OBJECTIVETo study the factors that affect mucosal absorption of gardenia extract.

METHODTake vitro frog skin as a model to study the vitro mucosal permeation. The impacts of the osmotic pressure and the pH value of permeation medium on the Papp of the Jasminoidin were studied, and the effect of frog skin on the stability of Jasminoidin was investigated also.

RESULTThe Papp of Jasminoidin were (0.53 +/- 0.01), (0.21 +/- 0.05), (0.44 +/- 0.12), (0.42 +/- 0.13), (0.26 +/- 0.03) cm x min(-1) by using the normal saline (pH 6.88), pure water, 1.8 % NaCl solution, normal saline (pH 4.05) and normal saline (pH 10.05) as permeation medium for each. The accumulated permeation rate was (55.69 +/- 9.81)% by 12 h, using normal saline as permeation medium respectively, and there was no obvious time lag. Jasminoidin began to degrade around 8 h by affectedof frog skin, the constant of degradation rate (K) was 1.999, and the t1/2 was 0.347 h.

CONCLUSIONThe mucosal permeability of gardenia extract by using the vitro model of frog skin is good, and consistent with zero level absorption process. The osmotic pressure and pH value significantly affected the permeation and the isotonic and partial neutral permeation medium are more conducive to the permeation and absorption of Jasminoidin. The degradation effect of frog skin to the Jasminoidin will not affect mucosal permeation research. In vitro model of frog skin is a suitable way to simulate mucosal permeation process of the gardenia extract.

Gardenia ; chemistry ; Hydrogen-Ion Concentration ; Mucous Membrane ; drug effects ; physiology ; Permeability ; drug effects ; Plant Extracts ; chemistry ; pharmacology ; Skin ; drug effects ; Skin Absorption ; drug effects ; physiology ; Solubility

OBJECTIVETo study the solubilization of O/W microemulsion system for volatile oil.

METHODPseudo-ternary phase diagrams were prepared by using the method of titration, then investigating the solubilization of microemulsion system for different kind of volatile oil was investigated with the diagrams, and the effect of the formulation of microemulsion on the solubilization of Citrus sinensis oil were studied.

RESULTKinds of volatile oil have an accelerated solubility in the microemulsion system. The species and dosage of oil phase and surfactant could influence the solubilization of microemulsion on Citrus sinensis oil.

CONCLUSIONIt is recommended to select a new method to solve the stabilization of volatile oil in the liquid preparation by the solubilization of suitable formulation of microemulsion.

Drugs, Chinese Herbal ; chemistry ; Emulsions ; Oils, Volatile ; chemistry ; Solubility ; drug effects ; Surface-Active Agents ; pharmacology ; Water ; chemistry

To prepare the herpetolide A nanosuspension lyophilized powder(HPA-NS-LP), in order to investigate its anti-hepatitis B virus(HBV) activity and the dissolution in vitro. Herpetolide A nanosuspension(HPA-NS) was prepared by ultrasonic precipitation method. The formulation and process of HPA-NS were optimized by the single factor experiment. Lyophilized powder(HPA-NS-LP) was prepared by freeze-drying method. Scanning electron microscopy was used to observe morphology of HPA-NS-LP. Paddle method was used to determinate the dissolution of HPT-NS-LP in vitro. The anti-HBV activity of herpetolide A coarse suspension lyophilized powder(HPA-CS-LP) and HPA-NS-LP was evaluated by HepG2.2.15 cell model. The mean particle size of optimized HPA-NS was(173.46±4.36) nm, with a polydispersity index of 0.110±0.012. After redispersion, the mean particle size and the polydispersity index of HPA-NS-LP increased, with changes within a rational range. Scanning electron microscopy showed that HPA-NS-LP was spherical in shape. Cumulative dissolution rate of HPA-NS-LP was more than 90% in 2 hours, which was higher than that of HPA-CS-LP. Both HPA-CS-LP and HPA-NS-LP could effectively inhibit the secretion of HepG2.2.15 cell antigens(HBsAg and HBeAg), and the inhibitory effect of HPA-NS-LP was significantly higher than that of HPA CS-LP(P<0.05). HBV-DNA test showed that high, medium and low-dose HPA-NS-LP(50, 25, 12.5 mg·kg~(-1)) significantly decreased the level of HBV-DNA(P<0.05), and the effect was better than that of the same dose of HPA-CS-LP(P<0.05). The results revealed that HPA-NS-LP exhibited anti-HBV activity in vitro, and its effect was superior to that of HPA-CS-LP.
Coumarins/pharmacology* ; Cucurbitaceae/chemistry* ; Hep G2 Cells ; Hepatitis B virus/drug effects* ; Humans ; Nanoparticles ; Particle Size ; Phytochemicals/pharmacology* ; Solubility ; Suspensions

