Traditional Chinese medicine has a long history of intranasal administration. Compared with the other administration routes, intranasal administration has the benefits of fast absorption, high bioavailability, high brain-targeting and non-invasive. In the past few years we take "Xingnaojing" and "Tongqiao Sanyu formula" as model drug and studied pharmacokinetics of effective components of different polarities. MDCK/MDCK-MDR1 cells were used to simulate blood brain barrier to study the permeate behaviors of different drug and the mechanism of enhancing effects of aromatic medicine. Then a microemulsion (modified by mPEG2000-PLA) was prepared for intranasal administration, and the pharmacokinetics and investigated tissue distribution were studied by fluorescence imaging. The irritation of the drug and different preparations were studied on human nasal epithelial cell (HNEC) cell and living animals. In this paper, we reviewed the achievements and hope that it can provide constructive suggestions for the future research.
Administration, Intranasal ; instrumentation ; methods ; Animals ; Biological Availability ; Blood-Brain Barrier ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Humans

An HPLC method for the determination of geniposide concentration in mouse plasma was developed and the pharmacokinetics after intranasal administration of Xingnaojing microemulsion (XNJ-M) and mPEG2000-PLA modified Xingnaojing microemulsion (XNJ-MM) were investigated. Eighty mice were treated by XNJ-M and XNJ-MM nasally. The plasma samples were collected at different times and the drug in samples was detected by HPLC. The pharmacokinetic parameters were calculated by the software of Kinetica. The pharmacokinetic parameters of geniposide of XNJ-M were C(max) (4.36 +/- 2.69) mg x L(-1), t(max) 1 min, MRT (29.73 +/- 4.54) min, AUC (53.63 +/- 14.03) mg x L(-1) x min. The pharmacokinetic parameters of geniposide of XNJ-MM were C(max) (9.75 +/- 4.14) mg x L(-1), t(max) 1 min, MRT(22.34 +/- 2.90) min, AUC (131.87 +/- 40.13) mg x L(-1) x min. Geniposide can be absorbed into blood in a higher degree after intranasal administration with XNJ-MM compared to XNJ-M, which maybe caused by its less irritating and more absorption.
Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Emulsions ; Iridoids ; blood ; pharmacokinetics ; Lactic Acid ; chemistry ; Male ; Mice ; Polyesters ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry

In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.
Administration, Cutaneous ; Animals ; Coumaric Acids ; administration & dosage ; pharmacokinetics ; Male ; Needles ; Rats ; Rats, Sprague-Dawley ; Skin Absorption

Using sustained release tablets of gardenia extract as model drug and DPPH radical scavenging capacity as antioxidant index, the feasibility of using pharmacodynamics index was explored to evaluate sustained release tablets. Applying the established quantifiable method of DPPH radical scavenging to the dissolved liquid of model drug, release profiles and biological effects profiles were drawn, and their correlation was discussed. A good correlation was observed by linear regression and f2 actor, suggesting that the indicator could be used to evaluate sustained release tabletsofextracts of gardenia in which iridoids were mainly involved.
Antioxidants ; metabolism ; pharmacology ; Biphenyl Compounds ; metabolism ; Delayed-Action Preparations ; metabolism ; pharmacokinetics ; Free Radicals ; metabolism ; Gardenia ; chemistry ; Kinetics ; Linear Models ; Oxidation-Reduction ; drug effects ; Picrates ; metabolism ; Plant Extracts ; metabolism ; pharmacokinetics ; Tablets

OBJECTIVETo develop a HPLC for the determination of plasma concentration of glycyrrhetic acid (GA) and study the pharmacokinetics of GA in rats.

METHODTo sample blood from rat which were injected GA by 1.0 mg x kg(-1) at 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 2, 3, 4, 6 h and use HPLC to determine the concentration of GA in it, the pharmaeokinetie parameters were accessed by DAS 1.0.

RESULTThe calibration curve was linear (r = 0.999 7) within the range of 50-2 000 ng x mL(-1) for GA in plasma. The average recovery was (105.2 +/- 2.23)%, (102.5 +/- 2.95)%, (98.4 +/- 2.32)%. The within-day and between-day derivation (RSD) were less than 4%. GA was fitted to a two compartment open pharmaeokinetie model in rats. The mainly pharmaeokinetie parameters were: t1/2alpha = (0.153 +/- 0.023) h, t1/2beta = (2.365 +/- 0.866) h, C(max) = (2.074 +/- 0.100) mg x L(-1), CL = (0.715 +/- 0.082) L x h(-1) x kg(-1), V(d) = (2.427 +/- 0.872) L x kg(-1), AUC(0-6 h) = (1.302 +/- 0.151) mg x h(-1) x L(-1).

CONCLUSIONThe method can be used to determine the concentration and to investigate the pharmacokinetics of GA in rat. GA was disposed extensively and rapidly in rats.

