[Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules].

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

Discriminating Lamiophlomis rotata According to Geographical Origin by (1)H-NMR Spectroscopy and Multivariate Analysis.

INTRODUCTION: Lamiophlomis rotata (Duyiwei) is a folk herbal medicine that traditionally has been used in China as a hemostatic agent. Raw plant materials used for medicinal products from different geographical regions are often inconsistent in chemical composition. Metabolic fingerprinting provides a new approach for distinguishing the geographical origins of L. rotata. OBJECTIVE: To identify metabolites that contribute to the different geographical regions of L. rotata samples. METHODS: Lamiophlomis rotata metabolomics were performed by (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses. The L. rotata metabolic profile was prepared for NMR measurements using methanol-d4 solvent. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to analyse the L. rotata (1)H-NMR spectroscopy data. RESULTS: Nine iridoid glycosides, one flavonoid and three phenylpropanoid glycosides were detected in L. rotata by (1)H-NMR spectroscopy. (1)H-NMR measurements and multivariate analysis were used to successfully discriminate samples from three different locations. CONCLUSION: The NMR-based analysis of L. rotata is a more comprehensive approach than traditional chromatographic methods. Simple sample preparation, rapidity and reproducibility of are additional advantages of NMR analysis.

Risk factors for surgery and postoperative recurrence: analysis of a south China cohort with Crohn's disease.

BACKGROUND AND AIMS: To investigate the risk factors for primary surgery and postoperative recurrence in a cohort of Chinese Crohn's disease (CD) patients. METHODS: Medical notes of consecutive diagnosed patients from 2003 until 2010 were reviewed. Fifty-seven postoperative patients--finished regular follow-up--were recruited for postoperative recurrence analysis. RESULTS: One hundred eleven of 323 (34.4%) patients of this cohort underwent primary surgery. The cumulative frequency of resection was 16.6%, 35.4%, 53%, and 94.5% for 1, 5, 10, and 30 years, respectively, after onset of disease. Male (OR: 1.994; 95% CI: 1.291-3.078, p = 0.002), stricture (OR: 4.832; 95% CI: 3.064-7.621, p = 0.000), or penetrating (OR: 4.923; 95% CI: 3.060-7.919, p = 0.000) were associated with an increased risk for primary surgery, while early use of immunomodulators was (OR: 0.438; 95% CI: 0.218-0.880, p = 0.020) associated with a decreased risk. Fifty-seven (21.1%) patients were diagnosed as postoperative clinical recurrence and the cumulative recurrence rates were 6.1%, 17.1%, and 36.8% for 1, 2, and 3 years, respectively. Perianal disease was associated with an increased risk for clinical recurrence (OR: 5.606; 95% CI: 1.59-19.766, p = 0.007). CONCLUSIONS: The operation frequency is high in CD. Male, penetrating, and stricture diseases are associated with an increased risk for primary surgery while early use of immunomodulators is associated with a decreased risk. The postoperative recurrence rate is also high. Patients with perianal disease are at higher risk for clinical recurrence.

In vitro Preparation and Evaluation of Sustained-Release Microcapsules of Salvianolic Acid.

OBJECTIVE: This study aims to investigate the preparation of sustained-release microcapsules of salvianolic acid. METHODS: The stability of salvianolic acid microcapsules was improved, and the time of action was prolonged in the present study. This was prepared using the spray-drying method, with chitosan as the carrier. In the preparation process, the prescription and process were optimized by L9 (34) using an orthogonal design, with yield and drug loading as indexes, in order to obtain optimum conditions. RESULTS: The optimal process and prescription for the preparation of salvianolic acid microcapsules were found to be as follows: mass concentration of chitosan, 1.5%; mass ratio of salvianolic acid to chitosan, 1:3; inlet air temperature, 190°C; and peristaltic pump speed, 300 mL·h-1. The surface of the microcapsules was round, the drug loading was 25.99% ± 2.14%, the yield was 51.88% ± 2.84%, the entrapment efficiency was 86.21% ± 2.89%, and the average particle size was 105.6 ± 2.56 nm. The microcapsules in vitro had certain sustained release characteristics. The internally fitted first-order release model equation was ln(1-Q) = -0.236 t + 4.591 7, r = 0.920. In addition, the results of differential scanning calorimetry show that the properties of salvianolic acid were not changed by the microcapsules. CONCLUSION: Sustained-release microcapsules of salvianolic acid can be successfully prepared by adopting marine polysaccharide as a carrier.