OBJECTIVETo evaluate the effects of processing methods of Hirudo.

METHODBoth water and alcohol extracts of Hirudo were studied according to Chinese Pharmacopeia (Edition 2005). The content of hypoxanthine in Hirudo was measured by high performance liquid chromatography (HPLC) and Hirudin was determined by thrombin.

RESULTThe contents of water, water soluble extraction, ethanol soluble extraction and hirudin in crude Hirudo are higher than those in processed Hirudo. But the contents of hypoxanthine in processed Hirudo is higher than in crude Hirudo.

CONCLUSIONHirudo fried by French chalk can decrease the active components with high intensive drug property, accordingly the toxicity of Hirudo was decreased. As a result, the effects of Hirudo as invigorate the circulation of blood and stimulate the menstrual flow were abated.

Animals ; Blood Circulation ; drug effects ; Ethanol ; chemistry ; Hirudins ; analysis ; Hirudo medicinalis ; chemistry ; Hypoxanthine ; analysis ; Menstrual Cycle ; drug effects ; Solubility ; Water ; chemistry

To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL, respectively. 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.
Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Crystallization ; Fluorouracil ; chemistry ; Humans ; Liver Neoplasms ; Niacinamide ; chemistry ; Solubility

The borneol was included with β-CD and prepared Fufang Danshen intestinal adhesion pellets. GC method for determination of borneol in Fufang Danshen intestinal adhesion pellets was established to study its in vitro dissolution and make a comparison with the Fufang Danshen tablet, in this way, the rationality of dosage form was evaluated. The first method of dissolution determination was used for determining the in vitro dissolution of borneol in Fufang Danshen intestinal adhesion pellets in artificial intestinal juice, and Fufang Danshen tablet in artificial gastric juice and intestinal juice, respectively. Result shows: the concentration of borneol in Fufang Danshen intestinal adhesion pellets and Fufang Danshen tablet was 0.79% and 0.80%, respectively. Its in vitro dissolution was nearly 70% within 12 h in Fufang Danshen intestinal adhesion pellets, and in Fufang Danshen tablet, the dissolution was about 60% within 20 min and more than 90% within 40 min, and in artificial gastric juice, was less than 20% within 40 min but more than 80% till 150 min. Research suggests that in comparison with Fufang Danshen tablet, in vitro dissolution of borneol in the Fufang Danshen intestinal adhesion pellets showed an obvious sustained release behavior. The borneol in Fufang Danshen intestinal adhesion pellets was included with β-CD and prepared enteric preparations. To some extent, the stimulation on stomach and intestinal mucosa can be reduced and safety can be improved.
Bornanes ; adverse effects ; chemistry ; pharmacology ; Chemistry, Pharmaceutical ; methods ; Dosage Forms ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; Models, Biological ; Solubility

OBJECTIVETo investigate the intervention effect of aqueous fractions from Boschniakia rossica (BRAF) on hepatic oxidative stress in mice with liver injury induced by carbon tetrachloride (CCl4).

METHODThe experimental mice were randomly assigned into the normal control group, the model group, the silymarin (positive control) group, as well as high and low dose BRAF groups. Mice were treated intragastrically with silymarin or BRAF once every day for 7 days. At the end of the experiment, CCl4 was injected intraperitoneally into the mice to establish the acute liver injury model. The pathological changes was detected with hematoxylin and eosin (HE) staining, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) , catalase (CAT), glutathione peroxidase (GPx), Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, and the contents of reduced glutathione (GSH) and malondialdehyde (MDA) were detected by the colorimetric method.

