Preparation and Characterization of Silymarin Synchronized and Sustained Release Dropping Pill.

PURPOSE: This study aimed to develop a synchronized and sustained-release silymarin dropping pill, and to evaluate its pharmacokinetic characteristics. METHOD: Polyoxyethylene stearate, glyceryl monostearate, and stearic acid were used to prepare the dropping pills. X-ray powder diffraction, differential scanning calorimetry, and release were used to evaluate its physicochemical properties. The plasma concentration of silybin in beagle dogs after oral administration of silymarin dropping pills and silymarin capsule was determined by RP-HPLC. RESULTS: Synchronized release was achieved with high similarity factor f2 values between every set of two of the five components. Mean plasma concentration-time curves of silymarin after oral administration of dropping pills in beagle dogs were in accordance with first-order absorption and open twocompartment model. The Tmax, Cmax, and AUC0-∞ of dropping pills in beagle dogs were 0.8750±0.13 h, 0.8183±0.07 µg·ml-1, and 2.274±0.90 µg·h·ml-1, respectively. Silymarin dropping pills prolonged in vivo exposure and reduced maximum in vivo concentration, achieving a stable level in the serum. CONCLUSION: The combination of solid dispersion technique and dropping pill formulation allowed synchronized release of multiple components in herbal medicine, and has potential application in the development of sustained release in herbal medicine.

Preparation and characterization of silymarin synchronized-release microporous osmotic pump tablets.

The pharmacological activity of herbal medicine is an overall action of each component in accordance with their original proportion. An efficient, sustained, and controlled-release drug delivery system of herbal medicine should ensure the synchronized drug release of each active component during the entire release procedure. In this study, silymarin (SM), a poorly soluble herbal medicine, was selected as a model drug to develop a synchronized-release drug delivery system: an SM microporous osmotic pump (MPOP) tablet. The SM was conjugated with phospholipid (SM phytosome complex, SM-PC) to improve the solubility, and the difference in the apparent octanol-water partition coefficient between the two components was significantly reduced. The dissolution rate of SM-PC was significantly higher than SM active pharmaceutical ingredients and was the same as that of the commercial SM capsule. The SM-PC was used to generate the MPOP tablet. SM was mixed with poly(ethylene) oxide and sodium chloride (an osmotic agent) to form the MPOP core, followed by coating with cellulose acetate and poly(ethylene) oxide to generate the SM MPOP. The results demonstrated that SM MPOP could synchronically and sustainably release the five active components within 12 hours (the similar coefficient f 2 between two components was >65), and the average cumulative release rate was 85%. Fitting of the drug-release curve showed a zero-order release profile for SM MPOP. Our study showed that the phytosome complex technique combined with the MPOP system will achieve synchronized release of the various active components of herbal medicine and have potential applications in developing sustained release preparations in herbal medicine.

Etiology and outcomes of acute kidney injury in Chinese children: a prospective multicentre investigation.

BACKGROUND: The incidence of AKI appears to have increasing trend. Up to now, prospective, multi-center, large-sample epidemiological study done on pediatric AKI on aspects of epidemiological characteristics, causes and outcomes have not reported. It is necessary to develop prospective, multi-center, large-sample epidemiological study in our country on pediatric AKI. The aim of this study was to determine the clinical features, etiology, and outcomes of acute kidney injury (AKI) in Chinese children. METHOD: Paediatric patients (≤18 years old) admitted to 27 hospitals (14 children's hospitals and 13 general hospitals) affiliated with the Medical University were investigated. AKI was defined using the 2005 Acute Kidney Injury Network criteria. RESULTS: During the study period, 388,736 paediatric patients were admitted. From this total, AKI was diagnosed in 1,257 patients, 43 of whom died. The incidence and mortality of AKI was 0.32% and 3.4% respectively. The mean (± SD) age of patients was 48.4 ± 50.4 months. Among the 1,257 AKI paediatric patients, 632 were less than one year old. Among the AKI paediatric patients, 615 (48.9%) were in stage 1, 277 (22.0%) in stage 2, and 365 (29.0%) in stage 3. The most common causes of AKI were renal causes (57.52%), whereas postrenal (25.69%) and prerenal (14.96%) causes were the least common. The three most common causes of AKI according to individual etiological disease were urolithiasis (22.35%), of which exposure to melamine-contaminated milk accounted for the highest incidence (63.7%); acute glomerulonephritis (10.10%); and severe dehydration (7.48%). A total of 43 AKI patients (3.4%) died during their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis. CONCLUSION: Primary renal diseases are a major risk factor for paediatric AKI in China. In terms of specific etiological disease, urolithiasis (postrenal disease) was the leading cause of paediatric AKI in 2008, when the disease was linked to exposure to melamine-contaminated milk. Sepsis is the leading cause of death in Chinese paediatric AKI patients. Future studies should focus on effective ways of controlling renal disorders and sepsis to improve the clinical management of paediatric AKI in China.