[Over one year follow-up report for newly diagnosed pediatric Crohn's disease].

OBJECTIVE: To explore the clinical characteristics, therapeutic responses and outcomes of pediatric Crohn's disease (CD). METHODS: From a hospital-derived incidence cohort, 20 Crohn's disease patients (aged 0.5 - 15 years old at diagnosis), diagnosed from 2003 to 2009, received a follow-up period of more than one year. The patients were phenotyped according to Montreal standards. PCDAI was introduced to assess the disease activity and the Hyams J rules adopted to evaluate the therapeutic efficacies. The treatment was individualized based on the overall evaluation of child. RESULTS: Of these 20 patients, 55% were 7 - 12 years old at the diagnosis time. The male: female ratio was 1.5:1. At the time of diagnosis, the common manifestations included abdominal pain (95.0%), fever (80.0%) and diarrhea (80.0%). Growth retardation was detected in 50% of the cases. Complicated behavior was observed in 45% patients at diagnosis. The most frequent disease location at diagnosis was terminal ileum/colon (55%). Upper GI tract involvement was quite common in children (20%). Non-penetrating non-stricture (50%) behavior was most frequent at diagnosis. Ultimately, corticosteroids plus 6-MP/AZA treatment was administrated in 11 cases. Of these, 9 (82%) successfully withdrew the corticosteroids and maintained a complete remission. Colonoscopy was repeated in 6 complete remission cases and 4 of them achieved a complete mucosa healing. The mean follow-up period was 23 months (range: 12 - 59). At the endpoint of follow-up, 15 cases achieved a complete remission, 4 had a partial remission, 1 underwent operation and none of them died. The children who successfully withdrew from corticosteroids and achieved a complete remission could catch up the height of their age group. 6-MP/AZA associated severe adverse effects were reported at 17% in this group. CONCLUSION: Growth retardation is predominant in pediatric CD and it may provide diagnostic clues. Immunosuppressant therapy may improve the natural history of this disease. It is safe under close monitoring.

[Design, optimization and quality evaluation of curcumin self-emulsifying drug delivery system (SEDDS)].

OBJECTIVE: To develop the self-emulsifying drug delivery system (SEDDS) of curcumin, and evaluate its quality in vitro. METHODS: The excipients of curcumin SEDDS were selected via its solubility study in various oils, surfactants and co-surfactants and the formulation was optimized using ternary phase diagram study and central composite design-response surface methodology (oil, surfactant and co-surfactant percentages as factors; solubility, droplet size, polydispersity index and emulsifying time as responses). The appearance, droplet size and polydispersity index after emulsifying and the emulsifying time of optimized curcumin SEDDS were studied. The solubility of curcumin in the solution of SEDDS was determined. RESULTS: Castor oil-(tween-80) -ethanol = 28: 55: 20 (w/ w/w) was selected for optimum curcumin SEDDS. The droplet size was 222. 2 nm, polydispersity index was 0. 171. The time of self-emulsifying was 10 s and the solubility of curcumin in SEDDS was 1.93 mg/mL. CONCLUSION: Curcumin SEDDS formulation is selected and optimized successfully, and the preparation of curcumin SEDDS is simple, the quality is stable.

[Risk factors for initial bowel resection and postoperative recurrence in patients with Crohn disease].

