Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen) / 中草药·英文版

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

HPLC specific chromatogram spectrum-effect relationship for Shuanghuanglian on MDCK cell injury induced by influenza A virus (H1N1) / 中国中药杂志

To establish HPLC specific chromatogram and its correlation with the protection effect of Shuanghuanglian on MDCK (Madin-Darby canine kidney) cell injury induced by influenza A virus( H1N1). Nine recipes of Shuanghuanglian based on the official prescription were prepared according to orthogonal test for HPLC analysis and MDCK cells protection experiment separately (cytopathic effect (CPE) method was used for observing the virus infectivity and MTT staining results were used as the determining indexes for drug concentration selection and analyzing cell viability). The results suggested that all the other Shuang-Huang-Lian recipes except recipe1 demonstrate protecting effect on MDCK cell injury induced by influenza A virus (P < 0.01, P < 0.001). Stepwise regression analysis was used for analyzing the relationships between HPLC fingerprint and the protecting effect of Shuanghuanglian on influenza A virus induced MDCK cell injury. Peak 2, 3, 6, 8 and 12 were found to be strongly related with anti-influenza A virus efficacy. Stepwise regression analysis of recipes data and efficacy data showed that Lonicerae Japonicae Flos and Forsythiae Fructus were positively associated with the protecting effect of cells injury. From HPLC fingerprints, we found that peak 2, 3, 12 were from Lonicerae Japonicae Flos and peak 6, 8 were from Forsythiae Fructus. Four peaks were identified through comparing the retention time between the standard and Shuanghuanglian recipes, and they were chlorogenicacid, cryptochlorogenic acid, forsythoside B and 3,4-dicaffeoylquinic acid respectively. Caffeic acid derivatives in Lonicerae Japonicae Flos and Forsythiae Fructus were found to be greatly correlated with anti-influenza A virus efficacy and maybe the substance basis of Shuanghuanglian.

Comparison of total phenol of magnolia solid dispersion prepared by different methods / 中国中药杂志

To compare the difference of total phenol of magnolia solid dispersion prepared by different methods. Hot melt extrusion, solvent evaporation method, and fusion-cooling method were used to prepare total phenol of Magnolia accessory solid dispersion, Plastone S-630 and HPC. The drug dispersion state in the prepared solid dispersion was evaluated with DSC and X-ray diffraction; FT-IR method was used to analyze the possible connections between drug and accessories. Finally, accelerated stability-in vivo dissolution test was use to compare the stability differences between these three processes. The results of DSC and X-ray diffraction showed that all of the drug in solid dispersion processed by three processes can exist in amorphous form; FT-IR results also could not distinguish the difference between the three processes; accelerated stability-in vivo dissolution test showed the stability of solid dispersion prepared by HPC was better than Plastone S-630, and the same kinds of materials solid dispersion prepared by hot melt extrusion showed a better stability than the other two processes.

Intestinal absorption of three alkaloids in Plumula Nelumbinis by rat single-pass perfusion in situ model / 中国药学杂志

OBJECTIVE: To investigate the intestinal absorption behaviors of three main active components, liensinine, isoliensinine and neferine in Plumula Nelumbinis extracts in intestine of rats. METHODS: With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and the concentrations of the alkaloids in perfusion solution in different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC. RESULTS: Liensinine, isoliensinine and neferine were absorbed in whole intestinal segments with saturation phenomena. The absorption rate constant (Ka) and/or effective permeability values (Peff) of the three alkaloids mostly had significant difference (P<0.05) at middle and high concentrations of perfusion solution vs those at low concentrations. Liensinine, isoliensinine and neferine possessed better absorption in ileum and colon of intestine. The absorption in duodenum and jejunum mostly displayed no significant difference (P≤0.05). In middle concentration group (117.3 μg·mL-1), neferine was absorbed best among the three alkaloids in colon; in other intestinal sections, the Kd and Peff of the three alkaloids were sequenced as follows: neferine ≤ liensinine ≤ isoliensinine. CONCLUSION: The transport mechanism of liensinine, isoliensinine and neferine in vivo may be active transport or facilitated diffusion.

Studies on effects of Achyranthes bidentata on tongsaimai pellets main active ingredients chlorogenic acid, isoliquiritin, harpagoside and glycyrrhizin in vivo pharmacokinetics / 中国中药杂志

To study on the effects of Achyranthes bidentata on Tongsaimai pellets main active ingredients chlorogenic acid, isoliquiritin, harpagoside and glycyrrhizin in rats in vivo pharmacokinetic behaviors, a method for the simultaneous determination of chlorogenic acid, isoliquiritin, harpagoside and liquiritigenin in rat plasma was established by UPLC-MS/MS. The analysis was performed on a waters Acquity BEH C18 column (2.1 mm x 100 mm, 1.7 microm) with the mixture of acetonitrile and 0.1% formic acid/water as mobile phase, and the gradient elution at a flow rate of 0.3 mL x min(-1). The analytes were detected by tandem mass spectrometry with the electrospray ionization (ESI) source and in the multiple reaction monitoring (MRM) mode. It turned out that the analytes of Tongsaimai pellets groups C(max) and AUC(Q-infinity) values were higher than that with A. bidentata group, and the C(max) values of chlorogenic acid had significantly difference (P < 0.05), the AUC(0-infinity) values of chlorogenic acid and glycyrrhizin had significantly difference (P < 0.05); The T(max) and CL values of two groups had no significantly difference. Results showed that the established method was specific, rapid, accurate and sensitive for the studies of Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic, and A. bidentata have varying degrees of effects on Tongsaimai pellets four main active ingredients in rat in vivo pharmacokinetic behaviors.

