Total paeony glycoside (TPG) is extracted and purified from a traditional Chinese herbal medicine. It has many biological and pharmacological activities. However, there are few dosage forms of TPG in the market because of its low bioavailability. Self-microemulsifying drug delivery system (SMEDDS) is a vital tool in solving low bioavailability of poor absorption drugs. So the objective of this study is to develop a new TPG-SMEDDS for the oral delivery of poorly soluble TPG. Through the construction of pseudo-ternary phase diagrams, the optimum prescription was obtained, which consisted of 18.70% TPG, 16.27% ethyl oleate as oil, 43.34% Cremophor RH40 as surfactant and 21.73% Transcutol P as cosurfactant. The characterizations of TPG-SMEDDS including morphological characterization, droplet size, zeta-potential, emulsification time, and dissolution study of TPG-SMEDDS were evaluated. The results showed that TPG-SMEDDS is stable and its release rate is high in four different media (0.1 mol x L(-1) HCl, pH 6.8 PBS, pH 7.4 PBS, and water). The relative bioavailability of SMEDDS was dramatically enhanced in an average of 1.52-fold that of TPG-suspension. It is concluded that the bioavailability of TPG is enhanced greatly by SMEDDS.
Administration, Oral ; Animals ; Biological Availability ; Drug Delivery Systems ; Drug Stability ; Emulsions ; Ethylene Glycols ; chemistry ; Glycosides ; administration & dosage ; chemistry ; isolation & purification ; pharmacokinetics ; Oleic Acids ; chemistry ; Paeonia ; chemistry ; Particle Size ; Pharmaceutical Vehicles ; chemistry ; Plants, Medicinal ; chemistry ; Polyethylene Glycols ; chemistry ; Rats ; Solubility

OBJECTIVETo prepare the quercetin self-emulsified formulation and evaluate its quality.

METHODThe quercetin self-emulsified formulation was optimized based on the quercetin solubility in different oils, and the self-microemulsified efficiency of various combinations of emulsifier and co-emulsifier evaluated using the pseudo-ternary phase diagram. The microemulsion of morphology, size and zeta potential were examined. The quercetin of solubility in self-emulsified system was tested and the formulation stability was investigated by accelerated experiment.

RESULTThe blank self-emulsified system was composed of ethyl oleate/Cremophor EUL/butanol with weight ratio of 10: 54: 36. After being dilutied with water, the morphology of microemulsion was homogeneous small spherical drops observed under the electro-microscopy. The particle size and the zeta potential were 16.3 +/- 4.6 nm and 2.1 +/- 0.8 mV, respectively. The solubility of quercetin in self-emulsifing system was (62.42 +/- 0.11) mg x mL(-1), increased 2 229 folds compared with that of in water. The quality of quercetin self-emulsified formulation was stable during the 3 months storage at 40 degrees C.

CONCLUSIONThe solubility of quercetin is significantly increased in self-emulsified system and the formulation is stable and easy to prepare.

Antioxidants ; administration & dosage ; chemistry ; Butanols ; chemistry ; Chromatography, High Pressure Liquid ; Drug Delivery Systems ; Drug Stability ; Emulsions ; Glycerol ; analogs & derivatives ; chemistry ; Oleic Acids ; chemistry ; Particle Size ; Quercetin ; administration & dosage ; chemistry ; Solubility ; Solvents ; Technology, Pharmaceutical ; methods

OBJECTIVETo investigate the intervention and mechanism of ambroxol combined with low-dose heparin on oxidative stress, TNF-alpha and IL-1beta in rabbits with acute lung injury (ALI).

METHODSTwenty-four healthy Japanese rabbits were randomly divided into three groups: (1) Normal saline control group (NC), (2) Oleic acid injury group (OA), (3) Ambroxol + low-dose heparin therapy group (AH). After the success of ALI model, AH group was injected ambroxol + low-dose heparin, while the NC group and OA group were injected the same dose of normal saline by the same method. Arterial oxygen tension (PaO2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) at different time points were determined. The pathological manifestation of both side lungs was observed at the end of expeiment. The activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), xanthine oxidase (XO) and the content of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenate were tested. The apoptosis index was detected. The lung wet/dry (W/D) ratio was calculated. The pathological changes in lung tissue were observed by light microscopy, and the ultrastructural changes of lung tissue were observed by electron microscopy.

