In vivo distribution and pharmacokinetics of multiple effective components contained in Panax notoginseng saponins after intratympanic administration / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate in vivo distribution and pharmacokinetics of ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1 ) and sanchinoside R1 (R1) after intratympanic administration (IT) or intravenous administration (IV) of Panax notoginseng saponions (PNS) solution, and provide a novel route for delivering traditional Chinese medicine (TCM) to the brain.</p><p><b>METHOD</b>The guinea pigs were employed as experimental animal. Perilymph (PL), cerebrospinal fluid (CSF), brain tissue and plasma were collected periodically after IT and IV of PNS solution. The concentrations of Rb1, Rg1 and R1 were measured by high performance liquid chromatography (HPLC), and statistic program DAS was applied to the calculation of pharmacokinetic parameters. The self-defined weighting coefficients based on area under curve (AUC) of each component were created to obtain the holistic pharmacokinetic profiles of PNS. The integrated pharmacokinetic parameters were then calculated from non-compartmental model analysis.</p><p><b>RESULT</b>Rb1, Rg1 and R1 diffused through the round window membrane into PL of the inner ear, and then transported to the brain after IT of PNS solution. However, the pharmacokinetic parameters showed significant differences between the three components. Based on the self-defined AUC weighting coefficients integration approach, the holistic pharmacokinetic profiles of PNS were obtained, from which the integrated pharmacokinetic parameters were calculated. The C(max) in CSF and brain tissues following IT were respectively 1.5 and 0.4-fold higher than those following IV. After IT, the AUC in CSF and brain tissues increased by 0.5 and 1.2 times compared with IV. Furthermore, the C(max) and AUC in plasma following IT were respectively 45.9% and 33.1% lower than those following IV.</p><p><b>CONCLUSION</b>This novel intra-cochlear administration might serve as a potential and promising alternative to TCM delivery with enhanced brain-targeted efficiency.</p>

Preparation and release characterization in vitro of pulsed-release tablets of compound Danshen / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare pulsed-release tablet (PTS) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen.</p><p><b>METHOD</b>PTS were achieved by coating the core which contains drugs, CMS-Na, lactose, succinic acid and MCC with separation layer (Eudragit RL), swelling layer (HPMC E5), and controlled-release membrane (Eudragit RS-RL-EC).</p><p><b>RESULT</b>The results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release from the two-step release system. And it indicated that swelling was the basis and prerequisite for drug release from PTS, and the diffusion, organic acid-induced, and osmotic pumping mechanism were involved in drug release, but the latter they were the dominant factors.</p><p><b>CONCLUSION</b>Successfully obtained the PTS of a certain lag-time behind the rapid release which indicate that after bed time administration of such device, the drug plasma concentration-time curve CAN meet the requirements of chronotherapy of cardiovascular disease.</p>

Study on preparation and release mechanism of effervescent osmotic pump tablet of compound Danshen / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare effervescent osmotic pump tablet (EOPTs) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen and to study the mechanism of drug released of that tablets.</p><p><b>METHOD</b>Since compound Danshen consist of compounds with polyphenolic groups or carboxyl groups, such as phenolic acids, flavonoids, and triterpenoids that they were acidic. EOPTs were prepared from tablet cores which containing NaHCO3 as effervescent, NaCL and manitol as osmotic agents, HPMC as retarding agents coating with CA membrane. And study the mechanism of drug released according to the change of tablet osmotic pressure.</p><p><b>RESULT</b>The results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release EOPTs. The drug was completely released from the device with a zero-order release rate over 12 h.</p><p><b>CONCLUSION</b>EOPTs are Successfully obtained EOPT which the drug is released from the device over 12 h and the release mechanism of EOPTs is explained.</p>