OBJECTIVE: To investigate the risk factors for the initial bowel resection and postoperative recurrence in a cohort of patients with Crohn disease(CD). METHODS: A total of 216 consecutive patients who were regularly followed up in the Department of Gastroenterology at the First Affiliated Hospital of Sun Yat-sen University between 2003 and 2009 were included. Probabilities for initial intestinal resection were calculated with Kaplan-Meier method. The influence of concomitant covariates on the cumulative probability rates was examined using Cox proportional hazard model. The risk of postoperative recurrence, including endoscopic recurrence, clinical recurrence and surgical recurrence, was also investigated during the follow-up. Logistic analysis was performed for the risk factors of recurrence. RESULTS: The median follow-up was 55 months. A total of 44 patients(20.4%) underwent bowel resection. The cumulative frequency of surgery was 11%, 25%, and 45% at 1, 5, and 10 years after initial onset. Multivariate analyses showed that age at diagnosis and disease behavior were independent risk factors for initial intestinal resection(P<0.05). All but 4 patients had complete follow-up after the surgery with a median duration of 20.4 months. Endoscopic recurrence rate was 52.6% within 1 year, and clinical recurrence rate was 22.5%. Median time to clinical recurrence was 22.6 months. Multivariate analyses showed that perianal disease was the only independent risk factor for clinical recurrence(P<0.05). During the follow-up 2 patients(5%) underwent further operation and both had the same indications for the reoperation as that for the initial surgery. CONCLUSIONS: Patients with CD have a high frequency of surgery and the postoperative recurrent rate is also high. Age at diagnosis and disease behavior are associated with the probability of initial surgery. The presence of perianal disease is associated with a higher risk of clinical recurrence.

[Comparison of the pathogenesis of liver fibrosis induced by pig serum exposure and bile duct ligation in rats].

OBJECTIVE: To observe the occurrence and progression of liver fibrosis induced by pig serum exposure and bile duct ligation, and analyze the relationship between hepatic inflammation and liver fibrosis. METHODS: Chronically immune-mediated liver fibrosis was induced in rats by weekly injection of pig serum (IPS) into the peritoneal cavity at 3 ml/kg for 12 weeks. Cholestatic fibrosis was induced by common bile duct ligation (BDL). The Knodell score was used to evaluate the histological changes in the liver, and immunohistochemistry was performed using anti-SMA, anti-ED1, anti-CK7, and anti-CD45 antibodies. Quantitative real time PCR (qPCR) analysis was employed to quantify the mRNA expression of the genes related to inflammation, including interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), transforming growth factor-beta, platelet-derived growth factor A, as well as the genes associated with fibrogenesis, namely collagen 1, alphaSMA, MMP-9 and TIMP-1. RESULTS: Knodell scores for periportal necrosis, intralobular degeneration and focal necrosis, and portal inflammation were all significantly higher in the BDL group than in the IPS group (P<0.01), whereas the scores for fibrosis was higher in the IPS group (P<0.05). Immunohistochemistry showed obvious inflammation with numerous alphaSMA-positive cells in the liver of the rats in BDL group; the liver of the rats in IPS group showed numerous alphaSMA-positive myofibroblasts with limited inflammatory cell infiltration. qPCR demonstrated a significant up-regulation of the genes related to extracellular matrix remodeling such as collagen 1 (P<0.01), alphaSMA (P<0.01), MMP-9 (P<0.01) and TIMP-1 (P<0.01) in the rat liver in IPS group compared with those in the normal control group, and the mRNA expressions of the inflammation-related cytokines, except for RANTES, were comparable with those in the control. In contrast, the BDL group showed a significant up-regulation of all the pro-inflammatory genes examined with also increased expression of the fibrogenesis-related genes (P<0.05). CONCLUSION: Liver fibrosis induced by IPS is characterized by active ECM remodeling in the absence of obvious inflammation, indicating that chronic development of liver fibrosis can be independent of active hepatic inflammation. BDL-induced liver fibrosis highlights obvious inflammation and fibrous proliferation in the liver.