RESULTS(1) The instructive injury induced by ALI observed under electron microscope and light microscope and W/D was decreased significantly in AH group. (2) PaO2 was improved significantly in AH group, compared with that in OA group (P < 0.01). (3) The activity of GSH-Px and SOD in AH group increased significantly (P < 0.01 or P < 0.05) but the activity of XO and the content of MDA decreased significantly (P < 0.01), compared with those in OA group. (4) Except the content of IL-1beta in serum before treatment, the content of IL-1beta and TNF-alpha in serum, BALF, lung tissue homogenate of OA group increased significantly (P < 0.01), and those were obviously improved in AH group. (5) Apoptosis index (AI) in AH group decreased significantly (P < 0.01) compared with that in OA group.

CONCLUSIONIn ALI induced by OA, IL-1beta and TNF-alpha increases significantly and involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin can reduce lung cells oxidative stress to inhibit the release of IL-1beta and TNF-alpha, which play a role in the treatment of ALI.

Acute Lung Injury ; chemically induced ; drug therapy ; metabolism ; Ambroxol ; therapeutic use ; Animals ; Drug Therapy, Combination ; Female ; Heparin ; administration & dosage ; Interleukin-1beta ; metabolism ; Male ; Oleic Acids ; Oxidative Stress ; drug effects ; Rabbits ; Tumor Necrosis Factor-alpha ; metabolism

This study aimed to investigate the antibody responses in mice immunized with Gnathostoma spinigerum crude antigen (GsAg) incorporated with the combined adjuvant, a synthetic oligonucleotide containing unmethylated CpG motif (CpG ODN 1826) and a stable water in oil emulsion (Montanide ISA720). Mice immunized with GsAg and combined adjuvant produced all antibody classes and subclasses to GsAg except IgA. IgG2a/2b/3 but not IgG1 subclasses were enhanced by immunization with CpG ODN 1826 when compared with the control groups immunized with non-CpG ODN and Montanide ISA or only with Montanide ISA, suggesting a biased induction of a Th1-type response by CpG ODN. After challenge infection with live G. spinigerum larvae, the levels of IgG2a/2b/3 antibody subclasses decreased immediately and continuously, while the IgG1 subclass remained at high levels. This also corresponded to a continuous decrease of the IgG2a/IgG1 ratio after infection. Only IgM and IgG1 antibodies, but not IgG2a/2b/3, were significantly produced in adjuvant control groups after infection. These findings suggest that G. spinigerum infection potently induces a Th2-type biased response.
Adjuvants, Immunologic/*administration & dosage ; Animals ; Antibodies, Helminth/*blood ; Antigens, Helminth/*administration & dosage/*immunology ; Gnathostoma/*immunology ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Mannitol/administration & dosage/*analogs & derivatives ; Mice ; Oleic Acids/*administration & dosage ; Oligodeoxyribonucleotides/*administration & dosage ; Th1 Cells/immunology ; Th2 Cells/immunology

OBJECTIVE: To determine the safety and usefulness of a two-tiered approach to balloon-occluded retrograde transvenous obliteration (B-RTO) as a treatment for large gastric varices after portal hypertension. MATERIALS AND METHODS: 50 patients were studied who underwent B-RTO for gastric varices between October 2004 and October 2011 in our institution. The B-RTO procedure was performed from the right femoral vein and the B-RTO catheter was retained until the following morning. Distribution of sclerotic agents in the gastric varices on fluoroscopy was evaluated in all patients on days 1 and 2. When distribution of sclerotic agents in the gastric varices on day 1 had been none or very scanty even though the volume of the sclerotic agent infused was above the acceptable level, a second infusion was administered on day 2. When distribution was satisfactory, the B-RTO catheter was removed. RESULTS: In 8 (16%) patients, little or no sclerotic agent infused on day 1 was distributed in the gastric varices. However, on day 2, sclerotic agents were distributed in all gastric varices. Mean volume of ethanolamine oleate-iopamidol infused on day 1 was 24.6 mL and was 19.4 mL on day 2. Gastric varices were well obliterated with no recurrence. Complications caused by the sclerotic agent such as pulmonary edema or renal insufficiencies were not seen. CONCLUSION: When gastric varices are very large, a strategy involving thrombosis of only the drainage vein on the first day followed by infusing the sclerotic agent on the following day might be effective and feasible.
Adult ; Aged ; Aged, 80 and over ; Balloon Occlusion/*methods ; Catheters, Indwelling ; Collateral Circulation ; Drug Administration Schedule ; Esophageal and Gastric Varices/etiology/radiography/*therapy ; Female ; Femoral Vein ; Gastrointestinal Hemorrhage/etiology/*therapy ; Humans ; Hypertension, Portal/*complications ; Iopamidol/*administration & dosage/adverse effects ; Male ; Middle Aged ; Oleic Acids/*administration & dosage/adverse effects ; Recurrence ; Retrospective Studies ; Sclerosing Solutions/*administration & dosage/adverse effects ; Tomography, X-Ray Computed