Studies on effects of calycosin-7-O-β-D-glucoside on prim-O-glucosylcimifugin and cimifugin in vivo pharmacokinetics / 中国中药杂志

Study on the effects of Astragali Radix main active flavone calycosin-7-O-β-D-glucoside on Saposhnikoviae Radix main active ingredients prim-O-glucosylcimifugin and cimifugin, a UPLC-MS/MS method for simultaneous determination of prim-O-glucosylcimifugin and cimifugin in rat plasma was established, and the comparative pharmacokinetics of prim-O-glucosylcimifugin and cimifugin after oral administration of prim-O-glucosylcimifugin and calycosin-7-O-β-D-glucoside-prim-O-glucosylcimifugin to rats were carried out, which might be conductive in exploring the rationality of Astragali Radix - Saposhnikoviae Radix herb couple. Twelve male SD rats were divided into two groups. Prim-O-glucosylcimifugin and cimifugin in rat plasma of different time points after oral administration of prim-O-glucosylcimifugin and calycosin-7-O-β-D-glucoside - prim-O-glucosylcimifugin to rats were determinated. And the main pharmacokinetic parameters were investigated using DAS 3. 2. 4. The established method was rapid, accurate and sensitive for simultaneous determination of prim-O-glucosylcimifugin and cimifugin in rat plasma. The analysis was performed on a Waters Acquity BEH C18 column (2.1 mm x 100 mm, 1.7 μm) with the mixture of acetonitrile and 0.1% formic acid/water as mobile phase, and the gradient elution at a flow rate of 0.3 mL x min(-1). The analytes were detected by tandem mass spectrometry with the electrospray ionization (ESI) source and in the multiple reaction monitoring (MRM) mode. Compared with prim-O-glucosylcimifugin group, the AUC(0-t)., and AUC(0-∞) of p-O-glucosylcimifugin as well as the C(max) of cimifugin significantly increased (P < 0.05) in calycosin-7-O-β-D-glucoside-prim-O-glucosylcimifugin group. Calycosin-7-O-β-D-glucoside could enhance the absorption of prim-O-glucosylcimifugin and cimifugin and improve the bioavailability, explaining preliminarily the rationality of Astragali Radix-Saposhnikoviae Radix herb couple.

Study on HPLC chromatograms of different processed Euphorbia ebracteolata products and content change of three chemical components / 中国中药杂志

To prepare processed products with different methods, in order to study the impact of auxiliary materials and temperature on chemical components of Euphorbia ebracteolata, and establish specific chromatograms of different processed products. Wel-chorm-C18 column (4.6 mm x 250 mm, 5 microm) was used and eluted with a gradient program, with acetonitrile (A)-water(B). The column temperature was 25 degrees C, and the detection wave length was set at 226 nm. The aim was to determine the content of effective components in different processed products--ebracteolata cpd B, ebracteolata cpd C and jolkinolide B and establish respective characteristic fingerprints to compare with similarity. The results showed that the content of ebracteolata cpd B, ebracteolata cpd C first increased and then decreased with the rise in temperature. Different processed products showed significant difference in HPLC spectrograms, with a low similarity. This study showed great impacts of auxiliary materials and temperature on chemical components of E. ebracteolata. As the vinegar processing method had higher attenuation and and synergistic effects than other methods, the auxiliary material vinegar cannot be replaced by chemical reagent acetic acid.

Intestinal absorption properties of three components in salvianolic acid extract and the effect of borneol on their absorption in rats / 药学学报

This study aimed to investigate the effects of concentration, intestinal section and borneol on the intestinal absorption of salvianolic acids. The experiment not only studied the intestinal absorption properties of three concentrations of rosmarinic acid, salvianolic acid B and salvianolic acid A at duodenum, jejunum and ileum, but also of salvianolic acids compatible with borneol at different concentrations using single-pass intestinal perfusion model in rat with phenol red as the marker. The results showed that salvianolic acids was stable under weak-acid condition and affected by metabolism enzyme; The Peff and Ka significantly different among three concentrations of rosmarinic acid and salvianolic acid B, whose intestinal absorption were saturated in high concentration, suggesting that the transport mechanisms of rosmarinic acid and salvianolic acid B were similar to active transport or facilitated diffusion; However, there was inconspicuousness in the Peff and Ka of salvianolic acid A at different concentrations, whose absorption was not saturated in high concentration, indicating that the transport mechanisms of salvianolic acid A was passive diffusion; The Peff and Ka in the ileum obviously higher than those in the duodenum and jejunum, namely the ileum was the best absorption section; When concentration of borneol increased, the enhancing effect of intestinal absorption of salvianolic acids increased, but significantly decreased when borneol increased to some degree. The enhancing effect of medium borneol concentration was the optimum. This implied that borneol can enhance the intestinal absorption of salvianolic acids, and the capacity of enhancing effect was influenced by the concentration of borneol.