Influence of solid dispersion technique combination on dissolution of tanshinone IIA / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the influence on the dissolution of tanshinone IIA (TS IIA) solid dispersions in complex carriers and single, which used in preparation of TS IIA solid dispersions, and further enhance the dissolution of TS IIA.</p><p><b>METHOD</b>The TS IIA solid dispersions were prepared by solvent technique with polyvinylpyrrolidone K30 (PVPK30), poloxamer188 (F68) and combination of PVPK30 and F68 as carriers, respectively. The physical characteristics of TS IIA solid dispersions was studied using differential scanning calorimetry (DSC). Dissolution rates were studied using small cup method (CHP XC III). The solubility of TS IIA with the solid dispersions and pure drug form were determined by HPLC method.</p><p><b>RESULT</b>The DSC analysis suggested that TS IIA was dispersed as an amorphous form in the combination of PVPK30 and F68. Dissolution profile of the prepared solid dispersions could be described by Weibull equation (R>0.99). For tested three carries, Td value (calculated time to 63.2% of total drug release according to Weibull equation) were (90.40 +/- 2.82) min, (204.5 +/- 8.20) min and (25.83 +/- 0.13) min, respectively. The PVPK30/F68-TS IIA solid dispersion resulted in a significant increase of TS IIA solubility compared with prepared PVPK30-TS IIA and F68-TS IIA solid dispersions (P<0.01).</p><p><b>CONCLUSION</b>As compared to single use of PVPK30 or F68, the combination of PVPK30 and F68 improve the dissolution rate and solubility of TS IIA significantly in the prepared solid dispersions (P<0.01). The application of complex carriers in solid dispersion technology should be paid more attention to improvement of poorly soluble drugs dissolution in the future.</p>

Therapeutic effect and toxicity of compound vincristine liposome on breast cancer in nude mice / 生物医学工程学杂志

This study was intended to assess the therapeutic effect and toxicity of Compound vincristine liposome on breast cancer in nude mice. The mammary cancer models of BALB/c nude mice were set up using MCF-7 cells, and were divided into seven groups: MTO-VCR-LP, MTO-VCR-Soln, VCR-LP, VCR-Soln, MTO-LP, MTO-Soln and 0.9% NaCl. After the first treatment in the same day of transplantation, different treatments were given respectively. According to the design, the BLAB/c nude mice were given the therapy, the weight of nude mice and tumor volume were measured, and the tumor growth inhibitory rate was calculated. Bone marrow smears and extravasation injury were observed. The tumor growth inhibitory rates were higher in MTO-VCR-LP and MTO-VCR-Soln groups than in other groups. MTO-VCR-Soln, VCR-Soln and MTO-Soln led to severe local extravasation injury. MTO-VCR-Soln cause serious bone marrow inhibition of nude mice. The average weight of nude mice in the three liposome groups was higher than that in the three solution groups. So the use of liposome as the carriers of the two anticancer drugs could improve the cure rate of cancer and decrease the side-effects. This work, which not only expanded the research field of liposome but also brought in new ideas and new methods to treat cancer. Furthermore, the findings in this research may have the potential for use in clinical practice.

Structure charateristics of mitoxantrone transforsomes / 生物医学工程学杂志

This study sought to clarify the molecular location and the interaction between mitoxantrone and mitoxantrone transforsomes. The anthraquinone of mitoxantrone, a heterocyclic ring that intercalates in the lipid of bilayer, was determined by UV-spectrophotometry and electron probes scan microscopy. Two aminoethylamino side-chains of the drugs fit to the phosphates of lecithin were determined by 8-value, thus the interaction with lecithin was substantiated. Differential scanning calorimetry confirmed that mitoxantrone has remarkable stabilizing effect on the mitoxantrone transforsomes membrane. The mitoxantrone binds tightly to lecithin. So a high degree of encapsulation efficiency and the sustained-release character of mitoxantrone transforsomes are verified.

Study on the preparation of folate-conjugated albumin nanoparticles / 生物医学工程学杂志

Bovine serum albumin nanoparticles(BSANP) were prepared by desolvation method. The activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjuated to the surface of BSANP via the amino groups. Then the folate-conjugated BSANPs (folate-BSANP) were purified with Sephadex G-50 column and completely separated from unreacted folic acid. After chymotryptic hydrolysis, the extent of folate conjugation on the BSANP was determined by quantitative ultraviolet(UV) spectrophotometric analysis. It was found that the spectrum of trypsin digest of folate-conjugate BSANP is basically identical with that of folate, thus indicating folate is successfully expressed on the surface of BSANP. The folate-BSANP was averagely 66 nm in diameter and was spherical in shape. Folate-conjugated BSANP was achieved, which represents a potential new drug carrier for tumor cell-selective targeting.

