6.60)U·L-1;those in non-tuberculosis group and healthy control group were (16.90±6.35)and (8.70±5.98)U·L-1;the serum ADA level in pulmonary tuberculosis group was significantly higher than those in non-tuberculosis group and heathy control group (P<0.05).The positive rate of serum ADA level in diagnosis of pulmonary tuberculosis was 56% and the T-spot.TB positive rate in diagnosis of pulmonary tuberculosis was 87.9%. Combined use of parallel test, the detection sensitivity was 91.2%;using the series of joint tests,the specificity was 94.6%.Conclusion:Combined detection of serum level of ADA and T-spot.TB can significantly improve the clinical diagnosis efficacy of pulmonary tuberculosis.

Seven guaiane-type sesquiterpenoids, a new compound 6-formyl-5-isopropyl-3-hydroxymethyl-7-methyl-1H-indene (1), a new natural product 5-isopropyl-3, 7-dimethyl-1H-indene-1-one (2), along with five known compounds: guaiazulene (3), 4-formyl-7-isopropyl-10-methylazulene (4), sesquiterpene ketolactone (5), alismoxide (6) and guaia-1 (5), 6-diene (7), were isolated from gorgonian Muriceides collaris collected in South China Sea. Their structures were elucidated on the basis of extensive spectroscopic analysis [MS, IR, 1H NMR, 13C NMR (DEPT), HMQC, HMBC, NOESY] and by comparison of the spectral data with those of the literatures.
Animals ; Anthozoa ; chemistry ; Azulenes ; China ; Sesquiterpenes ; chemistry ; isolation & purification ; Sesquiterpenes, Guaiane

Adult ; Endocarditis ; complications ; microbiology ; Female ; Humans ; Pulmonary Embolism ; etiology ; Pulmonary Valve ; microbiology

0.05). Regarding to the grade of irradiation mucositis, the majority of patients in the treatment group were at stage Ⅰ-Ⅱ,while those in the control at stage Ⅲ-Ⅳ(P0.05).No adverse drug reaction was observed in both groups during irradiation process.Conclusion:Actovegin can postpone the development of irradiation oropharyngeal mucositis and decrease the incidence of gradeⅢ and Ⅳmucositis.

Objective To evaluate the effect of convalescent training on patients after special prosthesis replacement in treatment of giant cell tumors. Methods 20 patients with giant cell tumors were treated with convalescent trainings postoperatively,including trainings of muscle strength,joint movement, balance, noumenal sense and gait and were emphasized for earlier training of active muscle contraction. Results According to Enneking score system of bone and muscle postoperation, the lowest for extremitas superior postoperation score of 5 patiens was 20,the highest was 28, the average was 26.6. 4 patiens score was higher than 24, the good rate was 80.0 %.15 patiens extremitas inferior score was from 14 to 27, the average was 21.5, the good rate was 86.7 %. Conclusion Earlier staged joint functional rehabilitation exercise after special prosthesis replacement in treatment of giant cell tumors could prevent ankylosis,improve adhering of capsule,ligament and other soft tissue,and recover the joint function to maximum.

Point Zigong is an empirical point for acupuncture treatment of gynecological diseases. Now it is widely applied to clinical treatment and has a marked therapeutic effect. The therapeutic effect of point Zigong stimulation on gynecological diseases is closely related to the anatomical position, morphostructure specificity and action effect of the acupoint. In the present study on this acupoint, the single acupoint is seldom applied and the mechanism is not completely clear. It is needed to conduct a thoroughstudy in the future.

Objective: To develop a headspace gas chromatography ( HS-GC ) assay for simultaneous determination of dichloroacetic acid ( DCA ) and trichloroacetic acid ( TCA ) in urine. Methods: Urine samples (5 mL) were transferred to a 22 mL headspace bottle, added with 0.5 mL 10% sodium acetate solution , immediately sealed, and shaken evenly. The bottle was placed in the HS-GC system, and equilibrated at 90 ℃ for 60 minutes. The mixture was separated with the HP-INNOWAX chromatographic column, and the DCA and TCA concentrations were detected with the hydrogen flame detector. Results: Under the optimal experimental conditions, the correlation coefficient of DCA and TAC was both > 0.999 0 within the range of 10-500.0 μg/L, and the lowest detection limits of DCA and TAC were 2.0 and 3.5 μg/L, with the spike recovery rate of 87.40% to 101.44%, and relative standard deviations of 1.89% to 3.25%. Of the 35 urine samples sampled from occupational populations, DCA and TCA were not detected. Conclusions The establishment of the HS-GAS assay through addition of sodium acetate and optimization of the headspace conditions, has high recovery and precision, which is effective to meet the requirements for daily determination of DCA and TCA in urine samples.

Objective To explore the indication and the functional advantages of the high-flexion posterior stabilized (PS) rotating-platform mobile-bearing (RP-MB) total knee system. Methods A prospective randomized, controlled trial was performed. Osteoarthritis was the indicators for total knee arthroplasty.From Feb. 2009 to Apr. 2009, 75 patients (94 knees) were randomly assigned to to receive either a highflexion PS, RP-MB total knee system(PFC sigma RPF) or a standard one (PFC sigma RP). There were no statistical difference in the baselines, the preoperative scores of the Hospital for Special Surgery (HSS) and the knee range of motion (ROM) of both groups. The functional status were assessed with Hospital for Special Surgery and the ROM of the knee at the postoperative 1, 6, 12, 18 months. The satisfaction rates were assessed at the postoperative 18 months. The radiographic measurements were t assessed at the postoperative 3days and 3, 6, 12, 18 months. Results A total of 70 participants (87 knees) completed the 18-month followup. At the time of the final follow-up, the average Hospital for Special Surgery knee score was 92.4±5.0points in the standard group and 94.7±7.0 points in the high-flex ion group. The difference was not statistically significant(P ＞0.05). The average maximal flexion was 131.9±14 degrees in the high-flexion group and 123.0±15.3 degrees in the standard group. There was a statistical difference. But it was not enough to confirm our hypothesis that the difference should be higher than 10 degrees. Moreover, the satisfaction rate were 100% in both groups, and no statistical significant difference was found. Conclusion No significant differences were found between standard and high-flexion posterior-stabilized rotating-platform mobile-bearing total knee prostheses in terms of clinical outcomes or range of motion.