Synergetic taste masking of lipid coating and beta-cyclodextrin inclusion / 药学学报

Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.

Scutellarin starch microspheres' permeability through nasal mucosa of different animals in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To study scutellarin starch microspheres' permeability through nasal mucosa of different animals in vitro.</p><p><b>METHOD</b>The Franz diffusion cell method was used to experiment the permeability test (n = 4), taking fresh nasal mucosa of dog, swine and domestica in vitro as permeation barrier separately, with scutellarin starch microspheres (scutellarin 0.25 mg) above them, and blank pH 6.8 PBS as absorption liquid to detemine the scutellarin by HPLC.</p><p><b>RESULT</b>The permeability coefficient of scutellarin starch microspheres through nasal mucosa of dog, swine and domestica in vitro were (5.295 +/- 0.637) x 10(-3) (4.065 +/- 1.140) x 10(-3), (1.855 +/- 0.150) x 10(-3) cm x mL(-1) separately. The permeability coefficient order of scutellarin starch microspheres through nasal mucosa of different animals in vitro is dog > swine > domestica, and there are significant differences between the permeability coefficient of scutellarin starch microspheres through nasal mucosa of dog, swine in vitro, and that through nasal mucosa of swine and domestica in vitro.</p><p><b>CONCLUSION</b>Drugs in scutellarin starch microspheres could permeate through the above-mentioned nasal mucosa in vitro. There might be different permeability coefficient among different species.</p>

Evaluation of brain-targeted trendence of scutellarin nasal administration / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of developing brain-targeted nasal delivery system of scutellarin by the passage between nase and brain in nasal olfactory area.</p><p><b>METHOD</b>The samples of cerebrospinal fluid (CSF) and blood were prepared by cranial puncture and femoral artery catheterization methods respectively according to the certain sampling time after drug administered. The scuteIlarin concentration of samples were determined by 125 marked method. Pharmacokinetic parameters were calculated by trapezoidal rule. The brain-targeted trendence were evaluated by the value of the index AUC(brain)/AUC(plasma).</p><p><b>RESULT</b>The distribution of scutellarin in brain following intranasal administration was different between tissues. Drug concentration in olfactory bulb achieved to peak at 5-15 min after intranasal administration, while in brain tissue was 30-60 min. Above all, peak concentration in olfactory bulb and olfactory region respectively were (574.8 +/- 205.), (323.4 +/- 128.3) ng x g(-10, both are higher than CSF, which is (123.2 +/- 29.3) ng x g(-1). Moreover, the distribution of scutellarin given by intranasally in brain was: olfactory bulb (OB) > olfactory region (OR) > cerebrospinal fluid (CSF) > cerebellum(CB) > medulla oblongata (MO) > cerebrum (CR); AUC(0-240) of olfactory bulb, olfactory region and CSF after scutellarin intranasal administration were 5.54, 5.07 and 5.51 times of that after intravenous injection, respectively. And the AUC(0-240) of other brain tissues after intranasal administration were also higher than that after intravenous injection. AUC(brain tissue)/ AUC(plasma) of every brain tissues by intranasally are all higher than that by intravenously remarkably. For instance, 5 min after intranasal administration, the value of AUC(CSF)/ AUC(plasma), AUC(OB)/AUC(plasma), and AUC(CR)/AUC(plasma) were 30.34, 56.93, and 6.14 times of that by intravenously.</p><p><b>CONCLUSION</b>Part of scutellarin could be straightly transported into brain by the intranasal administration. Its absorption pathway was: the molecule of Scutellarin throughed olfactory mucosa in nasal cavity into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, CSF, cerebrum and cerebellum gradually. It showed that olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. It had a significant trendence of brain-targeted when compared to oral administration and intravenous injection, which indicated a certain feasibility to develop a brain-targeted nasal delivery system for scutellarin.</p>

Multidimensional spatial triangular area as an index for the evaluation of the release-absorption correlation of multiple component traditional Chinese medicines / 药学学报

The paper is aimed to provide a novel index, named as multidimensional spatial triangular area, for the evaluation of the release-absorption correlation of multiple component traditional Chinese medicines (TCMs). The applicability of the method was demonstrated by the example data. The method and standard practice for evaluation of the release-absorption correlation for western medicines with single compound could not be applied to TCMs with multiple components. The release percentage or absorption percentage of the multiple components for TCMs at the sampling time was a point in the multidimensional space. The area of the triangle formed byt the sequential three points rrepresented the changing characteristics of the components' release and absorption kinetics. The side lengths of the triangle could be calculated from the spatial distances between each two of the sequential three points. Then the triangle area could be obtained by the side lengths. The in vitro release-in vivo absorption correlation of the multiple components could be represented by the correlation between the integrating values of the release triangle areas and that of the absorption triangle areas. The results of the examples indicated that the multidimensional spatial triangular area method could treat the multiple components in a holistic way, in line with the holism the hi he TCMs. Therefore, the multidimensional spatial triangular area method provided new methodology for the release-absorption correlation of the TCMs with multiple components.