Preparation of valaciclovir loaded bovine serum albumin nanoparticles surface-modified with glycyrrhizin and its characteristics of targeting to liver / 生物医学工程学杂志

The valaciclovir was used as the model drug, the bovine serum albumin nanoparticles (BSA-NP) were prepared by desolvation process. Glycyrrhizin (GL) was oxidized by sodium periodate to be conjugated to surface reactive amino groups (SRAG) of the VACV-BSA-NP. Gel filtration method combined with HPLC method verified that GL was covalent coupling to the surface of VACV-BSA-NP with mean 9 GL residues per albumin molecule. The mean diameter of the VACV-BSA-NP-GL was 268 +/- 23 nm, the drug loading was 1.35%, and embedding ratio was 68.76%. The characteristics of release in vitro were in accord with two-phase kinetics. The uptake amount of VACV-BSA-NP-GL by primary cultured rat hepatocytes in vitro was higher, compared to the control-VACV-BSA-NP. 69.89% and 64.82% of the VACV were concentrated in liver at 15 min after i.v. VACV-BSA-NP-GL and VACV-BSA-NP, respectively. There is a significant difference between surface-modified group and control group (P<0.10). VACV-BSA-NP-GL was successfully prepared, which is considered to be a novel drug delivery system for targeting to hepatocytes.

Recent Advances in Metabolic Chemistry of Traditional Chinese Drugs / 中草药

Recent studies in the realm of metabolic chemistry of traditional Chinese drugs (TCD),appeared in literature were reviewed. Methods for such study were enumerated and commented upon.Some problems that arised in the study were discussed. It was suggested that the study of metabolic chem-istry on TCD and its compounded preparations should be further pursued.

Pharmacokinetics of cinnamic acid of BAOXIN PILL in rat / 中草药

Object To study the pharmacokinetics of cinnamic acid in BAOXIN PILL * in rat. Methods Plasma concentration of cinnamic acid was determined by HPLC under the following conditions: column: Hypersil ODS C 18 (150 mm?4.6 mm, 5 ?m); column temperature 30 ℃; mobile phase methanol-1% acetic acid (45∶55); flow rate 0.5 mL/min; detection wavelength 273 nm; aliquot injected 10 ?L. Results A method for the determination of plasma cinnamic acid concentration by HPLC was established. Regression equation of cinnamic acid peak area (Y) and plasma concentration (X) was found to be: Y= 4 973.534 8 +42 867.96 678 X; correlation factor r=0.999 8; rate of cinnamic acid recovery from plasma=97.50% and RSD=1.33%; detection limit=0.15 ng; minimal dectable concentration in rat plasma=75 ng/mL. Absorption pattern of cinnamic acid after ig does showed linearity, corresponding to a first order absorption and elimination of open chamber model. The t 1/2 (K a)=7.12 min; t max =53.29 min, C max =0.20 ?g/mL, and t 1/2 (Ke)=340.74 min. Conclusion The pharmacokinetic parameters obtained in this study may be attributed to the combined action of cinnamic acid and other constituents in the compound preparation of BAOXIN PILL.

Studies on the Influencial Factors Affecting the Efficiency of Chinese Materia Medica Extraction / 中草药

Factors which influence the extraction of Chinese materia Medica were comprehensively studied,by ex-tracting each single herb component in the compounded preparation Sinitang as the sample,and determiningthe extraction rate as well as the content of main active principle in each extract as the evaluation criteria. Thegeneral ru1e for the extraction of single herb material was then investigated. The results indicated that it isbetter to desigm the experiment in accordance with it's characteristic object with selection of proper evalua-tion criteria to obtain an optimum process for the extraction of Chinese traditional drugs.