The potential use of allogeneic platelet-rich plasma for large bone defect treatment: immunogenicity and defect healing efficacy.

Autologous platelet-rich plasma (PRP) has been extensively investigated for large bone defect treatment, but its clinical application is harassed by controversial outcome, due to highly variable PRP quality among patients. Alternatively, allogeneic PRP from well-characterized donors cannot only generate more consistent and reliable therapeutic effect but also avoid harvesting large quantities of blood, an additional health burdens to patients. However, the use of allogeneic PRP for bone defect treatment is generally less investigated, especially for its immunogenicity in such application. Here, we meticulously investigated the immunogenicity of allogeneic PRP and evaluated its healing efficacy for critical-sized defect treatment. Allogeneic PRP contained 4.1-fold and 2.7- to 4.9-fold higher amount of platelets and growth factors than whole blood, respectively. The intramuscular injection of allogeneic PRP to rabbits did not trigger severe and chronic immunoresponse, evidenced by little change in muscular tissue microstructure and CD4⁺/CD8⁺ T lymphocyte subpopulation in peripheral blood. The implantation of allogeneic PRP/deproteinized bone matrix (DPB) constructs (PRP+DPB) successfully bridged 1.5-cm segmental radial defects in rabbits, achieving similar healing capacity as autologous MSC/DPB constructs (MSC+DPB), with greater bone formation (1.1-1.5×, p<0.05) and vascularization (1.3-1.6×, p<0.05) than DPB alone, shown by histomorphometric analysis, bone mineral density measurement, and radionuclide bone imaging. Furthermore, the implantation of both allogeneic PRP- and autologous MSC-mediated DPB constructs (PRP + MSC + DPB) resulted in the most robust bone regeneration (1.2-2.1×, p<0.05) and vascularization (1.3-2.0×, p<0.05) than others (PRP+DPB, MSC+DPB, or DPB alone). This study has demonstrated the promising use of allogeneic PRP for bone defect treatment with negligible immunogenicity, great healing efficacy, potentially more consistent quality, and no additional health burden to patients; additionally, the synergetic enhancing effect found between allogeneic PRP and autologous MSCs may shed a light on developing new therapeutic strategies for large bone defect treatment.

[Preliminary analysis of urinary proteomics in children with steroid-resistant and steroid-sensitive nephrotic syndrome].

OBJECTIVE: To study and identify the protein markers in the urine of children with steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome(SRNS). METHODS: Total urinary proteins were extracted from children with SSNS before and after steroid therapy, SRNS, and healthy children (n=5 in each group). Urinary proteins were separated by immobilized pH gradient based on two-dimensional gel electrophoresis (2-DE). The silver-stained 2-DE gels were scanned with digital Image Scanner and analyzed with Image Master 2-DE Elite 3.01 software. Peptide mass fingerprint (PMF) of differential protein spots was obtained with MALDI-TOF-MS. Proteins were identified by Mascot software based on NCBI protein database. RESULTS: There were 66 spots with different expression of protein between SRNS children and SSNS children before steroid therapy, and 24 spots and 27 spots only occurred in SRNS children and SSNS children before steroid therapy, respectively. There were 75 spots with different expression of protein between SSNS children after steroid therapy and healthy controls, and 11 spots only occurred in SSNS children after steroid therapy. Eighteen protein spots with different expression (6 spots in each nephrotic group) were chose and analyzed by MALDI-TOF-MS, and 9 types of proteins were identified. CONCLUSIONS: Nine types of urinary proteins with different expression (6 spots in each nephrotic group) were identified between SRNS and SSNS children, and they might be the biomarkers for SRNS or SSNS.

[Observation of an injectable tissue-engineered bone constructed with autologous platelet-rich plasma and bone marrow stromal cells].

OBJECTIVE: To construct an injectable tissue-engineered bone graft with fibrin glue (FG), autologous platelet-rich plasma (PRP) and bone marrow stromal cells (BMSCs) cultured in vitro and study its biological characteristics and microscopic structures. METHODS: BMSCs isolated from rabbit iliac bone marrow were culture-expanded in vitro. The injectable tissue-engineered bone constructed from autologous PRP, FG, and BMSCs was cultured in vitro, and its biological characteristics were observed including the time of gel formation, histological features, seed cell survival and microscopic structures. RESULTS: The constructed injectable tissue-engineered bone began gel formation within 20 to 30 s, and after a week-long culture, the gelatine began to degrade, and numerous well viable fusiform cells could be seen to adhere to the bottom of the Petri dish. Scanning electron microscopy identified globular and olivary cells embedded in the fibrin glue, and numerous small particles could be seen around of the cells. CONCLUSION: Construction of an injectable tissue-engineered bone graft with FG, BMSCs and PRP does not require sophisticated techniques and ensures good biological property of the bone graft that can be easily shaped and allow good growth of the seed cells, suggesting great potential of this technique for clinical use.