Study on physicochemical properties and influence factors on stability of breviscapine / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the physicochemical constants such as equilibrium solubility and apparent partition coefficients (Papp), and study the effects of temperature, pH value and antioxidants on the stability of breviscapine solution.</p><p><b>METHOD</b>The equilibrium solubility of breviscapine in various medium and the Papp of breviscapine under different pH conditions were determinated by RP-HPLC, and the effects of temperature, pH value and antioxidants on the stability of solution were investigated by taking change rates of drug content in 10 h as detection index.</p><p><b>RESULT</b>The equilibrium solubility of breviscapine in saline, distilled water, pH 7.0 PBS, pH 7.5 PBS, Ringer's fluid, methanol and ethanol were (20.68 +/- 1.12), (79.35 +/- 0.68), (7954.62 +/- 34.90), (18,708.17 +/- 253.05), (3670.40 +/- 27.64), (210.71 +/- 0.74), (184.34 +/- 1.47) mg x L(-1) respectively; while in pH value 3.0, 4.0, 5.0, 6.5, 7.0 solution, the Papp were 5.362, 0.542, 0.371, 0.328 and 0.143 respectively. The stability of breviscapine in the Ringer's fluid was the worst and the stability was significantly decreased with the increase of temperature and pH value and it could be improved by EDTA-2Na.</p><p><b>CONCLUSION</b>The established HPLC assay was accurate and convenient. The Papp of breviscapine is decreased by increased the pH value, while in the aqueous solution the equilibrium solubility of breviscapine increase with the pH in crese. EDTA-2Na can be used as an antioxidant of breviscapine solution.</p>

Effects of Borneol on the Pharmackinetics of Scutellarin after Intranasal Administration in Rats / 浙江中医药大学学报

[Objective]To observe the effects of borneol on the pharmackinetics of scutellarin after intranasal administration in rats.[Method]The different time of plasma scutellarin concentration was determined by the method of 125I label after iv injection or intranasal administration,intranasal administration of scutellarin(combined with 1% borneol)0.4 mg?kg-1 in SD rats.To calculate the pharmacokinetic parameters by 3P87 software.[Result]The time of maximum concentration(Tmax)and the maximum concentration(Cmax)at the class of intranasal administration is 25.0 min,0.55ug/ml,at the class of intranasal administration(combined with borneol)46.5 min,0.50ug/ml;the absolute bioavailability of intranasal administration is 53.70%,while the intranasal administration(combined withborneol)is 52.86%,there is no statistically significant differences compared with each other.[Conclusion]The borneol prolongs the peak time of plasma scutellarin concentration after intranasal administration in rats,but AUC is not influenced.

Antitumor effect and its mechanism of actinidia Chinensis planch polysaccharide on B16-bearing mice / 中华中医药杂志

Objective:To investigate the antitumor effect of Actinidia Chinensis Planch polysaccharide(ACPS)in B16-bearing C57BL/6 mice and approach its mechanism.Methods:The C57BL/6 mice model was established by B16 subcutaneous inoculation,giving the polysaccharides from vena caudalis injection,and flow cytometer(FCM)was used to detect the distribution of tumor-cell cycle,and electron microscope was used to survey morphologic transformation about apoptosis.Results:ACPS can inhibit the growth of B16,the high,middle dose groups obviously restrained the tumor with the rate of 48.67%,40.90%and the control group 24.13%,and classical apoptosis corpuscles had been found through electron microscope in ACPS groups.Compared with control group,the ACPS promoted the spleen-index of B16-bearing mice and cut down the proliferation index,and the G1/S phase was at growth-inhibitory concentrations judged by the distributing analysis on cell-cycle.Conclusion:ACPS had obvious effect of restraining B16 and promoting the spleen index of tumor-bearing mice,which maybe due to its function of regulating immunization and the distributing of cell-cycle.

Effect of Tianyizhike Syrup on dispelling phlegm and relieving asthma / 中草药

Object To observe the effect of Tianyizhike Syrup on dispelling phlegm and relieving asthma. Methods The phenol red secreting tests in mice, capillary method in rats, asthma induced by spraying and trachea screwy strip method on guinea pig were adopted for observing the related pharmacological effect in different doses of Tianyizhike Syrup. Results Tianyizhike Syrup could obviously increase the amount of the mice secreting phenol red and the rat dispelling phlegm, prolong the latent period of the guinea pig asthma and significantly enlarge the bronchia smooth muscle. Conclusion Tianyizhike Syrup has a significant effect of dispelling phlegm and relieving asthma.

Study on quality assay of agkistrodon halys's crude venom / 中成药

Objective: To establish a method for controlling the quality of Agkistrodon halys's crude venom. Methods: The method of PAGE was carried out to identificate the Agkistrodon halys' crude venom, And the protein of crude venom was also assayed by Lowry's method. Results: The Agkistrodon halys's crude venom could be identified by the method of PAGE. The determintion of protein of crude venom showed a good linear relationship in a concentration range of 25 ?g?mL -1 ～250?g?mL -1 , the regression equation was Y=0.0147+ 1.4553X , and the correlation coefficient was 0.9992. The average recovery of the content reached 100.09, RSD=1.765(n=6). Conclusion: The method is simple, feasible, accurate and available, can be used to controlling of the quality of Agkistrodon halys's crude venom.