Pharmacokinetics of gastrodigenin in brain tissue of mice after intragastric administration of gastrodin / 中草药

Objective To establish an HPLC method for determination of gastrodigenin concentration in brain tissue of mice and investigate its pharmacokinetics after intragastric administration of gastrodin.Methods The brain homogenate was extracted with acetoacetate and analyzed by HPLC method.The separation was performed on a Diamonsil C18 column(250 mm ? 4.6 mm,5 ?m) under the following chromatographic conditions: mobile phase,acetonitrile-water(10.5∶89.5);column temperature,25 ℃;flow rate,1.0 mL/min;detection wavelength,221 nm;and sampling amount,20 ?L.Results The calibration curve showed good linearity within the concentration range of 50-1 616 ng/mL(r= 0.999 6).The relative recoveries were 93.8%-95.1%,and the RSDs of the intra-and inter-day precision were less than 10%.The concentration-time profile of gastrodigenin in brain tissue of mice showed double peaks(tmax1=15 min,tmax2=90 min).The AUC was 52 822.5 ng?min/g,and t1/2(ke) was 54.8 min.Conclusion The analytical method established for assay of gastrodigenin in brain tissue of mice is sensitive and accurate.The result indicates that gastrodin could rapidly distribute to the brain,be metabolized into gastrodigenin,and be eliminated after oral administration.

Quantitative Determination of Emod in and Chrysophanic Acid in Compound Rhubarb Spray by RP -HPLC / 中药新药与临床药理

Objective To establish a method for the determi nation of emodin and chrysophanic acid in Compound Rhubarb Spray by HPLC.Methods The ODS column was applied.methanol∶water(87∶13)served as mobile phase.The detectio n wavelength was at 254nm and the flow r ate was 0.65ml /min.Results The average recovery of emodin was 99.48%with relative standard deviation being 1.75%(n=9)and the average recovery of chrysoph anic acid was 101.46%with rela-tive standard deviation being 2.85%(n=9).Conclusion The method was simple,rapid and reli able.It is suitable for the quality control of Compound Rhubarb Spray.

Comparative study of extraction on Rhubarb through multiple linear regression and range analysis / 中成药

Objective: To optimize the extraction process for Rhubarb. Methods: Colomrimetric analysis was used to measure the content of active ingredients; Besides, orthogonal design was applied to optimize the technologies of Rhubarb in comparision with two ways to deal with the experimental results. Results: The different optimum extraction processes can be obtained by different ways to deal with the experiment results but the same experiment results were found. Conclusion: The multivariate regression analysis can make up shortage of sense The equation of regression is more helpful for explanation of result and optimum of preparation technology.

Determination of Tannins in Ershiwuweidatang Capsules / 中成药

Objective: To determine tannins in Ershiwuweidatang Capsules (Flos Carthami, Fructus Chebulae, Fructus Terminaliae Billericae, Fructus Phyllanthi, etc.). Methods:Tannins were determined by casein method.Results: The contents of tannins in Ershiwuweidatang Capsules were 0.96%, 0.90%, and 0.85%, respectively. The gallic acid calibration curves were linear at the ranges of 0.8 ～4.0 ?g?mL -1 ( r = 0.999 ). The average recovery of tannic acid was 96.2% with RSD =1.4%( n =5).Conclusion: The method was simple and reliable.

Determination of ester-alkaloids in Shiwuweirupeng Capsules by RP-HPLC / 中成药

Objective: To establish the determination method of ester alkaloids in Shiwuweirupeng Capsules. Methods:The chromatographic method was carried out on Aichrom TM C 18 column using CH 3OH 0.05 mol?L -1 KH 2PO 4 CH 3COOH-(CH 3) 2CHOH(67∶173∶4∶4) as a mobile phase. The detection wavelength was set at 230nm. The flow rate was 1mL?min -1 . The column temperature was 35?C. Results: The benzoic acid calibration curves were linear at the ranges of 0.0152～0.076?g( r =0.9998). The average recoveries of aconitine was 93.3% with RSD =1.9%.Conclusion: This method is simple, reliable and provides a reference standard for the quality control of Shiwuweirupeng Capsules.