Suitable pretreatment of biological samples can truly reflect the role of law of the measured components played in the body and will provide experimental evidence for the studies on metabolic process, material basis of efficacy, mechanism of action, pharmacology, toxicology and the others. Biological samples include blood, urine, hair, tears, etc. There are also many samples processing methods, such as the direct protein precipitation, liquid-liquid extraction and solid phase extraction and so on. These methods could be used alone or combined.
Animals ; Body Fluids ; chemistry ; Chemical Precipitation ; Chemistry Techniques, Analytical ; methods ; Humans ; Liquid-Liquid Extraction ; Proteins ; isolation & purification ; Solid Phase Extraction

Objective To study a method for the quality control of extracts from Zhizi (Fructus Gardeniae).Methods The quality control of extracts from Zhizi was carried out through thin-layer chromatography (TLC), examinations of moisture content, residue of ignition, heavy metals and arsenic salt, and ultraviolet spectrophotometry and HPLC. The main chromatographic peaks of fingerprint were identified.Results The experimental sample and control sample in TLC showed the same colored spots at the same position (negative without interference). The results of all examinations were accorded with the China National Pharmacopoeia. In the extracts from Zhizi the total iridoid glycosides showed a good linear relationship at a range of 5.592-35.712 μg (r=0.999 9), the recoveries of the samples in the concentrations of high, middle and low were 98.34%, 100.67% and 101.07% respectively, and RSD were 2.60%, 1.47% and 1.20% respectively (n=3). Geniposide showed a good linear relationship at a range of 0.228-1.140 μg (r=0.999 9), the recoveries of the samples in the concentrations of high, middle and low were 104.04%, 100.97% and 95.94% respectively, and RSD were 0.17%, 0.58% and 0.84% respectively (n=3).Conclusion TLC and HPLC-MS can be used to identify qualitatively the chemical constituents of extracts from Zhizi, ultraviolet spectrophotometry can be used to control the quantity of the total iridoid glycosides, and HPLC can be used to control the quantity of geniposide. The method is simple, accurate with a higher repeatability.

To establish a UPLC-MS/MS method for the simultaneous determination of geniposide, genipin 1-O-beta-D-gentiobioside and geniposidic acid in rat brains and study the brain pharmacokinetics of the three iridoid glycosides in stroke rat after the oral administration of Xingnaojing. In this experiment, brain samples were precipitated with protein for twice. Acquity BEH C18 column was adopted, with acetonitrile-0.1% formic acid-water as the mobile phase for gradient elution. ESI source was adopted for mass spectra; multiple reaction monitoring (MRM) was conducted to detect negative ions. The time for sample analysis was 3.5 min. the results showed good linear relations among the three iridoid glycosides, with the extraction recovery between 99.6% and 114.3%, good intra- and inter-day precisions and accuracies and stability in line with the requirements. The t1/2 and MRT in the three components were similar in brains of stroke rats. Geniposide and genipin 1-O-beta-D-gentiobioside showed double peaks; where as geniposidic acid showed a single peak. In conclusion, the method is so specific, sensitive, accurate and reliable that it can be used to study the brain pharmacokinetics of Xingnaojing oral preparation.
Animals ; Brain ; metabolism ; Brain Chemistry ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Iridoids ; chemistry ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

The coordination compound of L-hydroxyproline (Hyp)-Zn (II) was synthesized with Hyp and zinc sulfate as raw materials in water medium, coordination Synthesizing Mechanism and Antioxidant Activity of Hyp-Zn(II) coordination compound has been researched. Compared with Hyp, the infrared spectrogram of Hyp-Zn (II) coordination compound emerge a new absorption peak at 1100 cm(-1). Conclusion could be obtained that there exists a coordination effect between Hyp and ZnSO4; TG and DSC curve of Hyp and Hyp-Zn(II) coordination compound were analysed. Compared with Hyp, the peak of Hyp-Zn(II) disappear at 290 degrees C and 375 degrees C. This phenomenon confirmed the front conclusion; At the NMR graph of Hyp-Zn(II) coordination compound, the disappearance of the alpha-carboxyl-hydrogen and alpha-hydroxyl-hydrogen's peak at 3.5-3.9 ppm could indicate that combination's position of Hyp is alpha-carboxyl and alpha-hydroxyl; Structure of Hyp-Zn(II) coordination compound were exosyndrome by the Atomic Force microscopy. It is showed that centr-atom Zn(II) was surrounded by several Hyp at Hyp-Zn(II) coordination compound's phase diagram; The proportion of Hyp-Zn(H) coordination compound was determined by dialysis experiment, the proportion is 4:1; Above-mentioned determination and exosyndrome indicated that the molecular formula of Hyp-Zn (II) coordination compound is Zn(Hyp)4.H2O. The results indicated that the Hyp-Zn(II) coordination compound can inhibit hydroxyl free radicals of Zn(II), and the Percentage of Inhibition is 75.5%; the total antioxidant activities of Hyp-Zn(II) coordination compound is 80.167 u/mL, the anti-superoxide activities of Hyp-Zn (II) coordination compound is 53.19 u/mL.
Antioxidants ; chemistry ; Drug Compounding ; Hydroxyproline ; chemistry ; Zinc Sulfate ; chemistry

In order to test the equilibrium solubility of puerarin in different solvents and solubilizer,cilia toxicity and irritation of these excipient, the balance method, toad in the ciliary body toxicity and rat nasal mucosa irritation were used respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline solution as negative control and sodium deoxycholate as positive control, the effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia movement duration was recorded. The results indicated that there was no significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor HS 15 and normal saline group. The rats long-term nasal mucous membrane irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was studied, with normal saline solution as negative control. There were no significant difference revealed on rat nasal mucosa epithelial thickness among 30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30% PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and showed a lower cilia toxicity and irritation, and can be used as the solvent and solubilizer of puerarin nasal drops.
Administration, Intranasal ; methods ; Animals ; Anura ; Cilia ; chemistry ; Female ; Isoflavones ; chemistry ; Male ; Nasal Mucosa ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Solubility ; Solvents ; chemistry