Humans ; Nanoparticles ; toxicity ; Skin ; drug effects ; Skin Absorption

OBJECTIVETo prepare berberine microemulsion, and to investigate its properities and the absorption character in rat intestine in situ.

METHODThe optimum formulation of the blank microemulsion selected by pseudo tertiary phase diagrams and the berberine microemulsion was prepared based on the blank microemulsion. The viscosity, conductance, refraction rate and particle size of berberine microemulsion were surveyed. An in situ rat perfusion method was used to investigate the intestinal absorption of berberine microemulsion. A UV method for determination of berberine in the intestinal flux was established.

RESULTThe viscosity, conductance, refraction rate and particle size of berberine microemulsion were 2.11 cPas, 125.5 microomega, 1.363 and 24.0 nm, respectively. The absorption rate of berberine at the ileum was the best. The absorption of berberine microemulsion at the ileum was significantly higher than that of raw medicine (P < 0.01).

CONCLUSIONThe microemulsion system might improve the absorption of berberine in the intestinal tract.

Absorption ; Administration, Cutaneous ; Animals ; Berberine ; administration & dosage ; pharmacokinetics ; Drug Delivery Systems ; Drug Stability ; Female ; Ileum ; metabolism ; Intestinal Absorption ; drug effects ; Intestines ; metabolism ; Male ; Particle Size ; Rats ; Rats, Wistar ; Skin ; metabolism ; Skin Absorption ; drug effects ; physiology ; Solubility ; Technology, Pharmaceutical ; methods

The intestinal absorption of berberine (Ber) and its structural modified compound 8-hydroxy dihydroberberine (Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography (HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber (P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.
Absorption ; Animals ; Berberine ; administration & dosage ; analogs & derivatives ; Carbohydrate Metabolism ; drug effects ; Carbohydrates ; chemistry ; Chromatography, High Pressure Liquid ; Glucose ; metabolism ; Intestinal Absorption ; drug effects ; Rats

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

We investigated the clinical effects and drug toxicities of high concentrated recombinant human alpha-interferon eyedrops in acute epidemic keratoconjunctivitis(ARK). We examined the side effects of alpha-interferon eyedrops after instillation to the 34 general healthy patients, and compared the clinical effects after randomized blind administration of the different concentration eyedrops or placebo in 117 AEK. No significant ocular complications in the 34 general healthy patients was observed. In AEK, improvement of symptoms and signs were observed at the mean 3.2 days of 10.000 IU/ml group, 3.1 days of 100,000 IU/ml group, and 3.2 days of 500,000 IU/ml group after instillation of alpha-interferon. comparing 4.4 days of placebo(P<0.01). We have also observed early absorption of conjunctival pseudomembrane, and the decreased incidence of keratitis. We suggest that the topical application of alpha-interferon might be clinically useful to help early recovery and decrease the incidence of ocular complications of AEK.
Absorption ; Drug-Related Side Effects and Adverse Reactions ; Humans* ; Incidence ; Interferon-alpha* ; Keratitis ; Keratoconjunctivitis* ; Ophthalmic Solutions

OBJECTIVETo study the permeability of intact mouse abdominal skin to aniline and the protective capability of two typical lab gloves against aniline.

METHODSA Franz diffusion cell was used to perform in vitro transdermal absorption test and glove permeation test for aniline (0.102 mg/ml and 0.010 mg/ml). The permeabilities of intact mouse abdominal skin and gloves to aniline were measured by high performance liquid chromatography-diode array detection.

RESULTSThe transdermal penetration of the two concentrations of aniline followed zero order kinetics within 12 h, exhibiting total aniline permeabilities within 24 h of 51.71% and 48.31%, respectively. The absorption liquid had an aniline concentration of at least 18 µg/L. The medical disposable latex glove could not stop the penetration of 0.010 mg/ml aniline, but the industrial natural latex glove could.

CONCLUSIONThe penetration of 0.102 mg/ml and 0.010 mg/ml aniline through the mouse abdominal skin follows zero order kinetics within 12 h. The medical disposable latex glove cannot stop the penetration of 0.010 mg/ml aniline, but the industrial natural latex glove can.