Intestinal absorption of the effective components of Schisandra chinensis Baill by rats single-pass perfusion in situ / 药学学报

The aim of the study is to investigate rat intestinal absorption behavior of three main active components, schisandrol A, schisandrin A and schisandrin B in Schisandra chinensis Baill extracts in intestine of rats. With phenol red as the indicator, in situ single pass intestinal perfusion (SPIP) model was used and the concentrations of three main active components in perfusion solution of different intestinal segments (duodenum, jejunum, ileum, and colon) were determined by HPLC in combination with diode array detection. The results showed that the absorption rate constant (Ka) and effective permeability values (Peff) of three main active components in Schisandra chinensis Baill extracts had significant difference (P < 0.05) at different concentrations of perfusion solution, the Ka and Peff first increased and then decreased with the increase of drug concentration, the middle concentration was higher than those of the other two concentrations. The saturate absorption phenomena were observed, and it suggested that the transport mechanisms of three main active components in vivo were similar to active transport or facilitated diffusion. Three active components can be well absorbed in all of the intestinal segments, while duodenum is the best absorption region. The Ka and Peff of three active components in jejunum and ileum had no significant difference (P > 0.05). The absorption of the three active components displayed significant difference (P < 0.05) at different intestinal segments of rats. Schisandrin A had the best absorption in duodenum. The Ka and Peff among three active components were sequenced as follows: schisandrin A > schisandrin B > schisandrol A in other intestinal segments, and there is significant difference (P < 0.05) between them.

High performance capillary electrophoresis fingerprint of Corni Fructus pieces / 中草药

Objective: To establish a micellar electrokinetic chromatography method with high perfor mance capillary electrophoresis (HPCE) fingerprint of Corni Fructus pieces. Methods: Separation was performed on a fused-silica capillary column (64. 5 cm x 75 μm, effective length 56 cm) with 50 mmol/L borax solution -40 mmol/L SDS- 5% acetonitrile (pH 9. 5) as HPCE buffer. The running voltage was 10 kV, the detection wavelength was 240 nm, and column temperature was 18°C. Taking loganin as reference, the data were analysed by Fuzzy Cluster and Fingerprint Similarity Evaluation Software to compare the similarity of samples. Results: HPCE Fingerprint was established with nine common peaks. Conclusion The method is accurate, simple, and suitable to the quality control of Corni Fructus.

Clinical observation on acupuncture for treatment of paralytic strabismus / 中国针灸

<p><b>OBJECTIVE</b>To compare therapeutic effects of acupuncture at local points of eye and western medicine on paralytic strabismus.</p><p><b>METHODS</b>One hundred cases were randomly divided into an acupuncture group and a medication group. The acupuncture group (58 cases) was treated with acupuncture at local points of eye, Jingming (BL 1), Tongziliao (GB 1), Shangming (Extra) etc. were selected; and the medication group (42 cases) was treated with oral administration of Methycobal and Vitamin B1. After treatment of 5 courses, the therapeutic effects in the two groups were observed.</p><p><b>RESULTS</b>The total effective rate of 94.8% in the acupuncture group was superior to that of 85.7% in the medication group (P<0.01); the therapeutic effects of the acupuncture group for treatment of oculomotor nerve and abducent nerve were significantly better than that of the medication group (P<0.05); the acupuncture group was better than the medication group in synoptophore examination results and improvement of rima oculi and pupil (P<0.01, P<0.05), the acupuncture group was superior to the medication group in improvement of the function of paralysis eye muscle, including medial rectus and lateral rectus except superior oblique (P<0.01, P<0.05).</p><p><b>CONCLUSION</b>Acupuncture on local points of eye is an effective therapy for paralytic strabismus.</p>

Preparation and properties of sustained-release pellets of glycyrrhizin effective components / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare the glycyrrhizin pellets by extrusion-spheronization, and optimize the formulation of sustained release pellets of glycyrrhizin effective components coated with mixed Eudragit RS 100 and Eudragit RL 100.</p><p><b>METHOD</b>The sustained-release pellets of glycyrrhizin were prepared by Glatt fluid bed technique. The ratio of Eudragit RS 100 to Eudragit RL 100 in the formulation was optimized. The factors that influence the drug release behaviors and their properties were evaluated.</p><p><b>RESULT</b>The optimal coat for drug sustained-release was shown at the ratio of Eudragit RS 100 to Eudragit RL 100 of 4:1, the loading weight of copolymers of 5% and the plasticizer concentration of 15%. The curves of cumulative drug release were fit for Peppas and Higuchi equation.</p><p><b>CONCLUSION</b>The optimal sustained release of the glycyrrhizin effective component pellets is featured by adjusting the ratio of Eudragit RS 100 to Eudragit RL 100 and the loading weight of copolymers.</p>