RESULTBRAF significantly reduced ALT, AST and ALP activities in serum, alleviated hepatic injury induced by CCl4, increased SOD, CAT, GPx and GSH levels in liver, and SOD, Na + -K + -ATPase and Ca2+ -Mg2 + -ATPase activities in liver mitochondria, and decreased the MDA content in liver and liver mitochondria.

CONCLUSIONBRAF reduces hepatic oxidative stress in mice with acute liver injury induced by CCl4, thereby showing the protective effect on mice with acute liver injury induced by CCl4.

Animals ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; enzymology ; metabolism ; pathology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice ; Mitochondria ; drug effects ; metabolism ; Orobanchaceae ; chemistry ; Oxidative Stress ; drug effects ; Solubility ; Water ; chemistry

OBJECTIVEStudy the effect of self-microemulsifying drug delivery system(SMEDDS) on the solubility and absorption of tanshinones to guide the selection of composition of tanshinone SMEDDS.

METHODThe solubility of tanshinones in the solution of SMEDDS was determined by UV-spectrometer and the absorption of tanshinone SMEDDS was determined by HPLC as the detection method.

RESULTThe solubility of tanshinones in solution of SMEDDS was 10 times in water and 2.5 times in micelle solution. The solubility of tanshinones in solution of SMEDDS was increased with the increasing of oil (MCT) in composition of tanshinone SMEDDS. The absorption constants (Ka) in SMEDDS and micelle solution was 0.479 h(-1) and 0.326 h(-1) respectively, and the absorption half life (t1/2) was 1.44 h and 2.12 h respectively. The absorption was increased with the oil increasing in composition of tanshinone SMEDDS.

CONCLUSIONSMEDDS can increase the solubility and absorption of tanshinones significantly and the increasing of oil content (MCT) in SMEDDS composition promote the dissolution and absorption of tanshinones.

Animals ; Diterpenes, Abietane ; Drug Delivery Systems ; methods ; Emulsions ; Intestinal Absorption ; drug effects ; Male ; Phenanthrenes ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Solubility

OBJECTIVESeveral cryoprotectants were employed to study the protective effect on the freeze-drying process of the oleanolic acid-loaded nanosuspensions (OLA-LS) in order to select the optimum formulation.

METHODThe protective effect was evaluated by measuring the mean particle size of samples before and after freeze-drying process.

RESULTSucrose with the concentration of 10% was selected as the optimum cryoprotectant. The average size of excellent sample was 236.3 nm (versus 211.2 nm of fresh one), and a much higher polydispersity index of 0.242 (versus 0.180).

CONCLUSIONThe optimum lyophilized powder could be obtained with suitable type of cryoprotectant with appropriate concentration and proper freeze-drying conditions.

Cryoprotective Agents ; chemistry ; pharmacology ; Drug Stability ; Freeze Drying ; methods ; Microscopy, Electron, Transmission ; Nanoparticles ; chemistry ; ultrastructure ; Oleanolic Acid ; chemistry ; Particle Size ; Solubility ; drug effects ; Sucrose ; chemistry ; pharmacology ; Suspensions

OBJECTIVETo evaluate the effects of n-hexane insoluble fraction (HIF) of Ficus septica leaves in combination with doxorubicin on cytotoxicity, cell cycle and apoptosis induction of breast cancer T47D cell lines.

METHODSThe in vitro drugs-stimulated cytotoxic effects were determined using MTT assay. Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethydium bromide-acridin orange. The expression of cleaved-poly (ADP-ribose) polymerase (PARP) on T47D cell lines was identified using immunocytochemistry.

RESULTSThe combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells. In addition, combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis. HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G2/M to G1 phase. The combination also exhibited upregulation of cleaved-PARP in T47D cells.

CONCLUSIONSBased on this results, HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

Antineoplastic Agents ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Doxorubicin ; pharmacology ; Female ; Ficus ; chemistry ; Flow Cytometry ; Hexanes ; chemistry ; pharmacology ; Humans ; Immunohistochemistry ; Solubility