The aim of this study is to prepare self-microemulsifying drug delivery system (SMEDDS) of the mixture of paeonol (Pae) and borneol (Bor). Solubility test, ternary phase diagrams and simplex lattice method were employed to screen and optimize the formulation of the mixture of Pae and Bor-loaded SMEDDS. After formed into microemulsions, the particle diameter (PD) was determined and a TEM was employed to observe the microemulsions' morphology. The contents of Pae and Bor were determined by gas chromatography. As a result, while ethyl oleate (EO) as the oil phase, cremophor EL35 (EL35) as surfactant and Transcutol HP (HP) as cosurfactant, the range of the microemulsion on the ternary phase diagram was larger than other combinations. And at a ratio of 20:45:35, the microemulsions' PD was about 34 nm and the polydispersity index (PI) was about 0.2. There were 16% of Pae, 2% of Bor, 16% of EO, 37% of EL35 and 29% of HP in the prepared SMEDDS. The preparation process of the Pae and Bor-loaded SMEDDS based on Xingbi Fang is simple and feasible. This study provides a reference for the researches on the related traditional Chinese medicine and the related components.
Acetophenones ; administration & dosage ; toxicity ; Administration, Intranasal ; Animals ; Bornanes ; administration & dosage ; toxicity ; Bufonidae ; Cilia ; drug effects ; Drug Combinations ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Emulsions ; Ethylene Glycols ; chemistry ; Female ; Male ; Nasal Mucosa ; drug effects ; Oleic Acids ; chemistry ; Particle Size ; Polyethylene Glycols ; chemistry ; Solubility ; Surface-Active Agents ; chemistry

OBJECTIVE: To retrospectively evaluate the frequency and risk factors for developing thrombus in a systemic vein such as the infrarenal inferior vena cava or the iliac vein, in which a balloon-occluded retrograde transvenous obliteration (B-RTO) catheter was indwelled. MATERIALS AND METHODS: Forty-nine patients who underwent B-RTO for gastric varices were included in this study. The B-RTO procedure was performed from the right femoral vein, and the B-RTO catheter was retained overnight in all patients. Pre- and post-procedural CT scans were retrospectively compared in order to evaluate the development of thrombus in the systemic vein in which the catheter was indwelled. Additionally, several variables were analyzed to assess risk factors for thrombus in a systemic vein. RESULTS: In all 49 patients (100%), B-RTO was technically successful, and in 46 patients (94%), complete thrombosis of the gastric varices was achieved. In 6 patients (12%), thrombus developed in the infrarenal inferior vena cava or the right common-external iliac vein. All thrombi lay longitudinally on the right side of the inferior vena cava or the right iliac vein. One of the aforementioned 6 patients required anticoagulation therapy. No symptoms suggestive of pulmonary embolism were observed. Prothrombin time-international normalized ratio and the addition of 5% ethanolamine oleate iopamidol, on the second day, were related to the development of thrombus. CONCLUSION: Development of a thrombus in a systemic vein such as the inferior vena cava or iliac vein, caused by indwelling of the B-RTO catheter, is relatively frequent. Physicians should be aware of the possibility of pulmonary embolism due to iliocaval thrombosis.
Adult ; Aged ; Aged, 80 and over ; Balloon Occlusion/*methods ; Catheters, Indwelling/*adverse effects ; Esophageal and Gastric Varices/etiology/*therapy ; Female ; Femoral Vein ; Humans ; International Normalized Ratio ; Iopamidol/administration & dosage ; Male ; Middle Aged ; Oleic Acids/administration & dosage ; Prothrombin Time ; Retrospective Studies ; Risk Factors ; Statistics, Nonparametric ; Tomography, X-Ray Computed ; Treatment Outcome ; Venous Thrombosis/drug therapy/*etiology/*radiography