Study on Preparation Procedure of Grub Eye Drops / 中成药

Objective: To establish the optimum preparation procedure for Grub Eye Drops. Methods: The amount of extract abtained from extraction solutions, the contents of glutamic acid and glycine, nitrogen content and TLC spots were used to evaluate the extraction procedure for Grub Eye Drops by orthogonal design. Results: The optimum extraction condition was A 3B 2C 1. That is adding ten times amount of water to soaking for 30min, decocting for 1.5h, filtering to obtain filtrate Ⅰ, adding seven times of water into filter residue, decocting for 1h to obtain filtrate Ⅱ, combining filtrate Ⅰ and Ⅱ. Conclusion: The experimental method is suitable for the productive preparation of Grub Eye Drops.

Study on micro-emulsions of volatile oil in rhubarb of compound liquid spray by triangular phase diagram / 中成药

AIM: To optimize the best prescription of micro-emulsions of volatile oil in rhubarb of compound liquid spray by triangular phase diagram METHODS : Poloxamer-108 was used as emulsifiers,absolute alcohol as assistant emulsifiers,volatile oil from Lonicera dasystyla and Curcuma longa as the oil phase,the proportion between the emulsifier and append-emulsifier was established RESULTS : Optimized ratio of Poloxamer-108 and alcohol was 1∶10,the volatile oil in prescription formed micro-emulsions,distributing stably in the spray CONCLUSION : The study of micro-emulsions of volatile oil in compound liquid preparation of traditional Chinese medicine by triangular phase diagram offered a short-cut for resolving its stability. The experiment also suggested that the micro-emulsions could increase solubility of insoluble volatile oil from TCM.

Distribution in vivo of colon-oriented berberine hydrochloride-carboxymethyl konjac glucomannan pellets in rats / 中成药

AIM: To evaluate colon-oriented delivery characteristics of berberine hydrochloricde(BH) containing carboxymethyl konjac glucomannan(CMKGM) pellets. METHODS: BH-containing CMKGM pellets(pellets group) and BH-containing carboxymethyl cellulose suspension(control group) were intragastric administrated to rats at the dose of 50 mg/kg,respectively.Blood samples were obtained from the rat femoral artery,the gastric、entric、cecal、colonic tissues and their contents sampled at a given interval to measure the concentration of BH by HPLC.The bar charts of relative content of BH in different parts of the gastrointestinal tract and theirs contents were drawn.Drug delivery index(DDI) was calculated. RESULTS: Compared with the control group,the concentration and distribution of BH in gastric、enteric tissue and their contents decreased significantly,but in cecal、colonic tissue and their contents less at first,and more than the control group after 2～6 h.The DDI values of the pellets to gastric,enteric,cecal,colonic tissue and their contents were 0.392 4,0.478 6,3.916,4.193,(0.162 8,)0.619 4,3.843,4.087 against the control group,respectively. CONCLUSION: CMKGM pellets may be a useful colon-specific drug delivery system for BH.

Optimized formulation of resveratrol solid lipid nanoparticles by uniform design in combination with central composite design/response surface methodology / 中成药

AIM:To establish a method of optimizing the formulation of resveratrol solid lipid nanoparticles(SLN)quickly and accurately by uniform design in combination with central composite design and response surface.METHODS:Firstly,uniform design was used to optimize the main factors from the five influence factors such as entrapment efficiency,drug loading,average diameter,and PDI(Polydispersity Index).Then,on the ground of it,the main factors determined by unifrom design were optimized by central composite design with three evaluation parameters and response surfaces were nonlineated according to best-fit mathematic models,so optimized formulation was obtained.RESULTS:According to the optimal conditions,the entrapment efficiency,the drug loading,the average diameter and the PDI(Polydispersity Index)of the prepared Res-SLN were 56.77%,2.59%,167 nm and 0.176,respectively.CONCLUSION:The design of combination of uniform design with central composite design is a feasible and convenient method to optimize the prescription of Res-SLN.