Aniline Compounds ; pharmacokinetics ; toxicity ; Animals ; Gloves, Protective ; Mice ; Skin Absorption ; drug effects

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.
Biopharmaceutics ; Humans ; Intestinal Absorption ; Intestines ; drug effects ; Medicine, Chinese Traditional ; Perfusion ; Permeability

L_9(3~4) orthogonal experiment design was used to optimize the preparation of the patches,and investigate its affecting factors and skin irritation. Eugenol was taken as the index component to study the release behavior in vitro and percutaneous penetration of Cangai oil transfersomes patches by HPLC.The results showed that the optimal prescription for preparing Cangai oil transfersomes patches were Eudragit E100 0.6 g, succinic acid 0.08 g,triethyl citrate 0.25 g,glycerol 0.2 g.Patches prepared by the preferred preparation had a flat appearance without obvious bubbles.The initial adhesion was 18.33±2.52, the stickiness was(30.01±2.45) min,and the peel strength was(5.62±0.95) kN·m~(-1).The results of affecting factors experiment showed the order of factors affecting its adhesion was humidity>temperature>lighting,and the skin irritation test results showed no significant skin irritation after 24 h of single administration. The results of drug release behavior in vitro showed that the release and the percutaneous penetration of both Cangai oil patches and Cangai oil transfersomes patches conformed to the Higuchi equation.The release amount of eugenol were 80.66% and 82.25% at 72 h, with no significant difference. The cumulative permeation area of eugenol per unit area reached(0.195 6±0.065 9),(0.131 0±0.045 5) mg·cm~(-2) at 72 h, with significant differences(P<0.05).The experiment results proved that the preparation process of Cangai oil transfersomes patches was stable,and the prepared patches had a good adhesion. At the same time,the preparation of transfersomes patches could alleviate and control the release of the drug to a certain extent, and provide a certain experimental basis for clinical pediatric drug safety.
Administration, Cutaneous ; Drug Carriers ; Drug Liberation ; Humans ; Plant Oils/pharmacology* ; Polymethacrylic Acids ; Skin/drug effects* ; Skin Absorption ; Transdermal Patch

The aim of this paper was to investigate the effect of terpene penetration enhancers on membrane fluidity and membrane potential using HaCaT keratinocytes, and study the potential mechanisms of these terpene compounds using as natural transdermal penetration enhancer. Six terpene compounds, namely menthol, limonene, 1,8-cineole, menthone, terpinen-4-ol and pulegone, were chosen in this study on account of their good penetration-enhancement activities. The cytotoxicity of these terpene compounds was measured using an MTT assay. The fluorescence recovery after photobleaching (FRAP) technique was employed to measure the change of membrane fluidity of HaCaT cells. The flow cytometer was used to study the alteration of membrane fluidity of HaCaT cells, and investigate the effect of terpene compounds on intracellular Ca2+. It was found that 6 terpene compounds possessed low cytotoxicity in comparison to the well-established and standard penetration enhancer azone. Those terpene compounds could significantly enhance HaCaT cells membrane fluidity and decrease HaCaT cells membrane potentials. Meanwhile, after treated with various terpene compounds, the Ca2(+)-ATPase activity and intracellular Ca2+ of HaCaT cells was decreased significantly. Terpene penetration enhancers perhaps changed the membrane fluidity and potentials of HaCaT cells by altering the Ca2+ balance of the cell inside and outside, resulting in the low skin permeability to increase the drug transdermal absorption.
Cell Line ; Drugs, Chinese Herbal ; pharmacokinetics ; Humans ; Keratinocytes ; drug effects ; metabolism ; Membrane Fluidity ; drug effects ; Skin Absorption ; drug effects ; Terpenes ; pharmacokinetics

To explore the mechanism of the absorption enhancement of borneol, the effect of borneol on the intestinal absorption and the pharmacokinetics of tetramethylpyrazine phosphate after oral administration were investigated. In situ intestinal recirculation was performed to study the effect of various concentrations of borneol on the absorption of tetramethylpyrazine phosphate at duodenum, jejunum, ileum and colon. After oral administration of tetramethylpyrazine phosphate, the mixture of tetramethylpyrazine phosphate and borneol and the mixture of tetramethylpyrazine phosphate and verapamil in rats, the concentrations of tetramethylpyrazine phosphate in plasma were determined by RP-HPLC at predesigned time. The pharmacokinetic parameters were compared based on the results of the three animal experiments, and analyzed with software program 3p97. The result showed that tetramethylpyrazine phosphate could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: colon > duodenum > jejunum > ileum, but without saturation, which demonstrated that tetramethylpyrazine phosphate was absorbed via simple diffusion. Borneol could enhance the intestinal absorption of tetramethylpyrazine phosphate, however, not in proportion. There was no obvious difference between the test group and the control group when 10 microg x mL(-1) borneol was added (P > 0.05), while when the concentration comes to 25 microg x mL(-1) and 50 microg x mL(-1), significant differences were observed (P < 0.05). Borneol and verapamil did enhance the bioavailability of tetramethylpyrazine phosphate after oral administration in rats. The enhancing effect of borneol showed only when the concentration came to a certain level but with no specific sites existed in the intestine. One of the mechanisms of borneol on the enhancing effect on absorption of tetramethylpyrazine phosphate might be the inhibition of the metabolism of CYP 3A and exocytosis of P-gp.
Animals ; Biological Availability ; Bornanes ; pharmacokinetics ; Herb-Drug Interactions ; Intestinal Absorption ; drug effects ; Male ; Pyrazines ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley